bluuebunny/crossref_metadata_2025_split huggingface dataset:
Current status of stroke in hemodialysis patients on a remote island
Authors: Nakamura Hikaru , Hiu Takeshi , Yamamoto Yasuhito , Oda Shinya , Izumo Tsuyoshi , Matsuo Takayuki 
Published: September 2023

Objectives
Hemodialysis patients have a higher incidence of stroke than healthy individuals. Hemodialysis patients living on remote islands are subject to additional distance and transportation difficulties. Therefore, we aimed to study the association between stroke and hemodialysis in patients living on remote islands.

Materials and methods
We conducted a retrospective cohort study based on the medical records of maintenance hemodialysis patients in Shinkamigoto-Cho, Nagasaki, Japan, between June 1, 2005, and June 31, 2022. The clinical characteristics, probability of hemorrhagic stroke, acute ischemic stroke-free rate, and survival probability with or without a history of anticoagulant/antiplatelet use were evaluated. The survival probability among the hemorrhagic stroke, acute ischemic stroke, and non-stroke groups was also evaluated.

Results
This study involved 142 patients. Nine patients (6.3%) had intracerebral hemorrhage, one (0.7%) had subarachnoid hemorrhage, eight (5.6%) had acute ischemic stroke, and 124 (87.3%) had no stroke. The number of patients with severe disabilities (modified Rankin Scale 5/6) was significantly higher in the hemorrhagic stroke group. The probability of hemorrhagic stroke and acute ischemic stroke-free rate, or survival probability with or without a history of anticoagulant/antiplatelet use, were not significantly different. The acute ischemic stroke group was not associated with a lower survival probability than the other groups. The hemorrhagic stroke group had a significantly lower survival probability than the acute ischemic stroke group.

Conclusions
This is the first study to report the status of stroke in hemodialysis patients living on remote islands, thus providing valuable information for improved stroke management in such patients.
Timeliness of diagnostic evaluation for postmenopausal bleeding: A retrospective cohort study using claims data
Authors: Xu Xiao , Chen Ling , Nunez-Smith Marcella , Clark Mitchell , Wright Jason D. 
Published: September 2023

Background
Postmenopausal bleeding (PMB) is a common gynecologic condition. Although it can be a sign of uterine cancer, most patients have benign etiology. However, research on quality of diagnostic evaluation for PMB has been limited to cancer patients. To extend this research, we examined the timeliness of diagnostic evaluation for PMB among patients with benign conditions.

Methods
Using the 2008–2019 MarketScan Research Databases, we identified 499176 patients (456741 with commercial insurance and 42435 with Medicaid insurance) who presented with PMB but did not have gynecologic cancer. For each patient, we measured the time from their PMB reporting to the date of their first diagnostic procedure. The association between patient characteristics and time to first diagnostic procedure was examined using Cox proportional hazards models (for the overall sample and then stratified by insurance type).

Results
Overall, 54.3% of patients received a diagnostic procedure on the same day when they reported PMB and 86.6% received a diagnostic procedure within 12 months after reporting PMB. These percentages were 39.4% and 77.1%, respectively, for Medicaid patients, compared to 55.7% and 87.4%, respectively, for commercially insured patients (p<0.001 for both). Medicaid patients had an 18% lower rate of receiving a diagnostic procedure at any given time point than commercially insured patients (adjusted hazard ratio = 0.82, 95% CI: 0.81–0.83). Meanwhile, older age and non-gynecologic comorbidities were associated with a lower rate whereas concomitant gynecologic conditions and recent use of preventive care were associated with a higher rate of receiving diagnostic procedures. Analysis stratified by insurance type identified additional risk factors for delayed diagnostic procedures (e.g., non-metropolitan versus metropolitan location for commercially insured patients and Black versus White race for Medicaid patients).

