bluuebunny/crossref_metadata_2025_split huggingface dataset:
Depression in public officials during the COVID-19 pandemic in Paraguay: a web-based study
Authors: Kim Ji Eon , Lee Ji Ho , Kang Yanghee , Lee Sun Ha , Shin Hyein , Rönnebeck Nadia , Rönnebeck Renato , Nam Eun Woo 
Published: October 2021

Abstract
Background
According to the World Health Organization, the coronavirus disease 2019 (COVID-19) pandemic has created situations that have a negative effect on people and threaten their mental health. Paraguay announced the Estado de Emergencia Sanitaria (Presidential Decree No. 3456) on March 16, 2020, which was followed by the imposition of a 24-h restriction on movement order on March 21. Self-quarantine at home may have been the most effective method of preventing the spread of infectious diseases; however, with the global pandemic becoming more prolonged and the consequent lengthening of the 24-h self-quarantine period, it is highly probable that both physical and psychological problems will arise.

Methods
In this study, a web-based cross-sectional method was used to analyze the factors influencing COVID-19-induced depressive feelings in Paraguayan public officials.

Results
Public officials reported a high level of depressive symptoms with a high level of apprehension in early stage of COVID-19. In addition, this study identified that when the self-quarantine period increased, levels of depressive feelings also increased. Since self-quarantine is characterized by the requirement that individuals endure an undetermined period within a confined area, it may have caused stress and anxiety, as well as the consequent experience of depressive feelings.

Conclusions
Paraguayan government should develop a program for the delivery of mental health care and services to public officials in COVID-19 Pandemic period. Moreover, a program is required for people facing deteriorating mental health due to social isolation and loneliness caused by social distancing during the prolonged period of self-quarantine. Finally, mental health care programs should be organized in a community-focused way by utilizing online systems to enhance the effectiveness of mental health recovery.
miR-30a-5p inhibits osteogenesis and promotes periodontitis by targeting Runx2
Authors: Liu Xiangdong , Yang Bo , Zhang Yan , Guo Xiaorui , Yang Qianjuan , Liu Xiaojing , Bai Qingxia , Lu Qun 
Published: October 2021

Abstract
Background
Periodontitis is the most extensive chronic inflammatory bone resorption disease. MiRNAs offer a potential way for potential therapy. Indeed, miR-30a-5p had an increasing expression in periodontitis gingivae, but whether it promotes osteogenesis and inhibits inflammation remains unknown.

Methods
Periodontitis model was exhibited by wire ligation and verified by micro-CT and HE staining; qPCR was used to detect the expression of miR-30a-5p; miR-30a-5p inhibitors and mimics were transfected into MC3T3-E1 cell line by lipofectamine 3000; The dual luciferase reporter gene experiment and RIP experiment were used to detect the relationship between miR-30a-5p and Runx2; Rescue experiment was used to verify the relationship between miR-30a-5p and Runx2.

Results
Periodontitis model was exhibited successfully and miR-30a-5p was overexpressed at the bone and gingival tissues of this model. miR-30a-5p inhibitors not only promoted the osteogenesis but also relieved inflammation. Runx2 is a target of miR-30a-5p by dual luciferase reporter gene experiment and RIP experiment. Rescue experiments revealed that miR-30a-5p inhibitors would promote osteogenesis and relieve inflammation by targeting Runx2 in inflammation of MC3T3-E1 cell line.

Conclusions
That all suggested that miR-30a-5p-mediated-Runx2 provided a novel understanding of mechanism of periodontitis.
Response to: viva la VOSCE?
Authors: Motie Lucinda Zahrah , Kaini Shahil 
Published: October 2021

AbstractBoyle et al. discuss the development and implementation of a Virtual Objective Structured Clinical Examination due to the COVID-19 pandemic lockdown precluding face-to-face Objective Structured Clinical Examinations, something we too as clinical medical students studying at University College London have experienced. We commend Boyle et al. for promptly creating and delivering this assessment. However, we believe this style of assessment has the potential to exacerbate the ethnic and social inequalities that currently exist within medical education. Going forward, it is imperative that the home environment is considered in an attempt to level the playing field.
COVID-19 pandemic and waiting times in outpatient specialist care in Germany: an empirical analysis
Authors: Muschol Jennifer , Gissel Christian 
Published: October 2021

