Search

Abstract Background The volume of health science publications is escalating rapidly. Thus, keeping up with developments is becoming harder as is the task of finding important cross-domain connections. When geographic location is a relevant component of research reported in publications, these tasks are more difficult because standard search and indexing facilities have limited or no ability to identify geographic foci in documents. This paper introduces HEALTH GeoJunction, a web application that supports researchers in the task of quickly finding scientific publications that are relevant geographically and temporally as well as thematically. Results HEALTH GeoJunction is a geovisual analytics-enabled web application providing: (a) web services using computational reasoning methods to extract place-time-concept information from bibliographic data for documents and (b) visually-enabled place-time-concept query, filtering, and contextualizing tools that apply to both the documents and their extracted content. This paper focuses specifically on strategies for visually-enabled, iterative, facet-like, place-time-concept filtering that allows analysts to quickly drill down to scientific findings of interest in PubMed abstracts and to explore relations among abstracts and extracted concepts in place and time. The approach enables analysts to: find publications without knowing all relevant query parameters, recognize unanticipated geographic relations within and among documents in multiple health domains, identify the thematic emphasis of research targeting particular places, notice changes in concepts over time, and notice changes in places where concepts are emphasized. Conclusions PubMed is a database of over 19 million biomedical abstracts and citations maintained by the National Center for Biotechnology Information; achieving quick filtering is an important contribution due to the database size. Including geography in filters is important due to rapidly escalating attention to geographic factors in public health. The implementation of mechanisms for iterative place-time-concept filtering makes it possible to narrow searches efficiently and quickly from thousands of documents to a small subset that meet place-time-concept constraints. Support for a more-like-this query creates the potential to identify unexpected connections across diverse areas of research. Multi-view visualization methods support understanding of the place, time, and concept components of document collections and enable comparison of filtered query results to the full set of publications.

Human monoclonal antibodies (mAbs) are an important segment in precision therapeutics. Various methodologies are available for generating them. Recombinant human mAbs expression from sorted single B cells is preferred for its rapid expression using mammalian vectors while maintaining in vivo immunoglobulin (Ig) pairing. The success rate of generating recombinant mAbs from single sorted human B cells directly relies on Ig heavy (IgH) and light (IgL) gene coverage of the PCR primers. Existing primer sets fail to cover all functional human Ig gene rearrangements, exhibit high degeneracy leading to non-specific amplifications and mutations arising from primer mismatch/degeneracy, and require high amplification cycles. Some existing primer sets have high coverage but are not designed for expression as recombinant mAbs. Here, we have designed a primer set to amplify all functional V(D)J transcripts in human B cell repertoire using a nested RT-PCR approach. The resultant amplicons can be cloned into mammalian vectors for expression of recombinant mAb. Non-specific amplifications were minimized using isotype-specific primers for cDNA synthesis and limiting primer degeneracy. We validated the designed primers on single sorted B cells, bulk sorted B cells and peripheral blood mononuclear cells. We were successfully able to amplify paired heavy and light chain transcripts in 38.46 % (80/208) from naive, memory and B1 B cell subsets sorted as single B cells. Paired Ig transcripts from five single B cells were cloned into expression vectors and purified from mammalian cells as recombinant mAbs. Thus, our new primer set offers significant advantages over existing primers as it allows amplification of all functional V(D)J rearrangements, facilitating rapid generation of antigen-specific recombinant antibodies from diverse human B cell repertoires following vaccinations and infections previously inaccessible due to primer limitations., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2025. Published by Elsevier B.V.)

