bluuebunny/crossref_metadata_2025_split huggingface dataset:
Upregulated spinal histone deacetylases induce nociceptive sensitization by inhibiting the GABA system in chronic constriction injury–induced neuropathy in rats
Authors: Wen Zhi-Hong , Chen Nan-Fu , Cheng Hao-Jung , Kuo Hsiao-Mei , Chen Pei-Yu , Feng Chien-Wei , Yao Zhi-Kang , Chen Wu-Fu , Sung Chun-Sung 
Published: November 2024

Abstract

Introduction:
Neuropathic pain (NP) affects countless people worldwide; however, few effective treatments are currently available. Histone deacetylases (HDACs) participate in epigenetic modifications in neuropathy-induced nociceptive sensitization. Gamma-aminobutyric acid (GABA) is a major inhibitory neurotransmitter that can inhibit NP. The present study aimed to examine the role of spinal HDAC and its isoforms in neuropathy.

Methods:
Male Wistar Rat with chronic constriction injury (CCI)-induced peripheral neuropathy and HDAC inhibitor, panobinostat, was administrated intrathecally. We performed quantitative real-time polymerase chain reaction (RT-qPCR), western blot, and immunohistochemical analysis of lumbar spinal cord dorsal horn and nociceptive behaviors (thermal hyperalgesia and mechanical allodynia) measurements.

Results:
Herein, RT-qPCR analysis revealed that spinal hdac3, hdac4, and hdac6 were upregulated in CCI rats. Western blotting and immunofluorescence staining further confirmed that HDAC3, HDAC4, and HDAC6 were significantly upregulated, whereas GABA and its synthesis key enzyme glutamic acid decarboxylase (GAD) 65 were dramatically downregulated. Intrathecal panobinostat attenuated nociceptive behavior and restored the downregulated spinal GAD65 and GABA expression in CCI rats.

Conclusions:
HDAC upregulation might induce nociception through GAD65 and GABA inhibition in CCI-induced neuropathy. These findings strongly suggest that HDACs negatively regulate inhibitory neurotransmitters, constituting a potential therapeutic strategy for an epigenetic approach to manage NP.
Phosphaturic Mesenchymal Tumor and Tumor-Induced Osteomalacia: A Report of 5 Cases, Including 2 Skull Base Cases With Arterial Spin Label Perfusion
Authors: Grewal Inayat , Fischbein Nancy , Dodd Robert , Lee K. Christine , Fernandez-Miranda Juan , Sellmeyer E. Deborah , Pham Nancy 
Published: November 2024

Abstract
Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome characterized by renal phosphate wasting and impaired bone mineralization secondary to secretion of fibroblast growth factor 23 (FGF23) from mesenchymal tumors (phosphaturic mesenchymal tumors, PMTs). PMTs have wide anatomical distribution but typically affect extremities and craniofacial bones. Diagnosis of TIO/PMT is often delayed, and a high index of suspicion is essential in patients with unexplained fractures, but many physicians lack familiarity with TIO/PMT and simply attribute fractures to the more common diagnosis of osteoporosis. We present 5 cases of TIO, with 4 having long histories of multiple insufficiency fractures prior to recognition of TIO and localization of a PMT. Four patients were treated surgically, while 1 preferred medical management. Two patients had lesions localized to the skull base, both of which showed marked hypervascularity on arterial spin label perfusion imaging. Thus, arterial spin label may not only help to localize these tumors, but may also be a helpful supplemental imaging finding in supporting this diagnosis. PMT should be considered in the differential diagnosis for hypervascular skull base masses, especially if the patient has any history of insufficiency fracture or imaging evidence of osteopenia, as early diagnosis of TIO can help prevent disabling complications.
Improving Image Quality and Visualization of Hepatocellular Carcinoma in Arterial Phase Imaging Using Contrast Enhancement–Boost Technique
Authors: Yoon Gayoung , Ahn Jhii-Hyun , Jeon Sang-Hyun 
Published: November 2024

Objective
This study aimed to evaluate the image quality and visualization of hepatocellular carcinoma (HCC) on arterial phase computed tomography (CT) using the contrast enhancement (CE)–boost technique.