AbstractBackgroundInternational healthcare systems face the challenge that waiting times may create barriers to accessing medical care, and that those barriers are unequally distributed between different patient groups. The disruption of healthcare systems caused by the COVID-19 pandemic could exacerbate this already strained demand situation. Using the German healthcare system as an example, this study aims to analyze potential effects of the COVID-19 pandemic on waiting times for outpatient specialist care and to evaluate differences between individual patient groups based on their respective insurance status and the level of supply.MethodsWe conducted an experiment in which we requested appointments by telephone for different insurance statuses in regions with varying levels of supply from 908 outpatient specialist practices in Germany before and during the COVID-19 pandemic. Data from 589 collected appointments were analyzed using a linear mixed effect model.ResultsThe data analysis revealed two main counteracting effects. First, the average waiting time has decreased for both patients with statutory (mandatory public health insurance) and private health insurance. Inequalities in access to healthcare, however, remained and were based on patients’ insurance status and the regional level of supply. Second, the probability of not receiving an appointment at all significantly increased during the pandemic.ConclusionsPatient uncertainty due to the fear of a potential COVID-19 infection may have freed up capacities in physicians’ practices, resulting in a reduction of waiting times. At the same time, the exceptional situation caused by the pandemic may have led to uncertainty among physicians, who might thus have allocated appointments less frequently. To avoid worse health outcomes in the long term due to a lack of physician visits, policymakers and healthcare providers should focus more on regular care in the current COVID-19 pandemic.
The evolution of pelvic canal shape and rotational birth in humans
Authors: Stansfield Ekaterina , Fischer Barbara , Grunstra Nicole D. S. , Pouca Maria Villa , Mitteroecker Philipp 
Published: October 2021

Abstract
Background
The human foetus typically needs to rotate when passing through the tight birth canal because of the complex shape of the pelvis. In most women, the upper part, or inlet, of the birth canal has a round or mediolaterally oval shape, which is considered ideal for parturition, but it is unknown why the lower part of the birth canal has a pronounced anteroposteriorly oval shape.

Results
Here, we show that the shape of the lower birth canal affects the ability of the pelvic floor to resist the pressure exerted by the abdominal organs and the foetus. Based on a series of finite element analyses, we found that the highest deformation, stress, and strain occur in pelvic floors with a circular or mediolaterally oval shape, whereas an anteroposterior elongation increases pelvic floor stability.

Conclusions
This suggests that the anteroposterior oval outlet shape is an evolutionary adaptation for pelvic floor support. For the pelvic inlet, by contrast, it has long been assumed that the mediolateral dimension is constrained by the efficiency of upright locomotion. But we argue that the mediolateral elongation has evolved because of the limits on the anteroposterior diameter imposed by upright posture. We show that an anteroposteriorly deeper inlet would require greater pelvic tilt and lumbar lordosis, which compromises spine health and the stability of upright posture. These different requirements of the pelvic inlet and outlet likely have led to the complex shape of the pelvic canal and to the evolution of rotational birth characteristic of humans.
Emerging roles of dysregulated adenosine homeostasis in brain disorders with a specific focus on neurodegenerative diseases
Authors: Chang Ching-Pang , Wu Kuo-Chen , Lin Chien-Yu , Chern Yijuang 
Published: October 2021

