bluuebunny/crossref_metadata_2025_split huggingface dataset:
Attributes of primary health care in Mato Grosso do Sul state: PCAT-Brazil paired for users and health professionals, 2018
Authors: Bomfim Rafael Aiello , Leite Hazelelponi Querã Naumann Cerqueira , Zafalon Edilson José , De-Carli Alessandro Diogo , Santos Mara Lisiane de Moraes dos 
Published: July 2022

Abstract
Objective
The objective of the present study was to analyse the quality of adults and older adults health care in Primary Health Care (PHC) services in the State of Mato Grosso do Sul, 2018.

Methods
A quantitative survey was carried out in which the municipalities participating in the study included the four macro-regions following the Director Regional Plan (DRP). In this study, the quality of care was verified using the validated version of the PCAT-Br for adult and older adults users over 18 years of age and professionals. The professional’s and users’ views were compared between PHC attributes in the State of Mato Grosso do Sul. We performed the paired student t-test. STATA v.14.2 software (College Station, TX, USA) was used for the analyses. Sensitivity analysis was done to compare socio-demographic characteristics.

Results
Eight hundred twenty-five users and 424 professionals participated in the study. According to users, the Accessibility attribute had the worst performance in all macro-regions (mean score PCAT = 3.58). There were significant differences between the perception of users and professionals (PCAT = 5.32 for users and PCAT = 7.11 for professionals) in all attributes evaluated.

Conclusions
There was a difference in users’ and professionals’ perceptions between PHC attributes. Therefore, it is necessary to strengthen PHC care networks in the State, mainly considering the users’ perspectives.
Severe inflammation in new-borns induces long-term cognitive impairment by activation of IL-1β/KCC2 signaling during early development
Authors: Zhang Donghang , Yang Yujiao , Yang Yaoxin , Liu Jin , Zhu Tao , Huang Han , Zhou Cheng 
Published: July 2022

Abstract
Background
Neonatal sepsis can induce long-term cognitive impairment in adolescence or adulthood, but the underlying molecular mechanism is not fully understood. The expression of K+-Cl– co-transporter 2 (KCC2) plays a pivotal role in the GABAergic shift from depolarizing to hyperpolarizing during early postnatal development. In this study, we aimed to determine whether neonatal severe inflammation-induced cognitive impairment was associated with the expression of KCC2 during early development.

Methods
Neonatal severe inflammation was established by intraperitoneal injection of high dose lipopolysaccharide (LPS, 1 mg kg–1) in postnatal day 3 (P3) rats. The Morris water maze task and fear conditioning test were used to investigate long-term cognitive functions. ELISA, RT-PCR and Western blotting were used to examine the expression levels of proinflammatory cytokines and KCC2. Perforated patch-clamping recordings were used to determine the GABAergic shift.

Results
Neonatal severe inflammation led to long-term cognitive impairment in rats. Meanwhile, sustained elevation of interleukin-1 beta (IL-1β) levels was found in the hippocampus until P30 after LPS injection. Elevated expression of KCC2 and hyperpolarized GABA reversal potential (EGABA) were observed in CA1 hippocampal pyramidal neurons from the P7-P10 and P14-P16 rats after LPS injection. Specific knockdown of IL-1β mRNA expression rescued the elevated expression of KCC2 and the hyperpolarized EGABA at P7-P10 and P14-P16. Accordingly, specific knockdown of IL-1β or KCC2 expression improved the cognitive impairment induced by neonatal severe inflammation.

Conclusions
Sustained elevation of IL-1β in the hippocampus may induce cognitive impairment by upregulation of KCC2 during early development.
Increased blood-based intratumor heterogeneity (bITH) is associated with unfavorable outcomes of immune checkpoint inhibitors plus chemotherapy in non-small cell lung cancer
Authors: Zhou Juan , Bao Minwei , Gao Guanghui , Cai Yiran , Wu Lihong , Lei Lei , Zhao Jing , Ji Xianxiu , Huang Ying , Su Chunxia 
Published: July 2022

Abstract
Background
The combination of immune checkpoint inhibitors (ICIs) and chemotherapy has been the standard first-line treatment for advanced non-small cell lung cancer (NSCLC) patients with driver-gene negative. However, efficacy biomarkers for ICIs-based combination therapy are lacking. We aimed to identify potential factors associated with outcomes of ICIs plus chemotherapy at baseline and dynamic changes in peripheral blood.

