bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Tesamorelin on Neurocognitive Impairment in Abdominally Obese Persons with HIV
Authors: Ellis Ronald J , Vaida Florin , Hu Keren , Dube Michael , Henry Brook , Chow Felicia , Heaton Robert K , Lee Daniel , Sattler Fred 
Published: January 2025

Abstract

Background
In people with HIV (PWH) who are virally suppressed (VS) on antiretroviral therapy (ART), abdominal obesity (AO) is linked to neurocognitive impairment (NCI), potentially due to visceral adiposity, inflammation, and reduced insulin-like growth factor 1 (IGF-1). Tesamorelin, a growth hormone-releasing hormone, reduces AO and increases IGF-1, suggesting it might mitigate NCI in VS PWH.

Methods
This 6-month, Phase II randomized, open-label clinical trial compared Tesamorelin versus standard-of-care (SOC) for NCI in abdominally obese PWH. Participants had VS, NCI, and AO (elevated waist circumference [WC]). Exclusions included conditions other than HIV causing NCI, active substance use disorder, and malignancy.

Results
Seventy-three participants were randomized 3:2 to Tesamorelin or SOC (2mg subcutaneously daily). The primary outcome was the change in neurocognitive performance at 6 months, with secondary outcomes including WC, mood, and daily functioning. The groups were well-matched at baseline. The Tesamorelin group showed a trend toward improved neurocognitive performance after 6 months (mean change: 0.146, 95% CI: -0.002 to 0.294, p=0.060), while the SOC group did not (0.103, 95% CI: -0.095 to 0.301, p=0.295), but the between-group difference was not significant (p=0.673). IGF-1 levels increased, but changes did not correlate with sRCS or WC. The Tesamorelin group had a greater reduction in WC than the SOC group (median difference -2.7 cm, p=0.015).

Conclusions
While tesamorelin reduced WC, the cognitive benefits did not significantly differ between groups. Recognizing the limitations of insufficient power and no placebo arm, this study suggests no clear benefit of short-term AO reduction with tesamorelin on NCI.
Human HKU1-reactive CD4 T cells are enriched for cytolytic potential that persists in older adults
Authors: White Chantelle L , Richards Katherine A , Huertas Nelson , Nayak Jennifer L , Sant Andrea J 
Published: January 2025

Abstract
The emergence of SARS-CoV-2 increased interest in cellular immunity established by infections with human coronaviruses (HCoVs). Using PBMC from a cohort of human subjects collected prior to 2019, we assessed the abundance and phenotype of these CD4 T cells using cytokine Elispot assays. Unexpectedly, cytotoxic potential was uniquely enriched amongst HKU1-reactive CD4 T cells, as measured by quantification of granzyme producing cells. Also, although dramatic losses in HCoV-specific CD4 T cells abundance for OC43, NL63 and 229E-specific cells were observed in older subjects relative to younger adults, HKU1-reactive cells exhibited minimal age-dependent differences in this phenotype.
Estimating indoor tile friction coefficient using visual information
Authors: Yang Jung-Hwan , Yoon Kang-Il , Ha Seunghyeon , Hong Andy , Lim Soo-Chul 
Published: January 2025

Abstract
Slip and fall accidents are common both indoors and outdoors, posing and risks from minor to serious injuries. An effective way to prevent these accidents is for pedestrians to know the friction properties of their path beforehand. Developing a network that can discern the frictional properties of surfaces from camera-captured images and convey this information to pedestrians could significantly reduce the incidence of slips. However, predicting the indoor friction coefficient of tiles accurately is challenging due to reflections from multiple fluorescent lights and the tiles themselves. Additionally, water accumulation on tiles due to cleaning or leakage greatly contributes to slip accidents. This paper presents an algorithm that accurately predicts floor friction coefficients in real indoor environments, accounting for image distortions caused by light reflections and water on the floor. Experimental results validate that the proposed system reliably predicts indoor floor friction coefficients despite factors such as lighting angles and water presence. Moreover, to demonstrate its practical applicability, a user-application has been developed to predict the friction coefficient for specific areas as required. This system can be integrated into various devices, including walkers, canes, and smartphones, to assist pedestrians in navigating safely.
A multi-threshold image segmentation method based on arithmetic optimization algorithm: A real case with skin cancer dermoscopic images
Authors: Hao Shuhui , Huang Changcheng , Chen Yi , Wang Mingjing , Liu Lei , Xu Suling , Chen Huiling 
Published: January 2025

