bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of COVID-19 on patient access to health services for noncommunicable diseases in Latin America: a perspective from patient advocacy organizations
Authors: Kruse Meredith H. , Durstine Alessandra , Evans Dabney P. 
Published: April 2022

Abstract
Background
The COVID-19 pandemic has been felt acutely in Latin America with several countries having among the highest numbers of SARS-CoV-2 cases and related deaths. Individuals living with underlying health conditions have an increased risk of severe disease or death from COVID-19. Patient advocacy organizations often provide supportive services to these individuals and can offer a unique perspective of the patient experience. The objective of this study was to assess the effects of COVID-19 on access to health services in Latin America, as reported by patient advocacy organizations representing individuals living with autoimmune, chronic, and noncommunicable diseases.

Methods
A cross-sectional study was conducted in August 2020 with patient advocacy organizations in Latin America to measure perceived effects from COVID-19 and reported access to health services among individuals living with autoimmune, chronic, and noncommunicable diseases. An original, online survey was developed and deployed in Spanish and Portuguese. Univariate and bivariate analysis was conducted across two main subject areas: perceived patient effects from COVID-19 and patient access to health services. The main outcomes of analysis considered patient access to care during COVID-19 based on type of chronic illness and geographical region in Latin America.

Results
A total of 81 survey responses were analyzed. A majority (83%) of patient advocacy organizations reported their patients experienced delays receiving their treatment and care services; 52% experienced delays of 30 days or more. Telemedicine was considered available, but not accessible to patients (37%) and a majority (76%) of patients faced challenges with electronic prescriptions. Patients were not likely to receive a multi-month prescription from their doctor (38%) or successfully fill it at the pharmacy (26%).

Conclusions
According to responses from patient advocacy organizations, individuals living with noncommunicable diseases in Latin America have faced unique challenges during the COVID-19 pandemic. As countries re-evaluate their health systems, it is critical that chronic diseases are considered so that all can fully realize the right to health.
Symptoms and functional limitations related to respiratory health and carbon monoxide poisoning in Tanzania: a cross sectional study
Authors: Zoller Thomas , Mfinanga Elirehema H. , Zumba Tresphory B. , Asilia Peter J. , Mutabazi Edwin M. , Wimmersberger David , Mhimbira Francis , Haraka Frederick , Reither Klaus 
Published: April 2022

Abstract
Background
The burden of chronic respiratory symptoms and respiratory functional limitations is underestimated in Africa. Few data are available on carbon monoxide (CO) poisoning in sub-Saharan Africa and existing data is derived from CO in ambient air, but not from biomarkers in the blood.

Methods
Data from the Tanzanian Lung Health study, a cross-sectional study on lung health among outpatients and visitors to an urban as well as a rural hospital in Tanzania, was analyzed to describe respiratory symptoms and functional limitations. Saturation of peripheral blood with carbon monoxide (SpCO) was measured transcutaneously and non-invasively in participants using a modified pulse oxymeter indicative of CO poisoning. Univariate and multivariate analysis was performed.

Results
Nine hundred and ninety-seven participants were included in the analysis, the median age of participants was 46 years (49% male). 38% of participants reported some degree of chronic shortness of breath and 26% felt limited in their daily activities or at work by this symptom. The median SpCO was 7% (IQR 4–13, range 2–31%) among all participants without active smoking status (N = 808). Participants cooking with gas or electricity had the lowest SpCO (median 5%), followed by participants cooking with charcoal (median 7%). Cooking with wood, particularly using a stove, resulted in highest SpCO (median 11.5%). Participants from households where cooking takes place in a separate room had the lowest SpCO as compared to cooking outside or cooking in a shared room inside (6% vs. 9% vs.10.5%, p < 0.01). Sex or the activity of cooking itself was not associated with a difference in SpCO. Multivariate analysis confirmed cooking in a separate room (as compared to cooking outside) and living in a rural vs. urban setting as protective factors against high SpCO.

