bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lower Dorsal Putamen D2/3 Receptor Availability and Amphetamine-Induced Dopamine Release are Related to Poorer Cognitive Function in Recently Abstinent People Who Smoke and Healthy Controls
Authors: Cheung Frances , Calakos Katina C , Gueorguieva Ralitza , Hillmer Ansel T , Cosgrove Kelly P , Zakiniaeiz Yasmin 
Published: February 2024

Abstract

Introduction
In the dopamine system, the mesolimbic pathway, including the dorsal striatum, underlies the reinforcing properties of tobacco smoking, and the mesocortical pathway, including the dorsolateral prefrontal cortex (dlPFC), is critical for cognitive functioning. Dysregulated dopamine signaling has been linked to drug-seeking behaviors and cognitive deficits. The dorsal striatum and dlPFC are structurally and functionally connected and are key regions for cognitive functioning. We recently showed that people who smoke have lower dlPFC dopamine (D2/3R) receptor availability than people who do not, which is related to poorer cognitive function.

Aims and Methods
The goal of this study was to examine the same brain-behavior relationship in the dorsal striatum. Twenty-nine (18 males) recently abstinent people who smoke and 29 sex-matched healthy controls participated in 2 same-day [11C]-(+)-PHNO positron emission tomography scans before and after amphetamine administration to provoke dopamine release. D2/3R availability (binding potential; BPND) and amphetamine-induced dopamine release (%ΔBPND) were calculated. Cognition (verbal learning and memory) was assessed with the CogState computerized battery.

Results
There were no group differences in baseline BPND. People who smoke have a smaller magnitude %ΔBPND in dorsal putamen than healthy controls (p = .022). People who smoke perform worse on immediate (p = .035) and delayed (p = .011) recall than healthy controls. In all people, lower dorsal putamen BPND was associated with worse immediate (p = .006) and delayed recall (p = .049), and lower %ΔBPND was related to worse delayed recall (p = .022).

Conclusions
Lower dorsal putamen D2/3R availability and function are associated with disruptions in cognitive function that may underlie difficulty with resisting smoking.

Implications
This study directly relates dopamine imaging outcomes in the dorsal striatum to cognitive function in recently abstinent people who smoke cigarettes and healthy controls. The current work included a well-characterized subject sample in terms of demographics, smoking characteristics, and a validated neurocognitive test of verbal learning and memory. The findings of this study extend previous literature relating dopamine imaging outcomes to cognition in recently abstinent people who smoke and people who do not smoke, expanding our understanding of brain-behavior relationships.
Artificial intelligence compared with human-derived patient educational materials on cirrhosis
Authors: Pradhan Faruq , Fiedler Alexandra , Samson Kaeli , Olivera-Martinez Marco , Manatsathit Wuttiporn , Peeraphatdit Thoetchai 
Published: February 2024

Background:The study compared the readability, grade level, understandability, actionability, and accuracy of standard patient educational material against artificial intelligence chatbot-derived patient educational material regarding cirrhosis.Methods:An identical standardized phrase was used to generate patient educational materials on cirrhosis from 4 large language model-derived chatbots (ChatGPT, DocsGPT, Google Bard, and Bing Chat), and the outputs were compared against a pre-existing human-derived educational material (Epic). Objective scores for readability and grade level were determined using Flesch-Kincaid and Simple Measure of Gobbledygook scoring systems. 14 patients/caregivers and 8 transplant hepatologists were blinded and independently scored the materials on understandability and actionability and indicated whether they believed the material was human or artificial intelligence-generated. Understandability and actionability were determined using the Patient Education Materials Assessment Tool for Printable Materials. Transplant hepatologists also provided medical accuracy scores.Results:Most educational materials scored similarly in readability and grade level but were above the desired sixth-grade reading level. All educational materials were deemed understandable by both groups, while only the human-derived educational material (Epic) was considered actionable by both groups. No significant difference in perceived actionability or understandability among the educational materials was identified. Both groups poorly identified which materials were human-derived versus artificial intelligence-derived.Conclusions:Chatbot-derived patient educational materials have comparable readability, grade level, understandability, and accuracy to human-derived materials. Readability, grade level, and actionability may be appropriate targets for improvement across educational materials on cirrhosis. Chatbot-derived patient educational materials show promise, and further studies should assess their usefulness in clinical practice.
Sintilimab plus bevacizumab combined with radiotherapy as first-line treatment for hepatocellular carcinoma with portal vein tumor thrombus: A multicenter, single-arm, phase 2 study
Authors: Zhu Meiyan , Liu Zelong , Chen Shuling , Luo Zhenhua , Tu Jianfei , Qiao Liangliang , Wu Jian , Fan Wenzhe , Peng Zhenwei 
Published: February 2024

