bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of the COVID-19 pandemic on population-based cancer screening, a nationwide retrospective study in Taiwan
Authors: Su Chih-Hsuan , Hsu Pi-Shan , Lin Chu-Sheng 
Published: August 2023

Abstract
Background
The Coronavirus disease 2019 (COVID-19) pandemic has placed a great burden on Taiwan’s health care system. It has also had a great impact on other public health issues, including cancer screening. Delayed cancer screening was also noticed in the U.S. during the pandemic, which may have led to both delayed diagnosis and poor prognosis. In Taiwan, population-based cancer screening for breast cancer, oral cancer, colon cancer and cervical cancer has been executed and ongoing for years.

Method
In this study we have analyzed the change in screening numbers for cancer during the period of the 2019 to 2021 COVID-19 outbreak in Taiwan.

Results
Through our results we found that total cancer screening numbers decreased from 307,547 to 103,289 (a 66% decrease) from the years 2020 to 2021. Specifically, a 63%, 79%, 65% and 71% decrease in screening cases was seen for colon cancer, oral cancer, cervical cancer and breast cancer, respectively, during that period. A similar condition was noticed when comparing 2019 to 2021 when the disclosed total cancer screening numbers decreased by 70% (2019–2021); 65%, 83%, 70% and 76% in colon cancer, oral cancer, cervical cancer and breast cancer, respectively. Among these various cancer screenings, oral cancer screening showed the greatest reduction rate (a drop of 83% compared to 2019 and 79% compared to 2020). We also compared the reduction rates taken from different regions in Taiwan. It was in Taipei, where most COVID-19 cases were noted, that the greatest reduction rate of cancer screening numbers occurred (a drop of76% compared to 2019 and 74% compared to 2020). A proportional decrease of screening cases was also noticed in all areas when confirmed COVID-19 cases rose.

Conclusions
Screening for cancers dropped significantly due to the pandemic and its effect on long-term health needs to be evaluated. Additionally, efforts should be taken to address these cancer screening number deficits which have taken place during the COVID-19 pandemic.
Abnormal generation of IL-17A represses tumor infiltration of stem-like exhausted CD8+ T cells to demote the antitumor immunity
Authors: Zhang Ruochan , Chen Kun , Gong Caifeng , Wu Zhiyuan , Xu Chungui , Li Xing-Ning , Zhao Fei , Wang Dongmei , Cai Jianqiang , Zhou Aiping , Qu Chunfeng 
Published: August 2023

Abstract
Background
Variated anti-cancer therapies are combined with immune checkpoint blockades (ICBs) for improving ICB therapeutic efficacy. Occurrence of tissue damage is common that triggers multiple inflammatory cytokine generation. Gastrointestinal organs are the commonly affected. We investigated the impact of acute colitis on tumor infiltration of antigen-specific CD8+ cytotoxic T lymphocytes (CTLs) for controlling tumor growth and responding to antibody against PD-1 (anti-PD-1).

Methods
Several tumor cell lines were inoculated into syngeneic mice subcutaneously or intra-hepatically. When tumor mass formed, activated CTLs were intravenously transferred into the tumor-bearing mice, that were given the drinking water containing 2% dextran sulfate sodium (DSS) for acute colitis induction. Tumor growth, infiltration of two exhausted CTL subsets, and the CTL interaction with tumor vascular endothelium were examined.

Results
Acute colitis dampened CTL-mediated antitumor effects, correlating with IL-17A elevation in the inflamed intestine. In the tumor bed, stem-like exhausted CTLs, which were defined as PD-1+Slamf6+Tim3−, expressed higher IL-17A receptor heterodimers and lower leukocyte function-associated antigen-1 (LFA-1) than terminally exhausted CTLs did, that were defined as PD-1+Slamf6−Tim3+. IL-17A stimulation reduced LFA-1 surface expression on stem-like exhausted CTLs and the counterpart ICAM-1 (intracellular adhesion molecule-1) on tumor vascular endothelium. IL-17A stimulation suppressed the extravasation across tumor vascular endothelium and self-renewal of stem-like, not the terminally exhausted CTLs. Administration of anti-IL-17A neutralizing antibody to the colitis mice restored the CTL tumor infiltration and enhanced anti-PD-1 treatment efficacy against tumors. In 33 hepatocellular carcinoma patients being treated with anti-PD-1 plus antibody against vascular endothelial growth factor, disease progression of 15 patients, that exhibited serum IL-17A increase 24 h post-therapy as compared to pre-therapy level, was poorer than that of 18 patients that exhibited serum IL-17A no-increase.