AbstractIn modern societies, with an increase in the older population, age-related neurodegenerative diseases have progressively become greater socioeconomic burdens. To date, despite the tremendous effort devoted to understanding neurodegenerative diseases in recent decades, treatment to delay disease progression is largely ineffective and is in urgent demand. The development of new strategies targeting these pathological features is a timely topic. It is important to note that most degenerative diseases are associated with the accumulation of specific misfolded proteins, which is facilitated by several common features of neurodegenerative diseases (including poor energy homeostasis and mitochondrial dysfunction). Adenosine is a purine nucleoside and neuromodulator in the brain. It is also an essential component of energy production pathways, cellular metabolism, and gene regulation in brain cells. The levels of intracellular and extracellular adenosine are thus tightly controlled by a handful of proteins (including adenosine metabolic enzymes and transporters) to maintain proper adenosine homeostasis. Notably, disruption of adenosine homeostasis in the brain under various pathophysiological conditions has been documented. In the past two decades, adenosine receptors (particularly A1and A2Aadenosine receptors) have been actively investigated as important drug targets in major degenerative diseases. Unfortunately, except for an A2Aantagonist (istradefylline) administered as an adjuvant treatment with levodopa for Parkinson’s disease, no effective drug based on adenosine receptors has been developed for neurodegenerative diseases. In this review, we summarize the emerging findings on proteins involved in the control of adenosine homeostasis in the brain and discuss the challenges and future prospects for the development of new therapeutic treatments for neurodegenerative diseases and their associated disorders based on the understanding of adenosine homeostasis.
Improving access to primary health care: a cross-case comparison based on an a priori program theory
Authors: Spooner Catherine , Lewis Virginia , Scott Cathie , Dahrouge Simone , Haggerty Jeannie , Russell Grant , Levesque Jean-Frederic , Dionne Emilie , Stocks Nigel , Harris Mark F. ,   IMPACT team
Published: October 2021

Abstract
Background
Inequitable access to primary health care (PHC) remains a problem for most western countries. Failure to scale up effective interventions has been due, in part, to a failure to share the logic and essential elements of successful programs. The aim of this paper is to describe what we learned about improving access to PHC for vulnerable groups across multiple sites through use of a common theory-based program logic model and a common evaluation approach. This was the IMPACT initiative.

Methods
IMPACT’s evaluation used a mixed methods design with longitudinal (pre and post) analysis of six interventions. The analysis for this paper included four of the six sites that met study criteria. These sites were located in Canada (Alberta, Quebec and Ontario) and Australia (New South Wales). Using the overarching logic model, unexpected findings were reviewed, and alternative explanations were considered to understand how the mechanisms of each intervention may have contributed to results.

Results
Each site addressed their local access problem with different strategies and from different starting points. All sites observed changes in patient abilities to access PHC and provider access capabilities. The combination of intended and observed consequences for consumers and providers was different at each site, but all sites achieved change in both consumer ability and provider capability, even in interventions where there was no activity targeting provider behaviors.

Discussion
The model helped to identify, explore and synthesize intended and unintended consequences of four interventions that appeared to have more differences than similarities. Similar outcomes for different interventions and multiple impacts of each intervention on abilities were observed, implying complex causal pathways.

Conclusions
All the interventions were a low-cost incremental attempt to address unmet health care needs of vulnerable populations. Change is possible; sustaining change may be more challenging. Access to PHC requires attention to both patient abilities and provider characteristics. The logic model proved to be a valuable heuristic tool for defining the objectives of the interventions, evaluating their impacts, and learning from the comparison of ‘cases’.
Crosstalk between cancer-associated fibroblasts and immune cells in the tumor microenvironment: new findings and future perspectives
Authors: Mao Xiaoqi , Xu Jin , Wang Wei , Liang Chen , Hua Jie , Liu Jiang , Zhang Bo , Meng Qingcai , Yu Xianjun , Shi Si 
Published: October 2021

AbstractCancer-associated fibroblasts (CAFs), a stromal cell population with cell-of-origin, phenotypic and functional heterogeneity, are the most essential components of the tumor microenvironment (TME). Through multiple pathways, activated CAFs can promote tumor growth, angiogenesis, invasion and metastasis, along with extracellular matrix (ECM) remodeling and even chemoresistance. Numerous previous studies have confirmed the critical role of the interaction between CAFs and tumor cells in tumorigenesis and development. However, recently, the mutual effects of CAFs and the tumor immune microenvironment (TIME) have been identified as another key factor in promoting tumor progression. The TIME mainly consists of distinct immune cell populations in tumor islets and is highly associated with the antitumor immunological state in the TME. CAFs interact with tumor-infiltrating immune cells as well as other immune components within the TIME via the secretion of various cytokines, growth factors, chemokines, exosomes and other effector molecules, consequently shaping an immunosuppressive TME that enables cancer cells to evade surveillance of the immune system. In-depth studies of CAFs and immune microenvironment interactions, particularly the complicated mechanisms connecting CAFs with immune cells, might provide novel strategies for subsequent targeted immunotherapies. Herein, we shed light on recent advances regarding the direct and indirect crosstalk between CAFs and infiltrating immune cells and further summarize the possible immunoinhibitory mechanisms induced by CAFs in the TME. In addition, we present current related CAF-targeting immunotherapies and briefly describe some future perspectives on CAF research in the end.
Prescription rate and treatment patterns for allergic rhinitis from 2010 to 2018 in South Korea: a retrospective study
Authors: Son Jaemin , Kim Eun-San , Choi Hee-seung , Ha In-Hyuk , Lee Donghyo , Lee Yoon Jae 
Published: October 2021

