bluuebunny/crossref_metadata_2025 huggingface dataset:
Beyond Borders, Beneath Words: Using Natural Language Processing to Map Student Reflections on International Service Learning to Physical Therapy Values
Authors: Borstad Alexandra L. , Appling Susan A. , Kloos Anne D. , Spangler Lynda , Marc David T.
Published: February 2025

Introduction.

Advances in artificial intelligence (AI) offer physical therapy educators opportunities to improve student learning. We applied AI to identify themes and determine the extent to which physical therapy professional values were reflected upon by students during a high-impact international service learning (ISL) course in México.

Review of Literature.

Natural language processing (NLP), a subfield of AI, organizes and interprets language nuances, efficiently providing insight into the meaning expressed in written work. Efficient methods to measure written work are needed.

Subjects.

Reflection statements (n = 802) from 21 third-year, Doctor of Physical Therapy students were analyzed.

Methods.

Natural language processing methods executed in the R statistical software were K-means clustering to parse reflections by theme, and the semantic distance metric, cosine similarity (cos θ), to quantify the similarity of meaning between reflections and 7 physical therapy professional values.

Results.

Using NLP, 3 themes emerged in the reflections: educating patients and caregivers, providing new treatment ideas, and learning about a different culture. Eighty-four percent of reflections were highly similar (cos θ = 0.59) to the value excellence. Reflections were also highly similar to integrity (cos θ = 0.61) and compassion and caring (cos θ = 0.51) and least similar to professional duty (cos θ = 0.24). Reflections on the theme of learning about a different culture were most similar to 5 of the 7 values compared with other themes.

Discussion and Conclusion.

Natural language processing enabled a detailed understanding of the values woven throughout students' written reflections on ISL. The experience implicitly promoted the development of physical therapy core values, in particular excellence, affirming it as a high-impact educational practice for professional development. Natural language processing's automated, quantitative, and debiased outcomes advance reflection analytics, an example of one of the new and powerful approaches AI offers educators and researchers that will transform our field.
Merkel cell carcinoma in a patient with basal cell carcinoma: a case of localized disease with negative sentinel node biopsy
Authors: Shahani Hiba Arshad , Ali Masab , Babar Ilsa , Javeria Sana , Ahmad Muhammad Husnain , Saeed Humza , Ahmad Uswa , Sehbai Aasim
Published: February 2025

Introduction:

Merkel cell carcinoma (MCC) is a rare but aggressive neuroendocrine skin cancer with a high risk of recurrence and metastasis. It typically affects sun-exposed areas in elderly or immunocompromised individuals. Early diagnosis and management are essential due to its rapid progression and potential for early metastasis.

Case presentation:

We report the case of a 65-year-old male with a history of diabetes mellitus and basal cell carcinoma who developed MCC on his left upper extremity. Initial imaging, including a sentinel lymph node biopsy (SLNB) and magnetic resonance imaging (MRI), localized the tumor and assessed lymph node involvement. The SLNB was negative for metastasis, and a wide excision confirmed no residual MCC. Further imaging with positron emission tomography (PET) and computed tomography (CT) scans showed no distant metastasis, indicating localized disease. The patient underwent wide excision followed by radiation therapy (RT) (50 Gy in 25 fractions), experiencing mild post-radiation effects such as swelling and erythema.

Clinical discussion:

MCC poses significant diagnostic and therapeutic challenges due to its nonspecific presentation and rapid progression. In this case, early detection and appropriate imaging allowed for timely intervention. Negative SLNB results and localized disease justified the use of wide excision and MC. Multimodal treatment, including surgery and radiation, is crucial in managing localized MCC.

Conclusion:

This case emphasizes the importance of early detection, comprehensive imaging, and multimodal therapy in the management of MCC. Close follow-up remains essential, especially in cases with negative SLNB, to monitor for recurrence or metastasis.
Acute Seizure Activity During F-18 FDG PET/CT Imaging
Authors: Huang Juncheng , Loi Hoi Yin , Pillai Sajith Velappan , Chidambaram Kannan , Sinha Arvind Kumar
Published: February 2025

We report a 62-year-old man with acute seizure during FDG PET/CT imaging. Initially admitted for newly diagnosed epilepsy, CT and MRI brain studies were unremarkable. Subsequent PET/CT showed focal tracer uptake in the left hippocampus with jerking of bilateral upper limbs and trunk. Delayed PET/CT supported the initial findings of transient seizure activity. This timely diagnosis allowed for rapid optimization of his anti-epileptic agents for the rest of the admission. This case illustrates a rare presentation of seizure during FDG PET/CT scanning and highlights the importance of distinguishing between motion artifacts and genuine seizure activity for timely diagnosis and management.
Spectral Shaping Computed Tomography Applications
Authors: Wong Julian , Kutschera Peter , Lau Kenneth K.
Published: February 2025

Spectral shaping (also known as spectral filtration) has been utilized in some of the latest computed tomography (CT) systems. This technique involves using tin (Sn) or silver (Ag) filters, which selectively absorb low-energy photons. This review aims to demonstrate the utility of spectral shaping across a wide range of protocols and clinical situations. Spectral-shaped CT protocols using tin filters allow for the acquisition of diagnostic images and greatly reduce the radiation dose, metal artifacts, and photon starvation. These features make spectral shaping suitable for various clinical situations in diagnostic and interventional CT imaging.
Seminal Vesicle Involvement of Waldenström Macroglobulinemia on 18F-FDG PET/CT
Authors: Bin Li , Liu Huiting , Liu Xue , Gao Cailiang
Published: February 2025

