bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incidental Detection of Brain Metastases From a Pulmonary Large Cell Neuroendocrine Carcinoma at 18F-Fluorocholine PET/CT in a Context of Primary Hyperparathyroidism
Authors: Didier Mathilde , Godard François , Fraisse Cléa , Morin Léo , Drouet Clément 
Published: September 2024

Abstract
This 65-year-old man suffering from hypercalcemia in a context of hyperparathyroidism treated by calcimimetics was referred to our institution to perform an 18F-fluorocholine PET/CT in order to localize the pathological parathyroid gland(s). We incidentally discovered a brain metastatic pulmonary large cell neuroendocrine carcinoma in addition to a parathyroid adenoma. This case illustrates the value of FCH PET/CT in hyperparathyroidism workup event under calcimimetic treatment, as well as the potential of FCH PET/CT to reveal occult malignancies.
Analysis of Clinical Diagnosis and Treatment Modes for Congenital Branchial Cleft Anomalies
Authors: Cai Jian-sheng , Wang Yi-e , Wu Yu-qi , Chen Jing-han , Wang Jia-rong 
Published: September 2024

Objective:
The objective of this study was to investigate and assess the clinical data of 123 patients diagnosed with congenital branchial cleft anomalies (CBCAs), to summarize pivotal aspects concerning their clinical diagnosis and treatment process.

Materials and Methods:
The authors conducted a retrospective analysis of 123 patients who underwent surgical intervention for CBCAs at our institution between August 2005 and September 2021. The clinical demographic characteristics of the patients, primary symptoms, treatment chronology, preoperative diagnostic assessments, surgical strategies, occurrences of postoperative complications, and rates of recurrence were subjected to statistical analysis.

Results:
Among the enrolled patients, there were 43 cases (34.9%) of congenital first branchial cleft anomalies (CFBCA), 76 cases (61.8%) of congenital second branchial cleft anomalies (CSBCA), and 4 cases (3.3%) of congenital third branchial cleft anomalies (CTBCA), with no cases of congenital fourth branchial anomalies (CFBA). Notably, among all cases, 43 anomalies were situated in the upper one-third of the sternocleidomastoid muscle, while 80 anomalies were located in the lower one-third. Different surgical approaches were selected for patients based on the specific type of anomaly presented. Following surgery, there was recurrence in 14 cases, with factors such as patient age, clinical categorization, lesion type, and history of preoperative infection and surgical intervention identified as primary risk factors for it.

Conclusion:
CBCAs represent comparatively uncommon disorders affecting the head and cervical regions in clinical practice. Diagnostic modes such as ultrasonography and lipiodol contrast radiography can be used for accurate diagnosis, with surgical intervention serving as the primary therapeutic method.
Outcomes of Older Primary Kidney Transplant Recipients by Induction Agent and High-risk Viral Discordance Status in the United States
Authors: Ryan Randi J. , Bentall Andrew J. , Issa Naim , Dean Patrick G. , Smith Byron H. , Stegall Mark D. , Riad Samy M. 
Published: September 2024

Background.
The impact of induction type or high-risk viral discordance on older kidney transplant recipients is unclear. Herein, we analyzed the association between induction type, viral discordance, and outcomes for older recipients.

Methods.
We analyzed the Scientific Registry of Transplant Recipients standard analysis file for all primary kidney transplant recipients older than 55 y who were transplanted between 2005 and 2022. All transplants were crossmatch negative and ABO-compatible. Recipients were discharged on tacrolimus and mycophenolate ± steroids. Recipients were categorized into 3 groups by induction received: rabbit antithymocyte globulin (r-ATG; N = 51 079), interleukin-2 receptor antagonist (IL-2RA; N = 22 752), and alemtuzumab (N = 13 465). Kaplan-Meier curves were generated for recipient and graft survival, and follow-up was censored at 10 y. Mixed-effect Cox proportional hazard models examined the association between induction type, high-risk viral discordance, and outcomes of interest. Models were adjusted for pertinent recipient and donor characteristics.

Results.
Induction type did not predict recipient survival in the multivariable model, whereas Epstein-Barr virus high-risk discordance predicted 14% higher mortality (1.14 [1.07-1.21], P < 0.01). In the multivariable model for death-censored graft survival, alemtuzumab, but not IL-2RA, was associated with an increased risk of graft loss (1.18 [1.06-1.29], P < 0.01) compared with r-ATG. High-risk cytomegalovirus discordance predicted 10% lower death-censored graft survival (1.10 [1.01-1.19], P < 0.02). Live donor and preemptive transplantation were favorable predictors of survival.