Abstract
Multi-threshold image segmentation (MTIS) is a crucial technology in image processing, characterized by simplicity and efficiency, and the key lies in the selection of thresholds. However, the method's time complexity will grow exponentially with the number of thresholds. To solve this problem, an improved arithmetic optimization algorithm (ETAOA) is proposed in this paper, an optimizer for optimizing the process of merging appropriate thresholds. Specifically, two optimization strategies are introduced to optimize the optimal threshold process: elite evolutionary strategy (EES) and elite tracking strategy (ETS). First, to verify the optimization performance of ETAOA, mechanism comparison experiments, scalability tests, and comparison experiments with nine state-of-the-art peers are executed based on the benchmark functions of CEC2014 and CEC2022. After that, to demonstrate the feasibility of ETAOA in the segmentation domain, comparison experiments were performed using 10 advanced segmentation methods based on skin cancer dermatoscopy image datasets under low and high thresholds, respectively. The above experimental results show that the proposed ETAOA performs outstanding optimization compared with benchmark functions. Moreover, the experimental results in the segmentation domain show that ETAOA has superior segmentation performance under low and high threshold conditions.
Advances in breeding for enhanced iron and zinc concentrations in common bean in eastern Africa
Authors: Kimani Paul M 
Published: January 2025

Abstract
Micronutrient malnutrition is one of the most serious health challenges facing vast sectors of the population of Africa, particularly resource-poor women and children. The main deficiencies include iron (Fe), zinc (Zn), and vitamin A. Plant breeding has frequently been advocated as the most sustainable strategy to provide varieties of different food crop species with enhanced micronutrient density to combat the global hidden hunger problem which affects &gt;2 billion people. However, there are few research programmes which have implemented this approach, from concept stage to finished products, which can be widely disseminated and commercialized to create meaningful impact. The east African bean biofortification programme offers a case study of such a programme. The aim of this programme was to develop well-adapted, high-yielding, Fe- and Zn-rich bush and climbing bean cultivars and agronomic approaches that enhance expression of the high mineral trait. The objective of this review is to provide a synthesis of the progress made in the last 22 years, with a focus on genetic diversity, inheritance, bioavailability of Fe and Zn, and cooking quality, as well as to identify research gaps and suggest future directions.
Mechanistic determinants and dynamics of cA6 synthesis in type III CRISPR-Cas effector complexes
Authors: Jungfer Kenny , Moravčík Štefan , Garcia-Doval Carmela , Knörlein Anna , Hall Jonathan , Jinek Martin 
Published: January 2025

Abstract
Type III clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas) systems (type III CRISPR-Cas systems) use guide RNAs to recognize RNA transcripts of foreign genetic elements, which triggers the generation of cyclic oligoadenylate (cOA) second messengers by the Cas10 subunit of the type III effector complex. In turn, cOAs bind and activate ancillary effector proteins to reinforce the host immune response. Type III systems utilize distinct cOAs, including cyclic tri- (cA3), tetra- (cA4) and hexa-adenylates (cA6). However, the molecular mechanisms dictating cOA product identity are poorly understood. Here we used cryoelectron microscopy to visualize the mechanism of cA6 biosynthesis by the Csm effector complex from Enterococcus italicus (EiCsm). We show that EiCsm synthesizes oligoadenylate nucleotides in 3′–5′ direction using a set of conserved binding sites in the Cas10 Palm domains to determine the size of the nascent oligoadenylate chain. Our data also reveal that conformational dynamics induced by target RNA binding results in allosteric activation of Cas10 to trigger oligoadenylate synthesis. Mutations of a key structural element in Cas10 perturb cOA synthesis to favor cA3 and cA4 formation. Together, these results provide comprehensive insights into the dynamics of cOA synthesis in type III CRISPR-Cas systems and reveal key determinants of second messenger product selectivity, thereby illuminating potential avenues for their engineering.
Cryo-EM structure of human TUT1:U6 snRNA complex
Authors: Yamashita Seisuke , Tomita Kozo 
Published: January 2025