Background and Aims:
Systemic treatments are listed as first-line therapies for HCC with portal vein tumor thrombus (PVTT), resulting in modest efficacy. We aimed to evaluate the efficacy and safety of sintilimab plus bevacizumab combined with radiotherapy in HCC with PVTT and to identify prognostic biomarkers.

Approach and Results:
This open-label, multicenter, single-arm, phase 2 clinical trial was conducted at 3 tertiary hospitals in China. A total of 46 patients with HCC with PVTT were enrolled. All the patients received the first cycle of i.v. sintilimab (200 mg, day 1) plus bevacizumab (15 mg/kg, day 1) within 3 days after enrollment. Radiotherapy (30–50 Gy/10 fractions) was administered after 2 cycles of Sin-Bev. Sin-Bev was disrupted during radiotherapy and resumed 2 weeks after radiotherapy and continued every 3 weeks thereafter until disease progression, unacceptable toxicity, or withdrawal of consent. The primary end point was objective response rate. Patients obtained an objective response rate of 58.7% and a disease control rate of 100%. After a median follow-up time of 26.0 months (95% CI: 24.0–26.0), the median OS was 24.0 months (95% CI: 19.0 to not applicable) and the median progression-free survival was 13.8 months (95% CI: 12.0–21.0), respectively. No unexpected adverse events or treatment-related deaths occurred. Mutations of PCTMD1 were predictive of shorter OS and progression-free survival.

Conclusions:
Sintilimab plus bevacizumab combined with radiotherapy provides favorable treatment response and survival outcomes along with an acceptable safety profile in the first-line setting for patients with HCC with PVTT (ClinicalTrials.gov Identifier: NCT05010434).
Effects of High-Intensity Resistance Versus Aerobic Training in PCOS Women at Risk for Psychological Trauma
Authors: Riaz Huma , Maqsood Mobeena , Afridi Ayesha , Ehsan Sarah , Jan Sadiq 
Published: February 2024

Background:
Polycystic ovarian syndrome (PCOS) is a prevalent and complex endocrine disorder that affects women of reproductive age. Its physical manifestations as the change in body image, fertility challenges, menstrual irregularities, and associated chronic health conditions increase their vulnerability to psychological trauma. Negative effects on psychological health significantly impact their quality of life.

Objectives:
The current study aimed to compare the effects of high-intensity resistance versus aerobic training on psychological health and quality of life in women with PCOS.

Study Design:
This was a single-blinded, randomized controlled trial.

Methods:
A randomized controlled trial was conducted from November 22 to April 23 at Riphah Rehabilitation Center, Islamabad, Pakistan. The female university students (n = 60), with an age range of 18 to 30 years, who were not part of any planned physical activity program, were not taking any medication, and were willing to participate in the exercise trial, were recruited. They were randomly allocated into 2 groups: high-intensity resistance (HIRG) and high-intensity aerobic (HIAG) groups. Both groups underwent exercise interventions for a duration of 12 weeks. Clinical and psychological health and quality of life were assessed using validated measures, including the polycystic ovary syndrome questionnaire (PCOS-Q) and the 36-item Short Form Survey (SF-36). Assessments were conducted at baseline, 6th, and 12th weeks. Data analysis was done using SPSS-21.

Results:
The mean age of women in the HIRG (n = 30) versus the HIAG (n = 30) was 22.40 ± 2.4 years versus 20.63 ± 2.1 years. Between-group analysis revealed no significant difference (P > .05) between the groups in terms of postintervention total scores of the PCOS-Q and SF-36 quality of life. However, within-group analysis has shown statistically significant improvement (P < .01) in both outcome measures.

