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The Wrong Animal: Genetic Mislabeling in Laboratory Mouse Research and the Promise of AI-Assisted Quality Control
Artificial Intelligence in Pulmonary Medicine and Critical Care: A Comprehensive Review of Current Applications, Challenges, and Future Directions
Background: Artificial intelligence (AI) and machine learning (ML) technologies are rapidly transforming pulmonary medicine and critical care, offering unprecedented opportunities for improved diagnosis, prognosis, and patient management. The intensive care unit (ICU) generates vast amounts of real-time data, creating an ideal environment for AI applications, while pulmonary medicine benefits from advanced imaging analysis and predictive modeling. Objective: This comprehensive review examines the current landscape of AI applications in pulmonary medicine and critical care, evaluating their clinical utility, performance metrics, implementation challenges, and future directions. Methods: A systematic literature search was conducted in PubMed, Web of Science, Scopus, and the IEEE databases for studies published between 2020 and 2025, focusing on AI/ML applications in respiratory disease diagnosis, mechanical ventilation optimization, sepsis prediction, sleep medicine, pulmonary function test interpretation, and chronic respiratory disease management. Results: AI systems demonstrate significant promise across multiple domains: lung cancer detection achieves over 90% sensitivity with reduced false positives by up to 30%; Acute Respiratory Distress Syndrome (ARDS) prediction models show pooled sensitivity of 0.81 and specificity of 0.82; sepsis prediction algorithms can alert clinicians up to 12 hours before clinical onset with AUC of 0.83; sleep apnea diagnosis using deep learning achieves 97% sensitivity for moderate-to-severe cases; and AI-based pulmonary function test interpretation achieves 86.6% diagnostic accuracy compared to 65.8% for pulmonologists. The FDA has authorized more than 950 AI-enabled medical devices, with pathology and radiology as major application areas. Discussion: Despite promising performance metrics, significant barriers to clinical implementation persist. Model transparency remains a critical concern, as many algorithms function as "black boxes" unsuitable for high-stakes medical decisions. Validation studies are predominantly single-center and retrospective, limiting generalizability across diverse populations and healthcare settings. Regulatory frameworks are evolving, with the FDA's Predetermined Change Control Plans pathway and the EU AI Act establishing new compliance requirements. Workflow integration challenges, including alarm fatigue and IT infrastructure demands, must be addressed. Ethical considerations regarding data privacy, algorithmic bias, and liability for AI-assisted decisions require ongoing attention. Importantly, the deployment of AI must maintain a qualified human clinician as the final arbitrator of all diagnostic and therapeutic choices, ensuring that AI augments rather than replaces physician expertise. Future directions include multimodal data integration, federated learning for privacy-preserving research, and explainable AI approaches to enhance clinician trust within a supervised deployment framework. Conclusions: AI technologies offer transformative potential for pulmonary medicine and critical care, though successful implementation requires addressing challenges including model transparency, workflow integration, regulatory compliance, and validation across diverse populations. Multi-center prospective trials are needed to establish clinical benefit and patient outcomes.
Chemotherapy and Radiation Therapy Completion Rates in Rural Patients With Stage III Lung Cancer: A Focus on Arkansas
Lung cancer remains the leading cause of cancer-related mortality in the United States, with stage III non-small cell lung cancer (NSCLC) presenting a particularly formidable clinical challenge. Concurrent chemoradiotherapy (cCRT) is the standard of care for patients with unresectable stage III NSCLC, yet treatment completion rates are influenced by geographic, socioeconomic, and structural factors that disproportionately affect rural populations. Arkansas, a state characterized by high rurality, elevated smoking prevalence, and significant oncology workforce shortages, exemplifies the intersection of these disparities. This narrative review synthesizes available evidence on chemotherapy and radiation therapy completion rates in rural patients with stage III lung cancer, with particular attention to the Arkansas context. The review draws upon population-based registry data, national cohort analyses, and state-level epidemiological reports to characterize the scope of rural treatment disparities. Findings indicate that rural patients are significantly less likely to receive guideline-concordant treatment for stage III NSCLC, with completion rates reduced by institutional-level resource limitations, provider shortages, transportation barriers, and socioeconomic disadvantage. In Arkansas, where lung cancer incidence ranks among the highest nationally (68.2 per 100,000) and smoking prevalence is second worst in the nation (18.7%), these disparities are compounded by limited access to screening, late-stage diagnosis, and a fragile rural healthcare infrastructure. The review concludes with recommendations for targeted interventions, including tele-oncology expansion, workforce development, and community-based navigation programs, to improve treatment completion and outcomes in rural Arkansas and similarly situated states.
From Stability to Distinction: A Strategic Roadmap for Elevating Dow University of Health Sciences into the Top 300 Global Medical UniversitiesA Five-Year Institutional Analysis and Strategic Framework, 2026-2030
Background: Dow University of Health Sciences (DUHS) achieved its highest-ever position in the QS World University Rankings by Subject 2026, entering the #501-550 band for Medicine, representing the first sustained upward movement in the institution's six-year QS ranking history. This advancement in the ranking of nearly 850 universities in Medicine is a strategic inflection point for institutional analysis and planning. Objective: This manuscript presents a data-driven strategic analysis of DUHS's current QS ranking position, indicator-level scorecard, domestic and regional competitive landscape, and a structured five-year strategic framework for advancing toward the QS Top 300 in Medicine by 2030. Methods: A systematic review of QS World University Rankings by Subject data (2021-2026) was conducted to characterize DUHS's ranking trajectory and indicator-level profile. Domestic and regional peer benchmarking was conducted using QS Medicine subject-ranking data for Pakistani and South Asian institutions. We developed a six-pillar strategic framework by analyzing indicator-specific growth levers, university ranking literature, and implementation precedents from comparable institutions. Results: DUHS's QS indicator profile reveals a pronounced asymmetry: Citations per Paper (64.3) and Employer Reputation (57.9) represent competitive strengths, while Academic Reputation (43.9) and International Research Network (40.9) are the primary constraints on overall ranking advancement. The gap between the strongest and weakest indicators is 23.4 points. DUHS is the only Pakistani public medical institution with a confirmed QS Medicine subject ranking, positioned approximately 250-300 bands below the only domestic peer with a stronger position, Aga Khan University (#201-250). Six strategic pillars are identified for targeted investment: global research partnerships, publication quality and citation strategy, signature research programs, faculty visibility and academic reputation, international research network expansion, and employer and alumni reputation development. Conclusions: The 2026 QS result confirms that DUHS's academic outputs are generating measurable global recognition. A sustained, focused five-year strategy targeting Academic Reputation and International Research Network scores represents the highest-return pathway to advancement into the Top 300. Implementation requires institutional infrastructure investment, leadership continuity, and a culture of structured international academic engagement.