Abstract
U6 snRNA (small nuclear ribonucleic acid) is a ribozyme that catalyzes pre-messenger RNA (pre-mRNA) splicing and undergoes epitranscriptomic modifications. After transcription, the 3′-end of U6 snRNA is oligo-uridylylated by the multi-domain terminal uridylyltransferase (TUTase), TUT1. The 3′- oligo-uridylylated tail of U6 snRNA is crucial for U4/U6 di-snRNP (small nuclear ribonucleoprotein) formation and pre-mRNA splicing. Here, we present the cryo-electron microscopy structure of the human TUT1:U6 snRNA complex. The AUA-rich motif between the 5′-short stem-loop and the telestem of U6 snRNA is clamped by the N-terminal zinc finger (ZF)–RNA recognition motif and the catalytic Palm of TUT1, and the telestem is gripped by the N-terminal ZF and the Fingers, positioning the 3′-end of the telestem in the catalytic pocket. The internal stem-loop in the 3′-stem-loop of U6 snRNA is anchored by the C-terminal kinase-associated 1 domain, preventing U6 snRNA from dislodging on the TUT1 surface during oligo-uridylylation. TUT1 recognizes the sequence and structural features of U6 snRNA, and holds the entire U6 snRNA body using multiple domains to ensure oligo-uridylylation. This highlights the specificity of TUT1 as a U6 snRNA-targeting TUTase.
A trigger-inducible split-Csy4 architecture for programmable RNA modulation
Authors: Zhang Lihang , Qiu Xinyuan , Zhou Yuting , Luo Zhengyang , Zhu Lingyun , Shao Jiawei , Xie Mingqi , Wang Hui 
Published: January 2025

Abstract
The CRISPR-derived endoribonuclease Csy4 is a popular tool for controlling transgene expression in various therapeutically relevant settings, but adverse effects potentially arising from non-specific RNA cleavage remains largely unexplored. Here, we report a split-Csy4 architecture that was carefully optimized for in vivo usage. First, we separated Csy4 into two independent protein moieties whose full catalytic activity can be restored via various constitutive or conditional protein dimerization systems. Next, we show that introduction of split-Csy4 into human cells caused a substantially reduced extent in perturbation of the endogenous transcriptome when directly compared to full-length Csy4. Inspired by these results, we went on to use such split-Csy4 module to engineer inducible CRISPR- and translation-level gene switches regulated by the FDA-approved drug grazoprevir. This work provides valuable resource for Csy4-related biomedical research and discusses important issues for the development of clinically eligible regulation tools.
Therapeutic manipulation and bypass of the blood–brain barrier: powerful tools in glioma treatment
Authors: Giantini-Larsen Alexandra M , Pandey Abhinav , Garton Andrew L A , Rampichini Margherita , Winston Graham , Goldberg Jacob L , Magge Rajiv , Stieg Philip E , Souweidane Mark M , Ramakrishna Rohan 
Published: January 2025

Abstract
The blood–brain barrier (BBB) remains an obstacle for delivery of chemotherapeutic agents to gliomas. High grade and recurrent gliomas continue to portend a poor prognosis. Multiple methods of bypassing or manipulating the BBB have been explored, including hyperosmolar therapy, convection-enhanced delivery (CED), laser-guided interstitial thermal therapy (LITT), and Magnetic Resonance Guided Focused Ultrasound (MRgFUS) to enhance delivery of chemotherapeutic agents to glial neoplasms. Here, we review these techniques, currently ongoing clinical trials to disrupt or bypass the BBB in gliomas, and the results of completed trials.
Dumbbell-shaped thrombectomy device for cerebral venous sinus thrombus removal with controllable axial and longitudinal maneuverability
Authors: Li Ming , Song Baoying , Wu Yan , Zhang Yang , Cao Xiaofeng , Zhang Hongkang , Xu Yi , Wu Chuanjie , Li Chuanhui , Zhou Chen , Liu Lu , Yan Feng , Li Sijie , Chen Jian , Meng Ran , Duan Jiangang , Wu Di , Zuo Lin , Xu Zikai , Li Zhou , Zheng Yufeng , Jiang Miaowen , Ji Xunming 
Published: January 2025

