bluuebunny/crossref_metadata_2025_split huggingface dataset:
Teasing out factors differentiating pathologic from benign pneumatosis intestinalis
Authors: Song Julia , Zhang Biqi , Mahvi David , Shariat Mahsa , Castillo-Angeles Manuel , Dey Tanujit , Askari Reza 
Published: February 2025

BACKGROUND
Pneumatosis intestinalis (PI) is a rare radiographic finding that can range from being a benign process to needing emergency surgery. Sufficiently powered studies are lacking, and recommendations for management remain unclear. The purpose of this study was to identify key predictors of pathologic PI using physical examination, laboratory, and radiographic findings.

METHODS
A retrospective cohort study was conducted at two quaternary academic centers (2010–2020). A total of 334 consecutive patients 18 years or older with radiographic evidence of PI were identified. Patients were excluded if they pursued comfort care or if there was concurrent radiographic evidence of vaso-occlusive process. Pathologic PI was defined as presence of ischemic and/or perforated bowel on exploratory laparotomy or death prior to planned surgery.

RESULTS
Of the 334 patients included in our study, 91 (27%) underwent exploratory laparotomy, of which 59 (65%) had ischemic and/or perforated bowel. These latter patients and 10 other patients who died before exploratory laparotomy defined the pathologic PI cohort. A stepwise model was created for predicting pathologic disease. Significant predictors were the presence of portal venous gas, multisegment PI, vasopressor use, peritonitis, increasing leukocyte count, and end organ injury, which were used to construct a nomogram for clinical use.

CONCLUSION
A nomogram score based on presence of portal venous gas, multisegment PI, vasopressor use, peritonitis, leukocytosis, and end organ injury may help predict the probability of pathologic PI and therefore can inform surgical decision making.

LEVEL OF EVIDENCE
Epidemiologic Study; Level III.
American Clinical Neurophysiology Society Technical Standards for Electrical Stimulation With Intracranial Electrodes for Functional Brain Mapping and Seizure Induction
Authors: Arya Ravindra , Baumer Fiona M. , Chauvel Patrick , Frauscher Birgit , Jayakar Prasanna , Kheder Ammar , Lega Bradley , Lesser Ronald P. , Miller Kai J. , Nuwer Marc R. , Pedersen Nigel P. , Ritaccio Anthony L. , Sabsevitz David S. , Sinha Saurabh R. , So Elson L. , Tatum William O. , Templer Jessica W. , Schuele Stephan U. 
Published: February 2025

Purpose:
These American Clinical Neurophysiology Society technical standards suggest best practices for electrical stimulation mapping (ESM) with subdural and stereotactic depth electrodes for seizure induction and mapping of brain function.

Methods:
A working group was convened from American Clinical Neurophysiology Society membership with expertise in ESM. PubMed searches were performed to identify pertinent peer-reviewed literature. Recurrent meetings reviewed progress, built consensus by discussion, and developed evidence-based recommendations to the extent possible.

Recommendations:
Stimulators used for ESM should have sufficient dynamic range, ability to interrupt a stimulus train, and ictal disrupt mechanism(s). Charge density should be calculated for the specific electrodes and ESM settings, the maximum safe limits being 52 to 57 μC/cm2/phase for subdural electrodes and not established for stereotactic depth electrodes. Subdural ESM for functional mapping is typically performed at 50-Hz pulse frequency, 200- to 300-µs pulse width, 2- to 8-s train duration, and 1- to 20-mA current strength. Stereo ESM is commonly performed using 2 different pulse frequencies: 1 Hz (300–500 µs pulse width, train duration up to 30 s, and often a constant current of 3–5 mA), and 50 Hz (100–500 µs pulse width, train duration 2-8 s, and 0.5–10 mA current intensity).

