bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhanced interactions within microenvironment accelerates dismal prognosis in HBV-related HCC after TACE
Authors: Wang Libo , Cao Jiahui , Liu Zaoqu , Wu Shitao , Liu Yin , Liang Ruopeng , Zhu Rongtao , Wang Weijie , Li Jian , Sun Yuling 
Published: October 2024

Background:
Transarterial chemoembolization (TACE) is the first-line treatment for patients with advanced HCC, but there are limited studies on the microenvironment alterations caused by TACE.

Methods:
Six fresh HBV-related HCC specimens with or without TACE intervention were used to perform single-cell RNA sequencing. The 757 bulk samples from 3 large-scale multicenter cohorts were applied for comprehensive analysis. The biological functions of the biomarkers were further validated by phenotypic experiments.

Results:
Using single-cell RNA sequencing analysis, we delineated the global cell atlas of post-TACE and demonstrated elevated tumor heterogeneity and an enhanced proinflammatory microenvironment induced by TACE. Cell-cell communication analysis revealed that markedly elevated interactions between NABP1+ malignant hepatocytes, neutrophils, and CD8+ T cells after TACE might accelerate the shift from CD8+ effector memory T cells to CD8+ effector T cells. This result was substantiated by the developmental trajectory between the 2 and dramatically decreased resident scores along the pseudotemporal trajectory. Integrating bulk data, we further found that the increased estimated proportion of NABP1+ malignant hepatocytes was related to poor TACE response and dismal prognosis, and its biomarker role could be replaced by NABP1. In vitro, multiple biological experiments consistently verified that NABP1 knockdown significantly inhibited the proliferation and migration of HCC cells.

Conclusions:
Based on our depicted global map of post-TACE, we confirmed that the enhanced interactions within the microenvironment after TACE may be the culprits for postoperative progression. NABP1 may become an attractive tool for the early identification of patients sensitive to first-line TACE in clinical practice.
Motion Restriction Caused by Thoracic-Lumbar-Sacral Orthoses During Activities of Daily Living
Authors: Vania Natasha , Jacofsky Marc , McCamley John 
Published: October 2024

ABSTRACT

Introduction
Lower back pain is a common musculoskeletal disability affecting individuals of every income and age. The main cause of lower back pain is still not fully understood, with some theories suggesting that it is related to posture and placement of the spine in compromising positions. This study investigated the ability of two styles of thoracic-lumbar-sacral orthoses to restrict range of motion during activities of daily living.

Materials and Methods
Fourteen able-bodied adults were recruited. Two styles of TLSOs from two companies were chosen for the comparison with the no-brace condition. Two brands of each brace style were selected for comparison. Subjects were first asked to perform motion in three planes, then asked to complete seven motions to simulate daily living.

Results
There were no significant differences between the no-brace and brace conditions for motion in the sagittal and coronal plane ranges of motion. There were significant reductions in transverse plane range of motion detected between the no-brace condition and both styles of brace. During bending, reaching, walking, and stair ascent differences between the brands of brace were observed.

Conclusions
The chosen brands were equivalent across most movements. All braces were able to restrict motion, though the level of restriction varied between brace during some tasks for some planes of motion. Understanding the differing restrictions will assist health care providers and consumers choose the best TLSO to provide the motion restriction they require.

Clinical Relevance
Health care providers and consumers can have options when choosing a TLSO depending on which planes of motion need to be restricted.
Effect of occlusion site on the effectiveness and safety of endovascular thrombectomy for large ischemic cores: A cohort study
Authors: Yang Shihai , Wu Lele , Shi Xiaolei , Guo Changwei , Yue Chengsong , Fan Shitao , Yang Jie , Song Jiaxing , Ye Dongsheng , Xu Xu , Peng Zhouzhou , Li Linyu , Huang Jiandi , Liu Chang , Huang Jiacheng , Yu Nizhen , Tian Yan , Ma Jinfu , Yang Dahong , Kong Weilin , Wang Zhixi , Sun Wenzhe , Yang Qingwu , Chen Boyu , Zi Wenjie 
Published: October 2024

Background:
Recent clinical trials have shown that patients with large ischemic cores have better outcomes with endovascular thrombectomy (EVT) compared with standard medical treatment (SMT) alone.We aim to assess whether the relationship between EVT and improvements in clinical outcomes varies depending on the location of the occlusive sites.