Conclusion
The findings demonstrate a high burden of chronic respiratory symptoms which also cause socioeconomic impact. High levels of SpCO indicate a relevant burden of carbon monoxide poisoning in the local population. The level of CO in the blood is more dependent on shared exposure to sources of CO with the type of housing and type of cooking fuel as most relevant factors, and less on person-individual risk factors or activities.
Circular RNA MTCL1 promotes advanced laryngeal squamous cell carcinoma progression by inhibiting C1QBP ubiquitin degradation and mediating beta-catenin activation
Authors: Wang Zheng , Sun Anqi , Yan Aihui , Yao Jian , Huang Haibo , Gao Ziming , Han Tao , Gu Jia , Li Ni , Wu Huizhe , Li Kai 
Published: April 2022

Abstract
Background
Circular RNAs (circRNAs) are involved in regulatory processes of ubiquitination and deubiquitination in various tumors at post-transcriptional epigenetic modification level. However, the underlying mechanism and its biological functions of circRNAs in the advanced laryngeal squamous cell carcinoma (LSCC) remain obscure.

Methods
RNA sequencing and quantitative real-time PCR (qRT-PCR) assays were applied to screen for circRNAs differentially expressed in LSCC tissues and cell lines. The candidate RNA-binding proteins and target signalling pathway were detected by RNA pull-down and mass spectrometry, in situ hybridization (ISH), immunohistochemistry (IHC), qRT-PCR assays, and bioinformatics analysis. The functional roles of these molecules were investigated using in vitro and in vivo experiments including EdU, transwell, wound healing, western blot assays, and the xenograft mice models. The molecular mechanisms were identified using RNA pull-down assays, RNA immunoprecipitation (RIP), Co-IP, ISH, Ubiquitination assay, bioinformatics analysis, and the rescue experiments.

Results
Here, we unveil that microtubule cross-linking factor 1 circRNA (circMTCL1, circ0000825) exerts its critical oncogenic functions by promoting complement C1q-binding protein (C1QBP)-dependent ubiquitin degradation and subsequently activating Wnt/β-catenin signalling in laryngeal carcinoma initiation and development. Specifically, circMTCL1 was remarkably up-regulated in the paired tissues of patients with LSCC (n = 67), which predicted a worse clinical outcome. Functionally, circMTCL1 exerted oncogenic biological charactersistics by promoting cell proliferative capability and invasive and migrative abilities. Ectopic circMTCL1 augumented cell proliferation, migration, and invasion of LSCC cells, and this effect could be reversed by C1QBP knocking down in vitro and in vivo. Mechanistically, circMTCL1 directly recruited C1QBP protein by harboring the specific recognized sequence (+ 159 − + 210), thereby accelerating the translation of C1QBP expression by inhibiting its ubiquitin–proteasome-mediated degradation. Importantly, the direct interaction of C1QBP with β-catenin protein was enhanced via suppressing the β-catenin phosphorylation and accelerating its accumulation in cytoplasm and nucleus.

Conclusion
Our findings manifested a novel circMTCL1-C1QBP-β-catenin signaling axis involving in LSCC tumorigenesis and progression, which shed new light on circRNAs-ubiquitous acidic glycoprotein mediated ubiquitin degradation and provided strategies and targets in the therapeutic intervention of LSCC.
Bacteria-driven hypoxia targeting delivery of chemotherapeutic drug proving outcome of breast cancer
Authors: Xiao Susu , Shi Huan , Zhang Yan , Fan Yu , Wang Li , Xiang Li , Liu Yanlin , Zhao Ling , Fu Shaozhi 
Published: April 2022

AbstractLocal hypoxia is a common feature of many solid tumors and may lead to unsatisfactory chemotherapy outcomes. Anaerobic bacteria that have an affinity to hypoxic areas can be used to achieve targeted drug delivery in tumor tissues. In this study, we developed a biocompatible bacteria/nanoparticles biohybrid (Bif@DOX-NPs) platform that employs the anaerobic Bifidobacterium infantis (Bif) to deliver adriamycin-loaded bovine serum albumin nanoparticles (DOX-NPs) into breast tumors. The Bif@DOX-NPs retained the targeting ability of B. infantis to hypoxic regions, as well as the cytotoxicity of DOX. The biohybrids were able to actively colonize the hypoxic tumors and significantly increased drug accumulation at the tumor site. The DOX concentration in the tumor masses colonized by Bif@DOX-NPs was 4 times higher than that in the free DOX-treated tumors, which significantly prolonged the median survival of the tumor-bearing mice to 69 days and reduced the toxic side-effects of DOX. Thus, anaerobic bacteria-based biohybrids are a highly promising tool for the targeted treatment of solid tumors with inaccessible hypoxic regions.
Graphical Abstract
Multistage pH-responsive codelivery liposomal platform for synergistic cancer therapy
Authors: Zhao Ting , Liang Ce , Zhao Yanrong , Xue Xiangdong , Ma Zhao , Qi Jinlong , Shen Haitao , Yang Shaokun , Zhang Jia , Jia Qingzhong , Du Qing , Cao Deying , Xiang Bai , Zhang Hailin , Qi Xianrong 
Published: April 2022