Methods
We collected plasma samples of 51 advanced NSCLC patients without EGFR/ALK/ROS1 alteration at baseline and/or after two treatment cycles of ICIs plus chemotherapy. A blood-based intratumor heterogeneity (bITH) score was calculated based on the allele frequencies of somatic mutations using a 520-gene panel. bITH-up was defined as a ≥ 10% increase in bITH score from baseline, with a second confirmatory measurement after treatment.

Results
At baseline, the number of metastatic organs and lung immune prognostic index (LIPI) were significantly associated with shorter progression-free survival (PFS) of ICIs plus chemotherapy, while bITH and other common molecular biomarkers, including ctDNA level, blood-based tumor mutational burden (bTMB), and PD-L1 expression, had no effect on PFS. LRP1B mutation at baseline was significantly associated with favorable outcomes to ICIs plus chemotherapy. There were 37 patients who had paired samples at baseline and after two cycles of treatment, with the median interval of 53 days. Intriguingly, patients with bITH-up had significant shorter PFS (HR, 4.92; 95% CI, 1.72–14.07; P = 0.001) and a lower durable clinical benefit rate (0 vs 41.38%, P = 0.036) than those with bITH-stable or down. Case studies indicated that bITH was promising to predict disease progression.

Conclusions
The present study is the first to report that increased bITH is associated with unfavorable outcomes of ICIs plus chemotherapy in advanced NSCLC patients.
Severe acute hepatitis of unknown aetiology in children—what is known?
Authors: Khader Susan , Foster Isabel , Dagens Andrew , Norton Alice , Sigfrid Louise 
Published: July 2022

AbstractThe ongoing investigations into clusters of children affected by severe acute hepatitis of unknown aetiology have put our global capacity for a coordinated, effective response to the test. The global health community have rapidly convened to share data and inform the response. In the UK, where most cases were initially identified, a coordinated public health and clinical research response was rapidly initiated. Since then, cases have been reported from other countries, predominantly from higher-income countries. While agencies are keeping an open mind to the cause, the working hypothesis and case notifications raise important questions about our capacity to detect emerging cases in lower-resourced settings with a recognised lack of access to diagnostics even for commonly circulating viruses such as hepatitis A. The limited capability to generate integrated global pathogen surveillance data is a challenge for the outbreak investigations, highlighting an urgent need to strengthen access to diagnostics, with a focus on lower-resourced settings, to improve the capacity to detect emerging diseases to inform care and to improve outcomes and outbreak control.
Mechanosensitive Piezo channels mediate the physiological and pathophysiological changes in the respiratory system
Authors: Xiong Huaiyu , Yang Jing , Guo Jun , Ma Aijia , Wang Bo , Kang Yan 
Published: July 2022

AbstractMechanosensitive Piezo ion channels were first reported in 2010 in a mouse neuroblastoma cell line, opening up a new field for studying the composition and function of eukaryotic mechanically activated channels. During the past decade, Piezo ion channels were identified in many species, such as bacteria, Drosophila, and mammals. In mammals, basic life activities, such as the sense of touch, proprioception, hearing, vascular development, and blood pressure regulation, depend on the activation of Piezo ion channels. Cumulative evidence suggests that Piezo ion channels play a major role in lung vascular development and function and diseases like pneumonia, pulmonary hypertension, apnea, and other lung-related diseases. In this review, we focused on studies that reported specific functions of Piezos in tissues and emphasized the physiological and pathological effects of their absence or functional mutations on the respiratory system.
Influence of diabetes on mortality and ICD therapies in ICD recipients: a systematic review and meta-analysis of 162,780 patients
Authors: Liu Hualong , Hu Jinzhu , Zhuo Wen , Wan Rong , Hong Kui 
Published: July 2022

Abstract
Background
The influence of diabetes on the mortality and risk of implantable cardioverter defibrillator (ICD) therapies is still controversial, and a comprehensive assessment is lacking. We performed this systematic review and meta-analysis to address this controversy.