Background: Pulmonary Langerhans Cell Histiocytosis (PLCH) is a rare interstitial lung disease primarily affecting young to middle-aged smokers. While traditionally linked to tobacco use, there is growing evidence that cannabis use may contribute to PLCH., Methods: We present a case of a 52-year-old male with PLCH associated with heavy cannabis use. Diagnostic evaluations included CT scan of the chest and histopathological examination of a lung biopsy. In addition, a comprehensive review of the literature was conducted to identify and analyze similar cases of PLCH linked to cannabis use. Databases searched included PubMed and Google Scholar, following PRISMA guidelines., Results: The patient presented with dyspnea, cough and unintentional weight loss. The patient had a 20-year history of smoking approximately ten cannabis blunts per day. Despite normal initial chest X-ray findings, a CT scan of his chest revealed upper lobe predominant cystic changes and emphysema. Histopathology from a transbronchial biopsy confirmed the presence of Langerhans cells, consistent with PLCH. Literature review identified five additional case reports of PLCH associated with cannabis use, involving patients aged 16 to 59 years, with a mean age of 35.8 years. Common clinical presentations included cough, dyspnea, and chest pain, with radiographic findings of nodules and cysts. Treatment was primarily targeted towards smoking cessation, which led to clinical improvement in all cases., Conclusions: This case underscores the potential association between heavy cannabis use and the development of PLCH. With the increasing prevalence of cannabis consumption, it is essential to recognize cannabis as a possible risk factor for PLCH. Further research is needed to understand the pathophysiological mechanisms underlying cannabis-related PLCH. As cannabis use becomes more prevalent with changing legislation, understanding its impact on lung health and potential role in diseases like PLCH is increasingly important., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Cortical interneurons play an important role in mediating the juvenile critical period for ocular dominance plasticity in the mouse primary visual cortex. Previously, we showed that transplantation of cortical interneurons derived from the medial ganglionic eminence (MGE) opens a robust period of ocular dominance plasticity 33-35 days after transplantation into neonatal host visual cortex. The plasticity can be induced by transplanting either PV or SST MGE-derived cortical interneurons; it requires transplanted interneurons to express the vesicular GABAergic transporter; and it is manifested by changes to the host visual circuit. Here, we show that transplantation of MGE-derived cortical interneurons into the adult host visual cortex also opens a period of ocular dominance plasticity. The transplanted interneurons must be active to induce plasticity, and the neuronal activity and tuning of visually evoked responses in transplanted and host PV and SST interneurons are modulated by the locomotor state of the host. We also show that changes in activity over the period of plasticity induction are different between PV and SST interneurons but similar between host and transplanted interneurons of each type. The present findings demonstrate that the transplant-induced plasticity generated in adult visual cortex has many features in common with the role of these interneurons during the normal, juvenile critical period.

Background: Anaplastic large-cell lymphoma primarily involving the omentum is an extremely rare entity with variable clinical presentation. Owing to its rarity and nonspecific clinical manifestation, omental T-cell lymphoma is often diagnosed at a later stage, riddled with complications. While imaging modalities such as computed tomography scan can help a physician reach a diagnosis, cases that present with complications may require a multidisciplinary approach that combines surgical exploration along with consultation from Oncology., Case Presentation: We hereby report a rare case of a 66-year-old African American male patient who presented to the emergency department with complaints of acute gastrointestinal obstruction. A computed tomography scan of the abdomen and pelvis revealed evidence of an internal hernia and surgical exploration revealed a hemorrhagic and infarcted omentum. Biopsies along with immunophenotypic studies confirmed the diagnosis of anaplastic T-cell lymphoma of the omentum complicated by Massilia timonae infection., Conclusion: The case highlights the significance of considering lymphoma, although rare, as a differential in a patient who presents with small bowel obstruction and the importance of investigating for malignancy for early diagnosis and treatment of primary omental lymphomas, before complications develop., (© 2024. The Author(s).)