Methods:
This study is a subgroup analysis conducted within a prospective, nationwide, multi-center registry. The cohort included patients with acute large vessel occlusion in the anterior circulation and an Alberta Stroke Program Early Computed Tomography Score of 0 to 5 within 24 hours from last known well. We utilized the adjusted common odds ratio for a shift toward better outcome on the modified Rankin Scale after EVT compared with SMT alone as the primary outcome. Safety outcomes included symptomatic intracranial hemorrhage (sICH).

Results:
A total of 745 patients with large ischemic cores were included: 272(36.5%) with internal carotid artery occlusion, 392(52.6%) with M1 segment of the middle cerebral artery occlusion, and 81(11.0%) with M2 segment of the middle cerebral artery occlusion. The adjusted common odds ratios were as follows: 1.98 (95% CI, 1.01-3.89) for ICA occlusions, 2.09 (95% CI, 1.35-3.23) for M1 occlusions, and 1.13 (95% CI, 0.43-2.94) for M2 occlusions. There was no significant treatment-by-occlusion site interaction observed (P=0.69). However, the incidence of sICH was significantly greater in all groups receiving EVT than in those receiving SMT alone. Additionally, we observed that the secondary outcomes and subgroup analyses were generally consistent with the main outcomes.

Conclusions:
In this study, we found that patients with internal carotid artery and M1 occlusion demonstrated a better outcome with EVT, while the benefit for patients with M2 occlusion remains uncertain.
An evolutionarily conserved role for VEGF signaling in the expansion of non-vascular tissue during regeneration
Authors: Savage Aaron M. , Wagner Alexandra C. , Kim Ryan T. , Gilbert Paul , Singer Hani D. , Chen Erica , Kim Elane M. , Lopez Noah , Dooling Kelly E. , Paoli Julia C. , Wu S.Y. Celeste , Bohm Sebastian , Chilambi Rachna , Froitzheim Tim , Blair Steven J. , Powell Connor , Abouelela Adnan , Luong Anna G. , Thornton Kara N. , Tajer Benjamin , Payzin-Dogru Duygu , Whited Jessica L. 
Published: October 2024

AbstractSalamanders are capable of regenerating whole limbs throughout life, a feat that is unmatched within tetrapods. Limb regeneration is dependent upon the formation of a blastema, which contains undifferentiated cells capable of giving rise to most cells of the regenerated limb. Innervation is required for regeneration, along with many signaling pathways, including FGF, BMP and Wnt, but the role of VEGF signaling during salamander limb regeneration is not well understood. Here we show that VEGF signaling is essential for limb regeneration and that blastema cells and limb fibroblasts display impaired proliferation in the absence of VEGF signaling. By performing analogous experiments in planaria, which lack vasculature, we show a potential evolutionarily conserved role for VEGF in the expansion of blastema tissues that is separable from angiogenesis. Moreover, loss of VEGF signaling reduces induction of EMT-like processes, suggesting VEGF signaling functions upstream of the expression of EMT transcription factors, includingSnai2. These findings highlight potential roles for VEGF signaling during regeneration which may extend beyond typical findings related to angiogenesis.
Maturity Onset Diabetes of the Young (MODY) is not always monogenic: candidate genes involved in a Latino Population
Authors: Moscona-Nissan Alberto , Marrero-Rodríguez Daniel , Andonegui-Elguera Sergio , Luna-Ávila Eduardo Salif , Martínez-Mendoza Florencia , Vela-Patiño Sandra , Ramírez-Ramos Itzel , Hinojosa-Alvarez Silvia , Hernandez-Perez Jesus , Chavez-Santoscoy Rocio A , Mercado-Medrez Sophia , León-Wu Kapy S , De Miguel-Ibáñez Regina , Mercado Moisés , Taniguchi-Ponciano Keiko , Ferreira-Hermosillo Aldo 
Published: October 2024