Conclusions.
In this large cohort of older transplant recipients, alemtuzumab, but not IL-2RA, induction was associated with an increased risk of graft loss compared with r-ATG. Cytomegalovirus and Epstein-Barr virus high-risk viral discordance portended poor graft and recipient survival, respectively.
Clinical Translation and Implementation of a Bioartificial Pancreas Therapy: A Qualitative Study Exploring the Perspectives of People With Type 1 Diabetes
Authors: de Jongh Dide , Lapré Silke , Özcan Behiye , Zietse Robert , Bunnik Eline M. , Massey Emma K. ,   the VANGUARD consortium
Published: September 2024

Background.
The development of a hybrid beta-cell replacement approach, referred to as a personalized, transplantable bioartificial pancreas (BAP), holds promise to treat type 1 diabetes (T1D). This interview study aimed to explore patients’ expectations, needs, concerns, and considerations when considering to undergo a BAP transplantation.

Research Design and Methods.
Semistructured interviews were conducted with 24 participants diagnosed with T1D. Data collection stopped once data saturation was reached. Audio recordings of the interviews were transcribed verbatim. The interviews were independently analyzed by 2 researchers. A qualitative content analysis using an inductive approach was used.

Results.
Three main themes emerged as follow: (1) hoped-for benefits, (2) concerns and decision-making considerations, and (3) procedural aspects. First, the participants expected benefits across medical, psychological, and social domains. Over these 3 domains, 9 subthemes were identified, including improved clinical outcomes, a cure for diabetes, more headspace, emotional relief, a shift in responsibility, protection of privacy, improved flexibility in daily life, less visible diseases, and improved relationships with others. Second, concerns and considerations about undergoing a BAP transplant comprised adverse events, the functionality of the BAP, the surgery procedure, the biological materials used, the transplant location, and the intrusiveness associated with follow-up care. Finally, procedural considerations included equitable access, patient prioritization, and trust and control.

Conclusions.
Incorporating insights from this study into the clinical development and implementation of the BAP is crucial to ensure alignment of the product and procedures with the needs and expectations of people with T1D.
Assortative mating across nine psychiatric disorders is consistent and persistent over cultures and generations
Authors: Fan Chun Chieh , Dehkordi Saeid Rasekhi , Border Richard , Shao Lucy , Xu Bohan , Loughnan Robert , Thompson Wesley K. , Hsu Le-Yin , Lin Mei-Chen , Cheng Chi-Fung , Lai Rou-Yi , Su Mei-Hsin , Kao Wei-Yi , Werge Thomas , Wu Chi-Shin , Schork Andrew J. , Zaitlen Noah , Demur Alfonso Buil , Wang Shi-Heng 
Published: September 2024

AbstractEmerging evidence has shown that assortative mating (AM) is a key factor that shapes the landscape of complex human traits. It can increase the overall prevalence of disorders, influence occurrences of comorbidities, and bias estimation of genetic architectures. However, there is lack of large-scale studies to examine the cultural differences and the generational trends of AM for psychiatric disorders. Here, using national registry datasets, we conduct the largest scale of AM analyses on nine psychiatric disorders, with up to 1.4 million mated cases and 6 million matched controls. We performed meta-analyses on AM estimates from Taiwan, Denmark, and Sweden, to examine the potential impact of cultural differences. Generational changes for people born after 1930s were investigated as well. We found that AM of psychiatric disorders are consistent across nations and persistent over generations, with a small proportion of disorders showing generational changes of AM. Our results provide additional insight into the mechanisms of AM across psychiatric disorders and have evident implications on the estimation of the genetic architectures of psychiatric disorders.
The impact of sugar diet on humidity preference, survival, and host landing in mosquitoes
Authors: Chen Shyh-Chi , Holmes Christopher J. , Ajayi Oluwaseun M. , Goodhart Grace , Eaton Daniel , Catlett Nathan , Cady Tabitha , Tran Hannah , Lutz Luke E. , Wang Lyn , Girard Ella , Savino Jaida , Bidiwala Amena , Benoit Joshua B. 
Published: September 2024

