Title: 2 Cases Suggest Stem Cell Transplant Might Ease 'Stiff Person' Syndrome
Category: Health News
Created: 8/26/2014 4:36:00 PM
Last Editorial Review: 8/27/2014 12:00:00 AM

Title: California Trees Harbor Fungus Deadly to People With HIV
Category: Health News
Created: 8/28/2014 9:35:00 AM
Last Editorial Review: 8/28/2014 12:00:00 AM

Title: Scientists Find Differences in Brains of Those With Dyslexia
Category: Health News
Created: 8/29/2014 9:36:00 AM
Last Editorial Review: 8/29/2014 12:00:00 AM

Title: Mandatory Life Jacket Laws Could Reduce Boating Deaths
Category: Health News
Created: 8/21/2015 12:00:00 AM
Last Editorial Review: 8/24/2015 12:00:00 AM

Title: After Heart Attack, Quitting Smoking Boosts Mental Health, Quality of Life
Category: Health News
Created: 8/25/2015 12:00:00 AM
Last Editorial Review: 8/26/2015 12:00:00 AM

Title: Health Tip: If Allergic to Eggs
Category: Health News
Created: 8/27/2015 12:00:00 AM
Last Editorial Review: 8/27/2015 12:00:00 AM

Title: High Blood Pressure During Pregnancy May Reappear Later in Life: Study
Category: Health News
Created: 8/27/2015 12:00:00 AM
Last Editorial Review: 8/28/2015 12:00:00 AM

Title: Gains in Life Spans Seen Around the Globe
Category: Health News
Created: 8/27/2015 12:00:00 AM
Last Editorial Review: 8/28/2015 12:00:00 AM

Title: Average Lifespan Longer for Twins
Category: Health News
Created: 8/23/2016 12:00:00 AM
Last Editorial Review: 8/24/2016 12:00:00 AM

Title: Autism-Linked Genes Often Differ Between Siblings
Category: Health News
Created: 8/25/2016 12:00:00 AM
Last Editorial Review: 8/26/2016 12:00:00 AM

Title: Health Tip: Identify Symptoms of a Concussion
Category: Health News
Created: 8/28/2017 12:00:00 AM
Last Editorial Review: 8/28/2017 12:00:00 AM

Title: Health Tip: Identify Bullying
Category: Health News
Created: 8/31/2017 12:00:00 AM
Last Editorial Review: 8/31/2017 12:00:00 AM

Title: College Grades Low? Try a Different Seat in the Classroom
Category: Health News
Created: 8/24/2018 12:00:00 AM
Last Editorial Review: 8/27/2018 12:00:00 AM

Title: Is Teen Drinking Tied to Aggressive Prostate Cancer Later in Life?
Category: Health News
Created: 8/29/2018 12:00:00 AM
Last Editorial Review: 8/29/2018 12:00:00 AM

Title: Tourist With Measles Visited Southern California Attractions
Category: Health News
Created: 8/26/2019 12:00:00 AM
Last Editorial Review: 8/26/2019 12:00:00 AM

Title: Staying Optimistic Might Lengthen Your Life, Study Shows
Category: Health News
Created: 8/26/2019 12:00:00 AM
Last Editorial Review: 8/27/2019 12:00:00 AM

Title: Dodge Dementia With Healthy Lifestyle
Category: Health News
Created: 8/26/2019 12:00:00 AM
Last Editorial Review: 8/27/2019 12:00:00 AM

Title: Why Some Gifts Are Better-Received Than Others
Category: Health News
Created: 8/23/2020 12:00:00 AM
Last Editorial Review: 8/24/2020 12:00:00 AM

Title: What If Many Americans Say No to a Coronavirus Vaccine?
Category: Health News
Created: 8/25/2020 12:00:00 AM
Last Editorial Review: 8/25/2020 12:00:00 AM

Title: Maine Summer Camps Identified, Isolated COVID-19 Cases
Category: Health News
Created: 8/27/2020 12:00:00 AM
Last Editorial Review: 8/27/2020 12:00:00 AM

Title: Hearing Persists at End of Life, Brain Waves of Hospice Patients Show
Category: Health News
Created: 8/26/2020 12:00:00 AM
Last Editorial Review: 8/27/2020 12:00:00 AM