A 57-year-old man was admitted to the hospital with recurrent pain in the lower abdomen for more than half a month. Computed tomography urography and MRI of the prostate gland suggested neoplastic lesions in bilateral seminal vesicle glands. An 18F-FDG PET/CT examination revealed multiple hypermetabolic nodules and masses in the prostate and bilateral seminal vesicle gland area. Later histopathology confirmed Waldenström macroglobulinemia with bilateral seminal vesicle gland involvement.
Early Perfusion [123I]FP-CIT SPECT Imaging With a 360-degree CZT Camera in Dementia With Lewy Bodies
Authors: Verger Antoine , Imbert Laetitia , Cecchin Diego
Published: February 2025

Dementia with Lewy bodies (DLB) can be diagnosed through a combination of clinical criteria, the loss of dopaminergic neuron terminals in presynaptic [123I]FP-CIT SPECT dopaminergic imaging, and diffuse [18F]FDG PET hypometabolism, which typically affects also the visual cortex. A 360-degree CZT SPECT systems offer advantages in terms of count sensitivity, and both contrast and energy resolution for perfusion and dopaminergic imaging as compared with conventional SPECT systems. As it happens for PET imaging protocols, a dual-time-window protocol with CZT SPECT imaging was used for a suspected DLB patient to capture both perfusion and dopaminergic states.
Referral to Geriatric Rehabilitation in the Netherlands, an Exploratory Study of Patient Characteristics
Authors: de Groot Aafke J. , Wattel Elizabeth M. , van Balen Romke , Hertogh Cees M. P. M. , van der Wouden Johannes C.
Published: February 2025

Purpose

Geriatric rehabilitation is intended for older adults with vulnerability, comorbidity, and acute functional impairments. To explore and evaluate referral criteria, this study followed hospital patients referred for rehabilitation in nursing homes.

Design

Exploratory, retrospective cohort study.

Methods

Participants were community living before acute hospitalization and referred for geriatric rehabilitation between January 15 and May 15, 2019. Data were collected at hospital admission, hospital discharge, and discharge from rehabilitation-oriented care. Outcome measure was the final discharge destination.

Results

Out of 87 hospital patients referred for rehabilitation (mean age = 76.3 years, SD = 10.7), 73 received rehabilitation-oriented post-acute care and 60 (82.2%) returned home after rehabilitation. Premorbid functional status was regained by 45 (61.6%) participants and mobility by 40 (54.8%). Independent baseline mobility, no complications during post-acute care, fewer cognitive symptoms, and multidomain vulnerability were associated with discharge destination after rehabilitation.

Clinical Relevance to Rehabilitation Nursing

A multidomain assessment can make vulnerability applicable in referral decisions and induce tailored individual rehabilitation programs.

Conclusion

This study explored the case-mix characteristics of hospital patients following rehabilitation trajectories. No frailty measures were available; vulnerability was refined into physical, cognitive, and social components. Careful assessment of vulnerability can support personalized referral decision-making.
Exosomal Biomarkers for Prognosis in Oral Squamous Cell Carcinoma—A Systematic Review of Emerging Technologies
Authors: Abdul Nishath Sayed , Ronsivalle Vincenzo , Shivakumar Sahana , Fiorillo Luca , Minervini Giuseppe
Published: February 2025

Background:

Oral squamous cell carcinoma (OSCC) is a significant health issue because of its aggressive nature and poor prognosis during the advanced stages. Exosomal biomarkers have emerged as promising entities for facilitating an enhanced existing assessment of diagnosis and prognosis in OSCC, particularly in monitoring the noninvasive behavior of tumors. The authors tried to assess the potential role of these exosomal biomarkers in the prognosis of OSCC through this systematic review.

Methods:

Seven databases, PubMed, Scopus, Web of Science, Embase, Cochrane Library, CINAHL, and ProQuest, were searched systematically. Boolean operators, along with MeSH terms, were utilized for refining the search strings to retrieve the appropriate studies. The authors included studies focusing on exosomal biomarkers derived from OSCC tissues or cell lines, with emphasis on their potential as a prognostic.

Results:

We included 7 studies that probed the role of miRNAs, lncRNAs, and proteins in exosomes. A few particular miRNAs, such as miR-155, miR-21, miR-126, and miR-130a showed significant correlation with the patients' outcomes along with the progression of OSCC. These miRNAs continuously showed association with pathways having activities related to the promotion of tumor growth, regulation of the immune system, and angiogenesis. Interestingly, the studies on proteins like Arginase-1 and CKAP4 demonstrated significance in metastasis via exosomes and could be exploited in the risk assessment for metastasis. Another group of lncRNAs screened in exosomal contents has opened the exciting possibility of uncovering the functions of noncoding RNAs in the pathogenesis of OSCC.

