bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of Lactococcus lactis strain Plasma on clearance of anal HPV infection in men who have sex with men: A single-center, double-blinded, randomized placebo-controlled trial (CLEAR HPV study)
Authors: Mizushima Daisuke , Takano Misao , Ando Naokatsu , Kitamura Hiroshi , Shiojiri Daisuke , Nakamoto Takato , Aoki Takahiro , Watanabe Koji , Shimizu Yosuke , Uemura Yukari , Gatanaga Hiroyuki , Oka Shinichi 
Published: October 2023

Background:
Anal cancer is a human papillomavirus-related cancer; specifically, it is preceded by high-grade squamous intraepithelial lesions, which are less likely to regress spontaneously than low-grade intraepithelial lesions. Although most human papillomavirus (HPV) infections are thought to clear spontaneously, anal HPV infection persists, especially in people living with HIV. Preliminary results from a recent small randomized placebo-controlled trial of oral bacteriotherapy using a high dose of probiotics demonstrated clearance of anal high-risk HPV (hr-HPV) infection and lower onset of new high-grade squamous intraepithelial lesions among people living with HIV. Lactococcus lactis strain Plasma is a lactic acid bacterium directly activating plasmacytoid dendritic cells and inducing release of type I and III interferons via Toll-like receptor 9 stimulation. Based on these findings, oral bacteriotherapy with LC-plasma may contribute to clearing anal hr-HPV infection and reducing anal precancerous lesions by activating innate and acquired immune responses. This randomized placebo-controlled trial aims to investigate the efficacy and safety of LC-plasma therapy in clearing anal hr-HPV infection and reducing anal precancerous lesions among men who have sex with men with or without HIV infection.

Methods:
Participants with anal hr-HPV infection will be included and receive test capsules. A total of 150 patients will be included in the intervention group with follow-up, which will consist of HPV genotype test, cytology by anal pap smear, and biopsy with high-resolution anoscopy. The primary endpoint will be the clearance rate of the hr-HPV genotype infection at the anal site at 180 days. The secondary endpoints will be changes in anal epithelial neoplasia detected using high-resolution anoscopy at 180 days; change in abnormal cytology by anal pap smear at 180 days; change in hr-HPV genotype at the anal site at 180 days; change or percentage change in peripheral blood CD4 positive T-lymphocyte numbers in HIV-infected participants at 180 days; changes in quantitative hepatitis B surface antigen levels at 180 days in the HBV-infected participants; and adherence to the study drugs.

Conclusion:
This randomized controlled study will provide data on the efficacy and safety of LC-plasma as a treatment for anal HPV infection and grade 2 or 3 anal intraepithelial neoplasia.
Treating rare tumors with liver transplantation
Authors: Melehy Andrew , Agopian Vatche 
Published: October 2023

Purpose of review
The success of liver transplantation (LT) in treating unresectable hepatocellular carcinoma (HCC) has resulted in interest in LT for other oncologic conditions. Here, we discuss the role of LT for rare oncologic indications including metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs), hepatic epitheliod hemangioendothelioma (HEHE), fibrolamellar hepatocellular carcinoma (FLC), and hepatic angiosarcoma (HAS).

Recent findings
Conditions reviewed have been documented indications for LT in the available literature. We summarize the experience of LT for these indications and proposed management guidelines.

Summary
GEP-NETs with isolated metastases to the liver can be treated with LT with excellent long-term outcomes (10-year survival 88%) if strict selection criteria are used (low-intermediate grade, Ki-67% < 20%, complete resection of primary tumor, stable disease for 6 months, <50% hepatic involvement). HEHE is a rare hepatic tumor for which LT can be performed with reported 10-year survival around 70%. FLC is a distinct clinical entity to HCC and is optimally treated with surgical resection though experience with LT is described in observational series (5-year survival 50%, recurrence in 10%). HAS is a rapidly progressive tumor with a dismal prognosis with or without treatment, including LT.
Assessment of a Novel, Adjustable Task Trainer for Cardiac Surgical Skills
Authors: White Abigail , Turner Simon R. , Moon Michael C. , Zheng Bin 
Published: October 2023

Introduction
A recent needs assessment in Canadian cardiac surgery programs identified the desire for a coronary artery bypass (CABG) and aortic valve replacement (AVR) simulation model for home practice. We aimed to develop and assess a portable, adjustable task trainer for cardiac surgical skills with high functional task alignment.

