tbuckley/cabot-search huggingface dataset:
One in, one out: Commensal fungus protects against infection
Authors: Rebecca A. Drummond
Journal: The Journal of Experimental Medicine (2024)

Gut-resident fungi have a broad influence over health and disease. In this issue of JEM, Sekeresova Kralova et al. (https://doi.org/10.1084/jem.20231686) identify a commensal yeast that displaced fungal pathogen Candida albicans and protected against subsequent invasive infections that originate from the gut.
<scp>HLA</scp>‐haploidentical stem cell transplantation in children with inherited bone marrow failure syndromes: A retrospective analysis on behalf of <scp>EBMT</scp> severe aplastic Anemia and pediatric diseases working parties
Authors: Stefano Giardino, Dirk‐Jan Eikema, Brian Piepenbroek, Mattia Algeri, Mouhab Ayas, Maura Faraci, Abdelghani Tbakhi, Marco Zecca, Mohammed Essa, Bénédicte Neven, Yves Bertrand, Gaurav Kharya, Tatiana Bykova, Sarah Lawson, Mario Petrini, Alexander Mohseny, Fanny Rialland, Beki James, Anca Colita, Mony Fahd, Simone Cesaro, Ansgar Schulz, Katharina Kleinschmidt, Krzysztof Kałwak, Selim Corbacioglu, Carlo Dufour, Antonio Risitano, Régis Peffault de Latour
Journal: American Journal of Hematology (2024)

Abstract Haploidentical stem cell transplantation (haplo‐SCT) represents the main alternative for children with inherited bone marrow failure syndrome (I‐BMF) lacking a matched donor. This retrospective study, conducted on behalf of the EBMT SAAWP and PDWP, aims to report the current outcomes of haplo‐SCT in I‐BMFs, comparing the different in vivo and ex vivo T‐cell depletion approaches. One hundred and sixty‐two I‐BMF patients who underwent haplo‐SCT (median age 7.4 years) have been registered. Fanconi Anemia was the most represented diagnosis (70.1%). Based on different T‐cell depletion (TCD) approaches, four categories were identified: (1) TCRαβ + /CD19 + ‐depletion (43.8%); (2) T‐repleted with post‐transplant Cyclophosphamide (PTCy, 34.0%); (3) In‐vivo T‐depletion with ATG/alemtuzumab (14.8%); (4) CD34 + positive selection (7.4%). The cumulative incidences (CI) of neutrophil and platelet engraftment were 84% and 76% respectively, while that of primary and secondary graft failure was 10% and 8% respectively. The 100‐day CI of acute GvHD grade III‐IV(95% CI) was 13%, while the 24‐month CI of extensive chronic GvHD was 4%. After a median follow‐up of 43.4 months, the 2‐year overall survival(OS) and GvHD/Rejection‐free Survival (GRFS) probabilities are 67% and 53%, respectively. The TCR CD3 + αβ + /CD19 + depletion group showed a significantly lower incidence of both acute and chronic GvHD and higher OS (79%; p0 . 013 ) and GRFS (71%; p &lt; . 001 ), while no significant differences in outcomes have been observed by different diagnosis and conditioning regimens. This large retrospective study supports the safety and feasibility of haplo‐SCT in I‐BMF patients. TCRαβ + /CD19 + depletion offers higher chances of patients' survival, with a significantly lower risk of severe a‐ and c‐GvHD in I‐BMFs compared to other platforms.
A cognitive-computational account of mood swings in adolescence
Authors: Klára Gregorová, Eran Eldar, Lorenz Deserno, Andrea M.F. Reiter
Journal: Trends in Cognitive Sciences (2024)

Teenagers have a reputation for being fickle, in both their choices and their moods. This variability may help adolescents as they begin to independently navigate novel environments. Recently, however, adolescent moodiness has also been linked to psychopathology. Here, we consider adolescents' mood swings from a novel computational perspective, grounded in reinforcement learning (RL). This model proposes that mood is determined by surprises about outcomes in the environment, and how much we learn from these surprises. It additionally suggests that mood biases learning and choice in a bidirectional manner. Integrating independent lines of research, we sketch a cognitive-computational account of how adolescents' mood, learning, and choice dynamics influence each other, with implications for normative and psychopathological development.
Established and emerging treatments for eating disorders
Authors: Callum Bryson, Daire Douglas, Ulrike Schmidt
Journal: Trends in Molecular Medicine (2024)