Conclusions:

Our results conclude that exosomal biomarkers, including miRNAs, lncRNAs, and proteins, have great potential to improve the accuracy of prognosis and thus outcomes in OSCC. Some miRNAs were proven to be particularly instrumental for non-invasive diagnostics, whereas proteins and lncRNAs were more informative concerning complicated mechanisms of progression. The above inconsistency in molecular targets between the studies indicates that exosomes play a complex role in OSCC and future studies should focus on combining these different types of biomarkers for further enhancement of potential clinical applications and management of OSCC patients.
Recognition of Aging-related Changes in the Mirror and Portraits in Ninth-century China: The Poems of Bai Juyi (白居易)
Authors: Hwang Se Won , Ashirbekovich Kerim
Published: February 2025

The aim of this study is to analyze Bai Juyi’s poems that explore the recognition of aging through the depiction of faces in mirrors and portraits. In the 2800 existing works of Bai Juyi (白居易, 772–846), around 70 poems address physical pain and disease. Among them, 7 poems were analyzed that described aging changes through mirrors or portraits. Among the 7 poems, 4 were related to mirrors, and 3 were related to his portraits. Each poem was written between the ages of 36 and 71. Most of the poems (85.7%) described hair. Three poems (42.9%) depicted facial skin and color. At the ages of 36 and 38, the poet first noticed gray hair in the mirror. By the age of 39, he observed an increase in gray hair. Between the ages of 40 and 44, he spotted gray hairs below his ears in the mirror. At 46, while looking at a portrait drawn 10 years earlier, he realized that his youthful appearance had vanished. At 58, viewing a portrait from roughly 20 years prior, he noted that his red face and black hair had disappeared. At 64, looking in the mirror, he wrote that both his beard and the hair below his ears were completely white. At 71, upon seeing his most recent portrait, drawn at the same age, he acknowledged the aging changes in his skin and hair. Advances in plastic surgery can improve the aging face and help maintain a youthful appearance for as long as possible.
The Role of Intraoperative Neurophysiologic Monitoring on Surgical Decision Making and Neurologic Outcomes in Pediatric Patients With Intramedullary Spinal Cord Tumors
Authors: Papadakis Joanna E. , Mosher Amanda , Slingerland Anna L. , Albanese John S. , Staffa Steven J. , Bose Mitali , Toczylowlski Matthew , Fehnel Katie P.
Published: February 2025

Purpose:

Maximal safe resection is recommended for intramedullary spinal cord tumors (IMSCT). Tools to minimize surgical morbidity are, therefore, critical. We review intraoperative neurophysiologic monitoring (IONM) in a large series of pediatric IMSCTs, focusing on its relationship with functional outcomes and surgical decision making.

Methods:

A single-institution, retrospective review of all IMSCT resections with IONM from 2000 to 2022 was conducted. Univariate analysis evaluated IONM changes with clinical and functional outcomes across an extended follow-up period.

Results:

Among the 59 IMSCT cases with IONM that met inclusion, somatosensory evoked potentials were used in 89.8%, motor evoked potentials in 86.4%, and Direct wave monitoring in 18.6%. Almost a third of patients experienced intraoperative changes in motor evoked potentials, somatosensory evoked potentials, and Direct waves, respectively, depending on the modality of IONM used. Monitoring alerts were more common in older patients (≥15 years) and those with larger tumors, and often led to longer hospital/intensive care unit stays and a higher rate of discharge to inpatient rehabilitation. Motor evoked potential and Direct wave alerts significantly affected the surgeon's decision to stop further resection (p = 0.001 and p = 0.067). Marked somatosensory evoked potential changes were associated with worse immediate postoperative sensory deficits (<6-weeks, p < 0.05). At 1-year follow-up, most patients experienced improved functional outcomes, with favorable motor and sensory recovery.

Conclusions:

Multiple IONM modalities are technically feasible in pediatric IMSCTs and help guide surgical decision making. Intraoperative neurophysiologic monitoring alerts were more common in patients with larger tumors and older ages, significantly affecting the surgeon's decision to stop further resection. Although associated with longer hospital/intensive care unit stays and increased discharge rates to rehabilitation, IONM changes did not significantly affect long-term functional outcomes.
Treatments for weight gain in schizophrenia
Authors: Elman Igor
Published: February 2025

Purpose of review

Obesity and related metabolic disorders are extremely common in psychiatric patients, particularly in those with schizophrenia. Elucidating this link's neurobiology may inform clinicians and researchers of rational therapeutic approaches necessary to optimize clinical outcomes.

Recent findings

Current literature highlights the pivotal role of the inflammation-oxidative stress-insulin resistance loop in the pathophysiology of both metabolic and neuropsychiatric disorders. The concept of ‘diabetophrenia’ is put forward to highlight the overlapping neurobiological mechanisms underlying metabolic dysfunction and schizophrenia symptoms. Innovative treatments, including the combination of xanomeline with trospium and incretin-based medicines, demonstrate encouraging potential in addressing such complex health challenges.

The nuanced dynamics of chronic inflammation and psychiatric symptomatology underscore the significance of addressing both metabolic and mental health factors in a cohesive fashion while considering unique psychosocial contexts, dietary preferences, and lifestyle choices. A multidisciplinary strategy is essential for incorporating counseling, dietary interventions, behavioral therapies, and pharmacotherapy into the management of schizophrenia. The ensuing enhanced collaboration among healthcare professionals may render obsolete the prevailing siloed conceptualizations of mental disorders, opening new vistas for generating synergistic insights into the mind-body systems and leading to improved health and quality of life for patients with schizophrenia and other psychiatric conditions.
A machine learning approach to predict treatment efficacy and adverse effects in major depression using CYP2C19 and clinical-environmental predictors
Authors: Calabrò Marco , Fabbri Chiara , Serretti Alessandro , Kasper Siegfried , Zohar Joseph , Souery Daniel , Montgomery Stuart , Albani Diego , Forloni Gianluigi , Ferentinos Panagiotis , Rujescu Dan , Mendlewicz Julien , Colombo Cristina , Zanardi Raffaella , De Ronchi Diana , Crisafulli Concetta
Published: February 2025

Background

Major depressive disorder (MDD) is among the leading causes of disability worldwide and treatment efficacy is variable across patients. Polymorphisms in cytochrome P450 2C19 (CYP2C19) play a role in response and side effects to medications; however, they interact with other factors. We aimed to predict treatment outcome in MDD using a machine learning model combining CYP2C19 activity and nongenetic predictors.