Artificial Intelligence in Early Detection of Diabetic Retinopathy
Artificial Intelligence in the Diagnosis of Colonic Lesions: Advancing Beyond ConventionalColonoscopy
Colorectal cancer (CRC) is the third most prevalent cancer in the world. Its rising incidence among young adults necessitates the development of improved early detection strategies. Although white light colonoscopy (WLC) is conventionally used as a primary screening tool, it has certain limitations, including operator dependency, inter-operator heterogeneity, Adenoma miss rates, endoscopist fatigue, and inadequate Bowel preparation. Nonetheless, histopathology of tissues remains the gold standard for diagnosis. Artificial intelligence (AI) has emerged as a powerful tool in colonoscopic practice, as it uses deep learning techniques to enhance real-time detection and characterization of colonic lesions. Two Computer-assisted diagnostic (CAD) tools: (CADe), which improves adenoma detection rate (ADR) and reduces adenoma miss rates, and (CADx), which facilitates optical diagnosis of lesions by combining various advanced techniques and helps prevent unnecessary polypectomy and reduce healthcare costs. Besides all these advancements in AI, there are still some challenges to overcome, such as limited real-world diversity, reduced algorithm transparency, and risk of automation bias. For achieving this multicenter validation, standard guidelines and improved clinician training are required. Thus, integrating AI into colonoscopy marks an important shift in clinical practice, providing enhanced precision and efficiency while highlighting its role as an assistive tool in clinical expertise rather than replacing it.
Medication–Meal Timing: An Underrecognized Determinant of Drug Efficacy and Safety
The letter to the editor does not contain an abstract.
Neonatal Hypoxic-Ischemic Encephalopathy: Pathophysiology, Neuroprotective Strategies, and Long-Term Neurodevelopmental Outcomes
Neonatal hypoxic-ischemic encephalopathy (HIE) is a major cause of neonatal mortality and long-term neurodevelopmental disability worldwide, particularly in low- and middle-income countries. It results from impaired cerebral perfusion and oxygen delivery during the perinatal period, initiating a complex and evolving cascade of metabolic failure, excitotoxicity, oxidative stress, inflammation, and cell death. The pathophysiology of HIE is now understood as a dynamic process consisting of primary energy failure, a latent phase, secondary injury, and a prolonged tertiary phase associated with chronic neuroinflammation and impaired brain repair. This evolving understanding has led to the identification of critical therapeutic windows for intervention. Therapeutic hypothermia remains the cornerstone of treatment and has significantly reduced mortality and neurodevelopmental impairment in infants with moderate to severe HIE. However, its neuroprotective effects are incomplete, and a substantial proportion of survivors continue to experience adverse outcomes, including cerebral palsy, epilepsy, cognitive deficits, and behavioral disorders. Consequently, there is growing interest in adjunctive neuroprotective strategies targeting multiple pathways of injury. Emerging therapies such as erythropoietin, melatonin, allopurinol, and stem cell-based interventions have demonstrated promising neuroprotective potential in preclinical and early clinical studies. Advances in neuroimaging, electrophysiological monitoring, and biomarker discovery are improving early diagnosis, risk stratification, and prognostication. Despite these developments, significant challenges remain, particularly in resource-limited settings where access to timely and effective interventions is constrained. A comprehensive approach integrating early identification, multimodal neuroprotection, and long-term neurodevelopmental follow-up is essential. Continued research focusing on precision medicine, combination therapies, and equitable healthcare delivery will be critical to improving outcomes for infants affected by HIE.
