bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cerebellar contribution to emotion regulation and its association with medial frontal GABA level
Authors: Oboshi Yumi , Iwabuchi Toshiki , Takata Yohei , Bunai Tomoyasu , Ouchi Yasuomi 
Published: December 2024

Abstract
As a tactic to regulate emotions, distancing involves changing perspectives to alter the psychological distance from stimuli that elicit emotional reactions. Using magnetic resonance spectroscopy and functional magnetic resonance imaging, this study aimed to examine (i) whether the neural correlates of emotion upregulation via distancing differ across emotional valence (i.e. emotional responses toward positive and negative pictures), and (ii) whether the gamma-aminobutyric acid (GABA) concentration in the medial prefrontal cortex (MPFC), one of the crucial areas of emotion regulation, is correlated with brain activity related to either negative or positive emotion upregulation. Thirty-four healthy Japanese adults participated in this study. Compared to the condition involving positive emotion upregulation, negative emotion upregulation induced increased activation in the MPFC, left temporoparietal junction, bilateral anterior insula, pre-supplementary motor area, and bilateral cerebellum. In contrast, when comparing positive emotion upregulation with negative emotion upregulation, no significant activation was found. Right cerebellar activity during negative emotion upregulation was positively correlated with GABA concentration in the MPFC. These findings provide evidence of cerebellar involvement in the upregulation of negative emotion via distancing and its association with the prefrontal GABA concentration.
Temporomandibular joint in patients with rheumatoid arthritis
Authors: Khalayli Naram , Hajali Diaa , Ataya Jawdat , Kudsi Mayssoun , Alkhouri Issam M. 
Published: December 2024

Introduction:
Our study aimed to evaluate temporomandibular joint involvement in rheumatoid arthritis (RA) patients and healthy individuals

Methods:
142 participants were recruited in two groups: 72 patients with RA and 70 healthy controls. All participants were tested for seropositivity of rheumatoid factor and anticitrullinated protein antibodies. TMD diagnosis was determined according to the standardized and validated diagnostic criteria for TMD (DC/TMD): myalgia, arthralgia, articular disc, displacement, degenerative joint disease, and headache attributed to TMD. Bruxism, a probable sleep and/or awake bruxism diagnosis was determined based on self-report and several clinical findings.

Results:
The prevalence of TMD was 44.44% in RA patients and 34.28% in the control group (P < 0.005). TMD-pain diagnosis presented either as myalgia, arthralgia, or both and for those who are having a degenerative joint disease. Within the RA group, seronegative patients had a TMD-pain diagnosis significantly more often than seropositive patients (P = 0.048).75% of participants used analgesics, especially paracetamol, during the last 24 h, without differences between participants with TMD-pain diagnosis or without (P = 0.759). No difference was found between the groups in maximum mouth opening, protrusion, and laterotrusion. There was reported no difference in probable sleep bruxism diagnosis between participants with TMD diagnosis and those without (P = 0.223).

Conclusion:
The prevalence of TMD pain is increased in seronegative RA patients and is associated with bruxism signs and symptoms. Health professionals should be alert to TMD pain in RA patients.
Area Deprivation and Patient Complexity Predict Low-Value Health Care Utilization in Persons With Heart Failure
Authors: Ledwin Kathryn M. , Casucci Sabrina , Sullivan Suzanne S. , Hewner Sharon 
Published: December 2024

Abstract

Background
Heart failure is a debilitating condition affecting over 6.7 million adults in the United States. Social risks and complexity, or personal, social, and clinical aspects of persons’ experiences, have been found to influence health care utilization and hospitalizations in persons with HF. Low-value utilization, or irregular outpatient visits with frequent emergency room use, or hospitalization is common among persons with complex conditions and social risk and requires further investigation in the heart failure population.

Objective
The purpose of this research was to assess the influence of complexity and social risk on low-value utilization in persons with heart failure using machine learning approaches.

Methods
Supervised machine learning, tree-based predictive modeling was conducted on an existing data set of adults with heart failure in the eight-county region of Western New York for the year 2022. Decision tree and random forest models were validated using a 70/30 training/testing data set and k-fold cross-validation. The models were compared for accuracy and interpretability using the area under the curve, Matthew’s correlation coefficient, sensitivity, specificity, precision, and negative predictive value.