Methods

A total of 1410 patients with MDD were recruited in a cross-sectional study. We extracted the subgroup treated with psychotropic drugs metabolized by CYP2C19. CYP2C19 metabolic activity was determined by the combination of *1, *2, *3, and *17 alleles. We tested if treatment response, treatment-resistant depression, and side effects could be inferred from CYP2C19 activity in combination with clinical-demographic and environmental features. The model used for the analysis was based on a decision tree algorithm using five-fold cross-validation.

Results

A total of 820 patients were treated with CYP2C19 metabolized drugs. The predictive performance of the model showed at best.70 accuracy for the classification of treatment response (average accuracy = 0.65, error = ±0.047) and an average accuracy of approximately 0.57 across all the tested outcomes. Age, BMI, and baseline depression severity were the main features influencing prediction across all the tested outcomes. CYP2C19 metabolizing status influenced both response and side effects but to a lower extent than the previously indicated features.

Conclusion

Predictive modeling could contribute to precision psychiatry. However, our study underlines the difficulty in selecting variables with sufficient impact on complex outcomes.
Multifunctional roles of Sec13 paralogues in the euglenozoan
Trypanosoma brucei
Authors: Sharif Mohamed , Greenberg Lydia , Bangs James
Published: February 2025

Secretory cargos are exported from the ER via COPII-coated vesicles that have an inner matrix of Sec23/Sec24 heterotetramers and an outer cage of Sec13/Sec31 heterotetramers. In addition to COPII, Sec13 is part of the nuclear pore complex (NPC) and the regulatory SEA/GATOR complex in eukaryotes, which typically have one Sec13 orthologue. The kinetoplastid parasite
Trypanosoma brucei
has two paralogues: TbSec13.1, an accepted component of both COPII and the NPC, and TbSec13.2. Little is known about TbSec13.2, but others have proposed that it, and its orthologue in the distantly related diplonemid
Paradiplonema papillatum
, operate exclusively in the SEA/GATOR complex, and that this represents an evolutionary diversification of function unique to the euglenozoan protists. Using RNAi silencing in trypanosomes, we show both TbSec13s are essential. Knockdown of each dramatically and equally delays transport of GPI-anchored secretory cargo, indicating roles for both in COPII-mediated trafficking from the ER. Immunofluorescence and proximity labelling studies confirm that both TbSec13.1 and TbSec13.2 co-localize with TbSec24.1 to ER exit sites, and thus are functional components of the COPII machinery. Our findings indicate that TbSec13.2 function is not restricted to the SEA/GATOR complex in trypanosomes.
Neural and sensory basis of homing behaviour in the invasive cane toad,
Rhinella marina
Authors: Shaykevich Daniel A. , Pareja-Mejía Daniela , Golde Chloe , Pašukonis Andrius , O'Connell Lauren A.
Published: February 2025

The behavioural, sensory and neural bases of vertebrate navigation are primarily described in mammals and birds. While many studies have explored amphibian navigation, none have characterized brain activity associated with navigation in the wild. To address this knowledge gap, we conducted a study on navigation in the cane toad,
Rhinella marina
. First, we performed a translocation experiment to describe how invasive cane toads in Hawaii navigate home and observed homing following displacements of up to 1 km. Next, we tested the effect of olfactory and magnetosensory manipulations on homing, as these senses are most commonly associated with amphibian navigation. We found that neither ablation alone prevents homing, further supporting that toad navigation is multimodal. Finally, we tested the hypothesis that the medial pallium, the amphibian homologue to the hippocampus, is involved in homing. Our comparisons of neural activity revealed evidence supporting a conservation of neural structures associated with navigation across vertebrates consistent with neural models of amphibian spatial cognition from recent laboratory studies. Our work furthers our evolutionary understanding of spatial behaviour and cognition in vertebrates and lays a foundation for studying the behavioural, sensory and neural bases of navigation in an invasive amphibian.
PP4Psy2regulates Rrm3 and Pif1 helicases to facilitate DSB resection across tandem retrotransposons
Authors: Campos Adrián , Pulido Lydia , Iglesias Lydia , Delgado Celia , Sánchez Mar , Villoria María Teresa , Clemente-Blanco Andrés
Published: February 2025