Conclusions
Abnormal generation of IL-17A mainly repressed tumor infiltration of stem-like exhausted CTLs. ICB-based immunotherapeutic efficacy could be upgraded with administration of anti-IL-17A, when treatment-related IL-17A elevation occurred due to tissue damage, such as acute colitis.
Border malaria: defining the problem to address the challenge of malaria elimination
Authors: Li Xiaohong , Snow Robert W. , Lindblade Kim , Noor Abdisalan M. , Steketee Richard , Rabinovich Regina , Gopinath Deyer , Gasimov Elkhan , Alonso Pedro L. 
Published: August 2023

AbstractBorder malaria is frequently cited as an obstacle to malaria elimination and sometimes used as a justification for the failure of elimination. Numerous border or cross-border meetings and elimination initiatives have been convened to address this bottleneck to elimination. In this Perspective, border malaria is defined as malaria transmission, or the potential for transmission, across or along shared land borders between countries where at least one of them has ongoing malaria transmission. Border malaria is distinct from malaria importation, which can occur anywhere and in any country. The authors’ analysis shows that the remaining transmission foci of malaria-eliminating countries tend to occur in the vicinity of international land borders that they share with neighbouring endemic countries. The reasons why international land borders often represent the last mile in malaria elimination are complex. The authors argue that the often higher intrinsic transmission potential, the neglect of investment and development, the constant risk of malaria importation due to cross-border movement, the challenges of implementing interventions in complex environments and uncoordinated action in a cross-border shared transmission focus all contribute to the difficulties of malaria elimination in border areas. Border malaria reflects the limitations of the current tools and interventions for malaria elimination and implies the need for social cohesion, basic health services, community economic conditions, and policy dialogue and coordination to achieve the expected impact of malaria interventions. Given the uniqueness of each border and the complex and multifaceted nature of border malaria, a situation analysis to define and characterize the determinants of transmission is essential to inform a problem-solving mindset and develop appropriate strategies to eliminate malaria in these areas.
A qualitative metasynthesis of stigma in women living with HIV in the United States
Authors: Sommer Sadie , Barroso Julie 
Published: August 2023

AbstractOur goal was to synthesize qualitative studies on HIV-related stigma as experienced by women living with HIV (WLWH) in the U.S. Qualitative metasynthesis techniques as developed by Sandelowski et al. (Res Nurs Health 30(1):99–111, 2007) were used to integrate and update findings on stigma in WLWH in the U.S. in 43 reports of qualitative studies conducted between 2004 and 2023 with 1118 participants. Developed themes explored a collective narrative of women first surviving the intersectionality of multiple sources of stigma, discovering non-linear pathways to transcend their stigma, and finally experiencing resilience through their transcendence of stigma. While this metasynthesis revealed similarities to an earlier metasynthesis in the ubiquity and persistence of stigma, they differ primarily in women’s abilities to find agency in managing and opposing their stigma. This cognitive reframing of their stigma helped women to redefine stigma as ignorance and move towards a more positive assessment of the self. In doing so, they separated themselves from their stigma and the damaging effects of it. Findings from this metasynthesis may serve as a useful tool for the development of stigma reduction interventions specific to the needs and experiences of WLWH in the U.S.
A novel approach to estimate the impact of health workforce investments on health outcomes through increased coverage of HIV, TB and malaria services
Authors: Bruckner Tim A. , Lin Tracy K. , Liu Jenny , Bornemisza Olga , Ajuebor Onyema , Diallo Khassoum , Cometto Giorgio 
Published: August 2023

Abstract
Background
Globally, HIV, TB and malaria account for an estimated three million deaths annually. The Global Fund partnered with the World Health Organization to assist countries with health workforce planning in these areas through the development of an integrated health workforce investment impact tool. Our study illustrates the development of a user-friendly tool (with two MS Excel calculator subcomponents) that computes associations between human resources for health (HRH) investment inputs and reduced morbidity and mortality from HIV, TB, and malaria via increased coverage of effective treatment services.