Results
Area deprivation index, a proxy for social risk, number of chronic conditions, age, and substance use disorders were predictors of low-value utilization in both the decision tree and random forest models. The decision tree model performed moderately, while the random forest model performed excellently and added hardship as an additional important variable.

Discussion
This is the first known study to look at the outcome of low-value utilization, targeting individuals who are underutilizing outpatient services. The random forest model performed better than the decision tree; however, features were similar in both models, with area deprivation index as the key variable in predicting low-value utilization. The decision tree was able to produce specific cutoff points, making it more interpretable and useful for clinical application. Both models can be used to create clinical tools for identifying and targeting individuals for intervention and follow-up.
Nuclear Medicine Cerebral Perfusion Studies as an Ancillary Test to Support Evaluation of Brain Death/Death by Neurologic Criteria: Single-Center Experience in Infants, 2005–2022*
Authors: Bach Ashley M. , McKinnon Nicole K. , Zhuang Hongming , Kaufman Elizabeth , Kirschen Matthew P. 
Published: December 2024

OBJECTIVE:
To describe the use of nuclear medicine cerebral perfusion studies as an ancillary test for brain death/death by neurologic criteria (BD/DNC) in infants aged under 1 year.

DESIGN:
Retrospective case series.

SETTING:
Single-center, quaternary, academic children’s hospital in the United States.

PATIENTS:
Patients younger than 1 year of age whose evaluation for BD/DNC included a nuclear medicine cerebral perfusion study as an ancillary test, 2005–2022.

INTERVENTIONS:
None.

MEASUREMENTS AND MAIN RESULTS:
Ten infants were identified from local databases. Mechanisms of brain injury included hypoxic-ischemic injury (8/10), traumatic brain injury (1/10), and intracranial hemorrhage (1/10). Testable components of the first BD/DNC examination were consistent with BD/DNC in all patients. Apnea testing was consistent with BD/DNC in 5 of 10 patients and deferred or terminated prematurely in 5 of 10 patients. All patients underwent ancillary testing with a nuclear medicine scan to assess cerebral perfusion using 99mTc-ethyl cysteinate dimer (99mTc-ECD). Indications were inability to complete the apnea test (5/10), presence of a confounder to the clinical examination (3/10), and clinician discretion (2/10). Nine studies were consistent with BD/DNC. The patient whose ancillary test was inconsistent with BD/DNC had their examination limited by the inability to assess the pupillary reflex and subsequently underwent withdrawal of life-sustaining technology.

CONCLUSIONS:
Radionuclide cerebral perfusion studies using 99mTc-ECD were used in our setting to support the determination of BD/DNC in infants aged younger than 1 year of age.
Personalized Medicine for Meningiomas: Drug Screening on Tumor Organoids Exposes Therapeutic Vulnerabilities to HDAC1/2i Panobinostat
Authors: Jungwirth Gerhard , Cao Junguo , Lotsch Catharina , Warta Rolf , Moustafa Mahmoud , Knoll Maximilian , Yu Tao , Braun Viktor , Jassowicz Lena , Dao Trong Philip , Younsi Alexander , Scherer Moritz , Bendszus Martin , Krieg Sandro M. , von Deimling Andreas , Debus Juergen , Sahm Felix , Abdollahi Amir , Unterberg Andreas , Herold-Mende Christel 
Published: December 2024