Eating disorders (EDs) are common mental health conditions that carry exceedingly high morbidity and mortality rates. Evidence-based treatment options include a range of psychotherapies and some, mainly adjunctive, pharmacological interventions. However, around 20–30% of people fail to respond to the best available treatments and develop a persistent treatment-refractory illness. Novel treatments for these disorders are emerging, but their efficacy and clinical relevance need further investigation. In this review article, we first outline the evidence-base for the established treatments of the three 'classical' EDs [anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED)]. We then review research on some of the most promising emerging treatment modalities, discussing the questions and challenges that remain.
Efficacy of a new injury prevention programme (FUNBALL) in young male football (soccer) players: a cluster-randomised controlled trial
Authors: Rilind Obërtinca, Rina Meha, Ilir Hoxha, Bujar Shabani, Tim Meyer, Karen aus der Fünten
Journal: British Journal of Sports Medicine (2024)

Objectives To evaluate the efficacy of a new multicomponent, exercise-based injury prevention programme in football players 13–19 years old. Methods Two-arm cluster-randomised controlled trial with clubs as the unit of randomisation. 55 football teams from Kosovo of the under 15, under 17 and under 19 age groups were randomly assigned to the intervention (INT; 28 teams) or the control group (CON; 27 teams) and were followed for one football season (August 2021–May 2022). The INT group performed the ‘FUNBALL’ programme after their usual warm-up at least twice per week, while the CON group followed their usual training routine. The primary outcome measure was the overall number of football-related injuries. Secondary outcomes were region-specific injuries of the lower limbs (hip/groin, thigh, knee, lower leg, ankle and foot) and injury severity. Results 319 injuries occurred, 132 in the INT and 187 in the CON group. The INT group used the ‘FUNBALL’ programme in 72.2% of all training sessions, on average 2.2 times per week. There was a significantly lower incidence in the INT group regarding the overall number of injuries (incidence rate ratio (IRR) 0.69, 95% CI 0.55 to 0.87), the number of thigh injuries (IRR 0.62, 95% CI 0.39 to 0.98), of moderate (time loss between 7 and 28 days) (IRR 0.65, 95% CI 0.44 to 0.97) and of severe injuries (time loss &gt;28 days) (IRR 0.51, 95% CI 0.28 to 0.91). Conclusion The ‘FUNBALL’ programme reduced the incidence of football-related injuries among male adolescent football players, and its regular use for injury prevention in this population is recommended. Trial registration number NCT05137015 .
Dynamic associations between glucose and ecological momentary cognition in Type 1 Diabetes
Authors: Z. W. Hawks, E. D. Beck, L. Jung, L. M. Fonseca, M. J. Sliwinski, R. S. Weinstock, E. Grinspoon, I. Xu, R. W. Strong, S. Singh, H. P. A. Van Dongen, M. R. Frumkin, J. Bulger, M. J. Cleveland, K. Janess, Y. C. Kudva, R. Pratley, M. R. Rickels, S. R. Rizvi, N. S. Chaytor, L. T. Germine
Journal: npj Digital Medicine (2024)