Methods
Intraoperative measurements were taken from patients undergoing elective CABG and AVR (N = 30). Measurements were taken in 3 axes and used to create a chest cavity that resembles the mediastinal constraints of a patient undergoing CABG and AVR. The task trainer is adjustable on the following 3 levels: (1) size of the incision, (2) depth of the chest, and (3) relative position of coronary artery or aortic valve model within the chest. Three groups (novices, intermediates, and experts) of cardiac surgery members evaluated the task trainer for functional task alignment and construct validity.

Results
The CABG and AVR model had high functional task alignment. There was a high satisfaction for both models and all participants would recommend the AVR and CABG model as an educational tool. Performance time significantly differed between the groups for both models (CABG: P = 0.032 and AVR: P = 0.001), as well as number of errors (CABG: P = 0.04 and AVR: P = 0.043).

Conclusions
Using real patient data, we were able to develop an adjustable task trainer for training principles of CABG and AVR. Our pilot study provides preliminary sources of evidence for validity and future study will look to assess transferability of skill to the operating room.
A blue-shifted genetically encoded Ca2+indicator with enhanced two-photon absorption
Authors: Aggarwal Abhi , Sunil Smrithi , Bendifallah Imane , Moon Michael , Drobizhev Mikhail , Zarowny Landon , Zheng Jihong , Wu Sheng-Yi , Lohman Alexander W. , Tebo Alison G. , Emiliani Valentina , Podgorski Kaspar , Shen Yi , Campbell Robert E. 
Published: October 2023

ABSTRACTSignificanceGenetically encoded calcium ion (Ca2+) indicators (GECIs) are powerful tools for monitoring intracellular Ca2+concentration changes in living cells and model organisms. In particular, GECIs have found particular utility for monitoring the transient increase of Ca2+concentration that is associated with the neuronal action potential. However, the palette of highly optimized GECIs for imaging of neuronal activity remains relatively limited. Expanding the selection of available GECIs to include new colors and distinct photophysical properties could create new opportunities forin vitroandin vivofluorescence imaging of neuronal activity. In particular, blue-shifted variants of GECIs are expected to have enhanced two-photon brightness, which would facilitate multiphoton microscopy.AimWe describe the development and applications of T-GECO1 – a high-performance blue-shifted GECI based on theClavularia sp.-derived mTFP1.ApproachWe used protein engineering and extensive directed evolution to develop T-GECO1. We characterize the purified protein and assess its performancein vitrousing one-photon excitation in cultured rat hippocampal neurons,in vivousing one-photon excitation fiber photometry in mice, andex vivousing two-photon Ca2+imaging in hippocampal slices.ResultsThe Ca2+-bound state of T-GECO1 has an excitation peak maximum of 468 nm, an emission peak maximum of 500 nm, an extinction coefficient of 49,300 M-1cm-1, a quantum yield of 0.83, and two-photon brightness approximately double that of EGFP. The Ca2+-dependent fluorescence increase is 15-fold and the apparentKdfor Ca2+is 82 nM. With two-photon excitation conditions at 850 nm, T-GECO1 consistently enabled detection of action potentials with higher signal-to-noise (SNR) than a late generation GCaMP variant.ConclusionT-GECO1 is a high performance blue-shifted GECI that, under two-photon excitation conditions, provides advantages relative to late generation GCaMP variants.
Automated and Interpretable Detection of Hippocampal Sclerosis in temporal lobe epilepsy: AID-HS
Authors: Ripart Mathilde , DeKraker Jordan , Eriksson Maria H , Piper Rory J. , Mo Jia-Jie , Su Ting-Yu , Kochi Ryuzaburo , Wang Irene , Winston Gavin P , Clark Chris A , D’Arco Felice , Mankad Kshitij , Khan Ali R. , Baldeweg Torsten , Adler Sophie , Wagstyl Konrad 
Published: October 2023