SUMMARYManaging aggressive meningiomas remains challenging due to limited treatment options besides surgical tumor removal and radiotherapy. To identify novel therapies for aggressive meningiomas, we established a multi-step drug screening workflow, focusing on targetable genes obtained from transcriptome data of highly aggressive grade 3 meningiomas.In vitroscreening of 107 targeted drugs identified nine effective inhibitors. To study these drugs in a more natural environment, we established a standardized patient-derived tumor organoid (TO) model preserving accurately the original tissue’s genotype and phenotype. Individual drug responses were assessed in TOs from 60 molecularly characterized meningioma cases. Especially the FDA-approved epigenetic drug panobinostat demonstrated high antimeningioma efficacy in 70% of TOs, mediated through HDAC1/2 inhibition. In addition, treatment in an orthotopicin vivomodel revealed a significantly improved survival. In a heavily pretreated patient suffering from an anaplastic meningioma, oral panobinostat treatment could delay the tumor growth rate. In search of the molecular mechanism underlying a potential intrinsic panobinostat resistance, we identified upregulation of the HDAC8-TGFβ-EMT axis in the TO model and subsequent HDAC8 depletion substantially increased the sensitivity to panobinostat. These data highlight the utility of personalized drug screenings on TOs to identify suitable drug targets and inhibitors for a more effective treatment of clinically aggressive meningiomas and help to advance our understanding of counteracting resistance mechanisms.One Sentence SummaryThis study provides strongin vitro,in vivo,ex vivo, and patient evidence for the efficacy of the HDACi panobinostat to treat clinically aggressive meningiomas and uncovered a potential intrinsic resistance mechanism by activation of the HDAC8-TGFβ-EMT axis.
DGKα and ζ Deficiency Causes Regulatory T-Cell Dysregulation, Destabilization, and Conversion to Pathogenic T-Follicular Helper Cells to Trigger IgG1-Predominant Autoimmunity
Authors: Li Lei , Huang Hongxiang , Wang Hongxia , Pan Yun , Tao Huishan , Zhang Shimeng , Karmaus Peer W.F. , Fessler Michael B. , Sleasman John W. , Zhong Xiao-Ping 
Published: December 2024

AbstractRegulatory T cells (Tregs) actively engage in immune suppression to prevent autoimmune diseases but also inhibit anti-tumor immunity. Although Tregs express a TCR repertoire with relatively high affinities to self, they are normally quite stable and their inflammatory programs are intrinsically suppressed. We report here that diacylglycerol (DAG) kinases (DGK) ( and ( are crucial for homeostasis, suppression of proinflammatory programs, and stability of Tregs and for enforcing their dependence on CD28 costimulatory signal. Treg-specific deficiency of both DGK( and ( derails signaling, metabolic, and transcriptional programs in Tregs to cause dysregulated phenotypic and functional properties and to unleash conversion to pathogenic exTregs, especially exTreg-T follicular helper (Tfh) 2 cells, leading to uncontrolled effector T cell differentiation, deregulated germinal center (GC) B-cell responses and IgG1/IgE predominant antibodies/autoantibodies, and multiorgan autoimmune diseases. Our data not only illustrate the crucial roles of DGKs in Tregs to maintain self-tolerance but also unveil a Treg-to-self-reactive-pathogenic-exTreg-Tfh-cell program that is suppressed by DGKs and that could exert broad pathogenic roles in autoimmune diseases if unchecked.
Research opportunities in precision oncology: Perspectives on biospecimen and genomic data sharing from adults with cancer in Ireland
Authors: O’Grady Shane , Ralston Jessica C. , McKiernan Eadaoin , Drummond Frances J. , Rynne Jan , Mitchell Derick , Gallagher William M. , Drury Amanda , Kolch Walter 
Published: December 2024

AbstractAlthough surveys of people living with cancer in other nations have generally found a high degree of willingness to donate to research services such as genomic databases and biobanks, these results can vary from country to country. Additional questions also remain surrounding issues such as preferred model of consent, reporting of findings and concerns surrounding potential commercial application of health data. To address some of these gaps in our current knowledge, we collected responses from 176 people living with and beyond cancer in Ireland over a 16-month period. Twenty-eight percent of our survey respondents had previously donated a biological sample to research, with the majority indicating that they did so for altruistic reasons. We found that the vast majority of those who had not previously donated samples would do so if given the opportunity, suggesting that there is a significant untapped pool of potential sample donors, and increased efforts by researchers and clinicians to recruit these individuals, in an ethically acceptable way, could yield a substantial improvement in the availability of biological samples and data for research. There was also a strong preference among respondents for total transparency with personal health data, with the vast majority wanting to know of any risk factors identified in their genome, even if these risks were not medically actionable. A strong level of trust in both the clinical and scientific community was also observed in the responses, with most indicating that this played a major role in influencing their decision to donate. Finally, we found that although most respondents did not have issues with the involvement of a commercial entity in the donation process, there was still a sizeable percentage (26%) who did have some reservations.
Assessing an ICD-10 Code Approach for Tracking Xylazine-Involved Overdose Deaths in the United States
Authors: Friedman Joseph R. 
Published: December 2024