Abstract Type 1 diabetes (T1D) is a chronic condition characterized by glucose fluctuations. Laboratory studies suggest that cognition is reduced when glucose is very low (hypoglycemia) and very high (hyperglycemia). Until recently, technological limitations prevented researchers from understanding how naturally-occurring glucose fluctuations impact cognitive fluctuations. This study leveraged advances in continuous glucose monitoring (CGM) and cognitive ecological momentary assessment (EMA) to characterize dynamic, within-person associations between glucose and cognition in naturalistic environments. Using CGM and EMA, we obtained intensive longitudinal measurements of glucose and cognition (processing speed, sustained attention) in 200 adults with T1D. First, we used hierarchical Bayesian modeling to estimate dynamic, within-person associations between glucose and cognition. Consistent with laboratory studies, we hypothesized that cognitive performance would be reduced at low and high glucose, reflecting cognitive vulnerability to glucose fluctuations. Second, we used data-driven lasso regression to identify clinical characteristics that predicted individual differences in cognitive vulnerability to glucose fluctuations. Large glucose fluctuations were associated with slower and less accurate processing speed, although slight glucose elevations (relative to person-level means) were associated with faster processing speed. Glucose fluctuations were not related to sustained attention. Seven clinical characteristics predicted individual differences in cognitive vulnerability to glucose fluctuations: age, time in hypoglycemia, lifetime severe hypoglycemic events, microvascular complications, glucose variability, fatigue, and neck circumference. Results establish the impact of glucose on processing speed in naturalistic environments, suggest that minimizing glucose fluctuations is important for optimizing processing speed, and identify several clinical characteristics that may exacerbate cognitive vulnerability to glucose fluctuations.
Lac-Phe mediates the effects of metformin on food intake and body weight
Authors: Shuke Xiao, Veronica L. Li, Xuchao Lyu, Xudong Chen, Wei Wei, Fahim Abbasi, Joshua W. Knowles, Alan Sheng-Hwa Tung, Shuliang Deng, Gaurav Tiwari, Xu Shi, Shuning Zheng, Laurie Farrell, Zsu-Zsu Chen, Kent D. Taylor, Xiuqing Guo, Mark O. Goodarzi, Alexis C. Wood, Yii-Der Ida Chen, Leslie A. Lange, Stephen S. Rich, Jerome I. Rotter, Clary B. Clish, Usman A. Tahir, Robert E. Gerszten, Mark D. Benson, Jonathan Z. Long
Journal: Nature Metabolism (2024)
Natural language instructions induce compositional generalization in networks of neurons
Authors: Reidar Riveland, Alexandre Pouget
Journal: Nature Neuroscience (2024)

Abstract A fundamental human cognitive feat is to interpret linguistic instructions in order to perform novel tasks without explicit task experience. Yet, the neural computations that might be used to accomplish this remain poorly understood. We use advances in natural language processing to create a neural model of generalization based on linguistic instructions. Models are trained on a set of common psychophysical tasks, and receive instructions embedded by a pretrained language model. Our best models can perform a previously unseen task with an average performance of 83% correct based solely on linguistic instructions (that is, zero-shot learning). We found that language scaffolds sensorimotor representations such that activity for interrelated tasks shares a common geometry with the semantic representations of instructions, allowing language to cue the proper composition of practiced skills in unseen settings. We show how this model generates a linguistic description of a novel task it has identified using only motor feedback, which can subsequently guide a partner model to perform the task. Our models offer several experimentally testable predictions outlining how linguistic information must be represented to facilitate flexible and general cognition in the human brain.
The dynamic state of a prefrontal–hypothalamic–midbrain circuit commands behavioral transitions
Authors: Changwan Chen, Mahsa Altafi, Mihaela-Anca Corbu, Aleksandra Trenk, Hanna van den Munkhof, Kristin Weineck, Franziska Bender, Marta Carus-Cadavieco, Alisa Bakhareva, Tatiana Korotkova, Alexey Ponomarenko
Journal: Nature Neuroscience (2024)

Abstract Innate behaviors meet multiple needs adaptively and in a serial order, suggesting the existence of a hitherto elusive brain dynamics that brings together representations of upcoming behaviors during their selection. Here we show that during behavioral transitions, possible upcoming behaviors are encoded by specific signatures of neuronal populations in the lateral hypothalamus (LH) that are active near beta oscillation peaks. Optogenetic recruitment of intrahypothalamic inhibition at this phase eliminates behavioral transitions. We show that transitions are elicited by beta-rhythmic inputs from the prefrontal cortex that spontaneously synchronize with LH ‘transition cells’ encoding multiple behaviors. Downstream of the LH, dopamine neurons increase firing during beta oscillations and also encode behavioral transitions. Thus, a hypothalamic transition state signals alternative future behaviors, encodes the one most likely to be selected and enables rapid coordination with cognitive and reward-processing circuitries, commanding adaptive social contact and eating behaviors.
Commentary on ‘Surgical outcomes and survival following esophagectomy for squamous cell carcinoma with or without liver cirrhosis: retrospective cohort study’
Authors: Kexun Li, Xuefeng Leng, Lin Peng
Journal: International Journal of Surgery (2024)