AbstractHippocampal Sclerosis (HS) can elude visual detection on MRI scans of patients with temporal lobe epilepsy (TLE), causing delays in surgical treatment and reducing the likelihood of postsurgical seizure-freedom. We developed an open-source software that (1) detects HS from structural MRI scans, (2) generalises across a heterogeneous multicentre cohort of children and adults, and (3) generates individualised predictions for clinical evaluation.We included a cohort of 363 participants (152 patients with HS, 90 disease controls with focal cortical dysplasia, and 121 healthy controls) from four epilepsy centres in the UK, North America, and China. We used the open-source software HippUnfold to extract morphological surface-based features and volumes of the hippocampus from T1w MRI scans. We compared pathological hippocampal morphology in patients with HS to normative growth charts generated from healthy controls, and to the contralateral hippocampi in patients with HS. HS was characterised by decreased volume, thickness and gyrification as well as increased mean and intrinsic curvature. A logistic regression classifier trained on these features detected 90.1% of HS patients, and accurately lateralised 97.4% of the HS cohort. Crucially, in patients with MRI-negative histopathologically confirmed HS, the classifier detected HS in 79.2% (19/24) and accurately lateralised the lesions in 91.7% (22/24). The Automated and Interpretable Detection of Hippocampal Sclerosis classifier (AID-HS) was packaged into an open-source pipeline, which detects and lateralises HS and generates individualised patient reports that characterise hippocampal developmental abnormalities.AID-HS is capable of accurately detecting and lateralising HS in a large, heterogeneous, multi-centre, cohort of paediatric and adult patients with diagnostically challenging HS. Moreover, by offering transparent, robust and interpretable results, AID-HS can support the presurgical evaluation of patients with suspected TLE.
Generalized Reporter Score-based Enrichment Analysis for Omics Data
Authors: Peng Chen , Chen Qiong , Tan Shangjin , Shen Xiaotao , Jiang Chao 
Published: October 2023

AbstractEnrichment analysis contextualizes biological features in pathways to facilitate a systematic understanding of high-dimensional data and is widely used in biomedical research. The emerging reporter score-based analysis (RSA) method shows more promising sensitivity, as it relies onp-valuesinstead of raw values of features. However, RSA cannot be directly applied to multi-group experimental designs and is often misused due to the lack of a proper tool. Here, we propose the Generalized Reporter Score-based Analysis (GRSA) method for multi-group and longitudinal omics data. A comparison with other popular enrichment analysis methods demonstrated that GRSA had increased sensitivity across multiple benchmark datasets. We applied GRSA to microbiome, transcriptome, and metabolome data and discovered new biological insights in omics studies. Finally, we demonstrated the application of GRSA beyond functional enrichment using a taxonomy database. We implemented GRSA in an R package, ReporterScore, integrating with a powerful visualization module and updatable pathway databases (https://github.com/Asa12138/ReporterScore). We believe the ReporterScore package will be a valuable asset for broad biomedical research fields.
Glomerular immune injury promotes anti-tumor activity
Authors: Avraham Shimrit , Korin Ben , Lo Jerry Hung-Hao , Cruz-Tleugabulova Mayra , Menon Hari , Darmanis Spyros , Liang Yuxin , Modrusan Zora , Durinck Steffen , Webster Joshua D , Shaw Andrey S 
Published: October 2023

AbstractRecent evidence suggests that the interaction between the tumor microenvironment (TME) and systemic host environment can alter the host immune system to promote anti-tumor activity. Here, we investigated whether glomerular immune injury affects cancer progression. We used nephrotoxic serum nephritis (NTN), a model for glomerular immune injury, and followed it by cancer cell implantation. NTS-injected mice developed smaller primary tumors compared with controls. Tumors of NTS-injected mice had more activated CD8 T cells, suggesting a role for the immune system in the anti-tumor phenotype. Using RNA-seq data, we identified transcriptomic alterations in the bone marrow following NTN. Moreover, using scRNA-seq of white blood cells following NTN we found these transcriptomic alterations were reflected in γδ T cells and neutrophils. This is the first study to show that glomerular immune injury changes the transcription of cells in the bone marrow to advance anti-tumor activity. Our study highlights the pivotal role of BM-mediated transcriptional alterations underlying the enhanced host immunity to tumor growth.
Latent Epigenetic Programs in Müller Glia Contribute to Stress, Injury, and Disease Response in the Retina
Authors: Norrie Jackie L. , Lupo Marybeth , Shirinifard Abbas , Djekidel Nadhir , Ramirez Cody , Xu Beisi , Dundee Jacob M. , Dyer Michael A. 
Published: October 2023