Conclusions:
This guideline provides technical standards for the performance of ESM, which will likely evolve over time with advances in technology and additional evidence (also see Graphical Abstract).
Chiral Single Molecule Localization Microscopy (chiralSMLM)
Authors: Aravinth S , Pant Neeraj , Mondal Partha P. 
Published: February 2025

Chiral fingerprints are unique to a molecule and convey information related to binding sites, conformation, and its immediate chemical environment. Deciphering these information is expected to aid a better understanding of the biological processes at the very molecular scale. Here, we present a new technique calledchiralSM LM, to selectively detect chiral enantiomers (left-handed and right-handed) of single molecules and generate a super-resolved map of their distribution in cell. Calibration, characterization, and optimization of the system is carried out using a polarized light source (left and right circularly) and by recording known structures (Actin filaments) in a cell. Subsequently, the distribution of Dendra2-Actin enantiomers on the actin filaments is mapped. Finally,chiralSM LMis employed to study the characteristic distribution of viral proteins (Hemaglutinin and NS3) in transfection studies of two diseases (Influenza type-A and Dengue type2) after 48 hrs of transfection. Single-molecule and cluster analysis reveals that left-handed HA and left-handed NS3 molecules have a larger footprint, suggesting the role of chiral molecules in promoting cluster formation during viral infection. This is amazing, considering the fact that Left-handed enantiomers are known to play a crucial role in a range of biological functions. The new classification of single molecules purely based on their chiral nature is expected to advance single-molecule imaging.Summary & SignificanceDeciphering the chirality of single molecules and studying its effect on the biological function of a cell is fabulous. This gives a new perspective for understanding functions purely based on the chiral nature of single biomolecules in a cell. We developed achiralSM LMmicroscopy system to demonstrate the effect of chirality on the clustering behavior of viral proteins in a cell-transfection study. Hence, the findings provide a new way of quantifying molecule-molecule and molecule-organelle interactions.
Spike Train Scalograms (STS): a Deep Learning Classification Pipeline for Neuronal Cell Types
Authors: Amprimo Gianluca , Martini Lorenzo , Bilir Begum , Bardini Roberta , Savino Alessandro , Olmo Gabriella , Di Carlo Stefano 
Published: February 2025

AbstractClassifying neuronal cell types is crucial for understanding the intricate circuitry of the cerebral cortex, which comprises diverse specialized neurons essential for brain function. Traditional Machine Learning (ML) approaches rely on manually engineered electrophysiological (EP) features, often overlooking subtle and complex patterns within spike train data. This study introduces a novel Spike Train Scalograms (STS)-based Deep Learning (DL) pipeline that integrates Continuous Wavelet Transform (CWT) scalograms with pre-trained Convolutional Neural Networks (CNN) architectures to classify neuronal cell types with high accuracy. Utilizing patch-clamp EP recordings from 5,590 murine cortical neurons, the pipeline transforms spike trains into time-frequency representations via CWT, capturing both transient and sustained signal characteristics. These scalograms are then processed by fine-tuned CNN architectures, includingInceptionV3, which achieved a balanced accuracy and weightedF1-Score of 90.53% and 90.03%, respectively. The STS pipeline effectively distinguishes between major neuronal types such as Pvalb, Sst, Vip/Lamp5, and Excitatory neurons, even in the presence of class imbalances. Moreover, an explainability analysis using saliency maps and SHAP revealed high correspondence between the DL approach, the ML baseline and biological knowledge of these neuronal types. The results demonstrate the efficacy of combining advanced spectral analysis with DL techniques, offering a scalable and automated method for precise neuronal classification.
Deep Learning-Driven EEG Analysis for Personalized Deep Brain Stimulation Programming in Parkinson’s Disease
Authors: Calvo Peiro Nicolas , Haugland Mathias Ramm , Kutuzova Alena , Graef Cosima , Bocum Aminata , Tai Yen Foung , Borovykh Anastasia , Haar Shlomi 
Published: February 2025

AbstractDeep Brain Stimulation (DBS) is an invasive procedure used to alleviate motor symptoms in Parkinson’s Disease (PD) patients. While brain activity can be used to optimise DBS parameters, the impact of DBS parameters on brain activity remains unclear. We aimed to identify the cortical neural response to changes in DBS parameters, which are sensitive to the effect of small changes in the stimulation parameters and could be used as neural biomarkers. We recorded in-clinic EEG data from seven hemispheres of PD patients during DBS programming sessions.Here we developed a siamese adaptation of the EEGNet deep learning architecture and trained it to distinguish whether two short (1-sec-long) segments of brain activity were taken with the same stimulation parameters, or if either the strength or location of the stimulation had changed. 13 independent models were trained independently in each hemisphere for stimulation amplitude or contact, and all achieved high accuracy with an average of 78%. Our models are sensitive to changes in brain activity recorded at the scalp of the patients following changes as small as 0.3mA in the DBS parameters.Next, we interpreted what our black-box AI models learned with an ablation-based explainability method, that extracts frequency bands learned by the models through a perturbation of the input’s frequency spectrum. We found that fast Narrow-Band Gamma oscillations (60-90Hz), contributed most to the models across all 7 hemispheres.This work, using a data-driven approach, joins a recent body of evidence suggesting cortical Narrow-Band Gamma activity as the potential range for digital biomarkers for DBS optimization.
Engaging doctoral students in peer review: a pre-post study evaluating the effectiveness of the “Peerspectives” course on review quality, knowledge and skills
Authors: Rohmann Jessica L. , Wülk Nadja , Rubarth Kerstin , Grillmaier Hannah , Abdikarim Iman , Simoes Mariana Lopes , Schroter Sara , Piccininni Marco , Kurth Tobias , Glatz Toivo 
Published: February 2025