Department of Thoracic Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China (Sichuan Cancer Hospital) Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. Published online ■ ■ *Corresponding author. Address: Department of Thoracic Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China (Sichuan Cancer Hospital) 55 Section 4, South Renmin Road, Chengdu, Chengdu 610041, China. Tel: +8618908178797. Fax: 86-028-85420156. E-mail address: [email protected] (L. Peng). This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0/
A commentary on ‘Effect of preoperative radiotherapy on stage IB2 and IIA2 cervical cancer: A retrospective cohort study’
Authors: Siyu Wu, Xiaoyu Yue, Yaping Wang
Journal: International Journal of Surgery (2024)

Department of Gynecology and Obstetrics, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, 266000 Qingdao, People's Republic of China Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. Published online ■ ■ *Corresponding author. Address: Department of Gynecology and Obstetrics, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, 266000 Qingdao, People's Republic of China. E-mail: [email protected] (Y. Wang). This is an open access article distributed under the Creative Commons Attribution-ShareAlike License 4.0, which allows others to remix, tweak, and build upon the work, even for commercial purposes, as long as the author is credited and the new creations are licensed under the identical terms. http://creativecommons.org/licenses/by-sa/4.0/
A lineage-specific <i>STAT5B</i>N642H mouse model to study NK-cell leukemia
Authors: Klara Klein, Sebastian Kollmann, Angela Hiesinger, Julia List, Jonatan Kendler, Thorsten Klampfl, Mehak Rhandawa, Jana Trifinopoulos, Barbara Maurer, Reinhard Grausenburger, Christof A. Betram, Richard Moriggl, Thomas Rülicke, Charles G. Mullighan, Agnieszka Witalisz-Siepracka, Wencke Walter, Gregor Hoermann, Veronika Sexl, Dagmar Gotthardt
Journal: Blood (2024)

Abstract Patients with T- and natural killer (NK)-cell neoplasms frequently have somatic STAT5B gain-of-function mutations. The most frequent STAT5B mutation is STAT5BN642H, which is known to drive murine T-cell leukemia, although its role in NK-cell malignancies is unclear. Introduction of the STAT5BN642H mutation into human NK-cell lines enhances their potential to induce leukemia in mice. We have generated a mouse model that enables tissue-specific expression of STAT5BN642H and have selectively expressed the mutated STAT5B in hematopoietic cells (N642Hvav/+) or exclusively in NK cells (N642HNK/NK). All N642Hvav/+ mice rapidly develop an aggressive T/NKT-cell leukemia, whereas N642HNK/NK mice display an indolent NK-large granular lymphocytic leukemia (NK-LGLL) that progresses to an aggressive leukemia with age. Samples from patients with NK-cell leukemia have a distinctive transcriptional signature driven by mutant STAT5B, which overlaps with that of murine leukemic N642HNK/NK NK cells. To our knowledge, we have generated the first reliable STAT5BN642H-driven preclinical mouse model that displays an indolent NK-LGLL progressing to aggressive NK-cell leukemia. This novel in vivo tool will enable us to explore the transition from an indolent to an aggressive disease and will thus permit the study of prevention and treatment options for NK-cell malignancies.
Risk Stratification to Reduce Excess Mortality in Early Psychosis
Authors: Brittany M. Gouse, Janice M. Weinberg, Hannah E. Brown
Journal: JAMA Network Open (2024)

Johannes Lieslehto, MD, PhD; Jari Tiihonen, MD, PhD; Markku Lähteenvuo, MD, PhD; Stefan Leucht, MD; Christoph U. Correll, MD; Ellenor Mittendorfer-Rutz, PhD; Antti Tanskanen, PhD; Heidi Taipale, PhD
Ableist Language in NIH’s Mission Statement
Authors: Paul M. Jost
Journal: JAMA (2024)

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Technology-supported behavior change interventions for reducing sodium intake in adults: a systematic review and meta-analysis
Authors: Yong Yang Yan, Lily Man Lee Chan, Man Ping Wang, Jojo Yan Yan Kwok, Craig S. Anderson, Jung Jae Lee
Journal: npj Digital Medicine (2024)