Abstract
Background
There has been little investigation on how guidelines for allergic rhinitis (AR) treatment are applied in current clinical practice. We aimed to analyze prescription trends and patterns for AR treatment according to patient characteristics over a 9-year period in Korea.

Methods
We used cross-sectional data from the Korean Health Insurance Review & Assessment Service National Patient Sample from 2010 to 2018. We analyzed 1,719,194 patients with AR as the principal diagnosis. Prescription rates of antihistamines, steroids, and other drugs; combination prescriptions; and first-choice prescriptions were analyzed.

Results
The prescription rate of first-generation antihistamines decreased over the years (2010: 29.13; 2018: 23.41). By contrast, the prescription rate of systemic steroids (2010: 23.60; 2018: 28.70), nasal steroids (2010: 9.70; 2018: 14.67), and leukotriene receptor antagonists (LTRAs) (2010: 11.13; 2018: 26.56) increased. The prescription rate of steroids was lower in patients aged 0–5 years and ≥ 65 years than in other age groups and that of LTRAs was the highest in patients aged 0–5 years. The rate of combination prescribing antihistamines and nasal steroids increased (2010: 7.99; 2018: 12.09). The rate of first-choice prescriptions with antihistamines and nasal steroids also increased (2010: 4.72; 2018: 7.24).

Conclusions
The results confirmed a decrease in antihistamine prescriptions, especially with first-generation, and an increase in steroid and LTRA prescriptions in patients with AR in Korea. Regarding prescription patterns, steroids were increasingly prescribed in combination with antihistamines. However, the trend was opposite in the 0–5 years and ≥ 65 years groups.
Quantitative proteomics by iTRAQ-PRM based reveals the new characterization for gout
Authors: Chen Guangqi , Cheng Jiafen , Yu Hanjie , Huang Xiao , Bao Hui , Qin Ling , Wang Ling , Song Yaxiang , Liu Xinying , Peng Ai 
Published: October 2021

Abstract
Background
Gout is a common and complex form of immunoreactive arthritis based on hyperuricemia, while the symptoms would turn to remission or even got worse. So, it is hard to early identify whether an asymptomatic hyperuricemia (AHU) patient will be susceptible to get acute gout attack and it is also hard to predict the process of gout remission to flare. Here, we report that the plasma proteins profile can distinguish among acute gout (AG), remission of gout (RG), AHU patients, and healthy controls.

Methods
We established an isobaric tags for relative and absolute quantification (iTRAQ) and parallel reaction monitoring (PRM) based method to measure the plasma proteins for AG group (n = 8), RG group (n = 7), AHU group (n = 7) and healthy controls (n = 8).

Results
Eleven differentially expressed proteins such as Histone H2A, Histone H2B, Thrombospondin-1 (THBS1), Myeloperoxidase (MPO), Complement C2, Complement component C8 beta chain (C8B), Alpha-1-acid glycoprotein 1 (ORM1), Inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4), Carbonic anhydrase 1 (CA1), Serum albumin (ALB) and Multimerin-1 (MMRN1) were identified. Histone H2A, Histone H2B and THBS1 might be the strongest influential regulator to maintain the balance and stability of the gout process. The complement and coagulation cascades is one of the main functional pathways in the mechanism of gout process.

Conclusions
Histone H2A, Histone H2B and THBS1 are potential candidate genes for novel biomarkers in discriminating gout attack from AHU or RG, providing new theoretical insights for the prognosis, treatment, and management of gout process.