AbstractIntroductionMODY misdiagnosis remains widespread, existing remarkable variability within genetic variants across populations. While diagnostic tools are based on Caucasian cohorts, Whole Exome Sequencing (WES) studies are needed to identify new genes in non-Caucasians, as up to 77% of patients do not harbor variants of significance in MODY-known genes. In Latino populations, no WES studies have addressed MODY genomic landscape beyond its canonical genes.MethodsWe carried out WES in 17 patients with MODY, 17 patients with type 2 diabetes (T2DM) and 17 healthy controls (HC). MODY diagnosis was established according to Exeter criteria (score ≥36%) in subjects with no or minimal insulin requirements. We compared the single nucleotide variant (SNV) landscape across groups.ResultsPatients with MODY present a polygenic landscape with allelic variants in canonical and non-canonical genes. Canonical MODY genes used for routine genetic diagnosis showed low discrimination utility, having similar frequencies between MODY, T2DM and HC in the Mexican population. We propose 14 genes with variants that distinguish MODY from T2DM and HC, as we detected variants in genes asMAP2K3, SYT15, TPTE, KCNJ12, PEX5,andOR2A1in 75-100% of MODY cases while were absent in T2DM and HC. Enrichment analysis revealed involvement in synaptic vesicle trafficking, insulin/IGF pathway-mitogen activated protein kinase kinase/MAPK cascade, and insulin/IGF pathway-protein kinase B/AKT signaling cascade.DiscussionMODY presents a polygenic landscape. Besides improving our understanding of glycemic regulation pathways, the candidate genes could serve as MODY diagnostic biomarkers in Latino populations.FundingSupported by grant R-2019-785-052 from Instituto Mexicano del Seguro Social.
SPECIAL CARE BABY UNIT NEONATAL DISEASE OUTCOMES IN A TERTIARY HOSPITAL IN NIGERIA: 2-YR RETROSPECTIVE CROSS-SECTIONAL ANALYSIS
Authors: Anosike Udochukwu Godswill , Amalahu Ugochukwu Godson , Ezenyeaku Chijioke Amara , Ubajaka Chika Florence , Osmond Anokwulu Ifeanyi , Nsude Chiamaka Sandra , Adeniyi Joseph Moses , Okonkwo Chinemerem , Nwajinka Uzoma Love , DivineFavour Malachy Echezona , Okeke Chukwuemelie Darlington , Akwiwu-Uzoma Chidozie Valentine 
Published: October 2024

ABSTRACTBACKGROUNDNeonatal diseases contribute significantly to global under-five mortality. The highest neonatal mortality rate in sub-Saharan Africa can be traced to Nigeria. This study aims to evaluate the outcomes of neonatal admissions in a select tertiary hospital in Nigeria.METHODSA retrospective analysis of data collected on 656 neonates admitted in the special care baby unit of Nnamdi Azikiwe University Teaching Hospital (NAUTH), Nigeria over a period of 2 years (January 2021and December 2022). Descriptive analysis and inferential statistics were done at p<0.05 using SPSS version 25.RESULTSMedian age at presentation was 4 hours (interquartile range 0.5,24) hours. The Median duration of hospital stay was 6 days (interquartile range 3,11). The commonest morbidities were perinatal asphyxia (n=295/656; 45.0%) and prematurity (n=158/656; 24%); while congenital anomalies (n=22/47; 46.8%), perinatal asphyxia (n=73/295; 24.7%) and prematurity (n=35/158; 22.2%) had the highest case fatality rates. Gestational age at birth, duration of hospital stay, place of delivery, and mode of delivery were the variables determined to be statistically associated with outcome of care.CONCLUSIONThis study showed a mortality of 22.9% (n=150/656) in our study area with perinatal asphyxia (48.7%; n=73/150), prematurity (24.0%; n=36/150), congenital anomalies (11.3%; n=22/150), and neonatal sepsis (6.7%; n=10/150) as the primary causes. This work highlights the need for emergency care of critically ill newborns through financing transition from special care baby unit to neonatal intensive care unit across tertiary institutions in Nigeria.KEY MESSAGESWhat is already known on this topicPoor outcome of neonatal disease is associated with lack of quality care at birth or skilled care and treatment immediately after birth and in the first days of life.Premature birth, birth asphyxia, neonatal infections and congenital anomalies are the prominent causes of neonatal deaths.What this study addsCase fatality rate, mortality rate and duration of hospital stay were the primary outcomes assessed in a spectrum of neonatal disease.Higher mortality was recorded among neonates within the first 7days of hospital stay.How this study might affect research, practice, or policy (implications)Our work informs the need for transition from special care baby unit to neonatal intensive care unit across tertiary institutions in Nigeria to enable comprehensive care for critically ill neonates or neonates with severe neonatal morbidities.Creates awareness on the need for incorporation of processes that enable safeguarding of neonatal hospital records for tracking of trends and research.
The Effect of Sensory Therapy on Upper Extremity Functions and Activities of Daily Living in Patients with Chronic Stroke: A Randomized Controlled Trial
Authors: Yazıcı Muhammed Rohat , Cekmece Cigdem 
Published: October 2024