Title: Could Long Naps Shorten Your Life?
Category: Health News
Created: 8/26/2020 12:00:00 AM
Last Editorial Review: 8/27/2020 12:00:00 AM

Title: Jesse Jackson, Wife Hospitalized With COVID
Category: Health News
Created: 8/24/2021 12:00:00 AM
Last Editorial Review: 8/24/2021 12:00:00 AM

Title: Pfizer Asks FDA to Approve Omicron-Specific Booster Shot
Category: Health News
Created: 8/22/2022 12:00:00 AM
Last Editorial Review: 8/23/2022 12:00:00 AM

Title: Wife of California Congressman Died After Using Herbal Remedy for Diabetes, Weight Loss
Category: Health News
Created: 8/25/2022 12:00:00 AM
Last Editorial Review: 8/25/2022 12:00:00 AM

Title: Vegan? Weightlifting May Protect Your Bones
Category: Health News
Created: 8/5/2022 12:00:00 AM
Last Editorial Review: 8/5/2022 12:00:00 AM

Title: How Can You Tell if Your Baby Has an Earache?
Category: Diseases and Conditions
Created: 6/16/2021 12:00:00 AM
Last Editorial Review: 8/23/2022 12:00:00 AM

Title: What Is the Life Expectancy of Someone With CLOVES Syndrome?
Category: Diseases and Conditions
Created: 8/26/2022 12:00:00 AM
Last Editorial Review: 8/26/2022 12:00:00 AM

Title: California Will Produce Its Own Insulin to Bring Down Prices
Category: Health News
Created: 7/8/2022 12:00:00 AM
Last Editorial Review: 7/8/2022 12:00:00 AM

Title: Is Brown Rice Safe if You Have Diabetes?
Category: Health and Living
Created: 7/13/2022 12:00:00 AM
Last Editorial Review: 7/13/2022 12:00:00 AM

Title: Lifestyle May Be Key to Helping You Avoid Dementia
Category: Health News
Created: 8/4/2022 12:00:00 AM
Last Editorial Review: 8/5/2022 12:00:00 AM

Title: What Happens If We Get AIDS?
Category: Diseases and Conditions
Created: 6/10/2022 12:00:00 AM
Last Editorial Review: 6/10/2022 12:00:00 AM

Title: How Do I Know if I Have an Ovarian Cyst or Tumor?
Category: Diseases and Conditions
Created: 7/7/2022 12:00:00 AM
Last Editorial Review: 7/7/2022 12:00:00 AM

Title: Metronidazole (Flagyl) vs. Fluconazole (Diflucan)
Category: Medications
Created: 11/27/2018 12:00:00 AM
Last Editorial Review: 8/24/2022 12:00:00 AM

Title: Kids With ADHD Have Differences in 'Neural Flexibility,' Brain Study Shows
Category: Health News
Created: 7/29/2022 12:00:00 AM
Last Editorial Review: 8/1/2022 12:00:00 AM

Title: Vaginal or C-Section, Method of Childbirth Won't Affect a Couple's Sex Life Later
Category: Health News
Created: 8/24/2022 12:00:00 AM
Last Editorial Review: 8/25/2022 12:00:00 AM

Title: Steps to Long Life: Short Walk Each Day Helps Folks Over 85
Category: Health News
Created: 8/25/2022 12:00:00 AM
Last Editorial Review: 8/25/2022 12:00:00 AM