Conclusion
A sizable proportion of patients did not receive prompt diagnostic evaluation for PMB. Both clinical and non-clinical factors could affect timeliness of evaluation.
Thymidylate synthase promotes esophageal squamous cell carcinoma growth by relieving oxidative stress through activating nuclear factor erythroid 2-related factor 2 expression
Authors: Yang Jian , Zhang Jingjing , Chen Jingtian , Yang Xiaolong , Sun Hui , Zhao Zhenxiang , Zhou Hui , Shen Hao 
Published: September 2023

Background
Thymidylate synthase (TYMS) is involved in the malignant process of multiple cancers, and has gained much attention as a cancer treatment target. However, the mechanism in carcinogenesis of esophageal squamous cell cancer (ESCC) is little reported. The present study was to clear the biological roles and carcinogenic mechanism of TYMS in ESCC, and explored the possibility to use TYMS as a tumor marker in diagnosis and a drug target for the treatment of ESCC.

Methods
Stably TYMS-overexpression cells established by lentivirus transduction were used for the analysis of cell proliferation. RNA sequencing was performed to explore the possible carcinogenic mechanisms.

Results
GEPIA databases analysis showed that TYMS expression in esophageal cancer tissues was higher than that in normal tissues. The MTT assay, colony formation assay, and nude mouse subcutaneous tumor model found that the overexpression of TYMS increased cell proliferation. Transcriptome sequencing analysis revealed that the promoted cell proliferation in TYMS-overexpression ESCC cells were mediated through activating genes expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and Nrf2 dependent antioxidant enzymes to relieve oxidative stress, which was confirmed by increased glutathione (GSH), glutathione peroxidase (GPX) activities, and reduced reactive oxygen species. Nrf2 active inhibitors (ML385) used in TYMS-overexpression cells inhibited the expression of Nrf2-dependent antioxidant enzyme genes, thereby increasing oxidative stress and blocking cell proliferation.

Conclusion
Our study indicated a novel and effective regulatory capacity of TYMS in the cell proliferation of ESCC by relieving oxidative stress through activating expression of Nrf2 and Nrf2-dependent antioxidant enzymes genes. These properties make TYMS and Nrf2 as appealing targets for ESCC clinical chemotherapy.
The impact of display saturation on visual search performance in congenital colour vision deficiency
Authors: Hathibelagal Amithavikram R. 
Published: September 2023

Background
Colour-related search tasks are common in many professional fields. The study investigated whether increasing chromatic saturation can enhance the visual performance of individuals with colour vision deficiency (CVD) in colour-related search tasks.

Methods
10 normal trichromats (5M, 5F; Mean (SD) age: 23.1 (3.3) years) and 15 individuals with CVD [8 deutans and 7 protans identified by HRR plates] (14M, 1F; aged 28.6 (8.7) years) participated in this study. Four naturalistic sceneries of everyday tasks/ birds, animals and flowers of 15 different colour combinations (1 pair of colours in each combination. e.g., ‘brown/black’ or ‘red/green’) were presented in ‘low’ saturation, ‘original’ (unaltered images) and ‘high’ saturation condition using the Psychopy program on a colour-calibrated monitor. On each trial, the subject was asked to identify a specific-coloured target.

Results
Overall, the visual search performance index (expressed as product of accuracy and a reciprocal of reaction time (%correct*s-1) of the normal trichromats [Mean (SD):77.76% correct*s-1 (16.32)] was significantly higher than CVD [45.71% correct*s-1 (18.95)] in the “original” test images (p = 0.001), but in individuals with CVD, there was no significant difference between ‘original’ [45.71% correct*s-1 (18.95)] and ‘high’ saturation condition ([47.43% correct*s-1 (20.07)]; p > 0.05). However, colour-wise, increased saturation showed improvements (≥ 10%) in protans mainly for ‘red’ combinations with other colours such as white (i.e., ‘red/white’), purple, orange, grey, green, brown and black.

Conclusion
The study suggests that increasing the saturation of certain colour combinations can potentially aid in the visual search performance of individuals with CVD. This knowledge will help in better counselling and management of the patients.
Spatial distribution, magnitude, and predictors of high fertility status among reproductive age women in Ethiopia: Further analysis of 2016 Ethiopia Demographic and Health Survey
Authors: Asmamaw Desale Bihonegn , Negash Wubshet Debebe , Aragaw Fantu Mamo , Belay Daniel Gashaneh , Asratie Melaku Hunie , Endawkie Abel , Belachew Tadele Biresaw 
Published: September 2023

Background
Women’s health and welfare, as well as the survival of their children, are adversely affected by high fertility rates in developing countries. The fertility rate in Ethiopia has been high for a long time, with some pockets still showing poor improvement. Thus, the current study is aimed to assess the spatial distribution and its predictors of high fertility status in Ethiopia.