Methods
We retrieved from the peer-reviewed literature quantitative estimates of the relation among HRH inputs and HRH employment and productivity. We converted these values to additional full-time-equivalent doctors, nurses and midwives (DNMs). We used log-linear regression to estimate the relation between DNMs and treatment service coverage outcomes for HIV, TB, and malaria. We then retrieved treatment effectiveness parameters from the literature to calculate lives saved due to expanded treatment coverage for HIV, TB, and malaria. After integrating these estimates into the tool, we piloted it in four countries.

Results
In most countries with a considerable burden of HIV, TB, and malaria, the health workforce investments include a mix of pre-service education, full remuneration of new hires, various forms of incentives and in-service training. These investments were associated with elevated HIV, TB and malaria treatment service coverage and additional lives saved. The country case studies we developed in addition, indicate the feasibility and utility of the tool for a variety of international and local actors interested in HRH planning.

Conclusions
The modelled estimates developed for illustrative purposes and tested through country case studies suggest that HRH investments result in lives saved across HIV, TB, and malaria. Furthermore, findings show that attainment of high targets of specific treatment coverage indicators would require a substantially greater health workforce than what is currently available in most LMICs. The open access tool can assist with future HRH planning efforts, particularly in LMICs.
Phosphodiesterase and psychiatric disorders: a two-sample Mendelian randomization study
Authors: Jiang Miaomiao , Yan Weiheng , Zhang Yuyanan , Lu Zhe , Lu Tianlan , Zhang Dai , Li Jun , Wang Lifang 
Published: August 2023

Abstract
Background
Phosphodiesterases (PDEs) have been associated with psychiatric disorders in observational studies; however, the causality of associations remains unestablished.

Methods
Specifically, cyclic nucleotide PDEs were collected from genome-wide association studies (GWASs), including PDEs obtained by hydrolyzing both cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) (PDE1A, PDE2A, and PDE3A), specific to cGMP (PDE5A, PDE6D, and PDE9A) and cAMP (PDE4D and PDE7A). We performed a bidirectional two-sample Mendelian randomization (MR) analysis to investigate the relationship between PDEs and nine psychiatric disorders. The inverse-variance-weighted (IVW) method, MR-Egger, and weighted median were used to estimate causal effects. The Cochran’s Q test, MR-Egger intercept test, MR Steiger test, leave-one-out analyses, funnel plot, and MR pleiotropy residual sum and outlier (MR-PRESSO) were used for sensitivity analyses.

Results
The PDEs specific to cAMP were associated with higher-odds psychiatric disorders. For example, PDE4D and schizophrenia (SCZ) (odds ratios (OR) = 1.0531, PIVW = 0.0414), as well as major depressive disorder (MDD) (OR = 1.0329, PIVW = 0.0011). Similarly, PDE7A was associated with higher odds of attention-deficit/hyperactivity disorder (ADHD) (OR = 1.0861, PIVW = 0.0038). Exploring specific PDE subtypes and increase intracellular cAMP levels can inform the development of targeted interventions. We also observed PDEs (which hydrolyzes both cAMP and cGMP) was associated with psychiatric disorders [OR of PDE1A was 1.0836 for autism spectrum disorder; OR of PDE2A was 0.8968 for Tourette syndrome (TS) and 0.9449 for SCZ; and OR of PDE3A was 0.9796 for MDD; P < 0.05]. Furthermore, psychiatric disorders also had some causal effects on PDEs [obsessive–compulsive disorder on increased PDE6D and decreased PDE2A and PDE4D; anorexia nervosa on decreased PDE9A]. The results of MR were found to be robust using multiple sensitivity analysis.

Conclusions
In this study, potential causal relationships between plasma PDE proteins and psychiatric disorders were established. Exploring other PDE subtypes not included in this study could provide a more comprehensive understanding of the role of PDEs in psychiatric disorders. The development of specific medications targeting PDE subtypes may be a promising therapeutic approach for treating psychiatric disorders.
Analysis of PERV-C superinfection resistance using HA-tagged viruses
Authors: Flecks Merle , Fischer Nicole , Krijnse Locker Jacomina , Tönjes Ralf R. , Godehardt Antonia W. 
Published: August 2023

