bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tuberculosis—Learning the Impact of Nutrition (TB LION): protocol for an interventional study to decrease TB risk in household contacts
Authors: Cintron Chelsie , Narasimhan Prakash Babu , Locks Lindsey , Babu Senbagavalli , Sinha Pranay , Rajkumari Nonika , Kaipilyawar Vaishnavi , Bhargava Anurag , Maloomian Kimberly , Chandrasekaran Padma , Verma Sheetal , Joseph Noyal , Johnson W. Evan , Wanke Christine , Horsburgh C. Robert , Ellner Jerrold J. , Sarkar Sonali , Salgame Padmini , Lakshminarayanan Subitha , Hochberg Natasha S. 
Published: October 2021

Abstract
Background
Comorbidities such as undernutrition and parasitic infections are widespread in India and other tuberculosis (TB)-endemic countries. This study examines how these conditions as well as food supplementation and parasite treatment might alter immune responses to Mycobacterium tuberculosis (Mtb) infection and risk of progression to TB disease.

Methods
This is a 5-year prospective clinical trial at Jawaharlal Institute of Post Graduate Medical Education and Research in Puducherry, Tamil Nadu, India. We aim to enroll 760 household contacts (HHC) of adults with active TB in order to identify 120 who are followed prospectively for 2 years: Thirty QuantiFERON-TB Gold Plus (QFT-Plus) positive HHCs ≥ 18 years of age in four proposed groups: (1) undernourished (body mass index [BMI] < 18.5 kg/m2); (2) participants with a BMI ≥ 18.5 kg/m2 who have a parasitic infection (3) undernourished participants with a parasitic infection and (4) controls—participants with BMI ≥ 18.5 kg/m2 and without parasitic infection. We assess immune response at baseline and after food supplementation (for participants with BMI < 18.5 kg/m2) and parasite treatment (for participants with parasites). Detailed nutritional assessments, anthropometry, and parasite testing through polymerase chain reaction (PCR) and microscopy are performed. In addition, at serial time points, these samples will be further analyzed using flow cytometry and whole blood transcriptomics to elucidate the immune mechanisms involved in disease progression.

Conclusions
This study will help determine whether undernutrition and parasite infection are associated with gene signatures that predict risk of TB and whether providing nutritional supplementation and/or treating parasitic infections improves immune response towards this infection. This study transcends individual level care and presents the opportunity to benefit the population at large by analyzing factors that affect disease progression potentially reducing the overall burden of people who progress to TB disease.
Trial registration ClinicalTrials.gov; NCT03598842; Registered on July 26, 2018; https://clinicaltrials.gov/ct2/show/NCT03598842
A multicenter study of short-term changes in mental health emergency services use during lockdown in Kitchener-Waterloo, Ontario during the COVID-19 pandemic
Authors: Dainton Christopher , Donato-Woodger Simon , Chu Charlene H. 
Published: October 2021

Abstract
Background
The COVID-19 pandemic and subsequent lockdown measures have led to increasing mental health concerns in the general population. We aimed to assess the short-term impact of the pandemic lockdown on mental health emergency services use in the Kitchener-Waterloo region of Ontario, Canada.

Methods
We conducted an observational study during the 6-month period between March 5 and September 5, 2020 using National Ambulatory Care Reporting System metadata from mental health visits to three regional Emergency Departments (ED); mental health and substance related police calls; and calls to a regional mental health crisis telephone line, comparing volumes during the pandemic lockdown with the same period in 2019. Quasi-Poisson regressions were used to determine significant differences between numbers of each visit or call type during the lockdown period versus the previous year. Significant changes in ED visits, mental health diagnoses, police responses, and calls to the crisis line from March 5 to September 5, 2020 were examined using changepoint analyses.

Results
Involuntary admissions, substance related visits, mood related visits, situational crisis visits, and self-harm related mental health visits to the EDs were significantly reduced during the lockdown period compared to the year before. Psychosis-related and alcohol-related visits were not significantly reduced. Among police calls, suicide attempts were significantly decreased during the period of lockdown, but intoxication, assault, and domestic disputes were not significantly different. Mental health crisis telephone calls were significantly decreased during the lockdown period. There was a significant increase in weekly mental health diagnoses starting in the week of July 12 – July 18. There was a significant increase in crisis calls starting in the week of May 31 – June 6, the same week that many guidelines, such as gathering restrictions, were eased. There was a significant increase in weekly police responses starting in the week of June 14 – June 20.

Conclusions
Contrary to our hypothesis, the decrease in most types of mental health ED visits, mental health and substance-related police calls, and mental health crisis calls largely mirrored the overall decline in emergency services usage during the lockdown period. This finding is unexpected in the context of increased attention to acutely deteriorating mental health during the COVID-19 pandemic.
Supporting participation in paid work of cancer survivors and their partners in the Netherlands: protocol of the SusTained Employability in cancer Patients and their partnerS (STEPS) multi-centre randomized controlled trial and cohort study
Authors: Zegers Amber D. , Coenen Pieter , Bültmann Ute , Retèl Valesca , Kieffer Jacobien M. , van der Beek Allard J. , Duijts Saskia F. A. 
Published: October 2021

Abstract
Background
Many cancer survivors experience physical and/or psychosocial problems affecting return to work (RTW) and work retention. Current interventions on RTW lack evidence regarding effectiveness, while interventions for work retention are missing. Partners of cancer survivors may also experience work- and health-related outcomes; yet, these consequences are not well understood. Here, the protocol of the STEPS study is described. The study aims are to: 1) evaluate the (cost-)effectiveness of a rehabilitation program for RTW and work retention in cancer survivors, and 2) assess health- and work-related outcomes among cancer survivors’ partners.