Conclusion:
It is concluded that both high-intensity modes of exercise, resistance, and aerobic training were found to be equally effective interventions for improving psychological health and quality of life in women with PCOS. Individualizing exercise programs to meet individual needs and preferences may aid in maximizing the psychological benefits of each exercise modality. Further investigation into the underlying processes and long-term impact of these therapies in this vulnerable population is required.
Comparison of Surgical Outcomes of Transoral Versus Open Thyroidectomy for Graves Disease
Authors: Wang Suo-Hsien , Chao Wu-Po , Lo Ta-You , Ng Soh-Ching , Chen Yu-Hsien 
Published: February 2024

Introduction:
The transoral endoscopic thyroidectomy vestibular approach (TOETVA) is a safe alternative to thyroidectomy for thyroid goiter and provides the benefit of being scarless. However, the data on the use of TOETVA in patients with Graves disease are limited. This retrospective study compared the outcomes of Graves disease patients who underwent TOETVA versus those who underwent open thyroidectomy (OT).

Materials and Methods:
Patients with Graves disease who received TOETVA or OT for bilateral total thyroidectomy between September 2017 and October 2022 were included. Patient demographics and surgical outcomes, including operation time, blood loss, length of stay, and complications, were compared.

Results:
There were 15 patients in each group. The mean age in the TOETVA group was 35.80±8.13 years, which was significantly younger than that in the OT group, which was 51.53±14.22 years. Females predominated in both groups. The other demographic characteristics were similar in both groups. The operation time and intraoperative blood loss were also comparable. The postoperative stay and complications, including hypoparathyroidism, recurrent laryngeal nerve injury, surgical site infection, postoperative hemorrhage, and recurrence of hyperthyroidism, were not different between the 2 groups. There were 11 patients in the TOETVA group and 10 in the OT group who had thyroglobulin levels <0.1 ng/dL, indicating the completeness of total thyroidectomy in the 2 groups. There was no conversion of TOETVA to an open procedure.

Conclusions:
For carefully selected Graves patients, TOETVA offers a safe, scarless, and feasible alternative to conventional open thyroidectomy.
Effect of Intraperitoneal Instillation of Dexmedetomidine With Local Anesthetics in Laparoscopic Cholecystectomy: A Systematic Review and Meta-analysis of Randomized Trials
Authors: Sun Chenxu , He Zhengguang , Feng Biao , Huang Yaping , Liu Dawei , Sun Zhihua 
Published: February 2024

Objective:
Dexmedetomidine (DEX) can strengthen the analgesic effects of local anesthetics (LAs) when used as an adjuvant through intrathecal, perineural, and intraperitoneal routes. Many studies have used intraperitoneal instillation of DEX with LAs in laparoscopic cholecystectomy (LC) to relieve postoperative pain. We performed a systematic review and meta-analysis to synthesize evidence of the efficacy and safety of intraperitoneal instillation of DEX as an adjuvant of LAs in patients undergoing LC.

Methods:
A comprehensive literature search of the MEDLINE, PubMed, EMBASE, and Cochrane Library databases was performed to identify randomized controlled trials in which patients received intraperitoneal instillation of DEX combined with LAs during LC. A meta-analysis and sensitivity analysis of the results were conducted. We also performed a subgroup analysis to investigate the source of heterogeneity. The Egger test was used to check for publication bias.

Results:
Eleven randomized controlled trials involving 890 patients were analyzed. We found that the addition of DEX to LAs significantly decreased pain scores at six postoperative time points (0.5, 1, 2, 4, 12, and 24 h) and significantly prolonged the time to the first analgesic request by patients. In addition, 24-hour postoperative analgesic consumption was decreased in the experimental group, and no significant difference in the incidence of nausea and vomiting was observed.

Conclusion:
Our findings indicate that intraperitoneal instillation of DEX with LAs can reduce postoperative pain and prolong the time to first request analgesia after LC.
Outcomes of Endoscopic Sleeve Gastroplasty Following Laparoscopic Adjustable Gastric Band: A Propensity Score–matched Analysis
Authors: Maselli Daniel B. , Wooley Chase , Lee Daniel , Waseem Areebah , Donnangelo Lauren L. , Secic Michelle , Coan Brian , McGowan Christopher E. 
Published: February 2024

Background:
The performance of endoscopic sleeve gastroplasty (ESG) in patients with prior laparoscopic adjustable gastric band (LAGB) has not been characterized.