Navigating the Efficacy-Safety Trade-off of Once-Weekly Insulin Icodec in Clinical Practice
The recent FDA approval of insulin icodec (Awiqli) on 26 March 2026- the first once-weekly basal insulin for adults with type 2 diabetes(T2D), marks a significant advancement in insulin therapy[1]. Icodec has the potential to increase adherence and overcome therapeutic inertia, two enduring obstacles to the best possible glycemic control, by lowering basal insulin doses from 365 to 52 annually. However, the balance between this agent's greater glycemic effectiveness and the regularly noted rise in hypoglycemia should be carefully considered as clinicians get ready to use it. In the phase 3a ONWARDS study trial, Icodec showed better A1c reductions than daily basal insulins in insulin-naive individuals. Icodec significantly increased time in range (71.9% vs. 66.9%) and decreased A1c by 1.55 percentage points in ONWARDS 1 (n=984) compared to 1.35 with glargine U100 [2].A double-blind trial called ONWARDS 3 (n=588) verified a 0.2 percentage-point advantage over degludec[3]. A meta-analysis of seven RCTs encompassing 3,286 patients reported a pooled A1c advantage of 0.15 percentage points with improved time in range [4]. However, this efficacy benefit came with a warning that medical professionals shouldn't ignore. Combined clinically moderate or severe hypoglycemia happened at 0.30 versus 0.16 occurrences per person-year with glargine U100 in ONWARDS 1 [2]. At 26 weeks, this difference was statistically significant in ONWARDS 3 (0.35 vs. 0.12 occurrences per person-year; P=0.01) [3]. Level 1 hypoglycemia rates were continuously higher with icodec throughout the ONWARDS program, with rate ratios ranging from 1.25 to 1.88, and combined level 2/3 hypoglycemia was considerably raised by 71–89% in three out of six trials [5]. Crucially, despite icodec's extended half-life, absolute hypoglycemia rates in insulin-naive T2D populations remained below 1 incident per person-year, and the length of individual hypoglycemic episodes was not increased. Since ONWARDS 6 showed much greater hypoglycemia rates in type 1 diabetes, the approval was suitably limited to T2D. These findings suggest that the potential benefits and risks associated with the use of ICODEC would best support the treatment of newly diagnosed type 2 diabetes (T2D) patients who are naive to exogenous insulin. This is because their use of weekly dosing of ICODEC would likely provide both increased patient compliance as well as a lower risk of severe hypoglycemia compared to many other diabetes treatments. However, other types of diabetic patients such as those currently using multiple daily injections or continuous subcutaneous insulin infusion (basal-bolus therapy), older diabetic patients, diabetic patients with impaired kidney function and altered blood glucose awareness may require further evaluation prior to initiating ICODEC.
Immuno-metabolic Reprogramming in Perioperative Medicine: A New Determinant of Surgical Outcomes
Chronic surgical stress represents a critical window during which surgical stress, anesthesia, and host immune responses interact to shape short- and long-term patient outcomes. Traditionally, perioperative physiology has been interpreted through isolated frameworks of inflammation, hemodynamics, and organ-specific injury. However, emerging evidence highlights a unifying paradigm—immunometabolic reprogramming—whereby immune cell function is tightly coupled to metabolic pathways. This dynamic interplay influences the magnitude and persistence of inflammation, tissue repair, and susceptibility to complications. Immunometabolism refers to the metabolic processes that govern immune cell activation, differentiation, and function. In the perioperative setting, surgical trauma induces a shift toward glycolysis-dominant metabolism in innate immune cells, supporting rapid cytokine production and inflammatory signaling. While this acute response is adaptive, persistent metabolic dysregulation can promote organ dysfunction, impaired healing, and adverse outcomes such as postoperative cognitive dysfunction, acute kidney injury, and sepsis. Recent advances have demonstrated that key metabolic pathways—including glycolysis, oxidative phosphorylation, fatty acid oxidation, and mitochondrial signaling—play central roles in modulating perioperative immune responses. Metabolites such as succinate and lactate act not merely as energy intermediates but as signaling molecules that amplify inflammatory cascades. Furthermore, mitochondrial dysfunction and reactive oxygen species generation contribute to inflammasome activation and cellular injury. Understanding these mechanisms opens new therapeutic avenues. Targeting immunometabolic pathways through pharmacological modulation, nutritional interventions, and anesthetic strategies may allow clinicians to recalibrate the perioperative immune response rather than simply suppress it. This approach represents a shift toward precision perioperative medicine, where interventions are tailored to the metabolic and immunological state of the patient. This narrative review synthesizes current evidence on immunometabolic reprogramming in perioperative medicine, highlights its role in surgical outcomes, and discusses emerging therapeutic strategies. Recognizing immunometabolism as a central determinant of perioperative physiology may transform how anesthesiologists approach inflammation, organ protection, and recovery in surgical patients.
Beyond Pain Control: The Expanding Perioperative Role of Spinal Cord Stimulation
Chronic pain is a major global health challenge affecting nearly one-third of the adult population and significantly impairing quality of life, psychological well-being, and functional independence. Conventional pain management strategies—including pharmacological therapy, physical rehabilitation, and surgical interventions—often provide inadequate relief for patients suffering from refractory neuropathic pain syndromes. Over the past two decades, spinal cord stimulation (SCS) has emerged as a promising neuromodulation therapy for patients with chronic pain conditions such as failed back surgery syndrome, complex regional pain syndrome, and peripheral neuropathic pain. SCS involves the delivery of controlled electrical impulses to the dorsal columns of the spinal cord through epidurally implanted electrodes connected to an implantable pulse generator. These electrical impulses modulate nociceptive signaling pathways and reduce pain perception by altering neural transmission within the central nervous system. Although the effectiveness of SCS in chronic pain management has been extensively documented, its implications for perioperative care remain under-recognized in anesthesiology practice. Patients with implanted SCS devices may present for unrelated surgical procedures, and anesthesiologists must consider potential interactions between neuromodulation devices and intraoperative equipment such as electrocautery, magnetic resonance imaging, and defibrillation systems. Additionally, perioperative pain management in these patients is often complex due to long-standing opioid exposure, altered pain pathways, and the presence of implanted neuromodulation devices. Recent clinical studies demonstrate that SCS can significantly reduce pain intensity, improve functional outcomes, and decrease reliance on opioid medications in selected patient populations (1)(2). Advances in neuromodulation technology—including high-frequency stimulation, burst stimulation, and closed-loop feedback systems—have further improved the therapeutic efficacy of SCS and expanded its clinical applications (3). These innovations have led to increased adoption of neuromodulation therapy worldwide, resulting in a growing population of patients presenting for surgery with implanted stimulators. The perioperative management of patients with SCS devices requires a multidisciplinary approach involving anesthesiologists, surgeons, and pain specialists. Preoperative evaluation should include identification of device type, assessment of device functionality, and coordination with the patient’s pain management team. Intraoperative management must focus on minimizing electromagnetic interference and preventing device malfunction. Postoperative care should emphasize multimodal analgesia strategies to maintain effective pain control while minimizing opioid consumption. This review explores the perioperative role of spinal cord stimulation in chronic pain patients and highlights important considerations for anesthesiologists involved in perioperative care. By integrating neuromodulation therapies into comprehensive pain management strategies, anesthesiologists can play a critical role in improving perioperative outcomes for patients living with chronic pain. Further research is needed to establish standardized guidelines for perioperative management of neuromodulation devices and to evaluate the impact of SCS therapy on surgical recovery and long-term pain outcomes.