AbstractIntroductionThe aim of this study was to investigate the effects of intensive sensory therapy on upper extremity functions, daily activity and life quality of stroke survivors.MethodsThis randomized controlled trial included 30 participants aged between 18 and 80 years, who were divided into a sensory-training group (n = 15) and a control group (n = 15). Both groups received 15 sessions of 30 minutes of physical therapy, occupational therapy, and 20 minutes of activity daily living training for three weeks. The ST group also received intensified sensory therapy during each session. Thumb localization, finger shift, and stereognosis tests were performed in both groups only before the start of intervention. The Jebsen Taylor Hand Function Test, Canadian Occupational Performance Measure, Modified Frenchay Scale, and Stroke Specific Quality of Life Scale (SS-QOL) were administered before and after intervention.ResultsStatistically significant differences were observed between the ST group and the control group across all tests, except for the Language, Thinking, and Vision parameters of the SS-QOL.ConclusionThese results suggest that sensory therapies applied with conventional interventions increased upper extremity functions, activity daily living performance, participation and quality of life of the stroke survivors.RegistrationURL:https://clinicaltrials.gov/study/NCTxxxxxxUnique identifier: NCTxxxxx.
CellStudio: a Modular, Tunable and Accessible Platform for Analysis of Growth Factors Secretions in Cell Cultures
Authors: Azuaje-Hualde Enrique , Lartitegui-Meneses Naiara , Alonso-Cabrera Juncal , Inchaurraga-Llamas Asier , Alvarez-Braña Yara , de Pancorbo Marian Martínez , Benito-Lopez Fernando , Basabe-Desmonts Lourdes 
Published: October 2024

AbstractTraditional cell culture methods face significant limitations in monitoring cell secretions with spatial and temporal precision. Advanced microsystems incorporating biosensors have been developed to address these challenges, but they tend to lack versatility, and their complexity, along with the requirement for specialized equipment, limits their broader adoption. CellStudio offers an innovative, user-friendly solution that exploits the Printing and Vacuum Lithography combined with bead-based assays to create modular and tunable cell patterns surrounded by biosensors. This platform allows for high-resolution, spatially resolved analysis of secreted proteins, such as VEGF and FGF-2, while being easily implementable in standard laboratory settings. CellStudio’s design is compatible with conventional laboratory equipment, facilitating its integration into existing workflows without the need for extensive training or specialized tools. Validation experiments using mesenchymal stem cells (MSCs) and HeLa cells demonstrated that CellStudio can detect small secretion levels from small cell clusters with high sensitivity as well as analyze diffusion profiles, remarking the possibilities for studying cell behavior. By offering a standardized, cost-effective approach to detailed cellular analysis, CellStudio significantly enhances the capabilities of traditional cell culture techniques, with broad applications across biological and biomedical research.
An improved TEAD dominant-negative protein inhibitor to study Hippo YAP1/TAZ-dependent transcription
Authors: Branch Briana , Yuan Yao , Cascone Mariastella , Raimondi Francesco , Iglesias-Bartolome Ramiro 
Published: October 2024

ABSTRACTHippo signaling is one of the top pathways altered in human cancer, and intensive focus has been devoted to developing therapies targeting Hippo-dependent transcription mediated by YAP1 and TAZ interaction with TEAD proteins. However, a significant challenge in evaluating the efficacy of these approaches is the lack of models that can precisely characterize the consequences of TEAD inhibition. To address this gap, our laboratory developed a strategy that utilizes a fluorescently traceable, dominant-negative protein named TEADi. TEADi specifically blocks the nuclear interactions of TEAD with YAP1 and TAZ, enabling precise dissection of Hippo TEAD-dependent and independent effects on cell fate. In this study, we aimed to enhance TEADi effectiveness by altering post-transcriptional modification sites within its TEAD-binding domains (TBDs). We demonstrate that a D93E mutation in the YAP1 TBD significantly increases TEADi inhibitory capacity. Additionally, we find that TBDs derived from VGLL4 and YAP1 are insufficient to block TAZ-induced TEAD activity, revealing crucial differences in YAP1 and TAZ displacement mechanisms by dominant-negative TBDs. Structural differences in YAP1 and TAZ TBDs were also identified, which may contribute to the distinct binding of these proteins to TEAD. Our findings expand our understanding of TEAD regulation and highlight the potential of an optimized TEADi as a more potent, specific, and versatile tool for studying TEAD-transcriptional activity.
An effective method of measuring nanobody binding kinetics and competition-based epitope mapping using biolayer interferometry
Authors: Bates Timothy A. , Gurmesa Sintayehu K. , Weinstein Jules B. , Trank-Greene Mila , Wrynla Xammy Huu , Anastas Aidan , Anley Teketay Wassie , Hinchliff Audrey , Shinde Ujwal , Burke John E. , Tafesse Fikadu G. 
Published: October 2024