Methods
Secondary data analysis was used using the 2016 Ethiopian Demographic and Health Survey (EDHS). The Bernoulli model was used by applying Kulldorff methods using the SaTScan software to analyze the purely spatial clusters of high fertility status. ArcGIS version 10.8 was used to visualize the distribution of high fertility status across the country. Mixed-effect logistic regression analysis was also used to identify the predictors of high fertility.

Result
High fertility among reproductive-age women had spatial variation across the country. In this study, a higher proportion of fertility occurred in Somali region, Southeastern part of Oromia region, and Northeastern part of SNNPR. About 45.33% (confidence interval: (44.32, 46.33) of reproductive-age women had high fertility. Education; no formal (aOR: 13.12, 95% CI: 9.27, 18.58) and primary (aOR: 5.51, 95% CI: 3.88, 7.79), religion; Muslim (aOR: 1.52, 95% CI: 1.28, 1.81) and Protestant (aOR: 1.48, 95% CI: 1.23, 1.78), age at first birth (aOR: 2.94, 95% CI: 2.61, 3.31), age at first sex (aOR: 1.70, 95% CI: 1.49, 1.93), rural resident (aOR: 3.76, 95% CI: 2.85, 4.94) were predictors of high fertility in Ethiopia.

Conclusion
The spatial pattern of high fertility status in Ethiopia is clustered. Hotspot areas of a problem were located in Somali, Central Afar, Northeastern part of SNNPR, and Southeastern part of Oromia region. Therefore, designing a hotspot area-based interventional plan could help to reduce high fertility. Moreover, much is needed to be done among rural residents, reducing early sexual initiations and early age at first birth, and enhancing women’s education. All the concerned bodies including the kebele administration, religious leaders, and community leaders should be in a position to ensure the practicability of the legal age of marriage.
Clinical presentation, microbiology, and prognostic factors of prosthetic valve endocarditis. Lessons learned from a large prospective registry
Authors: Ramos-Martínez Antonio , Domínguez Fernando , Muñoz Patricia , Marín Mercedes , Pedraz Álvaro , Fariñas Mª Carmen , Tascón Valentín , de Alarcón Arístides , Rodríguez-García Raquel , Miró José María , Goikoetxea Josune , Ojeda-Burgos Guillermo , Escrihuela-Vidal Francesc , Calderón-Parra Jorge ,   On behalf of the GAMES investigators
Published: September 2023

Background
Prosthetic valve endocarditis (PVE) is a serious infection associated with high mortality that often requires surgical treatment.

Methods
Study on clinical characteristics and prognosis of a large contemporary prospective cohort of prosthetic valve endocarditis (PVE) that included patients diagnosed between January 2008 and December 2020. Univariate and multivariate analysis of factors associated with in-hospital mortality was performed.

Results
The study included 1354 cases of PVE. The median age was 71 years with an interquartile range of 62–77 years and 66.9% of the cases were male. Patients diagnosed during the first year after valve implantation (early onset) were characterized by a higher proportion of cases due to coagulase-negative staphylococci and Candida and more perivalvular complications than patients detected after the first year (late onset). In-hospital mortality of PVE in this series was 32.6%; specifically, it was 35.4% in the period 2008–2013 and 29.9% in 2014–2020 (p = 0.031). Variables associated with in-hospital mortality were: Age-adjusted Charlson comorbidity index (OR: 1.15, 95% CI: 1.08–1.23), intracardiac abscess (OR:1.78, 95% CI:1.30–2.44), acute heart failure related to PVE (OR: 3. 11, 95% CI: 2.31–4.19), acute renal failure (OR: 3.11, 95% CI:1.14–2.09), septic shock (OR: 5.56, 95% CI:3.55–8.71), persistent bacteremia (OR: 1.85, 95% CI: 1.21–2.83) and surgery indicated but not performed (OR: 2.08, 95% CI: 1.49–2.89). In-hospital mortality in patients with surgical indication according to guidelines was 31.3% in operated patients and 51.3% in non-operated patients (p<0.001). In the latter group, there were more cases of advanced age, comorbidity, hospital acquired PVE, PVE due to Staphylococcus aureus, septic shock, and stroke.