AbstractMosquito-borne diseases have caused more than one million deaths each year. There is an urgent need to develop an effective way to reduce mosquito-host interaction to mitigate disease transmission. Sugar diets have long been linked to abnormal physiology in animals, making them potential candidates for mosquito control. Here, we show the impact of sugar diets on humidity preference and survival inAedes aegyptiandCulex pipiens. With two-choice assays between 100% and 75% relative humidity (RH), we demonstrate that the effect of sugar diets on humidity preference is species-specific whereAe. aegyptishowed significant differences and the reduced effects were noted inCx. pipiens. Among the sugar diets, arabinose significantly reduced the survival rate of mosquitoes even at low concentrations. Moreover, we found that host landing was not impacted by feeding on different sugar types. Our study suggests that specific sugar treatments could be applied to mosquito control by dampening their humidity preference and reducing their lifespan, thus reducing mosquito-borne disease transmission.
SUMO2 Inhibition Reverses Aberrant Epigenetic Rewiring Driven by Synovial Sarcoma Fusion Oncoproteins and Impairs Sarcomagenesis
Authors: Iyer Rema , Deshpande Anagha , Pedgaonkar Aditi , Bala Pramod Akula , Kim Taehee , Brien Gerard L. , Finlay Darren , Vuori Kristiina , Soragni Alice , Murad Rabi , Deshpande Aniruddha J. 
Published: September 2024

ABSTRACTSynovial Sarcoma (SySa) is an aggressive soft tissue sarcoma that accounts for 5 – 10% of all soft tissue sarcomas. Current treatment involves radiation and radical surgery including limb amputation, highlighting the urgent need to develop targeted therapies. We reasoned that transcriptional rewiring by the fusion protein SS18-SSX, the sole oncogenic driver in SySa, creates specific vulnerabilities that can be exploited for treatment. To uncover genes that are selectively essential for SySa, we mined The Cancer Dependency Map (DepMap) data to identify genes that specifically impact the fitness of SySa compared to other tumor cell lines. Targeted CRISPR library screening of SySa-selective candidates revealed that the small ubiquitin-like modifier 2 (SUMO2) was one of the strongest dependencies bothin vitroas well asin vivo. TAK-981, a clinical-stage small molecule SUMO2 inhibitor potently inhibited growth and colony-forming ability. Strikingly, transcriptomic studies showed that pharmacological SUMO2 inhibition with TAK-981 treatment elicited a profound reversal of a gene expression program orchestrated by SS18-SSX fusions. Of note, genetic or pharmacological SUMO2 inhibition reduced global and chromatin levels of the SS18-SSX fusion protein with a concomitant reduction in histone 2A lysine 119 ubiquitination (H2AK119ub), an epigenetic mark that plays an important role in SySa pathogenesis. Taken together, our studies identify SUMO2 as a novel, selective vulnerability in SySa. Since SUMO2 inhibitors are currently in Phase 1/2 clinical trials for other cancers, our findings present a novel avenue for targeted treatment of synovial sarcoma.SIGNIFICANCEOur study identifies SUMO2 as a selective dependency in synovial sarcoma. We demonstrate that the SUMO2/3 inhibitor TAK-981 impairs sarcomagenesis and reverses the SS18-SSX fusion-driven oncotranscriptome. Our study indicates that SUMO2 inhibition may be an attractive therapeutic option in synovial sarcoma.
Assembly and dynamics of the outer membrane exopolysaccharide transporter PelBC ofPseudomonas aeruginosa
Authors: Benedens Marius , Hernandez Cristian Rosales , Straathof Sabine A.P. , Loschwitz Jennifer , Berninghausen Otto , Maglia Giovanni , Beckmann Roland , Kedrov Alexej 
Published: September 2024