Methods
This retrospective study included 527 consecutive patients who underwent dynamic liver CT between June 2021 and February 2022. Quantitative and qualitative image analyses were performed on 486 patients after excluding 41 patients. HCC conspicuity was evaluated in 40 of the 486 patients with at least one HCC in the liver. Iodinated images obtained by subtracting nonenhanced images from arterial phase images were combined to generate CE-boost images. For quantitative image analysis, image noise, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) were measured for the liver, pancreas, muscles, and aorta. For qualitative analysis, the overall image quality and noise were graded using a 3-point scale. Artifact, sharpness, and HCC lesion conspicuity were assessed using a 5-point scale. The paired-sample t test was used to compare quantitative measures, whereas the Wilcoxon signed-rank test was used to compare qualitative measures.

Results
The mean SNR and CNR of the aorta, liver, pancreas, and muscle were significantly higher, and the image noise was significantly lower in the CE-boost images than in the conventional images (P < 0.001). The mean CNR of HCC was also significantly higher in the CE-boost images than in the conventional images (P < 0.001). In the qualitative analysis, CE-boost images showed higher scores for HCC lesion conspicuity than conventional images (P < 0.001).

Conclusions
The overall image quality and visibility of HCC were improved using the CE-boost technique.
Exploratory trial of urethral submucosa injection therapy of deflux for stress urinary incontinence after radical prostatectomy
Authors: Fujihara Atsuko , Shiraishi Takumi , Miyashita Masatsugu , Inoue Yuta , Saito Yumiko , Taga Hideto , Naitoh Yasuyuki , Iwami Yayoi , Horiguchi Go , Ito-Ihara Toshiko , Ukimura Osamu 
Published: November 2024

Background:
After robot-assisted laparoscopic radical prostatectomy (RARP) for localized prostate cancer, post-operative stress urinary incontinence (SUI) impacts patient quality-of-life (QOL). A simple and less invasive treatment for SUI in these patients is urgently needed. Deflux is a viscous gel that consists of a mixture of sodium hyaluronate and dextranomer beads. It is administered by transurethral approach for the treatment of vesicoureteral reflux. In this study, we aim to establish a minimally invasive treatment for post-prostatectomy SUI through transurethral Deflux injection.

Methods:
We will perform a single-center, exploratory clinical trial to evaluate the safety and efficacy of transurethral injection of Deflux for SUI after RARP. Inclusion criteria are patients with SUI, a urine leakage volume between 15 and 500 g in a 24-h pad test, and those who use more than two pads per day. Five patients are scheduled to be enrolled in this pilot study. Deflux is injected endoscopically at the 3 o’clock and 9 o’clock positions in the submucosa until coaptation of submucosal bulking is achieved from both intraurethral sides. The primary endpoint is safety following Deflux injection. The secondary endpoint is efficacy on both SUI volume and patients’ QOL.

Discussion:
The importance of this clinical trial is to propose a new minimally invasive treatment option for male SUI patients after RARP.
Surgical Recovery Among Patients With Chronic Pain Undergoing Pelvic Reconstructive Surgery
Authors: Werth Adrienne J. , Abalyan Victoria , Tunitsky-Bitton Elena , O'Sullivan David , Sappenfield Elisabeth 
Published: November 2024

Importance
Limited data exist on postoperative recovery among patients with chronic pain undergoing pelvic reconstructive surgical procedures.

Objective
The objective of this study was to evaluate if patients with versus without self-reported chronic pain experience different recovery after pelvic reconstructive surgery.

Study Design
From September 2022 to May 2023, this prospective cohort study enrolled patients with and without chronic pain, who were undergoing vaginal or laparoscopic procedures for pelvic organ prolapse. Preoperative pain was assessed using the Brief Pain Inventory (BPI) and Pepper Assessment Tool for Disability (PAT-D). Postoperative recovery was evaluated at 2, 4, and 12 weeks using the Postdischarge Surgical Recovery (PSR) scale, Global Surgical Recovery (GSR) index, and PAT-D questionnaire. The primary outcome was PSR scores at 4 weeks postoperatively.

Results
Ninety patients were recruited, with 43 reporting chronic pain and 47 without. Demographics were similar. Patients with chronic pain had higher preoperative BPI and PAT-D scores. Perioperative outcomes and hospital stay were similar. Patients with chronic pain used more postoperative opioids in the hospital (27.0 ± 27.8 vs 24.3 ± 60.3 morphine milligram equivalents [MME]; P = 0.03) and at home (40.1 ± 54.7 vs 19.9 ± 39.0 MME; P = 0.03). The PSR scores at 4 weeks were not significantly different. No differences were observed in PSR or GSR scores at all time points. Patients with chronic pain had a higher PAT-D score at 12 weeks. Fewer chronic pain patients returned to work by 12 weeks and desired more time off work.