Abstract
Background
Small interfering RNA (siRNA) is utilized as a potent agent for cancer therapy through regulating the expression of genes associated with tumors. While the widely application of siRNAs in cancer treatment is severely limited by their insufficient biological stability and its poor ability to penetrate cell membranes. Targeted delivery systems hold great promise to selectively deliver loaded drug to tumor site and reduce toxic side effect. However, the elevated tumor interstitial fluid pressure and efficient cytoplasmic release are still two significant obstacles to siRNA delivery. Co-delivery of chemotherapeutic drugs and siRNA represents a potential strategy which may achieve synergistic anticancer effect. Herein, we designed and synthesized a dual pH-responsive peptide (DPRP), which includes three units, a cell-penetrating domain (polyarginine), a polyanionic shielding domain (ehG)n, and an imine linkage between them. Based on the DPRP surface modification, we developed a pH-responsive liposomal system for co-delivering polo-like kinase-1 (PLK-1) specific siRNA and anticancer agent docetaxel (DTX), D-Lsi/DTX, to synergistically exhibit anti-tumor effect.

Results
In contrast to the results at the physiological pH (7.4), D-Lsi/DTX lead to the enhanced penetration into tumor spheroid, the facilitated cellular uptake, the promoted escape from endosomes/lysosomes, the improved distribution into cytoplasm, and the increased cellular apoptosis under mildly acidic condition (pH 6.5). Moreover, both in vitro and in vivo study indicated that D-Lsi/DTX had a therapeutic advantage over other control liposomes. We provided clear evidence that liposomal system co-delivering siPLK-1 and DTX could significantly downregulate expression of PLK-1 and inhibit tumor growth without detectable toxic side effect, compared with siPLK-1-loaded liposomes, DTX-loaded liposomes, and the combinatorial administration.

Conclusion
These results demonstrate great potential of the combined chemo/gene therapy based on the multistage pH-responsive codelivery liposomal platform for synergistic tumor treatment.

Graphical Abstract
Demoralization in oral cancer inpatients and its association with spiritual needs, quality of life, and suicidal ideation: a cross-sectional study
Authors: Chang Ting-Gang , Huang Pei-Ching , Hsu Chiann-Yi , Yen Ting-Ting 
Published: April 2022

Abstract
Background
Demoralization is a common problem in oral cancer patients owing to the chronic and severe nature of their affliction. However, the association between demoralization and the patient’s spiritual needs, quality of life, and suicidal ideation remains unclear. This study aims to provide insights into possible links between demoralization among oral cancer patients and its effects on the patient’s spiritual needs, quality of life, and suicidal ideation.

Methods
We examined 155 Taiwanese oral cancer inpatients in Taichung Veterans General Hospital, Taiwan, using the following three rating scales: (a) Demoralization Scale Mandarin Version (DS-MV), (b) Spiritual Interests Related to Illness Tool, and (c) The Taiwan Chinese versions of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire. Suicidal ideation was established if at least one of the two suicide-related items on the DS-MV scale were checked. We divided the participants into high- and low-demoralization groups, per the cutoff score of 30. We then explored group associations with sociodemographic features, quality of life, and spiritual needs. Logistic regression and receiver operating characteristic (ROC) curves were used to determine demoralization and its association between these variables.