Type 2 diabetes mellitus (T2DM) is associated with impaired leptomeningeal collateral compensation and poor stroke outcome. Neutrophils tethering and rolling on endothelium after stroke can also independently reduce flow velocity. However, the chronology and topological changes in collateral circulation in T2DM is not yet defined. Here, we describe the spatial and temporal blood flow dynamics and vessel remodeling in pial arteries and veins and leukocyte-endothelial adhesion following middle cerebral artery (MCA) stroke using two-photon microscopy in awake control and T2DM mice. Relative to control mice prior to stroke, T2DM mice already exhibited smaller pial vessels with reduced flow velocity. Following stroke, T2DM mice displayed persistently reduced blood flow in pial arteries and veins, resulting in a poor recovery of downstream penetrating arterial flow and a sustained deficit in microvascular flow. There was also persistent increase of leukocyte adhesion to the endothelium of veins, coincided with elevated neutrophils infiltration into brain parenchyma in T2DM mice compared to control mice after stroke. Our data suggest that T2DM-induced increase in chronic inflammation may contribute to the remodeling of leptomeningeal collateral circulation and the observed hemodynamics deficiency that potentiates poor stroke outcome., Competing Interests: Disclosure/Conflict of Interest: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Background: Serratia marcescens ( S. marcescens ) is an unusual cause of osteomyelitis. Infection may develop following open trauma, intravenous drug abuse, or in the presence of hardware, but osteoarticular infections outside of this context are atypical in the absence of immunodeficiency. Rarely, a chronic indolent infection may develop after open trauma with disease recurrence years after the initial injury., Case Description: We present the case of a 16-year-old male with extensive left lower extremity osteomyelitis secondary to S. marcescens eight years after an open fracture to this leg was complicated by an infection with the same organism. Suboptimal therapy of his initial infection may have contributed to persistent, latent disease before recurrence years later. Evaluation for immunodeficiency was negative and he responded well to ciprofloxacin antibiotic therapy., Conclusions: S. marcescens infection may complicate open fractures, and, if not adequately treated, a chronic, indolent infection may result, with disease recurrence years later. We stress the importance of adequate therapy for infectious complications following open fractures and discuss virulence factors of S. marcescens that may allow this organism to evade the immune system and survive subclinically within a host. The optimal therapy of S. marcescens osteomyelitis is not established and further studies are needed to best guide the therapeutic approach., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tp.amegroups.com/article/view/10.21037/tp-23-492/coif). J.A.M. received funding from the Indiana University Immunology and Infectious Disease Training Program T32 (No. NIH AI060519) and the Pediatric Infectious Diseases Society Fellowship Award funded by Stanley and Susan Plotkin and Sanofi, which supported his salary during fellowship training. The other authors have no conflicts of interest to declare., (2024 Translational Pediatrics. All rights reserved.)

Cohesin mediates chromatin loop formation across the genome by extruding chromatin between convergently oriented CTCF-binding elements. Recent studies indicate that cohesin-mediated loop extrusion in developing B cells presents immunoglobulin heavy chain (Igh) variable (V), diversity (D) and joining (J) gene segments to RAG endonuclease through a process referred to as RAG chromatin scanning. RAG initiates V(D)J recombinational joining of these gene segments to generate the large number of different Igh variable region exons that are required for immune responses to diverse pathogens. Antigen-activated mature B cells also use chromatin loop extrusion to mediate the synapsis, breakage and end joining of switch regions flanking Igh constant region exons during class-switch recombination, which allows for the expression of different antibody constant region isotypes that optimize the functions of antigen-specific antibodies to eliminate pathogens. Here, we review recent advances in our understanding of chromatin loop extrusion during V(D)J recombination and class-switch recombination at the Igh locus., (© 2022. Springer Nature Limited.)

Pulmonary fibrosis (PF) is a feared outcome of many pulmonary diseases which results in a reduction in lung compliance and capacity. The development of PF is relatively rare, but it can occur secondary to viral pneumonia, especially COVID-19 infection. While COVID-19 infection and its complications are still under investigation, we can look at a similar outbreak in the past to gain better insight as to the expected long-term outcomes of COVID-19 patient lung function. In the current article, we review the literature relative to PF via PubMed. We also performed a literature search for COVID-related pathological changes in the lungs. Finally, the paper was reviewed and summarized based on the studies' integrity, relative, or power calculations. This article provides a narrative review that endeavors to elucidate the current understanding of the pathophysiological mechanisms underlying PF and therapeutic strategies. We also discussed the potential for preventing progression to the fibrotic state within the context of the COVID-19 pandemic. With the massive scale of the COVID-19 pandemic, we expect there should more instances of PF due to COVID-19 infection. Patients who survive severe COVID-19 infection may suffer from a high incidence of PF.