Abstract

Background
Using pigs as organ donors has advanced xenotransplantation to the point that it is almost ready for clinical use. However, there is still a zoonotic risk associated with xenotransplantation, and the potential transmission of porcine endogenous retroviruses needs to be surveyed. Despite significant attempts to eliminate this risk, by the selection of PERV-C free pigs with low expression of PERV-A, -B, and by the genome-wide inactivation of PERV using CRISPR/Cas9, the impact of superinfection resistance (SIR) was not investigated. SIR is a viral trait that prevents reinfection (superinfection). For PERV, the underlying mechanism is unclear, whether and how cells, that harbor functional PERV, are protected. Using PERV-C(5683) as a reference virus, we investigated SIR in a newly developed in vitro model to pursue the mechanism and confirm its protective effect.

Results
We developed three PERV-C constructs on the basis of PERV-C(5683), each of which carries a hemagglutinin tag (HA-tag) at a different position of the envelope gene (SP-HA, HA-VRA, and RPep-HA), to distinguish between primary infection and superinfection. The newly generated PERV-C(5683)-HA viruses were characterized while quantifying the viral RNA, reverse transcriptase activity, protein expression analysis, and infection studies. It was demonstrated that SP-HA and RPep-HA were comparable to PERV-C(5683), whereas HA-VRA was not replication competent. SP-HA and RPep-HA were chosen to challenge PERV-C(5683)-positive ST-IOWA cells demonstrating that PERV-C-HA viruses are not able to superinfect those cells. They do not integrate into the genome and are not expressed.

Conclusions
The mechanism of SIR applies to PERV-C. The production of PERV-C particles serves as a defense mechanism from superinfection with exogenous PERV-C. It was demonstrated by newly generated PERV-C(5683)-HA clones that might be used as a cutting-edge tool. The HA-tagging of PERV-C is novel, providing a blueprint for the tagging of other human tropic PERV viruses. The tagged viruses are suitable for additional in vitro and in vivo infection studies and will contribute, to basic research on viral invasion and pathogenesis. It will maintain the virus safety of XTx.
Pharmacotherapeutic profile, polypharmacy and its associated factors in a cohort of people living with HIV in Brazil
Authors: da Silva Robson Pierre Nascimento , Marins Luana M. S. , Guaraldo Lusiele , Luz Paula Mendes , Cardoso Sandra W. , Moreira Ronaldo I. , Oliveira Vanessa da Gama , Veloso Valdilea G. , Grinsztejn Beatriz , Estrela Rita , Torres Thiago S. 
Published: August 2023

Abstract
Background
The increased survival provided by the access, development, and evolution of antiretroviral drugs (ARV) greatly increased the life expectancy of people living with HIV (PWH). This has also led to an increased occurrence of diseases or morbidities related to aging. In individuals with multiple comorbidities, the simultaneous use of multiple medications, also known as polypharmacy, is common, and rational use of medications is essential. This study aims to describe the pharmacotherapeutic profile, estimate the prevalence of polypharmacy and identify factors associated with polypharmacy in a cohort of adult PWH from a referral unit in Rio de Janeiro, Brazil.

Methods
Cross-sectional study including PWH on ARV who received at least one medical prescription (outpatient/hospitalized) in 2019. We described the proportion of prescribed medications according to ARV and Anatomical Therapeutic Chemical (ATC) classes stratified by age (< 50 vs. ≥50 years). Polypharmacy was defined as ≥ 5 medications prescribed beyond ARV. Logistic regression models assessed demographic and clinical factors associated with polypharmacy.

Results
A total of 143,306 prescriptions of 4547 PWH were analyzed. Median age was 44.4 years (IQR:35.4–54.1) and 1615 (35.6%) were ≥ 50 years. A total of 2958 (65.1%) participants self-identified as cisgender man, 1365 (30.0%) as cisgender woman, and 224 (4.9%) as transgender women. Most self-declared Black/Pardo (2582; 65.1%) and 1984 (44.0%) completed elementary education or less. Median time since HIV diagnosis was 10.9 years (IQR:6.2–17.7). Most frequently prescribed concomitant medications were nervous system (64.8%), antiinfectives for systemic use (60.0%), alimentary tract and metabolism (45.9%), cardiovascular system (40.0%) and respiratory system (37.1%). Prevalence of polypharmacy was 50.6% (95%CI: 49.2–52.1). Model results indicated that being older, self-identify as cisgender woman, having less education and longer time since HIV diagnosis increased the odds of polypharmacy.