ABSTRACTPrevious studies have demonstrated the dynamic changes in chromatin structure during retinal development that correlate with changes in gene expression. However, a major limitation of those prior studies was the lack of cellular resolution. Here, we integrate single-cell (sc) RNA-seq and scATAC-seq with bulk retinal data sets to identify cell type–specific changes in the chromatin structure during development. Although most genes’ promoter activity is strongly correlated with chromatin accessibility, we discovered several hundred genes that were transcriptionally silent but had accessible chromatin at their promoters. Most of those silent/accessible gene promoters were in the Müller glial cells. The Müller cells are radial glia of the retina and perform a variety of essential functions to maintain retinal homeostasis and respond to stress, injury, or disease. The silent/accessible genes in Müller glia are enriched in pathways related to inflammation, angiogenesis, and other types of cell-cell signaling and were rapidly activated when we tested 15 different physiologically relevant conditions to mimic retinal stress, injury, or disease in human and murine retinae. We refer to these as “pliancy genes” because they allow the Müller glia to rapidly change their gene expression and cellular state in response to different types of retinal insults. The Müller glial cell pliancy program is established during development, and we demonstrate that pliancy genes are necessary and sufficient for regulating inflammation in the murine retina in vivo. In zebrafish, Müller glia can de-differentiate and form retinal progenitor cells that replace lost neurons. The pro-inflammatory pliancy gene cascade is not activated in zebrafish Müller glia following injury, and we propose a model in which species-specific pliancy programs underly the differential response to retinal damage in species that can regenerate retinal neurons (zebrafish) versus those that cannot (humans and mice).
Fine-grained descending control of steering in walkingDrosophila
Authors: Yang Helen H. , Brezovec Luke E. , Serratosa Capdevila Laia , Vanderbeck Quinn X. , Adachi Atsuko , Mann Richard S. , Wilson Rachel I. 
Published: October 2023

SummaryLocomotion involves rhythmic limb movement patterns that originate in circuits outside the brain. Purposeful locomotion requires descending commands from the brain, but we do not understand how these commands are structured. Here we investigate this issue, focusing on the control of steering in walkingDrosophila. First, we describe different limb “gestures” associated with different steering maneuvers. Next, we identify a set of descending neurons whose activity predicts steering. Focusing on two descending cell types downstream from distinct brain networks, we show that they evoke specific limb gestures: one lengthens strides on the outside of a turn, while the other attenuates strides on the inside of a turn. Notably, a single descending neuron can have opposite effects during different locomotor rhythm phases, and we identify networks positioned to implement this phase-specific gating. Together, our results show how purposeful locomotion emerges from brain cells that drive specific, coordinated modulations of low-level patterns.
Ecological and Evolutionary Characteristics of Anthropogenic Roosting Ability in Bats of the World
Authors: Betke Briana A. , Gottdenker Nicole L. , Meyers Lauren Ancel , Becker Daniel J. 
Published: October 2023

SummaryAlthough the global conversion of wildlife habitat to built environments often has negative impacts on biodiversity, some wildlife have the ability to cope by living in human-made structures. However, the determinants of this adaptation on a global scale are not well understood and may signify species with unique conservation needs at the human–wildlife interface. Here, we identify the trait profile associated with anthropogenic roosting in bats globally and characterize the evolution of this phenotype using an original dataset of roosting behavior developed across 1,279 extant species. Trait-based analyses showed that anthropogenic roosting is predictable across bats and is associated with habitat generalism, small geographic ranges, small body size, temperate zone distributions, and insectivory. We identified moderate phylogenetic signal in this complex phenotype, which has undergone both gains and losses across bat evolution and for which speciation rates are lower compared to natural roosting bats.
A Non-invasive Detection of Parkinson’s Disease using PitArray: An Integrative Meta-Analysis and Machine Learning Approach
Authors: Bhattacharjee Arittra , Jamal Tabassum Binte , Ahammad Ishtiaque , Lamisa Anika Bushra , Arefin Md. Shamsul , Chowdhury Zeshan Mahmud , Hossain Mohammad Uzzal , Das Keshob Chandra , Keya Chaman Ara , Salimullah Md 
Published: October 2023

