Yale Journal of Biology and Medicine

Theoretical frameworks concerning cell fate typically center on proximate causes to explain how cells know what type they are meant to become. While major advances in cell fate theory have been achieved by these mechanism-focused frameworks, there are some aspects of cell decision-making that require an evolutionary interpretation. While mechanistic biologists sometimes turn to evolutionary theory to gain insights about cell fate (cancer is a good example), it is not entirely clear in cell fate theory what insights evolutionary theory can add, and why in some cases it is required for understanding cell fate...

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Objectives : To evaluate the comparative effectiveness of treatments, a randomized clinical trial remains the gold standard but can be challenged by a high cost, a limited sample size, an inability to fully reflect the real world, and feasibility concerns. The objective is to showcase a big data approach that takes advantage of large electronic medical record (EMR) data to emulate clinical trials. To overcome the limitations of regression analysis, a deep learning-based analysis pipeline was developed. Study Design and Setting : Lumpectomy (breast-conserving surgery) and mastectomy are the two most commonly used surgical procedures for early-stage female breast cancer patients...

Spondylocarpotarsal synostosis (SCT) syndrome is a very rare and severe form of skeletal dysplasia. The hallmark features of SCT are disproportionate short stature, scoliosis, fusion of carpal and tarsal bones, and clubfoot. Other common manifestations are cleft palate, conductive and sensorineural hearing loss, joint stiffness, and dental enamel hypoplasia. Homozygous variants in FLNB are known to cause SCT. This study was aimed to investigate the phenotypic and genetic basis of unique presentation of SCT syndrome segregating in a consanguineous Pakistani family...

Intellectual disability (ID) involves compromised intellectual, learning and cognitive skills, and behavioral capabilities with reduced psychomotor skills. One of the preventable causes of ID is congenital hypothyroidism (CH), which may be due to biallelic mutations in thyroid peroxidase ( TPO ). In low- and middle-income countries with no newborn screening programs, CH poses a great risk of ID and long-term morbidity. We report two large Pakistani families with a total of 16 patients afflicted with CH. Detailed clinical and behavioral assessments, SNP-based homozygosity mapping, linkage analysis, and exome sequencing were performed...

Background : Substance-related diagnoses (SRDs) are a common healthcare presentation. This study identified sociodemographic and health-related characteristics associated with having an SRD as the primary reason for a clinical encounter compared to those with an SRD who are treated for other reasons. Methods : Electronic health record (EHR) data on patients with an SRD (n=12,358, ages 18-90) were used to assess if an SRD was the primary reason for a clinical encounter from January 1, 2012-January 1, 2018. Patients were matched on key demographic characteristics at a 1:1 ratio...

Laron syndrome (LS) is a rare autosomal recessively segregating disorder of severe short stature. The condition is characterized by short limbs, delayed puberty, hypoglycemia in infancy, and obesity. Mutations in growth hormone receptor ( GHR ) have been implicated in LS; hence, it is also known as growth hormone insensitivity syndrome (MIM-262500). Here we represent a consanguineous Pakistani family in which three siblings were afflicted with LS. Patients had rather similar phenotypic presentations marked with short stature, delayed bone age, limited extension of elbows, truncal obesity, delayed puberty, childish appearance, and frontal bossing...

This issue of the Yale Journal of Biology and Medicine ( YJBM ) focuses on Big Data and precision analytics in medical research. At the Aortic Institute at Yale New Haven Hospital, the vast majority of our investigations have emanated from our large, prospective clinical database of patients with thoracic aortic aneurysm (TAA), supplemented by ultra-large genetic sequencing files. Among the fundamental clinical and scientific discoveries enabled by application of advanced statistical and artificial intelligence techniques on these clinical and genetic databases are the following: From analysis of Traditional "Big Data" (Large data sets) ...

We present a Pakistani kinship afflicted with a syndrome with features including short stature, reduced sitting height, orofacial symptoms including prominent forehead and thick eyebrows, short and broad thorax, and variable features such as long philtrum, short broad neck, barrel chest, thoracic kyphoscoliosis, hypogonadism, and hypospadias. Phenotypic variation even within different sibships was considerable. The unique combination of the phenotypic characteristics prompted us to determine the shared homozygosity regions in patient genomes and the pathogenic variants by next generation technologies like single nucleotide polymorphism (SNP) genotyping and whole exome sequencing (WES)...