Microglial Metabolic Reprogramming: The Missing Link in Chronic Neurodegeneration
Background: Microglial activation and sustained neuroinflammation are central features of chronic neurodegenerative diseases. Emerging evidence indicates that microglial function is tightly linked to intracellular metabolic state, with shifts between oxidative phosphorylation (OXPHOS) and glycolysis shaping inflammatory output, phagocytosis, and neurotoxicity. Objective: To synthesize mechanistic, translational, and disease-specific evidence that positions microglial metabolic reprogramming as a key driver and potential therapeutic target in chronic neurodegeneration. Methods: Narrative synthesis of preclinical and clinical studies addressing microglial metabolism, mitochondrial dysfunction, inflammasome activation, and immunometabolic interventions. Findings: Pro-inflammatory stimuli (LPS, amyloid-β, α-synuclein) induce glycolytic reprogramming in microglia, accompanied by mitochondrial dysfunction, ROS generation, and NLRP3 inflammasome activation (3,6,9). Disease-specific evidence links these metabolic shifts to impaired debris clearance and sustained cytokine release in Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, and ALS (8,10–13). Aging-associated metabolic drift primes microglia toward inflammatory phenotypes (14). Interventions targeting glycolysis, AMPK activation, or NLRP3 show preclinical promise (3,6,16). Conclusion: Microglial immunometabolism provides a mechanistic bridge between chronic inflammation and neurodegeneration. Precision metabolic modulation of microglia — recalibrating rather than suppressing activity — is a promising translational strategy warranting biomarker-guided clinical evaluation.
microglia; immunometabolism; glycolysis; oxidative phosphorylation; mitochondrial dysfunction; inflammasome; neurodegeneration
Digital PCR versus Quantitative PCR in Diagnostic Pathology: Principles, Clinical Applications, Validation, and Practical Workflow Recommendations — A Comparative Review
Polymerase chain reaction (PCR) technologies are foundational to modern diagnostic pathology. Quantitative PCR (qPCR) has long served as the clinical standard for nucleic acid detection and relative quantification, while digital PCR (dPCR) introduces enhanced analytical precision and sensitivity, particularly for low-abundance targets. This comparative review evaluates mechanistic differences, analytical performance, and clinical applications of qPCR and dPCR, with recommendations for validation and workflow optimization in diagnostic laboratories. Structured analysis demonstrates that both technologies occupy complementary roles in precision molecular pathology. Expanded discussion of validation metrics, clinical workflow, and practical recommendations provides a framework for integration of these technologies into modern diagnostic practice.
digital PCR; quantitative PCR; diagnostic pathology; molecular diagnostics; liquid biopsy; minimal residual disease; assay validation; copy number variation.
Navigating the Complexities of Vaccination in Immunocompromised Patients: Balancing Protection and Risk
Vaccination remains one of the most effective tools in modern medicine, significantly reducing the burden of infectious diseases across populations. In immunocompromised individuals—such as those with primary immunodeficiencies, recipients of solid organ or stem cell transplants, patients with autoimmune conditions, and those undergoing chemotherapy or long-term immunosuppressive therapy—the stakes are even higher. These patients are often at increased risk of contracting vaccine-preventable diseases, which can result in more severe outcomes compared to the general population. However, immunization in this vulnerable group is not straightforward. Immune dysregulation or suppression may lead to reduced immunogenicity, making vaccines less effective. Additionally, live attenuated vaccines may pose safety concerns, and there is ongoing debate about the timing, dosing, and selection of appropriate vaccines for these individuals. The balance between achieving sufficient immune protection and avoiding potential complications requires a nuanced, evidence-informed, and patient-specific approach. This complexity underscores the importance of individualized vaccination strategies, ongoing research, and interdisciplinary collaboration between infectious disease specialists, immunologists, and primary care providers. As the landscape of immunomodulatory therapies continues to evolve, so too must our frameworks for ensuring that immunocompromised patients receive safe and effective immunization.
The Paradox of Ubiquity: Reassessing the Reported Association Between Prenatal Acetaminophen (Tylenol) Exposure and Autism
Background: Observational studies have reported small positive associations between prenatal acetaminophen (Tylenol) use and autism spectrum disorder (ASD). Because acetaminophen is widely used in pregnancy and the indications for its use (e.g., infection, migraine) are themselves associated with neurodevelopmental risk, even tiny imbalances between users and non-users can generate noncausal signals, the paradox of ubiquity. Objective: To review current human studies on prenatal acetaminophen and ASD, explain how, given the high prevalence of exposure confounding by indication, family factors, and exposure misclassification can distort results, and identify designs that best address these issues, especially sibling analyses. Methods: We conducted a rapid, structured meta-analysis of human studies through September 5, 2025. Priority was given to: (1) large population-based cohorts with family-based (sibling) comparisons; (2) biomarker-based exposure assessments (umbilical cord blood, meconium); (3) high-quality evidence syntheses (e.g., Navigation Guide); and (4) professional guidance from the American College of Obstetricians and Gynecologists (ACOG) and the Centers for Disease Control and Prevention (CDC). The primary outcome was autism spectrum disorder (ASD); secondary outcomes were attention-deficit/hyperactivity disorder (ADHD) and intellectual disability (ID). Results: In the nationwide Swedish cohort (n = 2,480,797; 1995–2019), conventional models found marginal risk elevations (e.g., ASD hazard ratio [HR] 1.05, 95% confidence interval [CI] 1.02–1.08), but sibling-control analyses were null (ASD HR 0.98, ADHD HR 0.98, ID HR 1.01), and dose–response patterns vanished; absolute risk differences at age 10 were ≤ 0.21%. Biomarker work in selected cohorts reports higher odds of ASD/ADHD across exposure tertiles, but generalizability and residual confounding remain concerns. Multiple studies link maternal fever, especially in the second trimester and with repeated episodes, to higher ASD risk, consistent with confounding by indication. Conclusions: With ubiquitous exposures and indication-related use, naïve associations are prone to inflation. The strongest, bias-resistant designs (sibling comparisons) do not support a causal link between acetaminophen and ASD. Clinically, the use of acetaminophen remains appropriate when indicated, at the lowest effective dose and shortest duration. Fever, an independent risk factor, should be treated promptly.