Background: Homebound individuals with advanced Parkinson disease (PD) require intensive caregiving, the majority of which is provided by informal, family caregivers. PD caregiver strain is an independent risk factor for institutionalization. There are currently no effective interventions to support advanced PD caregivers. Studies in other neurologic disorders, however, have demonstrated the potential for peer mentoring interventions to improve caregiver outcomes. In the context of an ongoing trial of interdisciplinary home visits, we designed and piloted a nested trial of caregiver peer mentoring for informal caregivers of individuals with advanced PD., Objective: The aim of this study was to test the feasibility of peer mentoring for caregivers of homebound individuals with advanced PD and to evaluate its effects on anxiety, depression, and caregiver strain., Methods: This was a single-center, 16-week pilot study of caregiver peer mentoring nested within a year-long controlled trial of interdisciplinary home visits. We recruited 34 experienced former or current family caregivers who completed structured mentor training. Caregivers enrolled in the larger interdisciplinary home visit trial consented to receive 16 weeks of weekly, one-to-one peer mentoring calls with a trained peer mentor. Weekly calls were guided by a curriculum on advanced PD management and caregiver support. Fidelity to and satisfaction with the intervention were gathered via biweekly study diaries. Anxiety, depression, and caregiver strain were measured pre- and postmentoring intervention at home visits 2 and 3., Results: Enrollment and peer-mentor training began in 2018, and 65 caregivers enrolled in the overarching trial. The majority of mentors and mentees were White, female spouses or partners of individuals with PD; mentors had a mean of 8.7 (SD 6.4) years of caregiving experience, and 33 mentors were matched with at least 1 mentee., Conclusions: This is the first study of caregiver peer mentoring in PD and may establish an adaptable and sustainable model for disease-specific caregiver interventions in PD and other neurodegenerative diseases., Trial Registration: ClinicalTrials.gov NCT03189459; http://clinicaltrials.gov/ct2/show/NCT03189459., International Registered Report Identifier (irrid): DERR1-10.2196/34750., (©Jori E Fleisher, Faizan Akram, Jeanette Lee, Ellen C Klostermann, Serena P Hess, Erica Myrick, Melissa Levin, Bichun Ouyang, Jayne Wilkinson, Deborah A Hall, Joshua Chodosh. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 26.05.2022.)

Advancements in reprogramming somatic cells into induced pluripotent stem cells (iPSCs) have provided a strong framework for in vitro disease modeling, gene correction and stem cell-based regenerative medicine. In cases of skeletal muscle disorders, iPSCs can be used for the generation of skeletal muscle progenitors to study disease mechanisms, or implementation for the treatment of muscle disorders. We have recently developed an improved directed differentiation method for the derivation of skeletal myogenic progenitors from hiPSCs. This method allows for a short-term (2 weeks) and efficient skeletal myogenic induction (45-65% of the cells) in human pluripotent stem cells (ESCs/iPSCs) using small molecules to induce mesoderm and subsequently myotomal progenitors, without the need for any gene integration or modification. After initial differentiation, skeletal myogenic progenitors can be purified from unwanted cells using surface markers (CD10 + CD24 - ). These myogenic progenitors have been extensively characterized using in vitro gene expression/differentiation profiling as well as in vivo engraftment studies in dystrophic (mdx) and muscle injury (VML) rodent models and have been proven to be able to engraft and form mature myofibers as well as seeding muscle stem cells. The current protocol describes a detailed, step-by-step guide for this method and outlines important experimental details and troubleshooting points for its application in any human pluripotent stem cells.

Human Granulocytic Anaplasmosis (HGA) is an acute febrile tick-borne illness caused by the organism Anaplasma phagocytophilum. Patients often present with fever and a flu-like symptoms following a tick bite. In this case, the patient presented with subacute abdominal pain and severe hyponatremia consistent with SIADH. The patient was started on appropriate empiric antibiotics given the patient's tick exposure. Blood smear confirmed findings consistent with HGA and the patient continued antibiotic treatment with resolution of his symptoms. This case is unique in that the patient presented with severe hyponatremia that improved with treatment of the HGA. He also had subacute abdominal pain which is also a rare presentation of HGA. Our hope is that our case highlights the value of empiric treatment with appropriate monitoring to prevent downstream, severe sequelae from undiagnosed HGA. In the setting of climate change, increased duration of Ixodes spp. tick life cycles with emerging regional distribution of the ticks, coinfections with Borrelia burgdorferi and increased incidence of HGA in the last two decades, it is important to recognize this entity., (© 2021 The Authors.)

In this perspective, the potential application of stem cells for the treatment of COVID-19 related pneumonia and their potential mechanism of action have been overviewed., (© 2020 Wiley Periodicals LLC.)