Trial registration
This study is not a clinical trial.
Diabetes free life expectancy and years of life lost associated with type 2 diabetes: projected trends in Germany between 2015 and 2040
Authors: Tönnies Thaddäus , Baumert Jens , Heidemann Christin , von der Lippe Elena , Brinks Ralph , Hoyer Annika 
Published: October 2021

Abstract
Background
Type 2 diabetes (T2D) causes substantial disease burden and is projected to affect an increasing number of people in coming decades. This study provides projected estimates of life years free of type 2 diabetes (T2D) and years of life lost ($${\mathrm{YLL}}$$
YLL
) associated with T2D for Germany in the years 2015 and 2040.

Methods
Based on an illness-death model and the associated mathematical relation between prevalence, incidence and mortality, we projected the prevalence of diagnosed T2D using currently available data on the incidence rate of diagnosed T2D and mortality rates of people with and without diagnosed T2D. Projection of prevalence was achieved by integration of a partial differential equation, which governs the illness-death model. These projected parameters were used as input values to calculate life years free of T2D and $${\mathrm{YLL}}$$
YLL
associated with T2D for the German population aged 40 to 100 years in the years 2015 and 2040, while accounting for different assumptions on future trends in T2D incidence and mortality.

Results
Assuming a constant incidence rate, women and men at age 40 years in 2015 will live approximately 38 years and 33 years free of T2D, respectively. Up to the year 2040, these numbers are projected to increase by 1.0 years and 1.3 years. Assuming a decrease in T2D-associated excess mortality of 2% per year, women and men aged 40 years with T2D in 2015 will be expected to lose 1.6 and 2.7 years of life, respectively, compared to a same aged person without T2D. In 2040, these numbers would reduce by approximately 0.9 years and 1.6 years. This translates to 10.8 million and 6.4 million $${\mathrm{YLL}}$$
YLL
in the German population aged 40–100 years with prevalent T2D in 2015 and 2040, respectively.

Conclusions
Given expected trends in mortality and no increase in T2D incidence, the burden due to premature mortality associated with T2D will decrease on the individual as well as on the population level. In addition, the expected lifetime without T2D is likely to increase. However, these trends strongly depend on future improvements of excess mortality associated with T2D and future incidence of T2D, which should motivate increased efforts of primary and tertiary prevention.
Zinc-mediated activation of CREB pathway in proliferation of pulmonary artery smooth muscle cells in pulmonary hypertension
Authors: Xiao Genfa , Lian Guili , Wang Tingjun , Chen Weixiao , Zhuang Wei , Luo Li , Wang Huajun , Xie Liangdi 
Published: October 2021

Abstract
Background
Transcription factor CREB is involved in the development of pulmonary hypertension (PH). However, little is known about the role and regulatory signaling of CREB in PH.

Methods
A series of techniques, including bioinformatics methods, western blot, cell proliferation and luciferase reporter assay were used to perform a comprehensive analysis of the role and regulation of CREB in proliferation of pulmonary artery smooth muscle cells (PASMCs) in PH.

Results
Using bioinformatic analysis of the differentially expressed genes (DEGs) identified in the development of monocrotaline (MCT)- and hypoxia-induced PH, we found the overrepresentation of CRE-containing DEGs. Western blot analysis revealed a sustained increase in total- and phosphorylated-CREB in PASMCs isolated from rats treated with MCT. Similarly, an enhanced and prolonged serum-induced CREB phosphorylation was observed in hypoxia-pretreated PASMCs. The sustained CREB phosphorylation in PASMCs may be associated with multiple protein kinases phosphorylated CREB. Additionally, hierarchical clustering analysis showed reduced expression of the majority of CREB phosphatases in PH, including regulatory subunits of PP2A, Ppp2r2c and Ppp2r3a. Cell proliferation analysis showed increased PASMCs proliferation in MCT-induced PH, an effect relied on CREB-mediated transcriptional activity. Further analysis revealed the raised intracellular labile zinc possibly from ZIP12 was associated with reduced phosphatases, increased CREB-mediated transcriptional activity and PASMCs proliferation.

Conclusions
CREB pathway was overactivated in the development of PH and contributed to PASMCs proliferation, which was associated with multiple protein kinases and/or reduced CREB phosphatases and raised intracellular zinc. Thus, this study may provide a novel insight into the CREB pathway in the pathogenesis of PH.