Continuous monitoring and treatment of patients in intensive care units generates vast amounts of data. Critical Care Medicine clinicians incorporate this continuously evolving data to make split-second, life or death decisions for management of these patients. Despite the abundance of data, it can be challenging to consider every accessible data point when making the quick decisions necessary at the point of care. Consequently, Clinical Informatics offers a natural partnership to improve the care for critically ill patients...

The increasing volume of research submissions to academic journals poses a significant challenge for traditional peer-review processes. To address this issue, this study explores the potential of employing ChatGPT, an advanced large language model (LLM), developed by OpenAI, as an artificial intelligence (AI) reviewer for academic journals. By leveraging the vast knowledge and natural language processing capabilities of ChatGPT, we hypothesize it may be possible to enhance the efficiency, consistency, and quality of the peer-review process...

Diagnostic imaging reports are generally written with a target audience of other providers. As a result, the reports are written with medical jargon and technical detail to ensure accurate communication. With implementation of the 21st Century Cures Act, patients have greater and quicker access to their imaging reports, but these reports are still written above the comprehension level of the average patient. Consequently, many patients have requested reports to be conveyed in language accessible to them. Numerous studies have shown that improving patient understanding of their condition results in better outcomes, so driving comprehension of imaging reports is essential...

Ophthalmology stands at the vanguard of incorporating big data into medicine, as exemplified by the integration of The Intelligent Research in Sight (IRIS) Registry. This synergy cultivates patient-centered care, demonstrates real world efficacy and safety data for new therapies, and facilitates comprehensive population health insights. By evaluating the creation and utilization of the world's largest specialty clinical data registry, we underscore the transformative capacity of data-driven medical paradigms, current shortcomings, and future directions...

Background : Low-resolution administrative databases can give biased results, whereas high-resolution, time-stamped variables from clinical databases like MIMIC-IV might provide nuanced insights. We evaluated racial-ethnic disparities in life-sustaining ICU-treatments (Invasive Mechanical Ventilation (IMV), Renal Replacement Therapy (RRT), and Vasopressors (VP)) among patients with sepsis. Methods : In this observational retrospective cohort study, patients fulfilling sepsis-3 criteria were categorized by treatment assignment within the first 4 days...

Many chemicals and toxicants are released into our ecosystem and environment every day, which can cause harmful effects on human populations. Agricultural compounds are used in most crop production and have been shown to cause negative health impacts, including effects on reproduction and other pathologies. Although these chemicals can be helpful for pest and weed control, the compounds indirectly impact humans. Several compounds have been banned in the European Union but continue to be used in the United States...

The peculiar nature of scientific publishing has allowed for a high degree of market concentration and a non-collusive oligopoly. The non-substitutable characteristic of scientific journals has facilitated an environment of market concentration. Acquisition of journals on a capabilities-based approach has seen market concentration increase in favor of a small group of dominant publishers. The digital era of scientific publishing has accelerated concentration. Competition laws have failed to prevent anti-competitive practices...

Despite increasing awareness of the public and global health ramifications of climate change, there is a lack of curricula discussing climate change within medical education. Where greater societal awareness and improved scientific understanding have begun to grab the attention of members of the medical education community, there is the precedent, the desire, and the need to incorporate climate-health topics into medical education. We hosted semi-structured interviews (n=9) with faculty members at different institutions across the country who have been involved with climate change education...

Exposure to environmental variables including declining air quality and increasing temperatures can exert detrimental effects on human health including acute exacerbations of chronic diseases. We aim to investigate the association between these exposures and acute health outcomes in a rural community in Colorado. Meteorological and adult emergency department visit data were retrospectively collected (2013-2017); for asthma outcomes, additional data were available (2003-2017). Daily environmental exposure data included PM10 , maximum daily temperature (MDT), and mean humidity and precipitation...

Background : Relatively little attention has been paid to the potential effects of rising temperatures on changes in human behavior that lead to health and social consequences, including aggression. This study investigated the association between ambient temperature and aggression using assault death data from Seoul, South Korea (1991-2020). Methods : We conducted a time-stratified case-crossover analysis based on conditional logistic regression to control for relevant covariates. The exposure-response curve was explored, and stratified analyses were conducted by season and sociodemographic characteristics...

Background : The discontinuation of the Step 2 Clinical Skills Exam (CS) by the United States Medical Licensing Examination (USMLE) eliminated the need for personal travel to testing centers. The carbon emissions associated with CS have not been previously quantified. Objective : To estimate the annual carbon emissions generated by travel to CS Testing Centers (CSTCs) and to explore differences across geographic regions. Methods : We conducted a cross-sectional, observational study by geocoding medical schools and CSTCs to calculate the distance between them...