AbstractThe infamous opportunistic pathogenPseudomonas aeruginosaenhances its virulence and antibiotic resistance upon formation of durable biofilms. The biofilm stability is mediated by its matrix built of secreted exopolysaccharides, eDNA, and structural proteins. Exopolysaccharides ofP. aeruginosa– Pel, Psl and alginate – have the highest biomedical relevance, but the mechanisms behind their synthesis and secretion are poorly understood. Here, we employ cryogenic electron microscopy to resolve the 2.5 Å structure of the outer membrane complex PelBC for Pel exopolysaccharide, which is uniquely composed of the membrane-embedded β-barrel PelB and the asymmetrical ring of 12 lipoproteins PelC at the periplasmic interface. The assembly captured in the lipid-based nanodisc is stabilized by electrostatic contacts of PelC with the periplasmic loops of PelB and multiple interactions with PelB N-terminal helical domains. Within the membrane, the resolved acyl chains of the PelC lipoproteins are alternated by the tryptophan residues immersed into the lipid leaflet, thus offering a stable anchoring architecture. The highly anionic interior of the PelB β-barrel is sealed by three loops at the extracellular side, where the short Plug-S loop is aligned with the periplasmic helical scaffold, being the potential gating element for the Pel exopolysaccharide tunneling. Molecular dynamic simulations of PelB in native-like membrane environments suggest that Plug-S is sufficiently flexible to open a tunnel, and so serve as a gate. The gating model is further supported by single-channel conductivity measurements, which identify two conductance states of PelB. Via mutational analysis we confirm that Plug-S mediates opening of a narrow tunnel, as required for the controlled exopolysaccharide transport. Our structural and functional analysis of the pathogenicity-relevant complex offer a detailed and comprehensive view on this unique machinery and suggest the route taken by the exopolysaccharide at the final secretion step.
Leveraging neural networks to correct FoldX free energy estimates
Authors: Barnes Jonathan E. , América Chi L. , Marty Ytreberg F. , Patel Jagdish Suresh 
Published: September 2024

AbstractProteins play a pivotal role in many biological processes, and changes in their amino acid sequences can lead to dysfunction and disease. These changes can affect protein folding or interaction with other biomolecules, such as preventing antibodies from inhibiting a viral infection or causing proteins to misfold. The ability to predict the effects of mutations in proteins is crucial. Although experimental techniques can accurately quantify the effect of mutations on protein folding free energies and protein-protein binding free energies, they are often time-consuming and costly. By contrast, computational techniques offer fast and cost-effective alternatives for estimating free energies, but they typically suffer from lower accuracy. Enhancing the accuracy of computational predictions is therefore of high importance, with the potential to greatly impact fields ranging from drug design to understanding disease mechanisms. One such widely used computational method, FoldX, is capable of rapidly predicting the relative folding stability (ΔΔGfold) for a protein as well as the relative binding affinity (ΔΔGbind) between proteins using a single protein structure as input. However, it can suffer from low accuracy, especially for antibody-antigen systems. In this work, we trained a neural network on FoldX output to enhance its prediction accuracy. We first performed FoldX calculations on the largest datasets available for mutations that affect binding (SKEMPIv2) and folding (ProTherm4) with experimentally measured ΔΔG. Features were then extracted from the FoldX output files including its prediction for ΔΔG. We then developed and optimized a neural network framework to predict the difference between FoldX’s estimated ΔΔG and the experimental data, creating a model capable of producing a correction factor. Our approach showed significant improvements in Pearson correlation performance. For single mutations affecting folding, the correlation improved from a baseline of 0.3 to 0.66. In terms of binding, performance increased from 0.37 to 0.61 for single mutations and from 0.52 to 0.81 for double mutations. For epistasis, the correlation for binding affinity (both singles and doubles) improved from 0.19 to 0.59. Our results also indicated that models trained on double mutations enhanced accuracy when predicting higher-order mutations (such as triple or quadruple mutations), whereas models trained on singles did not. This suggests that interaction energy and epistasis effects present in the FoldX output are not fully utilized by FoldX itself. Once trained, these models add minimal computational time but provide a substantial increase in performance, especially for higher-order mutations and epistasis. This makes them a valuable addition to any free energy prediction pipeline using FoldX. Furthermore, we believe this technique can be further optimized and tested for predicting antibody escape, aiding in the efficient development of watch lists.
Impact of Antiretroviral Therapy on Anemia, Hepatotoxicity, and Immune Reconstitution Inflammatory Syndrome in HIV-Tuberculosis Co-Infected Patients
Authors: Gupta Priyanka , Tripathi Anil Kumar , Gupta Shikha , Gupta Abhishek 
Published: September 2024