Results
Fifty-five (35.5%) patients were categorized as having high demoralization (DS-MV scale score > 30), with scores for DS-MV for all patients being 27.2 ± 16.8. The rates of suicidal ideation were 29.1% (16/55) in the high-demoralization group and 2% (2/100) in the low-demoralization group, with an odds ratio (95% confidence interval) of 20.10 (4.41–91.55). Logistic regression analysis revealed significant effects of spiritual needs and global health status on the DS-MV scores (p < 0.001). Multivariate analyses further confirmed that only overall quality of life scores < 62.5 and spiritual needs < 3.7 significantly predicted the occurrence of high demoralization.

Conclusion
High demoralization is associated with low satisfaction with spiritual needs, poor quality of life, and high risk of suicidal ideation. DS-MV may potentially be an effective tool for achieving holistic health care among oral cancer patients.
Measuring carer quality of life in Duchenne muscular dystrophy: a systematic review of the reliability and validity of self-report instruments using COSMIN
Authors: Carlton Jill , Powell Philip A. ,   Project HERCULES Carer Group
Published: April 2022

AbstractIntroductionDuchenne muscular dystrophy is a rare, progressive, life-limiting genetic neuromuscular condition that significantly impacts the quality of life of informal caregivers. Carer quality of life is measured using heterogeneous self-report scales, yet their suitability for Duchenne remains unclear. This review aimed to identify and evaluate the reliability and validity of quality of life instruments in Duchenne carers.Materials and methodsSystematic searches were conducted in Embase, MEDLINE, CINAHL, PsycINFO, Cochrane Library and Google Scholar. Full research articles reporting data on multiple-item self-report quality of life instruments in informal Duchenne carers were included. Extracted evidence was qualitatively synthesised and evaluated, including risk of bias, against the Consensus-based Standards for the selection of health Measurement Instruments. Duchenne carer collaborators (N = 17) helped rate the instruments’ content validity.ResultsThirty-one articles featuring thirty-two quality of life instruments were included. Content validity was rated as “inconsistent” based on very low quality evidence. For Duchenne carer collaborators, the best instrument was PedsQL Family Impact Module. Only one instrument had evidence for structural validity (rated “unsatisfactory”) and measurement invariance (rated “satisfactory”). Instruments received “satisfactory” ratings for internal consistency and mixed ratings for construct validity and responsiveness. There was no evidence for reliability, measurement error, or criterion validity.DiscussionInstruments used to measure Duchenne carer quality of life have limited and often inconsistent supportive psychometric evidence. Further work must investigate instruments’ measurement properties in Duchenne carers and/or the development of new tools. In the interim, we recommend considering the PedsQL Family Impact Module based on Duchenne carer ratings.
Systematic review update and meta-analysis of randomized and non-randomized controlled trials of ovarian stimulation versus artificial cycle for endometrial preparation prior to frozen embryo transfer in women with polycystic ovary syndrome
Authors: Zhang Yingying , Wu Ling , Li Tin Chiu , Wang Chi Chiu , Zhang Tao , Chung Jacqueline Pui Wah 
Published: April 2022

Abstract
Purpose
This systematic review and meta-analysis aimed to compare the short-term reproductive and long-term obstetric outcomes after endometrial preparations by ovarian stimulation protocols and hormone replacement therapy (HRT) in women with polycystic ovary syndrome (PCOS) prior to frozen embryo transfer (FET).

Method
PubMed, EMBASE, Web of Science and the Cochrane Library were searched to identify relevant studies. Primary outcome was live birth rate, secondary outcomes included the rates of clinical pregnancy, miscarriage, implantation and hCG-postive, cycle cancellation, ectopic pregnancy, preterm birth, preeclampsia, gestational hypertension, gestational diabetes mellitus and abnormal placentation.

Results
Nine studies, including 8327 patients with PCOS, were identified. Live birth rate was significantly higher (RR = 1.11, 95% CI = 1.03–1.19) and miscarriage rate (RR = 0.60, 95% CI = 0.46–0.78) was significantly lower in stimulated protocol compared to the rates in HRT. While the rates of ongoing pregnancy, clinical pregnancy, implantation, hCG-positive, cycle cancellation and ectopic pregnancy showed no significant difference between the two protocols. Compared HRT with different stimulation protocols, significantly higher clinical pregnancy rate (RR = 1.54, 95% CI = 1.20–1.98) were found in letrozole group, but not in the other subgroups. For the obstetric outcomes, the preterm birth and preeclampsia rates were significantly lower in the stimulated group compared to that in the HRT group (RR = 0.85, 95% CI = 0.74–0.98; RR = 0.57, 95% CI = 0.40–0.82, respectively), while gestational hypertension, gestational diabetes mellitus and abnormal placentation rates showed no significant difference.