AbstractIntroductionThe national prevalence of the veterinary sedative xylazine in US overdose deaths rose between 2018 and 2021. More updated estimates are limited, partially due to the lack of a dedicated ICD-10 code—a primary mechanism used to specify drugs implicated in overdose deaths in the US, including in the CDC WONDER system, which provides public data requests with a 6-month lag. For other emerging substances lacking dedicated codes, over time umbrella codes have come tode factorepresent them, yet this has not yet been demonstrated for xylazine.MethodsOverdose deaths in CDC WONDER involving T42.7 (“Antiepileptic and sedative-hypnotic drugs, unspecified”) or T46.5 (“Other antihypertensive drugs, not elsewhere classified”) were compared to two more specific, albeit delayed, sources: NVSS describing national trends in 2018-2021 and SUDORS describing state-level trends in 2020-2022. The CDC WONDER approach was also used to visualize trends in xylazine-involved deaths through Q1 2024 by geography, race/ethnicity, substance co-involvement, and demographic categories.ResultsAt the national level, concordance between CDC WONDER records and previous NVSS estimates improved after 2019 and became highly similar in 2021 (3,480 vs 3,468 deaths). Concordance was also high for estimates stratified by race, age, and region. At the state-level, across 49 state-year pairs, correlation between CDC WONDER and SUDORS was 0.97. Xylazine-involved deaths doubled between 2021 and 2024 Q1, and racial inequalities widened.DiscussionT42.7 or T46.5, together, may have become thede-factocoding scheme representing xylazine-involved deaths. This approach provides more up-to-date results, showing increasing prevalence and worsening racial inequalities in xylazine-involved deaths into 2024.
Household Vulnerability and Coping Amid the COVID-19 Pandemic in Bamako, Mali: Assessing Sociodemographic Factors Associated with Household Hardships
Authors: Muir Jonathan A. , Onwuchekwa Uduma U. , Madewell Zachary J. , Traore Moussa O. , Kourouma Moussa , Keiri Fatima , Cunningham Solveig A. , Kotloff Karen L , Tapia Milagritos D. , Sow Samba O 
Published: December 2024

AbstractBackgroundCOVID-19 resulted in vast disruption to life in the 21stcentury as governments implemented containment measures to quell disease spread. We assessed knowledge of local interventions and household coping strategies used to attenuate the impact of household hardships. We further examined associations between household and community characteristics with household hardships.MethodsWe conducted a cross-sectional household survey between August and September 2022 through a retrospective questionnaire fielded in the Health and Demographic Surveillance System (HDSS) operating in Bamako, Mali. Logistic regression was used to analyze associations between household characteristics, government interventions, and household hardships during the pandemic.ResultsThe most commonly reported hardships were increases in food prices and food insecurity; roughly 18% of households reported experiencing at least 1 hardship. Common coping strategies included asking for help from family or friends (55.6%). Only 2.8% of households reported seeking government assistance. Households headed by younger individuals, males, and unemployed individuals were at greater risk of experiencing hardships. Government closure of businesses was strongly associated with household hardships.ConclusionsHouseholds in the Bamako HDSS experienced a variety of hardships during the pandemic— the most prevalent hardships were increases in local food prices and food insecurity. The association between government closure of businesses and household hardships points to the need for balancing public health measures with socioeconomic considerations. Households headed by individuals with lower education and/or unemployed were at greater risk of experiencing a hardship. Future policies and interventions should target aid to households reflecting these characteristics.
Drivers of disengagement from care during the first six months on antiretroviral therapy for HIV in South Africa: a mixed-methods study
Authors: Maskew Mhairi , Mutanda Nyasha , Scott Nancy , Morgan Allison , Benade Mariet , Ntjikelane Vinolia , Sande Linda , Malala Lufuno , Manganye Musa , Rosen Sydney 
Published: December 2024