Double-strand break repair is a tightly regulated process that relies on the coordinated activity of kinase and phosphatase complexes. Here we show that the PP4 phosphatase regulatory subunits, Psy2 and Psy4, act as positive and negative regulators of the holoenzyme during DSB repair. Cdk-dependent phosphorylation of Psy2 is crucial for DSB repair but is not required for DNA damage checkpoint inactivation. Lack of Psy2 leads to an asymmetric resection defect on one side of the DSB, a defect that is alleviated by expressing a phosphodeficient H2A variant or by depleting the checkpoint adaptor Rad9. This resection asymmetry is associated to the presence of tandem retrotransposons proximal to the DSB site, underlining the role of PP4Psy2in stimulating resection across repetitive heterochromatic regions. PP4Psy2support resection progression through paired transposable elements by reducing the phosphorylation state of Pif1 and Rrm3 helicases during the DSB response. These findings provide a comprehensive framework for the role of PP4Psy2in resection-mediated DSB repair, highlighting its function in coordinating helicases activity to preserve genomic stability in response to DNA damage.
Real-Time and Site-Specific Perturbation of Dynamic Subcellular Compartments Using Femtosecond Pulses
Authors: Ma Seohee , Dong Bin , Clark Matthew G. , Everly R. Michael , Mahapatra Shivam , Zhang Chi
Published: February 2025

Understanding laser interactions with subcellular compartments is crucial for advancing optical microscopy, phototherapy, and optogenetics. While continuous-wave (CW) lasers rely on linear absorption, femtosecond (fs) lasers enable nonlinear multiphoton absorption confined to the laser focus, offering high axial precision. However, current fs laser delivery methods lack the ability to target dynamic molecular entities and automate target selection, limiting real-time perturbation of biomolecules with mobility or complex distribution. Additionally, existing technologies separate fs pulse delivery and imaging, preventing simultaneous recording of cellular responses. To overcome these challenges, we introduce fs real-time precision opto-control (fs-RPOC), which integrates a laser scanning microscope with a closed-loop feedback mechanism for automated, chemically selective subcellular perturbation. fs-RPOC achieves superior spatial precision and fast response time, enabling single- and sub-organelle microsurgery of dynamic targets and localized molecular modulation. By applying a pulse-picking method, fs-RPOC independently controls laser average and peak power at any desired subcellular compartment. Targeting mitochondria, fs-RPOC reveals site-specific molecular responses resulting from fs-laser-induced ROS formation, H2O2 diffusion, and low-density plasma generation. These findings offer new insights into fs laser interactions with subcellular compartments and demonstrate fs-RPOC for precise molecular and organelle regulation.
Unveiling Candidate Drivers in Cancer Progression Using Somatic-IV Analysis
Authors: Zhang Wei , Gaffari Saba , Browne Andrew , Macintosh Carlos , Lu Xiaoyu , Dang Ha , Lopez Gonzalo , Wang Kai
Published: February 2025

Identifying causal drivers of cancer progression is crucial for developing effective anti-cancer therapies. However, disentangling causality from correlation remains challenging due to confounding factors within the complex genetic and transcriptomic landscapes of cancer. To address this challenge, we introduce the Somatic Instrumental Variable analysis (Somatic-IV), which integrates genetic, transcriptomic, and clinical outcome data to identify candidate driver genes likely playing a causal role in disease progression. Somatic-IV estimates genetic-exposure and genetic-outcome associations, utilizing MR-Egger regression to estimate bias-reduced causal effects. We assessed the statistical properties and performance of Somatic-IV through a simulation study and demonstrated its utility in pancreatic adenocarcinoma (PDAC) and colorectal cancer (CRC). Our analysis identified ZBED2 and CSNK2A2 as likely drivers of PDAC and CRC cancer progression, respectively. Somatic-IV is a novel approach for generating target hypotheses and guiding the development of effective therapies for cancer patients.
Structural Plasticity of RRE Stem-Loop II Modulates Nuclear Export of HIV-1 RNA
Authors: Ojha Manju , Hudson Lucia , Photenhauer Amanda , Zang Trinity , Lerew Lauren , Ekesan Solen , Daniels Jason , Nguyen Megan , Paudyal Hardik , York Darrin M. , Ohi Melanie D. , Marchant Jan , Bieniasz Paul D. , Koirala Deepak
Published: February 2025

The Rev Response Element (RRE) forms an oligomeric complex with the viral protein Rev to facilitate the nuclear export of intron-retaining viral RNAs during the late phase of HIV-1 infection. However, our structural understanding of this crucial virological process remains limited. In this study, we determined several crystal structures of an intact RRE stem-loop II in two distinct conformations, performed negative-staining electron microscopy and molecular dynamics simulations, and revealed that this three-way junction RNA exhibits remarkable structural plasticity. Through in vitro Rev-binding and in vivo Rev-activity assays using various stem-loop II mutants designed to favor one of the conformers, we demonstrated that the structural plasticity of stem-loop II modulates Rev binding and oligomerization. Our findings illuminate emerging perspectives on RRE dynamics-based regulation of HIV-1 RNA nuclear export and provide a framework for developing anti-HIV drugs that target specific RRE conformations.
A Metabolite-Based Resistance Mechanism Against Malaria
Authors: Figueiredo Ana , Rastogi Sonia Trikha , Ramos Susana , Nogueira Fátima , De Villiers Katherine , de Sousa António G. Gonçalves , Votborg-Novél Lasse , von Wedel Cäcilie , Tober-Lau Pinkus , Jentho Elisa , Pagnotta Sara , Mesquita Miguel , Cardoso Silvia , Bortolussi Giulia , Muro Andrés F. , Tranfield Erin M. , Thibaud Jessica , Duarte Denise , Sousa Ana Laura , Pinto Sandra N. , Kitoko Jamil , Mombo-Ngoma Ghyslain , Mischlinger Johannes , Junttila Sini , Alenquer Marta , Amorim Maria João , Vasavda Chirag , Bosma Piter J. , Violante Sara , Drotleff Bernhard , Paixão Tiago , Portugal Silvia , Kurth Florian , Elo Laura L. , Paul Bindu D. , Martins Rui , Soares Miguel P.
Published: February 2025