Conclusions
Patients with and without chronic pain had similar surgical outcomes and recovery. However, chronic pain patients required more postoperative opioid pain medication and preferred more time off work.
Use of Machine Perfusion in the United States Increases Organ Utilization and Improves DCD Graft Survival in Liver Transplantation
Authors: Wisel Steven A. , Steggerda Justin A. , Kim Irene K. 
Published: November 2024

Background.
Adoption of machine perfusion (MP) technology has rapidly expanded in liver transplantation without real-world data on utilization and outcomes, which are critical to understand the appropriate application of MP technology.

Methods.
The Organ Procurement and Transplant Network/Standard Transplant Analysis and Research database was used to identify all deceased donor livers procured with intent for transplant between October 27, 2015 (date of first recorded MP) and June 30, 2023 (n = 67 795). Liver allografts were cohorted by donation after brain death (DBD; n = 59 957) or circulatory death (DCD; n = 7873) and analyzed by static cold storage (SCS) or MP preservation method. Donor demographics, organ utilization, and graft survival were evaluated.

Results.
By 2023, 12.5% of all livers and 37.2% of DCD livers underwent MP preservation (82.6% normothermic, 6.7% hypothermic, and 10.8% other/unknown). Compared with SCS, MP liver donors were older (DBD: 48 versus 40 y [P < 0.001]; DCD: 43 versus 38 y [P < 0.001]) with higher body mass index (DBD: 28.8 versus 26.9 kg/m2 [P < 0.001]; DCD: 27.7 versus 26.9 kg/m2 [P = 0.004]). Donor livers had similar levels of macrosteatosis (median 5%). Graft utilization was higher for MP than SCS after DBD (96.4% versus 93.0%, P < 0.001) and DCD (91.4% versus 70.3%, P < 0.001) donation. Graft survival was similar between MP and SCS livers from DBD donors (P = 0.516), whereas MP-preserved grafts had superior survival from DCD donors at 1 and 3 y posttransplant (P = 0.013 and 0.037). Patient survival was similar across all groups at 3 y (P = 0.322).

Conclusions.
The use of MP in liver transplantation increased rates of liver utilization and improved graft survival after DCD. Further monitoring of MP outcomes is required to understand long-term benefits.
Social and emotional self-perception in people with mild to moderate Alzheimer disease compared to caregiver’s perspective in Brazil
Authors: Rangel da Silva Rogéria Cristina , Neto José Pedro Simões , Belfort Tatiana , Dourado Marcia Cristina Nascimento 
Published: November 2024

Introduction:
There was limited evidence on the ability of people with Alzheimer disease (AD) to perceive their own emotions. We aimed to compare socioemotional self-perception in persons with mild and moderate AD to their caregivers’ perspective.

Method:
Cross-sectional assessment of people with mild (n=102) and moderate (n=59) AD and caregivers. Each participant and their caregivers completed the socioemotional questionnaire (SEQ); a 30-item rating scale assessing five dimensions of socioemotional cognition (empathy, emotion recognition, social conformity, antisocial behavior, sociability). We evaluated global cognition, awareness of disease, dementia severity, functionality, neuropsychiatric symptoms, and caregiver burden.

Results:
Participants in the mild and moderate groups showed a similar pattern of socioemotional self-perception. They differed in the anger domain of the emotion recognition subscale, in the antisocial behavior dimension, and in the sociability subscale. In contrast, the caregivers’ perspective of people with mild and moderate AD showed a significant difference in the emotion recognition domain for fear, disgust, and sadness. There were also significant differences in the empathy subscale for disgust and in the sociability subscale. Cognition was correlated with self-reported reduced perception in social conformity, antisocial behavior, and sociability. Awareness was correlated with emotion recognition, antisocial behavior, and sociability. Neuropsychiatric symptoms were correlated with empathy, emotion recognition, and social conformity.