Attention-deficit/hyperactivity disorder
A Rare Case of Partial Gonadal Dysgenesis (46,XY) from Pakistan
46XY Partial gonadal dysgenesis(PGD) is a rare subset of disorders of sexual development (DSD). Diagnosing and managing such cases can be particularly challenging in resource-limited settings like Pakistan. We present the case of a 17-year-old male with ambiguous genitalia and hypospadias. On presentation, he was diagnosed with perineal hypospadias, rudimentary blind ending vagina, asymmetric testicular descent and a hypoplastic prostate. Hormonal tests revealed high levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) and low testosterone, and imaging studies showed a normal bladder shape but no prostate. Surgical treatment was performed in two steps. Stage one consisted of scrotoplasty, urethroplasty, chordea correction and grafting. The second operation involved tubular reconstruction of the urethra. Along with that, we also gave hormone replacement therapy for testosterone deficiency and sent the patient for psychological counselling. To our knowledge, no previously published cases of PGD have been reported from Pakistan. Nevertheless, a complete gonadal dysgenesis (Swyer Syndrome) case was described by Jawed et al in 2023. This case report describes this patient’s unique presentation thereby exemplifying the wide spectrum of clinical findings and management difficulties of this case while adding to the scant literature on DSD in Pakistan, in hopes of providing insight to improve patient outcomes.
Jobevne (Bevacizumab-nwgd): Transforming Cancer Treatment With Accessibility and Affordability Across Multiple Indications
Jobevne (Bevacizumab-nwgd) is a recently FDA-approved biosimilar to Avastin, developed by Biocon Biologics for multiple oncology indications. It targets vascular endothelial growth factor (VEGF), a key driver of angiogenesis in cancer, offering effective treatment for conditions such as metastatic colorectal cancer, non-small cell lung cancer, glioblastoma, and advanced ovarian cancer. Clinical trials confirm its safety and efficacy comparable to Avastin, while its lower cost enhances global accessibility. As the sixth biosimilar to Avastin, Jobevne represents a critical advancement in making high-quality cancer therapies more affordable, maintaining therapeutic equivalence with reduced financial burden for patients.
The Impact of Artificial Intelligence Tools on Human Cognitive Abilities: A Comprehensive Review
Background: The rapid integration of artificial intelligence (AI) tools into daily cognitive tasks has raised questions about their impact on human cognitive abilities. Objective: This review synthesizes current research on how the use of AI tools affects cognitive domains, including critical thinking, memory, creativity, and decision-making. Methods: We reviewed empirical studies, including randomized controlled trials, field experiments, and neurophysiological investigations, that examined AI's cognitive effects across educational and professional settings. Results: Evidence reveals a complex, non-linear relationship between AI use and cognition. Moderate AI usage shows minimal cognitive impact, while excessive reliance correlates with decreased critical thinking abilities (cognitive offloading effect), reduced metacognitive accuracy, and lower retention on delayed assessments. Field studies with approximately 1,000 students demonstrated improved immediate performance but worse unassisted outcomes following AI removal, particularly with unrestricted AI access. Neurophysiological data showed reduced brain network connectivity during AI-assisted tasks. Age-related differences emerged, with younger users (17-25 years) exhibiting greater dependence and lower critical-thinking scores. However, well-designed AI tutoring systems with scaffolding produced superior learning gains compared with traditional instruction. Discussion: The findings reveal a fundamental paradox: AI assistance frequently improves immediate task performance while simultaneously undermining durable skill acquisition. Three primary mechanisms mediate these effects: reduced cognitive effort through offloading, diminished metacognitive monitoring, and altered practice patterns. Critically, the cognitive impact of AI is not deterministic but depends on implementation design, with scaffolded AI systems that maintain active engagement producing dramatically different outcomes than those providing direct solutions. Age-related vulnerabilities, particularly among younger users (17-25 years), raise developmental concerns, though higher educational attainment appears to provide protective effects against cognitive offloading tendencies. Conclusions: AI tools do not inherently impair or enhance cognition; rather, their impact depends critically on implementation design, user agency, and interaction patterns. Strategic use that maintains active cognitive engagement can augment human capabilities, while passive reliance risks skill atrophy. Educational interventions promoting AI literacy and metacognitive awareness are essential for optimizing cognitive outcomes.