AbstractIntroductionFor clients on HIV treatment in sub-Saharan Africa, disengagement from HIV care in the early treatment period is a critical obstacle to achieving UNAIDS’s second 95 target. While South Africa’s Differentiated Service Delivery Guideline on Fast Track Initiation and Counseling (FTIC) define normative procedures, the effect of guideline implementation and the underlying drivers of disengagement remain unclear.MethodsThe PREFER mixed-methods study enrolled a prospective cohort of adult clients initiating ART, returning to care after a period of disengagement or already on ART for ≤6 months at 18 public sector healthcare facilities in South Africa. A survey collected data on demographic and clinical characteristics and preferences of participants who were followed up through routinely-collected medical visit records for up to 7 months after treatment initiation to estimate continuity of HIV care (attended all scheduled visits within 28 days). Focus group discussions (FGDs) were conducted approximately 12 months after enrollment among a subset of participants who had expressed concerns about treatment retention.ResultsDuring the study period 7/9/2022-30/6/2023, PREFER-SA enrolled 1,049 participants (72% female, median age=33 years, 24% with CD4 count<200cells/mm3); 122 of whom also participated in focus group discussions. By 6 months on ART, 23% were not continuously in HIV care. Those newly initiating ART at study enrollment were more likely to have disengaged or interrupted treatment by 6 months as those who had remained in care for ≥1 visit. Disengagement was also more likely among men and younger (18-24 years) participants, those reporting food scarcity, and those initiated on regimens other than Dolutegravir. Disengagement did not differ by gender, relationship status, or CD4 count. Qualitative FGD results suggest participants experience barriers to adherence within and between all levels of the socio-ecologic model. Challenges related to the facility experience were most prominent.ConclusionsAmong adults initiating or re-initiating ART in South Africa, the highest risk of disengagement is immediately after initiation. We identified several potentially modifiable individual and social characteristics associated with early disengagement. Improving the patient facility experience and strengthening implementation of SA’s Service Delivery Guidelines may increase retention during the early treatment period.
FMT Restores Colonic Protein Biosynthesis and Cell Proliferation in Patients with RecurrentClostridioides difficileDisease
Authors: Moreau G. Brett , Young Mary , Behm Brian , Tanyüksel Mehmet , Ramakrishnan Girija , Petri William A. 
Published: December 2024

AbstractRecurrentC. difficileinfection (CDI) is a major health threat with significant mortality and financial costs. Fecal Microbiota Transplantation (FMT) is an effective therapy, however the mechanisms by which it acts, particularly on the host, are poorly understood. Here we enrolled a prospective cohort of human patients with recurrent CDI (n=16) undergoing FMT therapy. Colonic biopsies were collected and bulk RNA sequencing was performed to compare changes in host gene expression pre- and two months post-FMT. Transcriptional profiles were significantly altered after FMT therapy, with many differentially expressed genes (∼15% of annotated genes detected). Enrichment analysis determined that these changes were reflective of increased protein production post-FMT, with enrichment of pathways such as Ribosome Biogenesis, Protein Processing, and signaling pathways (Myc, mTORc1, E2F) associated with cell proliferation and protein biosynthesis. Histology of H&E-stained biopsies identified a significant increase in colonic crypt length post-FMT, suggesting that this treatment promotes cell proliferation. Crypt length was significantly correlated with enriched Myc and mTOR signaling pathways as well as genes associated with polyamine biosynthesis, providing a potential mechanism through which this may occur. Finally, signaling pathways upstream of Myc and mTOR, notably IL-33 Signaling and EGFR ligands, were significantly upregulated, suggesting that FMT may utilize these signals to promote cell proliferation and restoration of the intestine.
Adaptive cellular evolution in the intestinal tracts of hyperdiverse African cichlid fishes
Authors: Fages Antoine , Luxey Maëva , Ronco Fabrizia , Huyghe Charlotte E.T. , Menon P. Navaneeth Krishna , Indermaur Adrian , Salzburger Walter , Tschopp Patrick 
Published: December 2024

AbstractAdaptations related to how nutrients are acquired and processed play a central role in the colonization of novel ecological niches and, therefore, in organismal diversification. While the evolution of feeding structures has been studied extensively in this context, the nature of dietary adaptations in the digestive tract remains largely unexplored. Here, we investigate the cellular and molecular basis of dietary adaptations in the massive radiation of cichlid fishes in Lake Tanganyika using comprehensive single-cell transcriptomic data derived from the intestines of 24 endemic cichlid species with distinct habitats and diets. We show that, at the cellular level, dietary adaptations are primarily driven by anterior enterocytes, and that both the relative abundance and gene expression profiles of these cells have evolved in response to rapid dietary specializations. These dietary adaptations are driven by rapidly evolving cell population-specific genes, suggesting that alterations in epithelial cell specification programs and molecular makeup promote ecological diversification.