AbstractIntroductionHIV continues to pose a significant global health challenge, causing gradual immune system decline and, if left untreated, progressing to AIDS. Although antiretroviral therapy (ART) has transformed the treatment landscape for HIV, it is frequently associated with adverse effects, including anemia, hepatotoxicity, and immune-related issues such as Immune Reconstitution Inflammatory Syndrome (IRIS), particularly in patients co-infected with tuberculosis (TB).Materials and methodsIn this prospective cohort study, 400 ART-naive, HIV-positive patients undergoing anti-tuberculosis therapy (ATT) at King George’s Medical University, Lucknow, India, were enrolled. The study evaluated the occurrence of opportunistic infections (OIs), ART regimen effectiveness, and key laboratory markers, including CD4 counts and hemoglobin levels.ResultsTB emerged as the most common OI, affecting 20.25% of the participants, with anemia present in 85% of the cohort. The prevalence of IRIS was notably higher in patients with a positive tuberculin skin test (20.6%) compared to those with a negative test (7.4%). Patients with IRIS exhibited significantly lower CD4 counts and hemoglobin levels compared to those without IRIS.ConclusionThis study underscores the importance of integrated management approaches for HIV patients co-infected with TB, focusing on the complex interaction between immune status, ART effectiveness, and comorbidities like anemia and hepatotoxicity. Properly addressing these factors is crucial for improving patient outcomes in this high-risk population.
Sex disparities in outcome of medication-assisted therapy of opioid use disorder: Nationally representative study
Authors: Butelman Eduardo R. , Huang Yuefeng , McFarlane Alicia , Slattery Carolann , Goldstein Rita Z. , Volkow Nora D. , Alia-Klein Nelly 
Published: September 2024

AbstractQuestionThe opioid epidemic causes massive morbidity, and males have substantially greater overdose mortality rates than females. It is unclear whether there are sex-related disparities at different stages in the trajectory of opioid use disorders, in “real world” settings.GoalTo determine sex disparities in non-medical opioid use (NMOU) at the end of outpatient medication-assisted treatment (MAT), using nationally representative data.DesignObservational epidemiological study of publicly funded outpatient MAT programs in the national “Treatment episode data set-discharges” (TEDS-D) for 2019.ParticipantsPersons aged ≥18 in their first treatment episode, in outpatient MAT for use of heroin or other opioids (N=11,549). The binary outcome was presence/absence of NMOU.ResultsIn univariate analyses, males had significantly higher odds of NMOU, compared to females (odds ratio=1.27; Chi2[df:1]=39.08; uncorrected p<0.0001; p=0.0041 after Bonferroni correction). A multivariable logistic regression detected a male>female odds ratio of 1.19 (95%CI=1.09-1.29; p<0.0001), adjusting for socio-demographic/clinical variables. Several specific conditions were revealed in which males had greater odds of NMOU compared to females (e.g., at ages 18-29 and 30-39; corrected p=0.012, or if they used opioids by inhalation; corrected p=0.0041).ConclusionsThis nationally representative study indicates that males have greater odds of NMOU in their first episode of MAT, indicating more unfavorable outcomes. The study reveals specific socio-demographic and clinical variables under which this sex disparity is most prominent.Highlights*It is unclear if there are sex-related disparities in outcomes for outpatient opioid medication-assisted therapy (MAT), in large-scale “real world” settings.*In this nationally representative “real world” study, adult males had significantly greater odds of non-medical opioid use (NMOU) in the month prior to discharge from their first MAT episode compared to females, adjusting for socio-demographic and clinical variables. Males were at higher risk than females for this undesirable outcome under several conditions (e.g., in younger age categories, or if their route of NMOU was by inhalation.*Sex disparities in MAT outcomes occur under specific conditions that can be examined and potentially addressed, with the goal of improving personalized approaches for OUD.
BRDKRM: An Explainable Framework for Disease Modifying Drug Identification
Authors: Chanda Aishik , Dey Ashmita , Chakraborty Mrittika , Maulik Utsav B. , Bandyopadhyay Sanghamitra 
Published: September 2024

AbstractDrug classification into disease-modifying (DM) and symptomatic (SYM) categories is crucial for clinical decision-making and therapeutic strategy development. To address the limitations of current methods, which often lack transparency and interpretability, we propose the Boundary Restricted Dynamic Key Route Mapping (BRDKRM) framework. This novel approach leverages the contextual overlap between disease and drug nodes in a heterogeneous graph, aggregating genes from the top K shortest paths to delineate disease neighborhood boundaries. Inspired by the classic Hansel and Gretel folklore, BRDKRM metaphorically marks boundary nodes along metapaths from disease to drug, akin to Hansel‘s breadcrumbs, which are then used to classify the therapeutic effect of candidate drugs. Our method achieved 86.78% accuracy in categorizing drug-disease treatments and identified 530 genes involved in both disease modification and symptomatic relief. The efficacy of BRDKRM is demonstrated through case studies on multiple sclerosis, offering an explainable approach to drug classification that bypasses extensive clinical trials. By providing biologically sound interpretations of drug classifications, our framework enhances understanding of therapeutic interventions, paving the way for more precise and efficient healthcare solutions while offering a novel approach to mapping disease-drug interactions.