Abstract The effects of technology-supported behavior change interventions for reducing sodium intake on health outcomes in adults are inconclusive. Effective intervention characteristics associated with sodium reduction have yet to be identified. A systematic review and meta-analysis were conducted, searching randomized controlled trials (RCTs) published between January 2000 and April 2023 across 5 databases (PROSPERO: CRD42022357905). Meta-analyses using random-effects models were performed on 24-h urinary sodium (24HUNa), systolic blood pressure (SBP), and diastolic blood pressure (DBP). Subgroup analysis and meta-regression of 24HUNa were performed to identify effective intervention characteristics. Eighteen RCTs involving 3505 participants (51.5% female, mean age 51.6 years) were included. Technology-supported behavior change interventions for reducing sodium intake significantly reduced 24HUNa (mean difference [MD] −0.39 gm/24 h, 95% confidence interval [CI] −0.50 to −0.27; I 2 = 24%), SBP (MD −2.67 mmHg, 95% CI −4.06 to −1.29; I 2 = 40%), and DBP (MD −1.39 mmHg, 95% CI −2.31 to −0.48; I 2 = 31%), compared to control conditions. Interventions delivered more frequently (≤weekly) were associated with a significantly larger effect size in 24HUNa reduction compared to less frequent interventions (&gt;weekly). Other intervention characteristics, such as intervention delivery via instant messaging and participant-family dyad involvement, were associated with larger, albeit non-significant, effect sizes in 24HUNa reduction when compared to other subgroups. Technology-supported behavior change interventions aimed at reducing sodium intake were effective in reducing 24HUNa, SBP, and DBP at post-intervention. Effective intervention characteristics identified in this review should be considered to develop sodium intake reduction interventions and tested in future trials, particularly for its long-term effects.
Serologic Response to the Epstein-Barr Virus Peptidome and the Risk for Multiple Sclerosis
Authors: Marianna Cortese, Yumei Leng, Kjetil Bjornevik, Moriah Mitchell, Brian C. Healy, Michael J. Mina, James D. Mancuso, David W. Niebuhr, Kassandra L. Munger, Stephen J. Elledge, Alberto Ascherio
Journal: JAMA Neurology (2024)

Importance It remains unclear why only a small proportion of individuals infected with the Epstein-Barr virus (EBV) develop multiple sclerosis (MS) and what the underlying mechanisms are. Objective To assess the serologic response to all EBV peptides before the first symptoms of MS occur, determine whether the disease is associated with a distinct immune response to EBV, and evaluate whether specific EBV epitopes drive this response. Design, Setting, and Participants In this prospective, nested case-control study, individuals were selected among US military personnel with serum samples stored in the US Department of Defense Serum Repository. Individuals with MS had serum collected at a median 1 year before onset (reported to the military in 2000-2011) and were matched to controls for age, sex, race and ethnicity, blood collection, and military branch. No individuals were excluded. The data were analyzed between September 1, 2022, and August 31, 2023. Exposure Antibodies (enrichment z scores) to the human virome measured using VirScan (phage-displayed immunoprecipitation and sequencing). Main Outcome and Measure Rate ratios (RRs) for MS for antibodies to 2263 EBV peptides (the EBV peptidome) were estimated using conditional logistic regression, adjusting for total anti–EBV nuclear antigen 1 (EBNA-1) antibodies, which have consistently been associated with a higher MS risk. The role of antibodies against other viral peptides was also explored. Results A total of 30 individuals with MS were matched with 30 controls. Mean (SD) age at sample collection was 27.8 (6.5) years; 46 of 60 participants (76.7%) were male. The antibody response to the EBV peptidome was stronger in individuals with MS, but without a discernible pattern. The antibody responses to 66 EBV peptides, the majority mapping to EBNA antigens, were significantly higher in preonset sera from individuals with MS (RR of highest vs lowest tertile of antibody enrichment, 33.4; 95% CI, 2.5-448.4; P for trend = .008). Higher total anti-EBNA-1 antibodies were also associated with an elevated MS risk (top vs bottom tertile: RR, 27.6; 95% CI, 2.3-327.6; P for trend = .008). After adjusting for total anti-EBNA-1 antibodies, risk estimates from most EBV peptides analyses were attenuated, with 4 remaining significantly associated with MS, the strongest within EBNA-6/EBNA-3C, while the association between total anti-EBNA-1 antibodies and MS persisted. Conclusion and Relevance These findings suggest that antibody response to EBNA-1 may be the strongest serologic risk factor for MS. No single EBV peptide stood out as being selectively targeted in individuals with MS but not controls. Larger investigations are needed to explore possible heterogeneity of anti-EBV humoral immunity in MS.