Whether jaundice, a common presentation ofPlasmodium(P.)falciparummalaria (1-3) arising from the accumulation of circulating bilirubin, represents an adaptive or maladaptive response toPlasmodiumspp. infection is not understood (1-3). We found that asymptomaticP. falciparuminfection was associated with a >10-fold higher ratio of unconjugated bilirubin over parasite burden, compared to symptomatic malaria. Genetic suppression of bilirubin synthesis by biliverdin reductase A (BVRA) (4) increased parasite virulence and malaria mortality in mice. Accumulation of unconjugated bilirubin in plasma, via genetic inhibition of hepatic conjugation by UDP glucuronosyltransferase family 1 member A1 (UGT1A1) (5), was protective against malaria in mice. Unconjugated bilirubin inhibitedP. falciparumproliferation in red blood cells (RBC) via a mechanism that suppressed mitochondrial pyrimidine synthesis. Moreover, unconjugated bilirubin inhibited hemozoin (Hz) crystallization and compromised the parasite’s food vacuole. In conclusion, jaundice represents a metabolic response toPlasmodium spp. infection that limits malaria severity.
Implicit and explicit attitudes toward people with physical disabilities in clinicians, rehabilitation assistants, and other occupations: A comparative study
Authors: Boisgontier Matthieu P.
Published: February 2025

Objective

Ableism is driven by attitudes that influence behaviors and decisions toward people with disabilities. To assess whether these attitudes vary by occupation, we compared the preferences for people with or without physical disabilities between healthcare practitioners and individuals in other professions.

Methods

Data from 213,191 participants collected through Project Implicit were analyzed, including 6445 clinicians, 3482 rehabilitation assistants, and 203,264 individuals in other occupations. Implicit attitudes were assessed using D-scores derived from the Implicit Association Test. Explicit attitudes were assessed using a Likert scale. Multiple linear regression models were conducted to examine the association between occupation groups and attitudes toward people with and without physical disabilities, while controlling for demographic variables.

Results

Healthcare practitioners showed both an implicit and explicit preference for people without physical disabilities. Equivalence tests showed that implicit attitudes of clinicians and rehabilitation assistants were equivalent to those in other occupations. Clinicians had less favorable explicit attitudes toward people with physical disabilities, whereas rehabilitation assistants had more favorable ones. Older age, male sex, and no personal experience of disability were associated with less favorable attitudes toward people with physical disabilities. Associations with education, race, geographic region, and year of data collection were also observed.

Conclusions

This study provides evidence of attitudes against people with physical disabilities among healthcare practitioners. Moreover, implicit attitudes of healthcare practitioners toward people with physical disabilities were not more favorable than those of other occupations; and explicit attitudes of clinicians were even less favorable.

Impact

Our findings suggest that despite ongoing educational shifts toward more inclusive approaches, the longstanding framework of disability as an abnormality to be normalized may still affect healthcare practitioners. This underscores the need for continued efforts to address ableism in healthcare by promoting disability-inclusive education and training.

Disclosures

None
The Impact of Virtual Reality Training on Immune-Related Mechanisms in Alzheimer’s Disease
Authors: Yusufu Nazuke , Hongyan Li
Published: February 2025

Objective

There is currently lack of research on the molecular mechanisms of VR therapy. In this study, we aimed to analyze the differential gene expression profiles and functional pathway enrichment of peripheral blood samples of AD related Mild Cognitive Impairment (MCI)patients before and after VR treatment using high-throughput sequencing methods and compare to normal controls to explore the targeted genes and potential intervention mechanisms of VR treatment.

Methods

Select five AD patients and five normal controls, collect peripheral blood samples, perform whole transcriptome sequencing to screen for differentially expressed mRNA genes before and after VR treatment and in comparison with the control group. Combine with GO and KEGG pathway enhancement to elucidate the underlying biological mechanisms and related pathways to predict the targeted genes and potential intervention mechanisms of VR treatment.

Results

Pre- and post-VR treatment group comparisons revealed a total of 1167 significantly differentially expressed genes in the mRNA data, with 165 genes upregulated and 1002 downregulated. Among these, ZFP36, FOS, JUN, FOSB, and PMAIP1 were identified as disease-related genes. Furthermore, immune infiltration analysis indicated that PMAIP1, ZFP36, and FOSB were correlated with immune cells. GO analysis highlighted significant enrichment in immune-related pathways.

Conclusion

VR treatment may modulate immune and transcriptional regulatory mechanisms, potentially contributing to its therapeutic efficacy in AD. The specific mechanisms require further research and validation.
Randomized Double Blind Inpatient Study of a Gluten-Free Diet in Persons with Schizophrenia
Authors: Kelly Deanna L. , Lee Christopher M. , Roche Daniel J.O. , Talor Monica V. , Clark Sarah , Eaton William W.
Published: February 2025

Background

Schizophrenia and related disorders (SRD) are characterized by positive and negative symptoms, such as anhedonia and avolition. There are no current FDA approved treatments for negative symptoms, which is a critical gap in our treatment of people with SRDs, since they are a major determinant of functional impairment. An emerging literature suggests that SRDs have a relationship with immune function and inflammation. Recently an SRD subgroup with high inflammation and elevated levels of anti-gliadin antibodies (AGA) of immunoglobulin G type (IgG) hasbeen characterized. Negative symptom improvement has been previously observed with gluten removal in this subgroup in two small clinical trials.