Methods
We systematically searched the PubMed, Embase, Web of Science and Cochrane Library databases to collect relevant literature. Fixed and random effects models were used to estimate the hazard ratio (HR) with 95% CIs.

Results
Thirty-six articles reporting on 162,780 ICD recipients were included in this analysis. Compared with nondiabetic ICD recipients, diabetic ICD recipients had higher all-cause mortality (HR = 1.45, 95% CI 1.36–1.55). The subgroup analysis showed that secondary prevention patients with diabetes may suffer a higher risk of all-cause mortality (HR = 1.89, 95% CI 1.56–2.28) (for subgroup analysis, P = 0.03). Cardiac mortality was also higher in ICD recipients with diabetes (HR = 1.68, 95% CI 1.35–2.08). However, diabetes had no significant effect on the risks of ICD therapies, including appropriate or inappropriate therapy, appropriate or inappropriate shock and appropriate anti-tachycardia pacing (ATP). Diabetes was associated with a decreased risk of inappropriate ATP (HR = 0.56, 95% CI 0.39–0.79).

Conclusion
Diabetes is associated with an increased risk of mortality in ICD recipients, especially in the secondary prevention patients, but does not significantly influence the risks of ICD therapies, indicating that the increased mortality of ICD recipients with diabetes may not be caused by arrhythmias. The survival benefits of ICD treatment in diabetes patients are limited.
Toxic metals in the regulation of epithelial–mesenchymal plasticity: demons or angels?
Authors: Chen Xu-Li , Xu Yan-Ming , Lau Andy T. Y. 
Published: July 2022

AbstractEpithelial cells can trans-differentiate into motile mesenchymal cells through a dynamic process known as epithelial–mesenchymal transition (EMT). EMT is crucial in embryonic development and wound healing but also contributes to human diseases such as organ fibrosis and cancer progression. Heavy metals are environmental pollutants that can affect human health in various ways, including causing cancers. The cytotoxicity and carcinogenicity of heavy metals are complex, and studies have demonstrated that some of these metals can affect the progress of EMT. Here, we focus on reviewing the roles of six environmentally common toxic metals concerning EMT: arsenic (AS), cadmium (Cd), cobalt (Co), chromium (Cr), nickel (Ni), and copper (Cu). Noteworthily, the effects of these elements on EMT may vary according to the form, dose, and exposure time; the dual role of heavy metals (e.g., AS, Cd, and Cu) on EMT is also observed, in which, sometimes they can promote while sometimes inhibit the EMT process. Given the vast number of toxicologically relevant metals that exist in nature, we believe a comprehensive understanding of their effects on EMT is required to dictate in what circumstances these metals act more likely as demons or angels.
Qualitative study on the use and maintenance of long-lasting insecticidal nets (LLINs) in Bouaké (Côte d’Ivoire), 17 months after the last mass distribution campaign
Authors: N’Guessan Gnagoran Kouakou Daniel , Coulibaly Fangala Hamidou , Barreaux Antoine Marc Gaby , Yapo Roseline Josée , Adou Kouassi Arsène , Tia Emmanuel , Fournet Florence 
Published: July 2022

Abstract
Background
The use of long-lasting insecticide-treated nets (LLINs) is one of the main malaria prevention method promoted by the World Health Organization (WHO) in Côte d'Ivoire. LLIN-coverage has reached 95% since 2015 and nearly 16 million LLINs were distributed in 2017. Despite these efforts, malaria incidence at the national level remains high (120‰ in 2012 to 164‰ in 2017) although this could be partly explained by increased screening efforts. This study aimed at determining what preventative measures were used against mosquito bites, as well as LLIN maintenance practices used by the inhabitants of the city of Bouaké, capital city of the Gbêkê region with a malaria incidence of 257‰ in 2017.

Methods
A descriptive qualitative investigation took place in Bouaké, in four neighbourhoods that were selected through purposive sampling based on their social composition. Data were collected using an interview guide based on convenience sampling.