High-throughput sequencing (HTS) technologies have been instrumental in investigating biological questions at the bulk and single-cell levels. Comparative analysis of two HTS data sets often relies on testing the statistical significance for the difference of two negative binomial distributions (DOTNB). Although negative binomial distributions are well studied, the theoretical results for DOTNB remain largely unexplored. Here, we derive basic analytical results for DOTNB and examine its asymptotic properties. As a state-of-the-art application of DOTNB, we introduce DEGage, a computational method for detecting differentially expressed genes (DEGs) in scRNA-seq data. DEGage calculates the mean of the sample-wise differences of gene expression levels as the test statistic and determines significant differential expression by computing the P-value with DOTNB. Extensive validation using simulated and real scRNA-seq data sets demonstrates that DEGage outperforms five popular DEG analysis tools: DEGseq2, DEsingle, edgeR, Monocle3, and scDD. DEGage is robust against high dropout levels and exhibits superior sensitivity when applied to balanced and imbalanced data sets, even with small sample sizes. We utilize DEGage to analyze prostate cancer scRNA-seq data sets and identify marker genes for 17 cell types. Furthermore, we apply DEGage to scRNA-seq data sets of mouse neurons with and without fear memory and reveal eight potential memory-related genes overlooked in previous analyses. The theoretical results and supporting software for DOTNB can be widely applied to comparative analyses of dispersed count data in HTS and broad research questions.

Most studies of genome organization have focused on intrachromosomal (cis) contacts because they harbor key features such as DNA loops and topologically associating domains. Interchromosomal (trans) contacts have received much less attention, and tools for interrogating potential biologically relevant trans structures are lacking. Here, we develop a computational framework that uses Hi-C data to identify sets of loci that jointly interact in trans. This method, trans-C, initiates probabilistic random walks with restarts from a set of seed loci to traverse an input Hi-C contact network, thereby identifying sets of trans-contacting loci. We validate trans-C in three increasingly complex models of established trans contacts: the Plasmodium falciparum var genes, the mouse olfactory receptor "Greek islands," and the human RBM20 cardiac splicing factory. We then apply trans-C to systematically test the hypothesis that genes coregulated by the same trans-acting element (i.e., a transcription or splicing factor) colocalize in three dimensions to form "RNA factories" that maximize the efficiency and accuracy of RNA biogenesis. We find that many loci with multiple binding sites of the same DNA-binding proteins interact with one another in trans, especially those bound by factors with intrinsically disordered domains. Similarly, clustered binding of a subset of RNA-binding proteins correlates with trans interaction of the encoding loci. We observe that these trans-interacting loci are close to nuclear speckles. These findings support the existence of trans-interacting chromatin domains (TIDs) driven by RNA biogenesis. Trans-C provides an efficient computational framework for studying these and other types of trans interactions, empowering studies of a poorly understood aspect of genome architecture.

The transcription factor (TF) cone-rod homeobox (CRX) is essential for the differentiation and maintenance of photoreceptor cell identity. Several human CRX variants cause degenerative retinopathies, but most are variants of uncertain significance. We performed a deep mutational scan (DMS) of nearly all possible single amino acid substitutions in CRX using a cell-based transcriptional reporter assay, curating a high-confidence list of nearly 2000 variants with altered transcriptional activity. In the structured homeodomain, activity scores closely aligned to a predicted structure and demonstrated position-specific constraints on amino acid substitution. In contrast, the intrinsically disordered transcriptional effector domain displayed a qualitatively different pattern of substitution effects, following compositional constraints without specific residue position requirements in the peptide chain. These compositional constraints were consistent with the acidic exposure model of transcriptional activation. We evaluated the performance of the DMS assay as a clinical variant classification tool using gold-standard classified human variants from ClinVar, identifying pathogenic variants with high specificity and moderate sensitivity. That this performance could be achieved using a synthetic reporter assay in a foreign cell type, even for a highly cell type-specific TF like CRX, suggests that this approach shows promise for DMS of other TFs that function in cell types that are not easily accessible. Together, the results of the CRX DMS identify molecular features of the CRX effector domain and demonstrate utility for integration into the clinical variant classification pipeline.