Methods

We conducted a 5-week confirmatory double-blind placebo-controlled trial of a gluten free diet (GFD) versus gluten-containing diet (GCD) for negative symptoms in people with SRD who have elevated AGA IgG (NCT03183609). Participants were between the ages of 18-64 years, had baseline negative symptoms and a diagnosis of schizophrenia or schizoaffective disorder. Those included were screened for an AGA IgG >20 U, no serologic evidence of celiac disease, and stable antipsychotic treatment and dose. All participants were inpatients, received a GFD and were randomized to 30 grams of gluten or rice flour daily delivered in protein shakes. The Clinical Assessment Interview for Negative Symptoms (CAINS) Motivation and Pleasure (MAP) scale was the primary outcome measure. We also examined the CAINS Expressivity (EXP) scale, the Scale for the Assessment of Negative Symptoms (SANS), the Brief Psychiatric Rating Scale (BPRS), the MATRICS Consensus Cognitive Battery (MCCB) and conducted regular side effect screening and laboratory measures for safety.

Findings

Between 2018 and 2024, we included 39 participants (N=21 GFD and N=18 GCD). There was a significant improvement over time in the CAINS MAP (treatment X timedf=30.1,F=2.78,p=0.045) in the GFD compared to GCD, but no significant change in the CAINS EXP, the SANS, BPRS or MCCB. The diet was well tolerated; the most frequently occurring side effects were constipation (38.1% GFD, 33.3% GCD), sedation (33.3% GFD, 50% GCD), dry mouth (33.3% GFD, 33.3% GCD), headache (33.3% GFD, 27.8% GCD), and insomnia (33.3% GFD, 27.8% GCD).

Interpretation

This is the first large scale double-blind randomized clinical trial in SRD with AGA IgG+. This replication of smaller studies suggests that negative symptoms, particularly anhedonia and avolition may be improved. However, we did not replicate our previous finding of cognitive improvement and COVID-19 likely impacted the extent of improvement in negative symptoms due to quarantines and lockdowns. More work is needed to determine the mechanism of action of gluten removal in this subgroup with hopes of developing new treatment targets for motivational deficits of this illness.
Reproducible Brain Charts: An open data resource for mapping brain development and its associations with mental health
Authors: Shafiei G , Esper NB , Hoffmann MS , Ai L , Chen AA , Cluce J , Covitz S , Giavasis S , Lane C , Mehta K , Moore TM , Salo T , Tapera TM , Calkins ME , Colcombe S , Davatzikos C , Gur RE , Gur RC , Pan PM , Jackowski AP , Rokem A , Rohde LA , Shinohara RT , Tottenham N , Zuo XN , Cieslak M , Franco AR , Kiar G , Salum GA , Milham MP , Satterthwaite TD
Published: February 2025

Major mental disorders are increasingly understood as disorders of brain development. Large and heterogeneous samples are required to define generalizable links between brain development and psychopathology. To this end, we introduce the Reproducible Brain Charts (RBC), an open data resource that integrates data from 5 large studies of brain development in youth from three continents (N=6,346; 45% Female). Confirmatory bifactor models were used to create harmonized psychiatric phenotypes that capture major dimensions of psychopathology. Following rigorous quality assurance, neuroimaging data were carefully curated and processed using consistent pipelines in a reproducible manner with DataLad, the Configurable Pipeline for the Analysis of Connectomes (C-PAC), and FreeSurfer. Initial analyses of RBC data emphasize the benefit of careful quality assurance and data harmonization in delineating developmental effects and associations with psychopathology. Critically, all RBC data – including harmonized psychiatric phenotypes, unprocessed images, and fully processed imaging derivatives – are openly shared without a data use agreement via the International Neuroimaging Data-sharing Initiative. Together, RBC facilitates large-scale, reproducible, and generalizable research in developmental and psychiatric neuroscience.
24-hour Physical Activity, Sedentary, and Sleep Profiles in Individuals with Cancer: A UK Biobank Cohort Study
Authors: Le Flora , Dumuid Dorothea , D'Elia Olivia , Haussmann Alexander , Stamatakis Emmanuel , Doherty Aiden , Liao Yue , Wiley Joshua F.
Published: February 2025

BackgroundThe 24h behaviour profile, including physical activity, sedentary time, and sleep, is disrupted following a cancer diagnosis and contributes to cancer-related outcomes. This study describes the 24h behaviour profiles of individuals with and without cancer.MethodsSeven days of accelerometer data from the UK Biobank (M ± SDage= 62.3 ± 7.8y; 56.4% female) were derived from machine learning models to assess the 24h behaviour profile in individuals with cancer (n = 10 152; M ± SDyears since diagnosis= 7.4 ± 6.1y) compared to individuals without cancer at their accelerometry measurement (including individuals with other conditions [n = 66 403], and healthy [n = 14 726]). Diagnoses were identified through ICD-10 coding within cancer registries, hospital inpatient records, self-reports, primary care, and death registers. Bayesian compositional data analysis compared 24h behaviour profiles between individuals with and without cancer, considering time since cancer diagnosis and cancer type.ResultsThe 24h behaviour profile of individuals with cancer consisted of 21.6 minutes in moderate-to-vigorous physical activity (MVPA), 303.5 minutes in light physical activity (LPA), 559.2 minutes in sedentary, and 555.7 minutes in sleep. Overall, they spent less time in MVPA -7.1 [-8.0, -6.1] min/day) and LPA -11.2 [-14.7, -7.7] min/day), accompanied by more sedentary time (+11.0 [7.2, 14.9] min/day) and sleep (+7.3 [4.6, 10.0] min/day), compared to healthy individuals. The least physically active profiles were observed within 1 year of cancer diagnoses and in individuals with blood, gastrointestinal tract, and lung cancer.ConclusionsThe 24h behaviour profiles differed by cancer history, time since diagnosis, and type. Specific behavioural trade-off strategies and support should be considered for cancer survivors, particularly in the year after diagnosis.
Global distribution of honeybee gut microbiome and pesticide-driven adaptations in opportunistic microbial species
Authors: Vardazaryan Nelli , Adunts Lusine , Bazukyan Inga , Zakharyan Magdalina , Liu Honglian , Melkonian Chrats , Nersisyan Lilit
Published: February 2025