Conclusions:
Significant differences were found between caregivers’ perspectives of socioemotional functioning in people with mild and moderate AD. Meanwhile, there were minimal differences in self-perception between the mild and moderate groups.
devider: long-read reconstruction of many diverse haplotypes
Authors: Shaw Jim , Boucher Christina , Yu Yun William , Noyes Noelle , Li Heng 
Published: November 2024

AbstractReconstructing haplotypes is important when sequencing a mixture of similar sequences. Long-read sequencing can connect distant alleles to disentangle similar haplotypes, but handling se-quencing errors requires specialized techniques. We presentdevider, an algorithm for haplotyping small sequences—such as viruses or genes—from long-read sequencing.devideruses a positional de Bruijn graph with sequence-to-graph alignment on an alphabet of informative alleles to provide a fast assembly-inspired approach compatible with various long-read sequencing technologies. On a synthetic Nanopore dataset containing seven HIV strains,deviderrecovered 97% of the haplotype content compared to 86% for the next best method while taking < 4 minutes and 1 GB of memory for > 8000× coverage. Benchmarking on synthetic mixtures of antimicrobial resistance (AMR) genes showed thatdeviderrecovered 83% of haplotypes, 23 percentage points higher than the next best method. On real PacBio and Nanopore datasets,deviderrecapitulates previously known results in seconds, disentan-gling a bacterial community with > 10 strains and an HIV-1 co-infection dataset. We useddeviderto investigate the within-host diversity of a long-read bovine gut metagenome enriched for AMR genes, discovering 13 distinct haplotypes for a tet(Q) tetracycline resistance gene with > 18, 000× coverage and 6 haplotypes for a CfxA2 beta-lactamase gene. We found clear recombination blocks for these AMR gene haplotypes, showcasingdevider’s ability to unveil ecological signals for heterogeneous mixtures.
Machine learning reveals novel targets for both glioblastoma and osteosarcoma
Authors: Li Nan , Ward Max , Bashir Muniba , Cao Yunpeng , Datta Amitava , Li Zhaoyu , Zhang Shuang 
Published: November 2024

SummaryGlioblastoma and osteosarcoma originate from the same lineage, yet patients with these two tumour types show significant differences in survival outcomes. Transcriptomic analysis comparing these tumours reveals that over 65% genes show similar expression patterns. Principal component analysis further demonstrates substantial similarities between these two tumour types, albeit with discernible differences. Deep learning analysis employing an autoencoder unveils nuanced distinctions and similarities of these two tumours at a high resolution. A classification model, leveraging gradient boosting with eXtreme Gradient Boosting (XGBoost), achieves high accuracy in distinguishing between these two tumour types. Identification of key contributors to the model’s performance is facilitated by SHapley Additive exPlanations (SHAP), yielding two lists of top target genes with and without considering gender. Notably, these SHAP targets tend to cluster within one or two networks of signalling pathways. Remarkably, gene expression levels of many of these SHAP targets alone can recapitulate survival differences solely based on clinical data between glioblastoma and osteosarcoma patients. Of particular interest, C2ORF72 emerges as a common target from both lists, representing an uncharacterised protein with promising potential as a novel target for diagnostic, prognostic, and therapeutic target for both glioblastoma and osteosarcoma.
In vivoengineered quadrivalent CAR-macrophages break tumor barrier, remodel TME and overcome tumor heterogeneity through antigen spreading
Authors: Zhang Shaolong , Lu Hengxing , Zhang Hailing , Ding Xizhong , Wu Qixin , Lei Anhua , Kong Na , Zhang Jin 
Published: November 2024

AbstractCAR-macrophages have shown promising prospect in treating solid tumors.Ex vivoengineered CAR-macrophages face the challenge of low transfection efficiency, long preparation cycle, and limited cell number. Here, we designed two novel CAR molecules, GPC3-CAR-Super IL-2 and FAP-CAR-△TGFβRII from the perspective of targeting tumor cells and improving tumor microenvironment, and generated quadrivalent CAR-macrophagesin vivofor treating solid tumors by the LNP-mRNA system. We found thatin vivoengineered quadrivalent CAR-macrophages can strongly activate tumor immunity and achieve complete tumor regression without significant side effects. Mechanically,in vivoengineered quadrivalent CAR-macrophages broke down physical barriers around the tumor constructed by CAFs and significantly promoted infiltration and expansion of CD8+T cells. Moreover, the transiently formed CAR-macrophagesin vivoare sufficient to form long-lasting T cell memory which can effectively prevent tumor recurrence. Most importantly,in vivoengineered CAR-macrophages also stimulated T cell memory against antigen-negative tumor cells through antigen spreading, which might effectively prevent the immune escape of heterogeneous tumor cells. Overall, we developed a platform ofin vivoCAR-macrophages with dual roles as a tumor-killing effector cell and a recurrence-preventing vaccine.
Identifying parsimonious pathways of accumulation and convergent evolution from binary data
Authors: Giannakis Konstantinos , Aga Olav N. L. , Moen Marcus T. , Drange Pål G. , Johnston Iain G. 
Published: November 2024