ABSTRACTObjectiveTo assess the effectiveness of thePeerspectivescourse on editor-judged quality of peer reviewDesignSingle arm, pre-post interventional studySettingPeerspectivesis a peer review training course developed for doctoral students at the Charité – Universitätsmedizin Berlin, GermanyParticipantsDoctoral students in health research domains who enrolled in thePeerspectivescourse between October 2020 and August 2022 and consented to participate (N= 80).Intervention:A semester-long course (approx. 18 weeks) providing training about the structure, purpose, and conduct of peer review and editing processes in biomedical journals. The course consisted of 12 hours of interactive lectures, weekly homework assignments, and 12 hours of hands-on, small-group workshops under guidance of mentors with reviewing and editing experience. Students peer-reviewed real scientific manuscripts under review at a partnering journal,The BMJ.Main outcome measuresThe overall quality of the peer review reports as judged by two independentBMJeditors using the global score of the Review Quality Instrument (RQI) pre- and post-intervention. Additionally, participants’ self-assessed knowledge and skills related to scholarly peer review (1-5 Likert scale).ResultsAfter course completion, participants’ RQI scores were higher than before the course (median increase of 0.5 points, p<0.001; mean increase of 0.36 points, p<0.001). The RQI scores of participants’ post-course reports were not non-inferior to those of actualBMJreviewers for the same manuscripts. Self-assessed peer review-related knowledge skills increased across all questionnaire items after course completion. Largest improvements were seen in understanding what is expected from a reviewer (increase in means from 2.9 to 4.5), confidence in own ability to review (2.5 to 3.9), and knowing what to look for in a manuscript while reviewing (2.8 to 4.2).ConclusionsProviding doctoral students with comprehensive training resulted in an editorially significant increase in review report quality and improved understanding of the role and expectations of peer reviewers in the scholarly publishing processes and confidence in giving constructive feedback.Study pre-registration:https://osf.io/vndcx
Optimisation of Xenium automated in situ sequencing for PAXgene-fixed tissue samples
Authors: Roberts Kenny , Bassett Andrew R. 
Published: February 2025

AbstractSpatial transcriptomics has transformed the study of gene expression in tissue samples, yet its application to non- standard sample preservation formats beyond fresh frozen and FFPE remains underexplored. PAXgene fixation offers advantages for genomic studies by preserving DNA and RNA without crosslinking but poses challenges for high-quality spatial transcriptomics. Here, we present an optimised workflow for applying Xenium, an automated in situ sequencing platform, to PAXgene-fixed paraffin-embedded (PFPE) tissues. Using our newly developed Xenium Tissue Optimisation (XTO) protocol, we systematically tested permeabilisation conditions across multiple mouse and human tissues. We show that pepsin digestion effectively enhances RNA accessibility in PFPE samples, with tuneable digestion times for tissue-specific optimisation, though a compromise may need to be reached between transcript detection rates and maintaining tissue integrity and morphological staining. Our results indicate that, under optimal conditions, PFPE samples can yield comparable or superior spatial RNA transcript detection to formalin-fixed paraffin-embedded (FFPE) samples. This study provides a framework for adapting in situ sequencing to PFPE tissues, broadening the applicability of spatial transcriptomics to archival and prospective sample collections.Visual abstract
Chalcone isomerase-like impedes the lactone shunt and enhances flux partitioning in a bifurcated pathway towards isoflavonoid biosynthesis
Authors: Raytek Lee Marie , Saltzman Brandon Corey , Sharma Meha , Lee Soon Goo , Dastmalchi Mehran 
Published: February 2025