Honeybees (Apis mellifera) rely on a specialized gut microbiome shaped by climate, flora, agrochemicals, and dietary supplements. Yet, how these factors alter microbiome composition and function remains unclear. We integrated 16S rRNA and shotgun metagenomics data from eight published studies across six regions, alongside newly generated 16S data from Armenia, to assess how environmental and agrochemical factors influence the honeybee gut microbiome. We also introduced a novel co-abundance and functional analysis pipeline to identify treatment-affected bacterial networks and associated pathways. We observed a stable core of six to twelve phylotypes in amplicon and metagenomic datasets respectively. However, we note significant geographic variation in relative abundances, likely reflecting differences in diet, climate, and local flora. Armenian data revealed distinct seasonal shifts, particularly elevated Commensalibacter in autumn and minor urban-rural differences. Pesticide treatments elicited varying responses: oxalic acid drove pronounced beta-diversity shifts; neonicotinoids had subtler effects, both primarily impacting opportunistic pathogens; and glyphosate disrupted core taxa with stronger effects in newly emerged bees under prolonged exposure. Co-abundance network analysis highlighted that the pesticide-associated community was enriched in adaptive pathways, including potential glyphosate degradation by Pseudomonas, biofilm formation, and aromatic amino acid synthesis. These findings reaffirm the stability of the honeybee core microbiome yet underscore that environmental and anthropogenic stressors induce distinct compositional and functional shifts. We emphasize the need for longitudinal metagenomic approaches that enable high-resolution functional profiling and co-abundance network analysis to clarify how these microbiome shifts impact bee health and colony sustainability.
Effects of Social Housing on Electrically Stimulated Dopamine Release in the Nucleus Accumbens Core and Shell in Female and Male Rats
Authors: Gonzalez Ivette L. , Becker Jill B.
Published: February 2025

Dopamine (DA) is a neurotransmitter that is important in the reward system and increased DA release is associated with rewarding properties of drugs. Highly addictive stimulants like methamphetamine (METH) increase DA release and block reuptake, causing the DA to stay in the synapse longer, enhancing its effects. Because the misuse of METH is increasing in the United States, it is important to investigate ways to protect against this highly addictive stimulant. Recent studies have shown that social support can be a protective factor against METH self-administration in females, but not males. Other studies using microdialysis have shown that socially housed females have lower DA release in the nucleus accumbens (NAc) compared to single housed females after treatment with METH. Additionally, researchers have shown that there are sex differences in stimulated DA release. The present study investigates whether social housing affects stimulated DA release after METH treatment. DA release in the NAc core and shell of socially housed and individually housed rats was measured using fast scan cyclic voltammetry (FSCV) with a chronic 16-channel carbon fiber electrode in the NAc. A stimulating electrode was aimed at the ventral tegmental area (VTA) to induce DA release in the NAc. The results showed that social housing enhances electrically stimulated DA release in males and that there was greater DA release in NAc core than shell in single males, but no difference in socially housed males. In females, social housing also enhanced ES DA release. In single females there was greater ES DA release in shell than in core. Additionally, in single housed females there was greater ES DA release over time, while the socially housed females had high ES DA release that remained stable over time. These results suggest that social housing protects females from sensitization, making single females more vulnerable to the addictive properties of METH.
Compositional architecture: Orthogonal neural codes for task context and spatial memory in prefrontal cortex
Authors: Park JeongJun , Holmes Charles D. , Snyder Lawrence H.
Published: February 2025

The prefrontal cortex (PFC) is crucial for maintaining working memory across diverse cognitive tasks, yet how it adapts to varying task demands remains unclear. Compositional theories propose that cognitive processes in neural network rely on shared components that can be reused to support different behaviors. However, previous studies have suggested that working memory components are task specific, challenging this framework. Here, we revisit this question using a population-based approach. We recorded neural activity in macaque monkeys performing two spatial working memory tasks with opposing goals: one requiring movement toward previously presented spatial locations (look task) and the other requiring avoidance of those locations (no-look task). Despite differences in task demands, we found that spatial memory representations were largely conserved at the population level, with a common low-dimensional neural subspace encoding memory across both tasks. In parallel, task identity was encoded in an orthogonal subspace, providing a stable and independent representation of contextual information. These results provide neural evidence for a compositional model of working memory, where representational geometry enables the efficient and flexible reuse of mnemonic codes across behavioral contexts while maintaining an independent representation of context.