AbstractParkinson’s disease (PD) is a progressive neurodegenerative disorder affecting the central nervous system, often diagnosed in its advanced stages due to the absence of sensitive biomarkers. With this objective in mind, our study conducted a comprehensive analysis of differentially expressed genes (DEGs) sourced from blood-based microarray datasets to uncover potential biomarkers and developed a machine learning based classifier to conduct two step validations. By analyzing gene expression of three projects, we identified 678 DEGs, consisting of 337 genes showing upregulation and 341 genes presenting downregulation. Additionally, insights from functional enrichment and the protein-protein network analysis indicate thatHLA-F,IRF-1, andRPS28have the potential to serve as biomarkers for diagnosing PD. Simultaneously, we employed feature selection techniques such as Least Absolute Shrinkage and Selection Operator with Cross Validation (LassoCV) followed by Recursive Feature Elimination with Cross Validation (REFCV) to filter our initial dataset of 13,249 genes down to 43 genes, which were subsequently used to train the machine learning-based classifier models. These 43 genes formed the basis for training and testing various machine learning models, including logistic regression, random forest, naive Bayes, k-nearest neighbors, support vector machine, and deep learning based artificial neural networks. Our models demonstrated robust performance, with Support Vector Machine outperforming others by 0.65 accuracy (95%CI: 0.58-0.66), 0.70 AUC-ROC (95%CI: 0.70-0.71) and 0.35 MCC (95%CI: 0.34-0.39). The model was implemented to develop the PitArray tool for non-invasive detection of PD from blood. PitArray is available at:https://github.com/Arittra95/PitArray.Key PointsHLA-F, IRF-1,andRPS28were identified as potential biomarkers for Parkinson’s disease diagnosis.Several sophisticated feature selection methods recognized 43 genes which were then used to build a machine learning model.A Support Vector Machine based tool named PitArray was developed which could distinguish Parkinson’s disease patients from healthy people based on blood transcriptome data.
Assessing the limits of zero-shot foundation models in single-cell biology
Authors: Kedzierska Kasia Z. , Crawford Lorin , Amini Ava P. , Lu Alex X. 
Published: October 2023

AbstractThe advent and success of foundation models such as GPT has sparked growing interest in their application to single-cell biology. Models like Geneformer and scGPT have emerged with the promise of serving as versatile tools for this specialized field. However, the efficacy of these models, particularly in zero-shot settings where models are not fine-tuned but used without any further training, remains an open question, especially as practical constraints require useful models to function in settings that preclude fine-tuning (e.g., discovery settings where labels are not fully known). This paper presents a rigorous evaluation of the zero-shot performance of these proposed single-cell foundation models. We assess their utility in tasks such as cell type clustering and batch effect correction, and evaluate the generality of their pretraining objectives. Our results indicate that both Geneformer and scGPT exhibit limited reliability in zero-shot settings and often underperform compared to simpler methods. These findings serve as a cautionary note for the deployment of proposed single-cell foundation models and highlight the need for more focused research to realize their potential.2
Cortical mapping of sensory responses reveals strong brain-state dependence of the late component
Authors: Montagni E , Resta F , Tort-Colet N , Scaglione A , Mazzamuto G , Destexhe A , Pavone FS , Allegra Mascaro AL 
Published: October 2023

ABSTRACTSensory information must be integrated across a distributed brain network for stimulus processing and perception. Recent studies have revealed specific spatiotemporal patterns of cortical activation for the early and late components of sensory-evoked responses, which are associated with stimulus features and perception, respectively. However, our understanding of how the brain state influences the sensory-evoked activation across the mouse cortex remains limited.In this study, we utilized isoflurane to modulate the brain state and conducted wide-field calcium imaging of Thy1-GCaMP6f mice to monitor the distributed activation evoked by multi-whisker stimulation. Our findings reveal that the level of anesthesia strongly shapes the spatiotemporal features and the functional connectivity of the sensory-activated network. As anesthesia levels decrease, we observe increasingly complex responses, accompanied by the emergence of the late component within the sensory-evoked response. The persistence of the late component under anesthesia raises new questions regarding the potential existence of perception during unconscious states.