As a major type of structural variants, tandem duplication plays a critical role in tumorigenesis by increasing oncogene dosage. Recent work has revealed that noncoding enhancers are also affected by duplications leading to the activation of oncogenes that are inside or outside of the duplicated regions. However, the prevalence of enhancer duplication and the identity of their target genes remains largely unknown in the cancer genome. Here, by analyzing whole-genome sequencing data in a non-gene-centric manner, we identify 881 duplication hotspots in 13 major cancer types, most of which do not contain protein-coding genes. We show that the hotspots are enriched with distal enhancer elements and are highly lineage-specific. We develop a HiChIP-based methodology that navigates enhancer–promoter contact maps to prioritize the target genes for the duplication hotspots harboring enhancer elements. The methodology identifies many novel enhancer duplication events activating oncogenes such as ESR1, FOXA1, GATA3, GATA6, TP63, and VEGFA, as well as potentially novel oncogenes such as GRHL2, IRF2BP2, and CREB3L1. In particular, we identify a duplication hotspot on Chromosome 10p15 harboring a cluster of enhancers, which skips over two genes, through a long-range chromatin interaction, to activate an oncogenic isoform of the NET1 gene to promote migration of gastric cancer cells. Focusing on tandem duplications, our study substantially extends the catalog of noncoding driver alterations in multiple cancer types, revealing attractive targets for functional characterization and therapeutic intervention.

Purpose:

Sexual misconduct by physicians is a consequential violation of patient trust. The purpose of this study was to determine the frequency and patterns of sexual misconduct by physicians certified by the American Board of Family Medicine (ABFM).

Artificial Intelligence (AI) is poised to revolutionize family medicine, offering a transformative approach to achieving the Quintuple Aim. This article examines the imperative for family medicine to adapt to the rapidly evolving field of AI, with an emphasis on its integration in clinical practice. AI's recent advancements have the potential to significantly transform health care. We argue for the proactive engagement of family medicine in directing AI technologies toward enhancing the "Quintuple Aim."

The article highlights potential benefits of AI, such as improved patient outcomes through enhanced diagnostic tools, clinician well-being through reduced administrative burdens, and the promotion of health equity by analyzing diverse data sets. However, we also acknowledge the risks associated with AI, including the potential for automation to diverge from patient-centered care and exacerbate health care disparities. Our recommendations stress the need for family medicine education to incorporate AI literacy, the development of a collaborative for AI integration, and the establishment of guidelines and standards through interdisciplinary cooperation. We conclude that although AI poses challenges, its responsible and ethical implementation can revolutionize family medicine, optimizing patient care and enhancing the role of clinicians in a technology-driven future.

Artificial intelligence (AI) is certainly going to have a large, potentially huge, impact on the practice of family medicine. The specialty is fortunate to have leading experts in the field to guide us along the way. One such team of forward thinkers provides insights into where AI can take the specialty. Another article reports on how well AI performed on the American Board of Family Medicine In-Training Examination. In addition to AI, we have 3 articles that investigate the intersection of social needs and the practice of medicine. Four clinical review articles cover nonalcoholic fatty liver disease, headache treatments, single maintenance and reliever therapy for asthma, and the use of cannabis in the setting of chronic pain. The clinical research articles cover point-of-care hemoglobin A1c testing, continuous glucose monitoring, and screening for HIV. Another group of articles examines the profession of family medicine, covering topics ranging from how women family physicians negotiate their first jobs to the words we use to define primary care.

The pursuit of harnessing data for knowledge creation has been an enduring quest, with the advent of machine learning (ML) and artificial intelligence (AI) marking significant milestones in this journey. ML, a subset of AI, emerged as the practice of employing mathematical models to enable computers to learn and improve autonomously based on their experiences. In the pharmaceutical and biopharmaceutical sectors, a significant portion of manufacturing data remains untapped or insufficient for practical use. Recognizing the potential advantages of leveraging the available data for process design and optimization, manufacturers face the daunting challenge of data utilization. Diverse proprietary data formats and parallel data generation systems compound the complexity. The transition to Pharma 4.0 necessitates a paradigm shift in data capture, storage, and accessibility for manufacturing and process operations. This paper highlights the pivotal role of AI in converting process data into actionable knowledge to support critical functions throughout the whole product life cycle. Furthermore, it underscores the importance of maintaining compliance with data integrity guidelines, as mandated by regulatory bodies globally. Embracing AI-driven transformations is a crucial step toward shaping the future of the pharmaceutical industry, ensuring its competitiveness and resilience in an evolving landscape.