Conclusions
Not performing cardiac surgery in patients with PVE and surgical indication, according to guidelines, has a significant negative effect on in-hospital mortality. Strategies to better discriminate patients who can benefit most from surgery would be desirable.
Effects of high-intensity respiratory muscle training on respiratory muscle strength in individuals with Parkinson’s disease: Protocol of a randomized clinical trial
Authors: Brito Sherindan Ayessa Ferreira de , Scianni Aline Alvim , Silveira Bruna Mara Franco , Oliveira Elem Rodrigues Martins de , Mateus Maria Eduarda , Faria Christina Danielli Coelho de Morais 
Published: September 2023

Objective
To investigate the efficacy of high-intensity respiratory muscle training (combined inspiratory and expiratory muscle training) in improving inspiratory and expiratory muscle strength, inspiratory muscle endurance, peak cough flow, dyspnea, fatigue, exercise capacity, and quality of life in this population.

Methods
A randomized controlled trial, concealed allocation, blinded assessments, and intention-to-treat analysis will be carried out. Altogether, 34 individuals with PD (age ≥ 50 years old, with maximum inspiratory pressure (MIP) <80cmH2O or maximum expiratory pressure (MEP) <90cmH2O) will be recruited. Patients will be randomly assigned to either (1) high-intensity respiratory muscle training (experimental group, 60% of MIP and MEP) or (2) sham training (control group, 0cmH2O). Individuals will perform a home-based intervention, with indirect home supervision, consisting of two daily 20-min sessions (morning and afternoon), seven times a week, during eight weeks. Primary outcomes are MIP and MEP. Secondary outcomes are inspiratory muscle endurance, peak cough flow, dyspnea, fatigue, exercise capacity, and quality of life. The effects of the training will be analyzed from the collected data using intention-to-treat. Between-group differences will be measured using a two-way ANOVA with repeated measures (2*3), considering baseline, post-intervention, and 12-week follow-up.

Impact
The results of this trial will provide valuable new information on the efficacy of high-intensity respiratory muscle training in improving muscle strength, functional outcomes, and quality of life in individuals with PD. Performing combined inspiratory and expiratory muscle training using a single equipment is cheaper and feasible, takes less time and is easy to use. In addition, this intervention will be carried out in the home environment that increases accessibility, reduces time, and costs of transport, which increases the feasibility to reproduce their findings in clinical practice.

Trial registration
NCT05608941. Registered on November 8, 2022.
Clinical protocol: Feasibility of evaluating abemaciclib neuropharmacokinetics of diffuse midline glioma using intratumoral microdialysis
Authors: Nduom Edjah K. , Glod John , Brown Desmond A. , Fagan Margaret , Dalmage Mahalia , Heiss John , Steinberg Seth M. , Peer Cody , Figg William D. , Jackson Sadhana 
Published: September 2023

Diffuse midline gliomas (DMG) are the most aggressive brain tumors of childhood and young adults, with documented 2-year survival rates <10%. Treatment failure is due in part to the function of the BBB. Intratumoral microdialysis sampling is an effective tool to determine brain entry of varied agents and could help to provide a better understanding of the relationship of drug permeability to DMG treatment responsivity. This is a non-randomized, single-center, phase 1 clinical trial. Up to seven young adult (18–39 years) patients with recurrent high-grade or diffuse midline glioma will be enrolled with the goal of 5 patients completing the trial over an anticipated 24 months. All patients will take abemaciclib pre-operatively for 4.5 days at twice daily dosing. Patients will undergo resection or biopsy, placement of a microdialysis catheter, and 48 hours of dialysate sampling coupled with timed plasma collections. If intratumoral tumor or brain dialysate sampling concentrations are >10nmol/L, or tumor tissue studies demonstrate CDK inhibition, then restart of abemaciclib therapy along with temozolomide will be administered for maintenance therapy and discontinued with evidence of radiologic or clinical disease progression. The poor survival associated with diffuse midline gliomas underscore the need for improved means to evaluate efficacy of drug delivery to tumor and peritumoral tissue. The findings of this novel study, will provide real-time measurements of BBB function which have the potential to influence future prognostic and diagnostic decisions in such a lethal disease with limited treatment options.
Trial registration: Clinicaltrials.gov, NCT05413304. Registered June 10, 2022, Abemaciclib Neuropharmacokinetics of Diffuse Midline Glioma Using Intratumoral Microdialysis.
Capturing drug use patterns at a glance: An n-ary word sufficient statistic for repeated univariate categorical values
Authors: Odom Gabriel J. , Brandt Laura , Castro Clinton , Luo Sean X. , Feaster Daniel J. , Balise Raymond R. ,   the CTN-0094 Team
Published: September 2023