Dow Entrepreneurial Network (DEN): A Presidential Initiative to Catalyze Physician-Led Innovation and Leadership Among Dow Graduates
Background: Physician leadership and entrepreneurship are increasingly recognized as essential for transforming health systems, yet most medical training still prioritizes individual clinical competence over systems thinking, innovation, and venture creation. Diaspora alumni associations represent an underused platform for cultivating these capabilities at scale. Objective: This narrative review describes the design and early implementation of the Dow Entrepreneurial Network (DEN), a 2025 presidential initiative of the Dow Graduates Association of North America (DOGANA). DEN aims to connect Dow alumni and students interested in entrepreneurship and leadership, using a structured series of virtual and in-person events, mentorship, and peer networking. Methods: We synthesized internal planning documents and program descriptions for the DEN activities in 2025 and interpreted them in light of published literature on physician leadership development and entrepreneurship education in medicine. The analysis focuses on program aims, structure, educational strategies, and anticipated benefits for participants and the wider Dow community. Results: DEN is organized around four core objectives: (1) fostering a global network of Dow alumni entrepreneurs; (2) providing a forum for dialogue on innovation, business models, and physician-led ventures; (3) educating students and alumni about entrepreneurial pathways; and (4) exploring programs that create jobs and opportunities for Dowites in North America, Pakistan, and globally. The initial implementation in 2025 includes a three-part virtual webinar series showcasing Dow alumni founders across clinical and non-clinical sectors, and an in-person DEN session at the DOGANA 2025 annual retreat featuring a health-system CEO as the keynote speaker. These activities are explicitly framed as a voluntary, non-commercial alumni platform with clear disclaimers regarding legal and financial liability. Discussion: DEN aligns closely with evidence that structured leadership and innovation programs improve physicians’ self-efficacy, broaden career trajectories, and can contribute to organizational performance when embedded in supportive ecosystems. By leveraging the Dow diaspora and DOGANA’s organizational infrastructure, DEN offers a low-cost, scalable model for seeding entrepreneurial mindsets, strengthening professional networks, and creating bidirectional pipelines between North American and Pakistan-based initiatives. Conclusion: DEN illustrates how an alumni-led initiative can operationalize physician entrepreneurship and leadership development without creating new degree programs or corporate structures. Future work should evaluate DEN’s impact on participant behavior, venture creation, and contributions to health and social outcomes.
Dow Graduates Association of North America
Aligning Allied Health Science Programs With Workforce Demand in the United States and Texas
Allied health professionals constitute the majority of the U.S. health workforce and are essential to addressing population aging, chronic disease, and rapid technological change. Recent projections, however, show uneven patterns of shortage and surplus across professions and geographies. This narrative, policy-oriented review synthesizes national and Texas data to identify allied health programs that are most aligned with workforce demand, with a particular focus on pathology diagnostics (histology, cytogenetics, and molecular diagnostics) and gateway entry roles such as medical assistants and phlebotomists. Using U.S. Bureau of Labor Statistics (BLS) projections, Health Resources and Services Administration (HRSA) workforce models, Texas workforce reports, vacancy surveys, and professional white papers, we find strong and persistent demand for diagnostic imaging, rehabilitation, respiratory care, clinical laboratory science, and anatomic/molecular pathology support roles, with especially acute shortages in Texas. Within laboratory medicine, histotechnology and clinical genomics, especially cancer cytogenetics and fluorescence in situ hybridization (FISH), emerge as high-need subspecialties where vacancy rates, retirement-driven openings, and the collapse of many formal National Accrediting Agency for Clinical Laboratory Sciences (NAACLS)-accredited cytogenetics programs combine to create structural workforce gaps. At the same time, rapid advances in the adoption of artificial intelligence (AI) are poised to reshape staffing models in these domains, shifting demand away from purely manual, repetitive bench work toward AI-enabled roles that emphasize data interpretation, quality oversight of automated workflows, informatics, and human–machine collaboration. In contrast, pharmacy and selected assistant-level occupations show signals of emerging surplus in some markets. Aligning academic portfolios with these patterns will require expanding and modernizing programs in histotechnology, clinical laboratory science, and cytogenetics/molecular diagnostics; explicitly integrating AI, digital pathology, and data science competencies into curricula; leveraging American Society for Clinical Pathology (ASCP)-recognized alternate training pathways and private–academic collaborations (such as Texas-based cytogenetics initiatives) to replace lost program capacity; using medical assistant and phlebotomy programs as structured on-ramps into higher-skill fields; and exercising caution in further expansion of programs where national projections point toward oversupply.
Fairness Begins at the Gate: Why Pakistan’s MDCAT Must Move Beyond Raw Scores
Background: The Medical and Dental College Admission Test (MDCAT) is the primary gatekeeper for entry into medical and dental education in Pakistan. Recent controversies surrounding MDCAT 2023–2024 paper leaks, skewed score distributions, and the use of raw scores across multiple sessions and years have raised serious concerns about fairness, validity, and public trust. Court judgments and parliamentary debates have further highlighted weaknesses in governance and psychometric practice. Objective: To critically evaluate the current use of raw scores in MDCAT across multiple test forms and years, compare this approach with international best practices in high-stakes testing, and propose a practical roadmap for psychometrically defensible and ethically robust reform. Methods: This narrative review synthesizes evidence from Pakistani legal documents, public notices, and media reports on MDCAT 2022–2024, alongside international standards in educational measurement and technical documentation from major testing agencies (e.g., ETS, NCCAOM, NCBE, AERAs Standards for Educational and Psychological Testing). Results: Findings indicate that: (1) MDCAT scores are currently reported and interpreted as raw percentages, while being declared valid for up to three years across cohorts under Section 17 of the PM&DC Act 2022; (2) multiple court proceedings and independent reviews have noted statistical anomalies, including very weak correlations between MDCAT and board marks, unusually high clusters of near-perfect scores, and credible allegations of paper leaks across sessions; and (3) international high-stakes examinations with multiple forms (e.g., MCAT, LSAT, GRE) rely on equating and scaled scores to ensure comparability, as required by professional standards. Discussion: Using unadjusted raw scores from non-equated forms in a multi-session, multi-year, high-stakes exam is psychometrically indefensible and ethically problematic. It risks hidden advantage, systemic disadvantage, and erosion of trust. Pakistan can align MDCAT with global best practice by legally mandating equated and scaled scoring, creating an independent National Center for Health Professions Assessment, adopting anchor-item designs and item response theory (IRT), and enhancing transparency. Conclusion: Scaling and equating are not statistical luxuries but instruments of justice. For a country where access to competent healthcare can mean life or death, fairness at the very first gate, who is allowed to become a doctor, is an ethical imperative.