Background: Tuberculosis (TB) is an uncommon disease in the Western hemisphere that can present with peritoneal involvement, as tuberculous peritonitis(TBP) causing abdominal pain and fever. The healthcare and economic burden of TBP in the United States remains unknown., Methods: The National Inpatient Sample database was utilized to investigate TBP hospitalizations from 2002 to 2014. Economic expenditures, patient and hospital demographics, and associations of certain comorbidities with TBP were analyzed., Results: A total of 5878 hospitalizations for TBP occurred over the 12-year duration, with $420 million in-hospital charges. The median patient age was 45 years (interquartile range: 31.1-61.7), with the majority being Hispanic (27.15%). Hospitalizations occurred primarily in the Western (31.3%) and Southern (31.7%) United States. Patient comorbidities and the respective odds ratio associated with TBP included HIV (33.56), continuous peritoneal dialysis (10.49), malnutrition (7.38), liver cirrhosis (6.87), and liver cirrhosis sequelae (6.91). Nearly 6.37% of TBP hospitalizations also had active pulmonary TB., Conclusion: Although TBP is uncommon in the United States, it should be considered in patients presenting with abdominal pain and fever and a history of HIV, continuous peritoneal dialysis, malnutrition, liver cirrhosis, or liver cirrhosis sequelae., Competing Interests: None

Hebbian plasticity is widely considered to be the mechanism by which information can be coded and retained in neurons in the brain. Homeostatic plasticity moves the neuron back towards its original state following a perturbation, including perturbations produced by Hebbian plasticity. How then does homeostatic plasticity avoid erasing the Hebbian coded information? To understand how plasticity works in the brain, and therefore to understand learning, memory, sensory adaptation, development and recovery from injury, requires development of a theory of plasticity that integrates both forms of plasticity into a whole. In April 2016, a group of computational and experimental neuroscientists met in London at a discussion meeting hosted by the Royal Society to identify the critical questions in the field and to frame the research agenda for the next steps. Here, we provide a brief introduction to the papers arising from the meeting and highlight some of the themes to have emerged from the discussions.This article is part of the themed issue 'Integrating Hebbian and homeostatic plasticity'., (© 2017 The Author(s).)

Purpose: Hodgkin lymphoma (HL) is the commonest cancer in adolescents and young adults (AYAs), aged 15-29 years. While the survival rate is high, many survivors experience adverse late effects of therapy. Yet, this age group in general makes limited use of health services. This study sought to determine whether the need for health services by HL survivors was mismatched to their health service utilization, as hypothesized a priori., Methods: A population-based cohort of survivors (N = 43) younger than 39 years of age was sent a mailed survey for self-assessment of need, as expressed in health-related quality of life (HRQOL), and utilization of health services by validated instruments; the Health Utilities Index and Health and Social Service Utilization Survey, respectively. Survivors who were AYAs at diagnosis were compared to children and older adults., Results: AYAs had the lowest mean HRQOL score (0.79 on a scale of 0.00-1.00) compared to children (0.86) and older adults (0.94)-clinically meaningful differences. The difference in the single attribute score for cognition reached statistical significance (0.89 vs. 0.99 vs. 1.00, p = 0.02). AYAs also had lower mean overall annual costs for health services (CAN$601) than children (CAN$753) and older adults (CAN$936) did., Conclusions: Survivors of HL who were AYAs at diagnosis had a mismatch between high need for and low utilization of health services. Providers of healthcare to this population should be made aware of this discrepancy, and the survivors should be encouraged to seek the health services they need.

Monocular deprivation (MD) during a critical period of visual development triggers a rapid remodeling of cortical responses in favor of the open eye. We have previously shown that this process is enhanced by sleep and is inhibited when the sleeping cortex is reversibly inactivated. A related but distinct form of cortical plasticity is evoked when the originally deprived eye (ODE) is reopened, and the non-deprived eye is closed during the critical period (reverse monocular deprivation (RMD)). Recent studies suggest that different mechanisms regulate the initial loss of deprived eye responses following MD and the recovery of deprived eye responses following RMD. In this study we investigated whether sleep also enhances RMD plasticity in critical period cats. Using polysomnography combined with microelectrode recordings and intrinsic signal optical imaging in visual cortex we show that sleep does not enhance the recovery of ODE responses following RMD. These findings add to the growing evidence that different forms of plasticity in vivo are regulated by distinct mechanisms and that sleep has divergent roles upon different types of experience-dependent cortical plasticity.