Results
The results of the study reveal that LLINs are the most reported used malaria prevention measure (66.4%). Environmental health (28.8%) came second in their declarations, smoke coils (23.5%) third and aerosol cans (18.8%) last. The percentage of respondents who answered that they had slept under an LLIN the previous night was 53%. 57.7% reported that they wash their LLINs, 12.1% that they do not wash them, and 4% that they replace dirty LLINs with new ones. The LLINs washing methods described by the respondents did not comply with the WHO recommendations and there was no mention of LLINs repairs.

Conclusion
Despite mass distributions of LLINs in Côte d'Ivoire, this key malaria control tool remains under-used by the population. Regarding LLIN maintenance, more than half of the population reports that they wash their nets while not complying with recommended practices or repairing them.
Polarization disorder of decidual NK cells in unexplained recurrent spontaneous abortion revealed by single-cell transcriptome analysis
Authors: Pan Dingchen , Liu Qian , Du Le , Yang Yang , Jiang Guojing 
Published: July 2022

Abstract
Background
Unexplained recurrent spontaneous abortion (URSA) is one of the most common diseases in pregnancy and is mainly caused by immune disorders. The foetus is similar to semiallogeneic maternal tissue, so the balance of immune tolerance must be dynamically maintained during pregnancy. Decidual natural killer (dNK) cells primarily mediate the immune tolerance microenvironment at the maternal–fetal interface. By using single-cell RNA sequencing (scRNA-seq) and high-throughput transcriptome sequencing analysis, we explored the characteristic distribution of dNK cells in URSA patients.

Methods
Control maternal–fetal interface tissue (from normal pregnant women, n = 3) and case maternal–fetal interface tissue (from patients with URSA, n = 3) samples were analysed by scRNA-seq and high-throughput transcriptome sequencing.

Results
By scRNA-seq, we demonstrated the maturation process of the transition of dNK cells from cytotoxic characteristics to immune tolerance in transcriptome analysis. Moreover, compared with normal pregnant women, serious disturbances in the polarization process of dNK cells were found in URSA. Simultaneously, the transcriptional level of the extracellular matrix (ECM) in URSA patients showed a significant decrease. The dNK cells interacted with extravillous trophoblasts to achieve immune-tolerant polarization.

Conclusions
Insufficient expression of KIRs during dNK cell differentiation might be a key reason why polarized dNK cells still had high cytotoxic reactivity in URSA patients. Abnormal expression of ECM may affect the interaction of dNK cells with EVTs, making dNK cells immature. Both resulted in maternal immune intolerance to the foetus during pregnancy.
Financial risk protection from out-of-pocket health spending in low- and middle-income countries: a scoping review of the literature
Authors: Rahman Taslima , Gasbarro Dominic , Alam Khurshid 
Published: July 2022

AbstractBackgroundFinancial risk protection (FRP), defined as households’ access to needed healthcare services without experiencing undue financial hardship, is a critical health systems target, particularly in low- and middle-income countries (LMICs). Given the remarkable growth in FRP literature in recent times, we conducted a scoping review of the literature on FRP from out-of-pocket (OOP) health spending in LMICs. The objective was to review current knowledge, identify evidence gaps and propose future research directions.MethodsWe followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines to conduct this scoping review. We systematically searched PubMed, Scopus, ProQuest and Web of Science in July 2021 for literature published since 1 January 2015. We included empirical studies that used nationally representative data from household surveys to measure the incidence of at least one of the following indicators: catastrophic health expenditure (CHE), impoverishment, adoption of strategies to cope with OOP expenses, and forgone care for financial reasons. Our review covered 155 studies and analysed the geographical focus, data sources, methods and analytical rigour of the studies. We also examined the level of FRP by disease categories (all diseases, chronic illnesses, communicable diseases) and the effect of health insurance on FRP.ResultsThe extant literature primarily focused on India and China as research settings. Notably, no FRP study was available on chronic illness in any low-income country (LIC) or on communicable diseases in an upper-middle-income country (UMIC). Only one study comprehensively measured FRP by examining all four indicators. Most studies assessed (lack of) FRP as CHE incidence alone (37.4%) or as CHE and impoverishment incidence (39.4%). However, the LMIC literature did not incorporate the recent methodological advances to measure CHE and impoverishment that address the limitations of conventional methods. There were also gaps in utilizing available panel data to determine the length of the lack of FRP (e.g. duration of poverty caused by OOP expenses). The current estimates of FRP varied substantially among the LMICs, with some of the poorest countries in the world experiencing similar or even lower rates of CHE and impoverishment compared with the UMICs. Also, health insurance in LMICs did not consistently offer a higher degree of FRP.ConclusionThe literature to date is unable to provide a reliable representation of the actual level of protection enjoyed by the LMIC population because of the lack of comprehensive measurement of FRP indicators coupled with the use of dated methodologies. Future research in LMICs should address the shortcomings identified in this review.
Reprogramming of glutamine metabolism and its impact on immune response in the tumor microenvironment
Authors: Ma Guofeng , Zhang Zhilei , Li Peng , Zhang Zhao , Zeng Manqin , Liang Zhijuan , Li Dan , Wang Liping , Chen Yuanbin , Liang Ye , Niu Haitao 
Published: July 2022