IntroductionThe efficacy of treatments for substance use disorders (SUD) is tested in clinical trials in which participants typically provide urine samples to detect whether the person has used certain substances via urine drug screenings (UDS). UDS data form the foundation of treatment outcome assessment in the vast majority of SUD clinical trials. However, existing methods to calculate treatment outcomes are not standardized, impeding comparability between studies and prohibiting reproducibility of results.MethodsWe extended the concept of a binary UDS variable to multiple categories: “+” [positive for substance(s) of interest], “–” [negative for substance(s)], “o” [patient failed to provide sample], “*” [inconclusive or mixed results], and “_” [no specimens required per study design]. This construct can be used to create a standardized and sufficient representation of UDS datastreams and sufficiently collapses longitudinal records into a single, compact “word”, which preserves all information contained in the original data.ResultsWe developed the R software packageCTNote(available on CRAN) as a tool to enable computers to parse these “words”. The software package contains five groups of routines: detect a substance use pattern, account for a specific trial protocol, handle missing UDS data, measure the longest period of consecutive behavior, and count substance use events. Executing permutations of these routines result in algorithms which can define SUD clinical trial endpoints. As examples, we provide three algorithms to define primary endpoints from seminal SUD clinical trials.DiscussionRepresenting substance use patterns as a “word” allows researchers and clinicians an “at a glance” assessment of participants’ responses to treatment over time. Further, machine readable use pattern summaries are a standardized method to calculate treatment outcomes and are therefore useful to all future SUD clinical trials. We discuss some caveats when applying this data summarization technique in practice and areas of future study.
Post-acute sequelae of COVID-19 and longitudinal antibody levels in a community-based cohort
Authors: Kopplin Noa , Garcia Angie , Reczek Annika , Wilkinson Kate , Yekkaluri Sruthi , Murphy Caitlin C. , Tiro Jasmin , Muthukumar Alagar R. , Masica Andrew , Singal Amit G. 
Published: September 2023

Background
Coronavirus disease 2019 (COVID-19) infection invokes variable immune responses and poses a risk of post-acute sequelae SARS-CoV-2 infection (PASC) symptoms; however, most data on natural history are derived from patients with severe infection. Further data are needed among patients with mild infection, who comprise most cases.

Methods
The Dallas Fort-Worth (DFW) COVID-19 Prevalence Study included 21,597 community-dwelling adults (ages 18–89) who underwent COVID-19 PCR and anti-nucleocapsid antibody testing between July 2020 and March 2021. We invited participants with positive COVID-19 results (cases) and a subset with negative results (controls), matched on age, sex, race/ethnicity, and ZIP code, to complete a follow-up questionnaire for PASC symptoms and repeat anti-nucleocapsid testing, and anti-spike antibody testing between July and December 2021.

Results
Of 3,917 adults invited to participate, 2260 (57.7%) completed the questionnaire– 1150 cases and 1110 controls. Persistent symptoms were reported in 21.1% of cases, with the most common being shortness of breath, fatigue, and loss of taste or smell. Among 292 cases with asymptomatic infection, >15% reported new fatigue and 8–10% reported new loss of taste/smell, myalgias, or headache. Median anti-nucleocapsid levels in cases decreased from 3.5U to 0.7U over a median follow-up of 8.6 months. Anti-spike antibody levels at 6–7 months post-vaccination in cases were similar to that of controls.

Conclusions
More than 1 in 5 patients with COVID-19 infection, including those with mild infection, reported persistent symptoms during follow-up. Both nucleocapsid and spike protein antibody levels decreased within six months following a COVID-19 infection and vaccination.