Pakistan Medical & Dental Admission Test
NOTCH1-Targeted Endothelialized Patches for Bicuspid Aortic Valve Repair: Precision Strategies to Prevent Early Calcific Degeneration
This Perspective outlines a precision-engineered roadmap for NOTCH1-targeted endothelialized patches designed for bicuspid aortic valve (BAV) repair, a population uniquely susceptible to early and aggressive calcific aortic valve disease (CAVD). It is directed toward translational scientists, device engineers, and regulatory strategists aiming to develop biologically active repair materials that can modulate the earliest molecular triggers of valve calcification. NOTCH1 is a central protective regulator of aortic valve biology, governing mechano-transduction, endothelial homeostasis, and suppression of osteogenic pathways (1–3). Loss or dysregulation of NOTCH1 signaling—whether genetic or due to altered flow patterns inherent to BAV anatomy—drives endothelial dysfunction, inflammatory priming, and osteoblastic transition of valvular interstitial cells (VICs) (2,4). This Perspective synthesizes NOTCH1 biology, summarizes developmental and single-cell transcriptomic insights (1,5), proposes design criteria for patches that restore endothelial NOTCH1 activity, and presents a translational pipeline with mechanical, biochemical, and regulatory milestones. It concludes with an implementation-focused roadmap to accelerate the development of living, mechanosensitive, anti-calcific repair patches for BAV patients.
Reimagining Health-Professions Education: A Roadmap for the AI University of Health and Medicine
Is AI a Bubble That Is About to Burst? A Systematic Review of Financial and Economic Evidence
Background: Extraordinary increases in equity valuations, expenditure, capital intelligence, and public attention have accompanied the rapid expansion of generative AI since 2022. Central banks, international financial institutions, and market analysts increasingly refer to a possible “AI bubble,” raising questions about whether the boom is sustainable or likely to end in a sharp correction. Objective: To systematically review recent evidence and expert assessments on whether current AI-related investments and asset valuations exhibit characteristics of a financial bubble that is likely to burst in the near term. Methods: A systematic search was conducted (January 2023–November 2025) across Google Scholar, SSRN, and websites of major financial institutions and research organizations (e.g., Bank of England, International Monetary Fund, Congressional Research Service, McKinsey Global Institute, Goldman Sachs Research, California Management Review), search terms combined concepts for AI with bubbles, market valuations, and macroeconomic impact. Eligible sources included empirical analyses, official reports, and analytical commentaries that (a) discussed AI in the context of asset valuations or macroeconomic outcomes and (b) provided explicit arguments regarding bubble-like or fundamental characteristics. Data were extracted on (i) valuation or investment metrics, (ii) productivity and growth estimates, and (iii) explicit bubble assessments. A narrative synthesis was performed because of heterogeneity in methods and outcomes. Results: Thirty-five sources met the inclusion criteria, grouped into four categories: (1) financial stability and bubble-risk assessments by central banks and international institutions; (2) macroeconomic modeling and productivity studies; (3) management and strategy reviews of AI and productivity; and (4) market and investment research on AI valuations. Central banks and the International Monetary Fund (IMF) highlight “stretched” valuations and the risk of a sharp market correction, explicitly comparing current AI exuberance to the late-1990s dot-com boom. Macroeconomic and consulting studies project sizable, long-run productivity and GDP gains from AI, although meta-analytic evidence finds no robust relationship between AI adoption and aggregate productivity to date. Primary market analyses acknowledge bubble-like features, rapid valuation growth, circular spending, and concentration, but argue that fundamentals and current earnings distinguish AI from prior purely speculative episodes. Conclusions: The evidence supports a hybrid view: segments of AI-exposed equity markets display speculative excess. They are vulnerable to correction, whereas AI, as a general-purpose technology, has credible long-run economic value. A complete collapse akin to a pure asset bubble appears unlikely; a pattern similar to the dot-com cycle, over-valuation, correction, and subsequent consolidation with lasting productivity effects is more consistent with the available data. For policymakers, firms, and investors, the key challenge is not to bet for or against “AI” in the abstract, but to distinguish bubble-like exposures from durable, productivity-enhancing applications.
Universities in Ruins or on the Cusp of Renewal? Dark Academia, Global Data, Liberal Arts, and the Coming AI Shock
Precision Elastin-Mimetic Electrospun Scaffolds for Aortic Root Reconstruction: Toward Regenerative, In-Situ Tissue Engineering
Reconstruction of the aortic root demands materials that endure complex cyclic loading while preserving native hemodynamics. Current prosthetic and biologic conduits restore patency but do not recapitulate the elastin-dependent compliance and fatigue resistance intrinsic to the aortic root, contributing to valve dysfunction, progressive dilation, and long-term failure. Elastin-mimetic electrospun scaffolds—combining elastin-like polypeptides (ELPs) or elastin-based recombinamers with structural biodegradable polymers such as polycaprolactone (PCL)—offer a rational path toward in-situ regeneration: immediate mechanical support, surface cues for endothelialization, and a degradative timetable that permits host extracellular matrix deposition. Here we synthesize current elastin and vascular tissue engineering literature, define quantitative design targets for aortic-root scaffolds, delineate a preclinical testing pipeline, and map regulatory considerations required for clinical translation. We present two tables that map design levers to mechanical/biologic criteria and preclinical endpoints with recommended assays and sample sizes. This Perspective aims to provide a concise, actionable roadmap for investigators and translational teams pursuing regenerative, elastin-mimetic solutions for aortic root reconstruction.