AbstractMetabolic reprogramming and immune escape play a major role in tumorigenesis. Increasing number of studies have shown that reprogramming of glutamine metabolism is a putative determinant of the anti-tumor immune response in the tumor microenvironment (TME). Usually, the predatory uptake of glutamine by tumor cells in the TME results in the limited utilization of glutamine by immune cells and affects the anti-tumor immune response. The cell-programmed glutamine partitioning also affects the anti-tumor immune response. However, the reprogramming of glutamine metabolism in tumors modulates immune escape by regulating tumor PD-L1 expression. Likewise, the reprogramming of glutamine metabolism in the immune cells also affects their immune function. Additionally, different types of glutamine metabolism inhibitors extensively regulate the immune cells in the TME while suppressing tumor cell proliferation. Herein, we discuss how metabolic reprogramming of tumor and immune cells regulates anti-tumor immune responses, as well as functional changes in different immune cells in the context of targeting tumor glutamine metabolism, which can better explain the potential of targeting glutamine metabolism in combination with immunotherapy for cancer.
The health, cost and equity impacts of restrictions on the advertisement of high fat, salt and sugar products across the transport for London network: a health economic modelling study
Authors: Thomas Chloe , Breeze Penny , Cummins Steven , Cornelsen Laura , Yau Amy , Brennan Alan 
Published: July 2022

Abstract
Background
Policies aimed at restricting the marketing of high fat, salt and sugar products have been proposed as one way of improving population diet and reducing obesity. In 2019, Transport for London implemented advertising restrictions on high fat, salt and sugar products. A controlled interrupted time-series analysis comparing London with a north of England control, suggested that the advertising restrictions had resulted in a reduction in household energy purchases. The aim of the study presented here was to estimate the health benefits, cost savings and equity impacts of the Transport for London policy using a health economic modelling approach, from an English National Health Service and personal social services perspective.

Methods
A diabetes prevention microsimulation model was modified to incorporate the London population and Transport for London advertising intervention. Conversion of calorie to body mass index reduction was mediated through an approximation of a mathematical model estimating weight loss. Outcomes gathered included incremental obesity, long-term diabetes and cardiovascular disease events, quality-adjusted life years, healthcare costs saved and net monetary benefit. Slope index of inequality was calculated for proportion of people with obesity across socioeconomic groups to assess equity impacts.

Results
The results show that the Transport for London policy was estimated to have resulted in 94,867 (4.8%) fewer individuals with obesity, and to reduce incidence of diabetes and cardiovascular disease by 2,857 and 1,915 cases respectively within three years post intervention. The policy would produce an estimated 16,394 additional quality-adjusted life-years and save £218 m in NHS and social care costs over the lifetime of the current population. Greater benefits (e.g. a 37% higher gain in quality-adjusted life-years) were expected to accrue to individuals from the most socioeconomically deprived groups compared to the least deprived.

Conclusions
This analysis suggests that there are considerable potential health and economic gains from restricting the advertisement of high fat, salt and sugar products. The population health and economic impacts of the Transport for London advertising restrictions are likely to have reduced health inequalities in London.