ABSTRACT
Cerebral venous sinus thrombosis (CVST) is frequently observed in younger adults and features in large thrombus volume. Due to the triangular-like cross-sectional shape and large diameter of the superior sagittal sinus, all the commercially available artery stent retrievers are not suitable for venous vessels. In this study, a dumbbell-like stent was designed and fabricated by 3D braided technology using NiTi wires; it was manually rotatable and stretchable with controlled length/diameter ratios (2.6–14.0) and reciprocating maneuverability. Computational modeling and an in vitro study were conducted to evaluate the mechanical properties of this device and its ability to trap and remove thrombi from occluded venous vessels was verified by using a swine model. A single-center retrospective clinical study of 10 patients using the Venus-TD to treat patients with CVST was also conducted. Pre/postoperative thrombus volume in 10 patients was quantitatively analysed (12 855.3 ± 6417.1 vs. 2373.1 ± 2759.0 mm³, P &lt; 0.001) with a high recanalization rate, yielding favorable clinical outcomes. This study offers a novel treatment option for patients with extensive CVST.
A Quantitative Polymerase Chain Reaction (qPCR) Protocol Predictive of Treatment Outcome in Cutaneous Leishmaniasis Caused by Leishmania braziliensis
Authors: Lordêlo Bianca , Magalhães Andréa , Noronha Almério , Oliveira Livia , Beiting Daniel , Scott Phillip , Carvalho Edgar M , Carvalho Lucas P 
Published: January 2025

Abstract
Leishmania braziliensis is the most prevalent agent causing cutaneous leishmaniasis (CL) in Brazil. While inflammation is a hallmark of CL, few parasites are found at the lesion site, leading to challenges regarding diagnosis. Using L braziliensis kDNA and human 18S rRNA as targets, the present study developed a quantitative polymerase chain reaction assay to determine parasite load in biopsies from patients with CL who were residing in an endemic area in northeastern Brazil. In addition, we investigated whether parasite load correlated with clinical outcome, and we observed that patients with higher parasite load were more likely to experience therapy failure. Moreover, patients with CL in the early phase of infection presented higher levels of parasite transcripts than individuals in later phases. Thus, our results suggest that parasite load as determined by quantitative polymerase chain reaction may constitute a valuable prognostic tool to aid in the determination of disease severity and treatment outcome.
The Icarian flight of antibody-drug conjugates: target selection amidst complexity and tackling adverse impacts
Authors: Liu Han , Zeng Hongye , Qin Xiaojing , Ning Wenjing , Xu Lin , Yang Shiting , Liu Xue , Luo Wenxin , Xia Ningshao 
Published: January 2025

Abstract
Antibody-drug conjugates (ADCs) represent a promising class of targeted cancer therapeutics that combine the specificity of monoclonal antibodies with the potency of cytotoxic payloads. Despite their therapeutic potential, the use of ADCs faces significant challenges, including off/on-target toxicity and resistance development. This review examines the current landscape of ADC development, focusing on the critical aspects of target selection and antibody engineering. We discuss strategies to increase ADC efficacy and safety, including multitarget approaches, pH-dependent antibodies, and masked peptide technologies. The importance of comprehensive antigen expression profiling in both tumor and normal tissues is emphasized, highlighting the role of advanced technologies, such as single-cell sequencing and artificial intelligence, in optimizing target selection. Furthermore, we explore combination therapies and innovations in linker‒payload chemistry, which may provide approaches for expanding the therapeutic window of ADCs. These advances pave the way for the development of more precise and effective cancer treatments, potentially extending ADC applications beyond oncology.
High-zinc rice and randomized nutrition training among women farmers: a panel data analysis of long-term adoption in Bangladesh
Authors: Valera Harold Glenn A , Antonio Ronald Jeremy , Habib Muhammad Ashraful , Puskur Ranjitha , Pede Valerien , Yamano Takashi 
Published: January 2025

Abstract
This paper aims to examine the effect of nutrition training on the adoption of high-zinc rice among female farmers with young children in Bangladesh. The authors first conducted a randomized controlled trial by providing female farmers with micronutrient training in randomly selected villages in May–June 2017, followed by a phone-based survey on high-zinc rice seeds among farmer trainees and counterparts in control villages. We conducted a three-visit panel survey in 2018–20 to measure the effect of nutrition training on high-zinc rice adoption. We found that the adoption of high-zinc rice in the Aman or rainy season during July–August declined from 59 per cent in 2018 to 8 per cent in 2020 among treated farmers and from 13 per cent to 2 per cent among control farmers. The regression analysis indicated that nutrition training had a significant but diminishing effect on the adoption of high-zinc rice. Unavailability of seeds and low yields were cited as the major reasons for not using high-zinc rice, while lack of knowledge about high-zinc rice was the dominant reason among the control farmers. The results have shown that continuous training, public messaging, and improving seed systems are required to sustain zinc rice adoption. The trainings should tackle the nutritional advantages of biofortified crops to ensure knowledge retention and farm practices and management techniques to achieve optimal production.
Impact of bladder management methods and other factors on sexual activity in women with chronic spinal cord injury/disease
Authors: Mahler Jasmin Lea , Schneider Salome , Wöllner Jens , Pannek Jürgen , Krebs Jörg 
Published: January 2025

Abstract

Background
Spinal cord injury/disease (SCI/D) profoundly affects both sexuality and urinary function. Catheterization is often necessary to manage bladder voiding and it can interfere with sexual activity.