Materials and Methods:
This is a retrospective propensity score–matched study of ESG after LAGB at 2 centers with expertise in bariatric endoscopy. The primary outcome was total weight loss (TWL) at 12 months. Secondary outcomes included TWL at 3 and 6 months, 12-month excess weight loss (EWL), procedural characteristics, predictors of TWL, and serious adverse events.

Results:
Twenty-six adults (88.5% female, age 50.8 y, BMI 36.5 kg/m2) with prior LAGB (median duration 8 y) underwent ESG at a median of 3 years after LAGB removal. A 2:1 age-matched, sex-matched, and BMI-matched comparator group was created, comprising ESG patients from the same organization and time frame but without prior LAGB. TWL for the LAGB-to-ESG cohort versus the ESG-only cohort was 10.1±5.5% versus 13.0±4.4% at 3 months (P=0.0256), 12.4±7.2% versus 16.0±5.4% at 6 months (P=0.0375), and 12.7±8.2% versus 18.4±6.5% at 12 months (P=0.0149). At 12 months, the LAGB-to-ESG cohort had an EWL of 52.5±50.0%, and 75% achieved TWL ≥10%. There was no association between TWL at 3, 6, or 12 months and the following traits: age or BMI at the time of ESG, patient sex, and time from LAGB removal to ESG. No serious adverse events occurred in either cohort.

Conclusion:
ESG after LAGB facilitates safe and clinically meaningful weight loss but is attenuated compared to primary ESG.
Developing machine-learning-based amyloid predictors with Cross-Beta DB
Authors: Gonay Valentin , Dunne Michael P. , Caceres-Delpiano Javier , Kajava Andrey V. 
Published: February 2024

AbstractDue to shifts in environmental conditions, mutations, or interactions with other biomolecules, some proteins that would normally be soluble can undergo aggregation, resulting in the formation of clumps of amyloid fibrils. Understanding of this phenomenon is of paramount importance due not only to its association with various diseases (including Alzheimer’s disease), but also due to increasingly abundant evidence for its functional roles. Numerous studies have demonstrated that the propensity to form amyloids is coded by the amino acid sequence and this finding has paved the way for the development of several computational predictors of amyloidogenicity. The ultimate objective of computational methods is to accurately predict the formation of disease-related and functionally relevant amyloids that occurin vivo. These amyloid fibrils are known to form very specific “cross-β” structures of protein regions longer than about 15 residues. Remarkably, despite the significance of the naturally occurring amyloids, there has been a lack of datasets specifically dedicated to them. Hence, we built Cross-Beta DB, a database composed of cross-β amyloids formed in natural conditions. This database is expected to be indispensable for benchmarking amyloid predictors. We used the Cross-Beta DB to train and benchmark several such algorithms, using machine learning. The best-performing of these, the random-forest-based Cross-Beta RF Predictor, demonstrated superior performance over the other existing methods, fostering high expectations for an improved prediction of naturally occurring amyloids.
Metal ion activation and DNA recognition by theDeinococcus radioduransmanganese sensor DR2539
Authors: Mota Cristiano , Webster Myles , Saidi Melissa , Kapp Ulrike , Zubieta Chloe , Giachin Gabriele , Manso José Antonio , de Sanctis Daniele 
Published: February 2024

AbstractThe accumulation of manganese ions is crucial for scavenging reactive oxygen species (ROS) and protecting the proteome ofDeinococcus radiodurans(Dr). However, metal homeostasis still needs to be tightly regulated to avoid toxicity. DR2539, a dimeric transcription regulator, plays a key role inDrmanganese homeostasis. Despite comprising three well-conserved domains: a DNA binding domain, a dimerization domain, and an ancillary domain, both the metal ion activation mechanism and the DNA recognition mechanism remain elusive. In this study, we present biophysical analyses and the structure of the dimerization and DNA binding domains of DR2539 in its holo form and in complex with the 21 bp pseudo-palindromic repeat of thedr1709promotor region. These findings shed light into the activation and recognition mechanisms. The dimer presents eight manganese binding sites that induce structural conformations essential for DNA binding. The analysis of the protein-DNA interfaces elucidates the significance of Tyr59 and helix H3 sequence in the interaction with the DNA. Finally, the structure in solution as determined by small angle X-ray scattering experiments and supported by AlphaFold modelling provides a model illustrating the conformational changes induced upon metal binding.
Deciphering Peptide-Protein Interactions via Composition-Based Prediction: A Case Study with Survivin/BIRC5
Authors: Anindya Atsarina Larasati , Olsson Torbjörn Nur , Jensen Maja , Garcia-Bonete Maria-Jose , Wheatley Sally P. , Bokarewa Maria I. , Mezzasalma Stefano A. , Katona Gergely 
Published: February 2024