ABSTRACTThe reconstitution of biosynthetic pathways in heterologous hosts is often challenged by the switch to a foreign cellular environment, lacking compatible structural or regulatory features. Auxiliary or non-catalytic proteins can play a critical role in modulating metabolic flux and pathway efficiency. Chalcone isomerase-like (CHIL) is a non-catalytic protein known to serve as a partner to chalcone synthase (CHS) in flavonoid biosynthesis, rectifying its promiscuous activity and preventing by-product formation, such as the aberrantp-coumaroyltriacetic acid lactone (CTAL). Here, we extended the characterization of CHILs to the legume-characteristic isoflavonoid pathway. We assessed four CHIL orthologs from diverse plant lineages:Glycine max(GmCHIL),Oryza sativa(OsCHIL),Selaginella moellendorffii(SmCHIL), andMarchantia polymorpha(MpCHIL). Structural modelling suggested that naringenin (flavanone) entry into the CHIL binding cleft may be sterically hindered compared to catalytic CHIs. Moreover, legume CHIL isoforms possess an additional bulky residue, Tyr48, that is expected to impose further constraints on ligand binding.In vitro,CHS produced up to 60% lactone CTAL instead of its desired output; however, CHIL suppressed this aberrant activity to 10%, concomitantly increasing target compound titers. Combinatorial enzyme and yeast biotransformation assays revealed a critical role for CHIL in conducting flux through chalcone, flavanone, and isoflavone biosynthesis. The inclusion of CHIL in our engineered yeast strains enhanced overall titers and, unexpectedly, promoted carbon flux toward the so-called deoxy-branch (isoliquiritigenin, liquiritigenin, and daidzein) by up to 67%, with a 33% increase in final daidzein titers. By extending CHIL characterization to the isoflavonoid pathway, we have revealed an expanded role for this auxiliary protein and underscored its utility in engineered metabolic contexts. Our findings reiterate the often-overlooked impact of non-catalytic proteins in shaping specialized metabolism.HIGHLIGHTSCombinatorial enzyme assays reveal a species-dependent preference for CHILs from more closely related plant phyla by soybean CHS, which improved chalcone and downstream flavanone output by suppressing aberrant lactone formation.Yeast co-expressing CHIL with the components of the isoflavonoid metabolon exhibited a 67% increase in flux through a legume-characteristic branch of the pathway, resulting in a 33% increase in titers of the major isoflavone, daidzein.CHIL proteins can be included to engineer the output of phenylpropanoid-derived intermediates preferentially toward isoflavonoid biosynthesis.Auxiliary components, such as CHIL, can be designed to refine metabolic composition in bifurcated pathways, as well as enhancing general flux through pathways.
Glucagon-like peptide-1 receptor activation and mental health: a drug-target Mendelian randomization study
Authors: Yang Guoyi , Burgess Stephen , Schooling C Mary 
Published: February 2025

AbstractConcerns have been raised about the psychiatric safety of glucagon-like peptide-1 receptor (GLP-1R) agonists, but trial evidence suggests that they ameliorate depressive symptoms. We aimed to assess the associations of GLP-1R activation with mental health well-being and the risk of mental health disorders and substance use disorders. We performed drug-target Mendelian randomization and colocalization analyses using the largest relevant publicly available genome-wide association studies in European ancestry individuals. After correcting for multiple comparisons, genetically predicted lower body mass index (BMI) via GLP-1R activation was associated with a better well-being spectrum (0.06 standard deviation [95% confidence interval 0.03-0.08]) and lower risk of depression (odds ratio 0.83 [0.74-0.94]) and bipolar disorder (odds ratio 0.61 [0.47-0.79]) per 1-kg/m2decrease in BMI. There was also suggestive evidence that genetically predicted lower BMI via GLP-1R activation was associated with lower risk of post-partum depression, attention deficit hyperactivity disorder, and substance use disorders, and that genetically predicted lower glycated hemoglobin (HbA1c) via GLP-1R activation was associated with higher risk of anorexia nervosa but lower risk of Tourette syndrome. These associations were stronger than the associations for genetically predicted lower BMI and lower HbA1c based on genome-wide variants. The posterior probabilities of a shared causal variant affecting both BMI and the outcome at theGLP1Rgene were 59.3% for the well-being spectrum, 3.8% for depression, and 45.9% for bipolar disorder. GLP-1R activation was associated with better mental health well-being and lower risk of depression and bipolar disorder beyond that expected from the reduction in BMI and HbA1c.
The Thermal Grill Elicits Central Sensitization
Authors: Cormie Matthew A. , Seminowicz David A. , Moayedi Massieh 
Published: February 2025