Visible particle is an important issue in the biopharmaceutical industry, and it may occur across all the stages in the life cycle of biologics. Upon the occurrence of visible particles, it is often necessary to conduct chemical identification and root cause analysis to safeguard the safety and efficacy of the biotherapeutic products. In this article, we present a number of typical particles and relevant root cause analysis in the categories of extrinsic, intrinsic, and inherent particles that are commonly encountered in the biopharma industry. In particular, the optical images of particles obtained both in situ and after isolation are provided, along with spectral and elemental information. The particle identification was carried out with multiple microscopic and microspectroscopic techniques, including stereo optical microscopy, Fourier-transform infrared microscopy, confocal Raman microscopy, scanning electron microscopy, and energy dispersive X-ray spectroscopy. Both commercial and in-house spectral databases were used for comparison and identification. In addition to particle identification, we placed significant efforts on the root cause analysis of the addressed particles with the intention to provide a relatively whole picture of the particle-related issues and practical references to particle mitigation for our peers in the biopharmaceutical industry.

Animal germline development and fertility rely on paralogs of general transcription factors that recruit RNA polymerase II to ensure cell type-specific gene expression. It remains unclear whether gene expression processes downstream from such paralog-based transcription is distinct from that of canonical RNA polymerase II genes. In Drosophila, the testis-specific TBP-associated factors (tTAFs) activate over a thousand spermatocyte-specific gene promoters to enable meiosis and germ cell differentiation. Here, we show that efficient termination of tTAF-activated transcription relies on testis-specific paralogs of canonical polymerase-associated factor 1 complex (PAF1C) proteins, which form a testis-specific PAF1C (tPAF). Consequently, tPAF mutants show aberrant expression of hundreds of downstream genes due to read-in transcription. Furthermore, tPAF facilitates expression of Y-linked male fertility factor genes and thus serves to maintain spermatocyte-specific gene expression. Consistently, tPAF is required for the segregation of meiotic chromosomes and male fertility. Supported by comparative in vivo protein interaction assays, we provide a mechanistic model for the functional divergence of tPAF and the PAF1C and identify transcription termination as a developmentally regulated process required for germline-specific gene expression.

Neural reflexes occupy a central role in physiological homeostasis. The vagus nerve is a major conduit for transmitting afferent and efferent signals in homeostatic reflex arcs between the body and the brain. Recent advances in neuroscience, immunology, and physiology have revealed important vagus nerve mechanisms in suppressing inflammation and treating rheumatoid arthritis and other autoimmune conditions. Numerous clinical trials indicate that there is significant benefit to vagus nerve stimulation therapy. Although many questions are still unanswered, it will be important, even necessary, to pursue answers that will be useful in guiding interventions to modulate immunological and physiological homeostasis.

The study of biological mechanisms, while crucial, cannot fully explain complex phenomena like the instinct to eat. The mind–body connection, as exemplified by the concept of "voodoo death," highlights the profound influence of belief and cultural context on physiology. Indigenous knowledge systems further emphasize the interconnectedness of humans with their environment. Recent discoveries in gut–brain communication reveal the intricate neural circuits that drive our visceral desires, but a holistic approach that integrates both physiological mechanisms and the subjective experience of life, informed by diverse cultural perspectives, will be essential to truly understand what it means to be alive.

Internal ribosomal entry sites (IRESs) recruit the ribosome to promote translation, typically in an m7G cap-independent manner. Although IRESs are well-documented in viral genomes, they have also been reported in mammalian transcriptomes, where they have been proposed to mediate cap-independent translation of mRNAs. However, subsequent studies have challenged the idea of these "cellular" IRESs. Current methods for screening and discovering IRES activity rely on a bicistronic reporter assay, which is prone to producing false positive signals if the putative IRES sequence has a cryptic promoter or cryptic splicing sites. Here, we report an assay for screening IRES activity using a genetically encoded circular RNA comprising a split nanoluciferase (nLuc) reporter. The circular split nLuc reporter is less susceptible to the various sources of false positives that adversely affect the bicistronic IRES reporter assay and provides a streamlined method for screening IRES activity. Using the circular split nLuc reporter, we find that nine reported cellular IRESs have minimal IRES activity. Overall, the circular split nLuc reporter offers a simplified approach for identifying and validating IRESs and exhibits reduced propensity for producing the types of false positives that can occur with the bicistronic reporter assay.