Funding Brains, Not Bytes: Keeping Seed Grants Focused on Investigators
Unveiling a Giant Hydatid Cyst of the Brain: A Neurosurgical Experience with a Rare Zoonotic Infection
Cerebral hydatid disease is a rare but important manifestation of Echinococcus granulosus, comprising 0.5%–2% of all hydatid cases. It primarily affects children in endemic regions and often remains asymptomatic until the cyst reaches a considerable size, making early diagnosis challenging. An 11-year-old boy from rural Punjab, Pakistan, presented with progressive headache and head enlargement for four months, without seizures or neurological deficits. MRI revealed a large, well-defined cyst (10.9 × 10.2 × 11.2 cm) in the left parieto-occipital region, producing significant mass effect and moderate hydrocephalus. Serology was negative, and systemic imaging ruled out extracranial involvement. The patient underwent parieto-occipital craniotomy, and the cyst was excised intact using the Dowling-Orlando technique to prevent rupture. Histopathology confirmed hydatid disease. Postoperatively, albendazole (10 mg/kg) was administered for 30 days along with anticonvulsants. Recovery was uneventful, and follow-up imaging showed no recurrence. This case underscores the importance of early recognition, meticulous surgical planning, and postoperative monitoring for successful outcomes in cerebral hydatid disease, particularly in endemic areas.
Care for the Caregivers: The Patient and Client First Paradox
TGFBR2-Guided Biomaterial Scaffolds for Aortic Root Reconstruction in Loeys-Dietz Syndrome: Toward Precision Aortopathy Repair
Loeys-Dietz syndrome (LDS) is a rare heritable aortopathy characterized by aggressive aneurysm formation and early dissection, frequently involving the aortic root. Mutations in TGFBR1 and TGFBR2 disrupt canonical TGF-β signaling, resulting in medial degeneration, elastin fragmentation, and aberrant matrix remodeling. Despite advances in surgical and endovascular repair, conventional grafts remain biologically inert and fail to address the underlying molecular dysregulation, predisposing patients to progressive downstream dilation and reoperation. Recent biomaterials research has introduced the concept of bioactive scaffolds—engineered vascular grafts capable of modulating local cell behavior and extracellular matrix (ECM) homeostasis. Emerging data suggest that targeted modulation of TGF-β signaling pathways can restore structural integrity in aneurysm-prone tissue. Incorporating TGFBR2-specific signaling cues within scaffold microarchitecture—via peptide-functionalized polymers or microRNA-loaded nanofibers—offers a precision approach to promote adaptive remodeling and reduce maladaptive fibrosis (1–3). Early in vitro studies using smooth muscle cell (SMC) cultures from TGFBR2-mutant models demonstrate partial normalization of elastogenesis and reduced MMP-2 expression when exposed to receptor-modulating environments (4). Beyond material design, computational modeling and machine learning can optimize scaffold composition, predicting mechanical resilience and cytokine release kinetics under pulsatile flow (5,6). Such integration aligns with the emerging paradigm of intelligent biomaterials—structures that dynamically respond to biomechanical and biochemical feedback, particularly vital in genetically mediated aortic disease. Proposed Translational Framework Preclinical modeling: Evaluate TGFBR2-guided scaffold prototypes in Loeys–Dietz syndrome (LDS) murine or porcine models to assess their ability to stabilize aneurysms, integrate histologically with host tissue, and restore normal TGF-β/SMAD signaling. Key outcomes will include improved medial architecture, reduced matrix degradation, and normalized smooth muscle cell phenotype. Computational optimization: Utilize finite element analysis (FEA) and AI-based predictive modeling to refine scaffold architecture—specifically fiber orientation, pore size, and mechanical compliance—to closely match native aortic root dynamics and minimize local stress concentrations. Simulations will guide iterative design improvements before in vivo testing. Regulatory readiness: Develop GMP-compliant fabrication protocols with standardized sterilization, material traceability, and quality control measures. Conduct biocompatibility and cytotoxicity testing according to ISO 10993 standards to ensure safety, regulatory alignment, and scalability for eventual clinical-grade production. Clinical Translation: Initiate first-in-human compassionate-use implants under rigorous ethical and regulatory oversight in high-risk LDS patients who are unsuitable for standard graft repair. Early outcomes will focus on safety, feasibility, and short-term aortic stability to inform subsequent clinical trial design. SMART Objectives Specific: Design TGFBR2-responsive scaffolds that actively modulate dysregulated TGF-β/SMAD signaling in human aortic smooth muscle cells (SMCs) to promote tissue homeostasis. Measurable: Demonstrate a ≥30% reduction in pathological MMP activity compared to standard ePTFE grafts, along with improved elastic modulus and reduced inflammatory response in preclinical models. Achievable: Employ polymer–nanoparticle hybrid scaffolds with tunable ligand density and controlled mechanical properties, using established materials and fabrication platforms to ensure feasibility. Relevant: Target the high reoperation rates in LDS patients caused by graft maladaptation and progression of aortic pathology beyond the repair site, addressing an unmet clinical need. Time-bound: Complete prototype optimization, preclinical validation, and regulatory documentation within 24 months, progressing from computational design to in vivo testing. By converging molecular genetics with adaptive biomaterial engineering, TGFBR2-guided scaffolds represent a promising avenue for patient-specific aortic repair. Such precision solutions could redefine management of genetically mediated aneurysms, transforming outcomes in a disorder where conventional materials fall short.