AbstractProtein-protein interactions (PPI) underpin nearly all biological processes, and understanding the molecular mechanisms governing these interactions is crucial for the progress of biomedical sciences. The emergence of AI-driven computational tools can help reshape the methods in structural biology, however model data often quires empirical validation. The large scale of predictive modeling data will therefore benefit from optimized methodologies for the high-throughput biochemical characterization of PPIs. Biolayer interferometry (BLI) is one of very few approaches that can determine the rate of biomolecular interactions, called kinetics, and of the commonly available kinetic measurement techniques, it is the most suitable for high-throughput experimental designs. Here, we provide step-by-step instructions on how to perform kinetics experiments using BLI. We further describe the basis and execution of competition and epitope binning experiments, which are particularly useful for antibody and nanobody screening applications. The procedure requires 3 hours to complete and is suitable for users with minimal experience with biochemical techniques.
Purification of micrococcal nuclease (MNase) for use in ribosomal profiling of high-salinity extremophiles
Authors: Gregorova Pavlina , Isada Matthew , DiRuggiero Jocelyne , Sarin L. Peter 
Published: October 2024

AbstractNucleases, i.e. enzymes that catalyze the hydrolysis of phosphodiester bonds in nucleic acids, are essential tools in molecular biology and biotechnology.Staphylococcus aureus nuclease (MNase) is particularly interesting due to its thermostability and Ca2+-dependence, making it the prime choice for applications where nuclease modulation is critical, such as ribosome profiling in bacteria and halophilic archaea. The latter poses a technical and economical challenge: high salt reaction conditions are essential for maintaining ribosome integrity but negatively impact the MNase activity, necessitating using large amounts of nuclease to achieve efficient cleavage. Here, we set out to generate an optimized production protocol for two forms of MNase — fully processed MNaseA and the 19 amino acid propeptide-containing MNaseB — and to biochemically benchmark them against a commercial nuclease. Our results show that both MNases are highly active in normal reaction conditions, but MNaseA maintains higher enzymatic activity in high salt concentrations than MNaseB. MNaseA also retains >90% of its activity after multiple freeze-thaw cycles when stored at -80 °C in a buffer containing 5% glycerol. Importantly, ribosome profiling experiments in the haloarchaeonHaloferax volcanii demonstrated that MNaseA produces ribosome footprints and hallmarks of active translation highly comparable to those obtained with the commercial nuclease, making it a suitable alternative for high-salt ribosome profiling applications. In conclusion, our method can be easily implemented for efficient MNaseA production, thereby providing access to an effective, robust, and cost-efficient alternative to commercial nucleases, as well as facilitating future translation studies into halophilic organisms.
Detection of a novel parahenipavirus from northern short-tailed shrews (Blarina brevicauda[Say, 1823])
Authors: Imai Sakiho , Kishimoto Mai , Horie Masayuki 
Published: October 2024

AbstractParahenipaviruses (genusParahenipavirus) are non-segmented negative strand RNA viruses belonging to the familyParamyxoviridaeof the orderMononegavirales. Parahenipaviruses have been detected from shrews and rodents, some of which have been reported to be associated with human diseases. Although many parahenipaviruses have been identified thus far, there still exist large phylogenetic gaps in parahenipaviruses, suggesting the existence of yet-to-be-identified parahenipaviruses. In this study, we analyzed public RNA-seq data and identified a novel parahenipavirus from northern short-tailed shrews (Blarina brevicauda[Say, 1823]), tentatively named Blarina brevicauda virus (BbV). Based on sequence comparisons between BbV and its most closely related viruses, which meet the International Committee on Taxonomy of Viruses species demarcation criteria, we propose that BbV is a novel species of virus in the genusParahenipavirus. Furthermore, mapping analysis using RNA-seq data derived from multiple tissues of northern short-tailed shrews suggested that BbV is kidney-tropic. This study provides novel insights into the diversity of parahenipaviruses, which would contribute to a deeper understanding of their evolution and control of infectious diseases.