AbstractHow stereotypical, and hence predictable, are evolutionary and accumulation dynamics? Here we consider processes – from genome evolution to cancer progression – involving the irreversible accumulation of binary features (characters), which can be modelled as Markov processes on a hypercubic transition network. We seek subgraphs of such networks that can generate a given set of paired before-after observations and minimize a topological cost function, involving criteria on out-branching which are interpretable in terms of biological parsimony. A transition network supporting a single, deterministic dynamic pathway is maximally simple and lowest cost, and branches (corresponding to possibly different next steps) increase cost, particularly if these branches are “deep”, occurring at early stages in the dynamics. In this sense, the lowest-cost subgraph measures how stereotypical the evolutionary or accumulation process is, and also identifies good start points for likelihood-based inference. The problem is solvable in polynomial time for cross-sectional observations by building on an existing method due to Gutin, and we provide a polynomial-time estimate in the more general case of pairs of observed states. We use this approach to define a “stereotypy index” reflecting the extent of evolutionary predictability. We demonstrate use cases in the evolution of antimicrobial resistance, organelle genomes, and cancer progression, and provide a software implementation athttps://github.com/StochasticBiology/hyperDAGs.
Canadian science graduate stipends lie below the poverty line
Authors: Fraass Andrew Jeffrey , Bailey Thomas J , Karunakumar Kayona , Wishart Andrea E. 
Published: November 2024

AbstractDespite the critical role of graduate students in the Canadian research ecosystem1, students report high levels of financial stress2. We collected graduate minimum stipends and tuition data from all university graduate programs in Canada in Ecological Sciences/Biology and Physics, along with cost of living measures for the cities in which they reside. This data is heterogeneous, complex, and in many cases simply not publicly available, making it challenging for potential graduate students to understand what support they should expect. We show Canadian minimum stipends are at values almost exclusively below the poverty threshold. Only two of 140 degree programs offered stipends which meet cost of living measures after subtracting tuition and fees. For graduate programs which offered a minimum guaranteed stipend, the average minimum domestic stipend is short ∼Can$9,468 (international ∼Can$16,899) of the poverty threshold after accounting for payment of tuition and fees. On average, approximately 34% of a minimum stipend is returned to the university by a domestic Canadian student and 78% (57% median) by an international student, though there are important caveats with the international student comparison. While international comparison is difficult, the highest Canadian minimum stipend is roughly equivalent or lower than the lowest stipend within the largest dataset of United States of America (US) Biology stipends3, and lower than the United Kingdom (UK) stipend. University endowment correlates with minimum stipend amount but intra- and inter-institutional differences suggest it is not solely institutional wealth which improves graduate pay. Canada is behind comparable countries in funding the next generation of scientists. Canadians who desire higher STEM education have three options: hope for significantly higher guaranteed support from a supervisor, department, or awards; incur substantial debts; or emigrate.
Molecular Simulations Meet Personalized Medicine. The Mechanism of Action of ClC-5 Antiporter and the Origin of Dent’s Disease
Authors: Macaluso Veronica , Pérez Carles , Soliva Robert , Westermaier Yvonne , Díaz Lucía , Wieczór Miłosz , Orozco Modesto 
Published: November 2024

ABSTRACTClC-5 is a Cl−/H+ antiporter crucial for the homeostasis of the entire organism, and whose functional deficiencies cause pathologies such as Dent’s disease, a rare genetic disorder that can have lethal consequences. While the clinical aspects of the pathology are known, its molecular basis is elusive, which hampers the development of potential therapies. We present here a systematic study, where we explore the mechanism of transport of ClC-5, deciphering the choreography of structural changes required for the transport of chloride ions and protons in opposing directions. Once the mechanism is determined, we explore how the 523ΔVal deletion linked to Dent’s disease hampers the correct functioning of the transporter, despite having a very minor structural impact. Our study highlights how state-of-the-art simulation methods can provide information on the origin of rare diseases and serve as a tool in personalized medicine.