AbstractIn the realm of atomic physics and chemistry, composition emerges as the most powerful means of describing matter. Mendeleev’s periodic table and chemical formulas, while not entirely free from ambiguities, provide robust approximations for comprehending the properties of atoms, chemicals, and their collective behaviours, which stem from the dynamic interplay of their constituents.Our study illustrates that protein-protein interactions follow a similar paradigm, wherein the composition of peptides plays a pivotal role in predicting their interactions with the protein survivin, using an elegantly simple model. An analysis of these predictions within the context of the human proteome not only illuminates the known cellular locations of survivin and its interaction partners, but also introduces novel insights into biological functionality. It becomes evident that an electrostatic- and primary structure-based descriptions fall short in predictive power, leading us to speculate that protein interactions are orchestrated by the collective dynamics of functional groups.
Functional characterization of two glycosyltransferases fromWithania somniferailluminates their role in withanosides biosynthesis and defence against bacteria
Authors: Anjali P , Narayanan Ananth Krishna , Parihar Durgesh , Patil Anusha , Nagegowda Dinesh A. 
Published: February 2024

AbstractThe medicinal properties of Ashwagandha (Withania somniferaL. Dunal) are attributed to the presence of unique class of natural products called as withanolides and their glycosylated forms, withanosides. Withanosides are proposed to be formed from withanolides by the action of glycosyltransferases (GTs). This study reports the functional characterization of two GTs (WsGT4andWsGT6) fromW. somniferathat exhibited induced expression in response to methyl jasmonate treatment and showed highest expression in leaves compared to other tissues. Biochemical assays with recombinant WsGT proteins showed that WsGT4 and WsGT6 formed glycosylated products with four and one of the seven tested withanolides substrates, respectively. WsGT4 catalyzed product formation using withanolide A, withanolide B, withanone, and 12-deoxywithastramonolide as substrates, with UDP-glucose serving as the glucose donor, while WsGT6 catalyzed the product formation only with withaferin A as substrate employing either UDP-glucose or UDP-galactose as sugar donors. Moreover,in plantastudies through virus-induced gene silencing and transient overexpression ofWsGT4andWsGT6inW. somniferaleaves modulated the levels of withanolides and withanosides, indicating their role in withanosides biosynthesis. Furthermore, while individual silencing of bothWsGT4andWsGT6inW. somniferareduced the tolerance toPseudomonas syringaeDC3000 growth, their overexpression enhanced the tolerance to the bacterium inW. somnifera. Taken together, these results shed light on the roles of WsGT4 and WsGT6 in withanoside biosynthesis and defence against model bacterial pathogen inW. somnifera.
Controlling for polygenic genetic confounding in epidemiologic association studies
Authors: Zhao Zijie , Yang Xiaoyu , Miao Jiacheng , Dorn Stephen , Barcellos Silvia H. , Fletcher Jason M. , Lu Qiongshi 
Published: February 2024

AbstractEpidemiologic associations estimated from observational data are often confounded by genetics due to pervasive pleiotropy among complex traits. Many studies either neglect genetic confounding altogether or rely on adjusting for polygenic scores (PGS) in regression analysis. In this study, we unveil that the commonly employed PGS approach is inadequate for removing genetic confounding due to measurement error and model misspecification. To tackle this challenge, we introduce PENGUIN, a principled framework for polygenic genetic confounding control based on variance component estimation. In addition, we present extensions of this approach that can estimate genetically-unconfounded associations using GWAS summary statistics alone as input and between multiple generations of study samples. Through simulations, we demonstrate superior statistical properties of PENGUIN compared to the existing approaches. Applying our method to multiple population cohorts, we reveal and remove substantial genetic confounding in the associations of educational attainment with various complex traits and between parental and offspring education. Our results show that PENGUIN is an effective solution for genetic confounding control in observational data analysis with broad applications in future epidemiologic association studies.