Conclusions
The present data suggest that ovarian stimulation protocol as an endometrial preparation regimen prior to FET might be superior to HRT protocol with a significantly higher rate of live birth, lower risk of miscarriage, preterm birth and preeclampsia. Our study showed stimulated protocol is better than HRT regimen as an endometrial preparation for women with PCOS. However, quality of the evidence is low, more well-designed RCT studies are still needed to confirm the results before clinical recommendation, particularly direct comparisons between letrozole and other stimulated regimens.
Association between ethnicity and health knowledge among the floating population in China
Authors: Han Bingxue , Guan Hongyi , Guan Ming 
Published: April 2022

Abstract
Background
Health equity remains a priority concerns by central government in China. This study aimed to explore ethnic gaps in access to health knowledge categories and sources based on the survey data from a publicly available dataset.

Methods
Data were from 2015 China Migrants Dynamic Survey issued by The National Health Commission in China. Descriptive analyses were performed to reflect geodemographic differences in the floating population of ethnic minority (EMFP) and Han majority (HMFP) with Chi-square test. Ethnic gaps in access to health knowledge categories and sources were explored with Poisson regressions, logistic regressions, and bivariate ordered probit regressions.

Results
In the sample, most of participants had inadequate health information literacy. There were significant differences regarding geodemographic factors between EMFP and HMFP. Illiterate EMFP had likelihood to obtain less health knowledge categories (IRR = 0.80, 95% CI 0.77–0.84) and sources (IRR = 0.83, 95% CI 0.80–0.86) as compared to illiterate HMFP. Most of correlations between health knowledge categories and sources were weak in the samples of EMFP and HMFP.

Conclusion
Ethnic disparities in access to health knowledge categories and sources among the floating population in China were confirmed. Further effective efforts should be provided to reduce ethnic disparities in access to health knowledge under the ethnicity-orientated support of public health resource.
The global, regional, and national disease burden of breast cancer attributable to low physical activity from 1990 to 2019: an analysis of the Global Burden of Disease Study 2019
Authors: Yin Xiaolin , Zhang Tongchao , Zhang Yuan , Man Jinyu , Yang Xiaorong , Lu Ming 
Published: April 2022

Abstract
Background
To assess the spatiotemporal variation in female breast cancer attributable to low physical activity (LPA) at a global scale from 1990 to 2019, which is essential to promote physical activity, as well as prevent and control breast cancer.

Methods
The number of deaths and disability-adjusted life years (DALYs), and the corresponding age-standardized rates (ASMR and ASDR) of LPA-related breast cancer in 204 countries and territories from 1990 to 2019 were retrieved from the Global Burden of Disease Study 2019 to measure the related breast cancer burden by age and region. The estimated annual percentage change (EAPC) was calculated to quantify the secular trend in breast cancer burden rates.

Results
From 1990 to 2019, globally, both breast cancer deaths and DALYs attributable to LPA nearly doubled, although the corresponding ASMR and ASDR decreased slightly, with EAPC of -0.46 (95% confidence interval: -0.52, -0.40) and -0.44 (95% confidence interval: -0.49, -0.39), respectively. The LPA-related breast cancer burden varied considerably across the world, with the highest-burden rates in Oceania, Tropical Latin America and Caribbean, and the fastest growth in North Africa and Middle East. The ASMR and ASDR showed a logarithmic association with the Socio-demographic Index, and a temporally upward trend in most of 204 countries regardless of the Socio-demographic Index or the ASMR in 1990.

Conclusions
Despite a decline in LPA-related breast cancer burden achieved in many countries during the last 3 decades like Bermuda, Myanmar, USA and China, an increase still occurred in most of 204 countries and territories, such as Solomon Islands, Equatorial Guinea, Japan and India. The findings can bring greater awareness to the importance of promoting physical activity for the local government to control the attributable breast cancer burden.