AbstractThe thermal grill, in which innocuous warm and cool stimuli are interlaced, can produce a paradoxical burning pain sensation—the thermal grill illusion (TGI). While the mechanisms underlying TGI remain unclear, prominent theories point to spinal dorsal horn integration of innocuous thermal inputs to elicit pain. It remains unknown whether the TGI activates peripheral nociceptors, or solely thermosensitive afferents and is integrated within the spinal cord. Different types of sensitization have established mechanisms and can inform TGI mechanisms: if the TGI elicits (1) primary hyperalgesia, peripheral nociceptors are activated; (2) secondary hyperalgesia in the absence of primary hyperalgesia, spinal integration is required; and (3) brush allodynia, wide-dynamic range neurons are involved in mediating the TGI. Here, we determine whether the TGI elicits primary hyperalgesia, secondary hyperalgesia or brush allodynia. Fifty-two participants underwent individually calibrated phasic thermal grill stimulation. We found that the TGI elicited primary hyperalgesia, but only in participants with component temperatures in the noxious range (<19°C and >41°C). The TGI also elicited secondary hyperalgesia, even in participants with strictly innocuous thermal inputs. No participants developed brush allodynia. We observed sex differences in primary hyperalgesia: only males exhibited thermal grill-induced primary hyperalgesia. These findings suggest that the TGI is integrated in the spinal dorsal horn, likely mediated by heat-pinch-cold (HPC) neurons, and, to some degree, by primary nociceptive afferents in males. This study shows that the TGI may have sex-dependent mechanisms and determines that HPC cells are involved in the illusory sensation of pain from innocuous thermal inputs.
Do negative social media sentiments affect firm risk?
Authors: Benjamin Samuel Jebaraj , Wellalage Nirosha , Biswas Pallab Kumar , Wasiuzzaman Shaista 
Published: February 2025

Purpose
This paper aims to empirically examine the link between negative social media sentiments (SMS) and firm risk, measured by total risk.

Design/methodology/approach
This paper collected data from Fortune 500 companies in the USA from 2010 to 2017. The analyses used the pooled ordinary least squares, Fama–McBeth regression, fixed-effects regression and propensity score matching.

Findings
The results show that negative SMS increase firm risk. In addition, this paper considers the effect of corporate social responsibility (CSR) disclosures on the relationship between negative SMS and firm risk. This paper finds that the effects of negative SMS on firm risk are attenuated in firms with better CSR disclosures.

Originality/value
This study offers fresh perspectives for investors and managers on firm risk and the influence of social media on firm outcomes, providing valuable insights for scholars and practitioners to understand the impact of negative social media sentiments on firm risk, along with the crucial roles played by CSR in this relationship.
Male migration, women’s decision-making autonomy and reproductive health-care utilization in Pakistan
Authors: Shah Nasra M. , Quddus Samar 
Published: February 2025

Purpose
The purpose of this study is to examine the association between international migration and utilization of reproductive health care among women left behind in Pakistan by male migrants, in comparison with women in non-migrant households.

Design/methodology/approach
From the nationally representative Pakistan Demographic and Health Survey, 2017–2018, 8,158 currently married women who had delivered a child during the five years before the survey were included. Among the 8,158 women, 811 lived in a household that had at least one international migrant, while 7,347 lived in households without migrant. Descriptive statistics as well as logistic regression was used to analyze reproductive health care. Satisfactory reproductive health was defined as: 4+ antenatal visits; 2+ tetanus injections; delivery in a health-care facility; and delivery by a skilled birth attendant.

Findings
Logistic regression indicates that women in migrant households had a significantly higher utilization of all four health-care services, after controlling for their autonomy level. However, once background characteristics (woman’s age, education, rural-urban residence and wealth status) were factored in, women in migrant households were not significantly different from those in non-migrant households, except for delivering in a medical health-care facility, the former being 1.3 times more likely to deliver in a health facility than the latter. A higher level of autonomy was associated significantly with greater utilization of reproductive health services.

Originality/value
This study adds the dimension of international migration to the existing knowledge on utilization of health-care services, a subject that is relatively under researched in Pakistan.