Conclusions
We found high rates of polypharmacy and concomitant medication use in a cohort of PWH in Brazil. Targeted interventions should be prioritized to prevent interactions and improve treatment, especially among individuals using central nervous system and cardiovascular medications, as well as certain groups such as cisgender women, older individuals and those with lower education. Standardized protocols for continuous review of patients’ therapeutic regimens should be implemented.
Methods for integrating postural control into biomechanical human simulations: a systematic review
Authors: Shanbhag Julian , Wolf Alexander , Wechsler Iris , Fleischmann Sophie , Winkler Jürgen , Leyendecker Sigrid , Eskofier Bjoern M. , Koelewijn Anne D. , Wartzack Sandro , Miehling Jörg 
Published: August 2023

AbstractUnderstanding of the human body’s internal processes to maintain balance is fundamental to simulate postural control behaviour. The body uses multiple sensory systems’ information to obtain a reliable estimate about the current body state. This information is used to control the reactive behaviour to maintain balance. To predict a certain motion behaviour with knowledge of the muscle forces, forward dynamic simulations of biomechanical human models can be utilized. We aim to use predictive postural control simulations to give therapy recommendations to patients suffering from postural disorders in the future. It is important to know which types of modelling approaches already exist to apply such predictive forward dynamic simulations. Current literature provides different models that aim to simulate human postural control. We conducted a systematic literature research to identify the different approaches of postural control models. The different approaches are discussed regarding their applied biomechanical models, sensory representation, sensory integration, and control methods in standing and gait simulations. We searched on Scopus, Web of Science and PubMed using a search string, scanned 1253 records, and found 102 studies to be eligible for inclusion. The included studies use different ways for sensory representation and integration, although underlying neural processes still remain unclear. We found that for postural control optimal control methods like linear quadratic regulators and model predictive control methods are used less, when models’ level of details is increasing, and nonlinearities become more important. Considering musculoskeletal models, reflex-based and PD controllers are mainly applied and show promising results, as they aim to create human-like motion behaviour considering physiological processes.
Prevalence and characteristics of HTLV-associated uveitis in patients from Bahia, an endemic area for HTLV − 1 in Brazil
Authors: Piai Ozores Daniele , Rathsam Pinheiro Regina , Boa-Sorte Ney , Campos e Silva Dias Maurício , Silva Lima Raianne , Hialla Almeida Araújo Thessika , Galvão-Castro Bernardo , Grassi Maria Fernanda Rios 
Published: August 2023

Abstract
Background
HTLV-1-associated uveitis (HAU) is an inflammatory reaction of the choroid, retina, optic nerve and vitreous that can lead to vision impairment. The worldwide prevalence of HAU varies widely.

Objective
To determine the prevalence of HAU in patients from Salvador, Bahia-Brazil, and describe uveitis type and associated symptoms.

Methods
Cross-sectional analytical study to determine the prevalence of uveitis in HTLV-1-infected patients recruited in Bahia, Brazil, a region considered endemic for HTLV-1. Patients were enrolled at a local reference center for HTLV (infected) and at an outpatient ophthalmology clinic (noninfected group). All patients were examined by the same ophthalmologist following a single protocol. Prevalence ratios (PR) were calculated.

Results
A total of 168 consecutively examined HTLV-1-infected patients and 410 noninfected patients (randomly selected) were included. Females predominated (82.1%) in the HTLV-1-infected group (versus 64.4% in the uninfected group) (p < 0.001). The mean age of infected and uninfected patients was 53.2 and 62.8 years, respectively (p < 0.001). The prevalence of uveitis in HTLV-1+ and HTLV-1− patients was 7.14% and 0.73%, respectively (PR = 9.76; 95CI%:2.79–34.15; p < 0.01). Bilateral intermediate uveitis, associated with symptoms including visual disturbances and floaters, was most commonly identified in the HTLV-1-infected patients, whereas unilateral anterior uveitis, in association with symptoms such as blurring and ocular pain, was more common in the uninfected group.

Conclusion
The prevalence of uveitis in patients with HTLV-1 was markedly higher than in uninfected subjects. HAU patients were mostly asymptomatic and exhibited bilateral presentation, with uveitis more frequently localized in the intermediate chamber.