Aim
We aim to investigate the effect of the bladder evacuation method on sexual activity in women with chronic SCI/D.

Methods
This cross-sectional study at a specialized SCI/D rehabilitation center recruited women ≥18 years with chronic SCI/D using intermittent or suprapubic catheterization. We assessed sexual activity and sexual function with the German version of the Sexual Behaviour Questionnaire and the Female Sexual Function Index (FSFI) and a study-specific questionnaire.

Outcomes
The primary outcome was sexual activity and secondary outcomes included factors influencing sexual activity, such as age and SCI/D characteristics.

Results
Around half of the evaluated women were sexually active, regardless of bladder evacuation method. However, significantly (P = .018) more women using intermittent catheterization (IC) (66.7%, 20/30) were sexually active compared to those with a suprapubic catheter (SPC) (29.4%, 5/17). The main concern for women using IC was urinary incontinence during sex (43.3%, 13/30), while those with a SPC struggled with self-image due to the catheter (58.8%, 10/17). Not having a partner was the most common reason for sexual inactivity in both groups (59.1%). The median FSFI total score was significantly (P = .049) greater in the IC group (median 26.4, lower quartiles [LQ] 8.9/upper quartiles [UQ] 28.8) compared to the SPC group (median 11.5, LQ 5.4/UQ 25.5), which represents a lower grade of sexual dysfunction in women using IC.

Clinical Translation
Sexual education is crucial and should be adapted to the different types of bladder management.

Strength & Limitations
This study shows first data on the effect of catheter on sexual activity in women. Limitation of our study is the small sample size and response bias by the high rejection rate of women with SPC.

Conclusions
Few women with SPC remain sexually active after SCI/D, while the majority of women using IC do, highlighting issues around self-image and urinary incontinence.
Can erector spinae plane block replace intrathecal morphine in cesarean section? A prospective randomized controlled study on opioid consumption
Authors: Sirin Betul Yusra , Teomete Gulsen , Bilgili Beliz 
Published: January 2025

Objectives:
After cesarean, optimal analgesia is important for early mobilization, mitigating thromboembolic risks, and mother-infant communication. Our study aims to compare the postoperative analgesic effects of intrathecal morphine (ITM) and Erector Spinae Plane Block (ESPB) in elective cesarean section under spinal anesthesia.

Methods:
82 patients were randomized into ESPB and ITM groups. Both groups received spinal anesthesia with 10 mg of heavy bupivacaine. In the ITM group, intrathecal morphine (100 mcg) was added. The ESPB group received bilateral T10 level ESPB with 20 ml 0.25% bupivacaine postoperatively. Postoperative pain control included intravenous paracetamol 4x1gr, intravenous patient-controlled analgesia with tramadol, and diclofenac 75 mg for rescue analgesia when NRS > 4. NRS, tramadol consumption, and side effects were recorded 24 hours postoperatively. The primary outcome of this study is to compare 24-hour postoperative opioid consumption after cesarean sections. Secondary outcomes include postoperative pain scores, rescue analgesia needs, and potential side effects.

Results:
NRS scores ≤ 4 at all time intervals and were comparable among groups. The total 24-hour tramadol consumption was significantly higher in ESPB group (median: 75; Q1,Q3[40,140]) compared to ITM (50 [27.5,60], P = 0.008). Tramadol consumption was similar among groups during 0-6 and 6-12 hours. In the 12-24 hours, it was significantly higher in ESPB group (22.5 [15,57.5]) compared to ITM (15 [12.5,25],P = 0.005). In ITM group, nausea and vomiting were observed in 3 patients, itching in 1 patient; no adverse effects were observed in ESPB group.

Discussion:
Patients undergoing cesarean section under spinal anesthesia, intrathecal morphine reduced opioid consumption more effectively than ESPB. ESPB is not recommended as a primary analgesic option for cesarean sections.