Methods
In a multicentre Randomized Controlled Trial (RCT), 236 working-age cancer survivors with an employment contract will be randomly allocated to a usual care group or an intervention group receiving a multidisciplinary rehabilitation program, combining occupational therapy facilitating work retention (e.g., energy management and self-efficacy training) and reintegration consultation addressing work-related issues (e.g., RTW planning and discussing workplace or task modifications with the supervisor). Alongside the RCT, a prospective cohort study will be conducted among cancer survivors’ partners (n = 267). Participants in the RCT and cohort study will be asked to complete questionnaires at baseline, and after six and 12 months, assessing work- and health-related outcomes. Generalized estimating equations will be used to assess intervention’s effectiveness, compared to usual care, regarding primary (i.e., working hours per week) and secondary outcomes. Also economic and process evaluations will be performed. For the cohort study, logistic or linear regression modelling will be applied assessing work- and health-related outcomes (primary outcome: working hours) of cancer survivors’ partners, and what factors predict these outcomes.

Results
The study is planned to start in September 2021; results are expected in 2023.

Conclusion
Compared to usual care, the STEPS intervention is hypothesized to be (cost-)effective and the intervention could be a valuable addition to standard care helping cancer survivors to sustain employment. Further, it is expected that living with a cancer survivor has a substantial impact on work and health of partners, while specific groups of partners that are at particular risk for this impact are likely to be identified.

Trial registration
Dutch Trial Register (NTR;NL9094; 15-12-2020).
Achieving a “step change” in the tuberculosis epidemic through comprehensive community-wide intervention: a model-based analysis
Authors: Shrestha Sourya , Kendall Emily A. , Chang Rebekah , Joseph Roy , Kasaie Parastu , Gillini Laura , Fojo Anthony Todd , Campbell Michael , Arinaminpathy Nimalan , Dowdy David W. 
Published: October 2021

Abstract
Background
Global progress towards reducing tuberculosis (TB) incidence and mortality has consistently lagged behind the World Health Organization targets leading to a perception that large reductions in TB burden cannot be achieved. However, several recent and historical trials suggest that intervention efforts that are comprehensive and intensive can have a substantial epidemiological impact. We aimed to quantify the potential epidemiological impact of an intensive but realistic, community-wide campaign utilizing existing tools and designed to achieve a “step change” in the TB burden.

Methods
We developed a compartmental model that resembled TB transmission and epidemiology of a mid-sized city in India, the country with the greatest absolute TB burden worldwide. We modeled the impact of a one-time, community-wide screening campaign, with treatment for TB disease and preventive therapy for latent TB infection (LTBI). This one-time intervention was followed by the strengthening of the tuberculosis-related health system, potentially facilitated by leveraging the one-time campaign. We estimated the tuberculosis cases and deaths that could be averted over 10 years using this comprehensive approach and assessed the contributions of individual components of the intervention.

Results
A campaign that successfully screened 70% of the adult population for active and latent tuberculosis and subsequently reduced diagnostic and treatment delays and unsuccessful treatment outcomes by 50% was projected to avert 7800 (95% range 5450–10,200) cases and 1710 (1290–2180) tuberculosis-related deaths per 1 million population over 10 years. Of the total averted deaths, 33.5% (28.2–38.3) were attributable to the inclusion of preventive therapy and 52.9% (48.4–56.9) to health system strengthening.

Conclusions
A one-time, community-wide mass campaign, comprehensively designed to detect, treat, and prevent tuberculosis with currently existing tools can have a meaningful and long-lasting epidemiological impact. Successful treatment of LTBI is critical to achieving this result. Health system strengthening is essential to any effort to transform the TB response.
Degradation of epigallocatechin and epicatechin gallates by a novel tannase TanHcw from Herbaspirillum camelliae
Authors: Lei Jia , Zhang Yong , Ni Xuechen , Yu Xuejing , Wang Xingguo 
Published: October 2021

Abstract
Background
Herbaspirillum camelliae is a gram-negative endophyte isolated from the tea plant. Both strains WT00C and WT00F were found to hydrolyze epigallocatechin-3-gallate (EGCG) and epicatechin-3-gallate (ECG) to release gallic acid (GA) and display tannase activity. However, no tannase gene was annotated in the genome of H. camelliae WT00C.

Results
The 39 kDa protein, annotated as the prolyl oligopeptidase in the NCBI database, was finally identified as a novel tannase. Its gene was cloned, and the enzyme was expressed in E. coli and purified to homogeneity. Moreover, enzymatic characterizations of this novel tannase named TanHcw were studied. TanHcw was a secretary enzyme with a Sec/SPI signal peptide of 48 amino acids at the N-terminus, and it catalyzed the degradation of tannin, methyl gallate (MG), epigallocatechin-3-gallate (EGCG) and epicatechin-3-gallate (ECG). The optimal temperature and pH of TanHcw activities were 30 °C, pH 6.0 for MG and 40 °C, pH 7.0 for both EGCG and ECG. Na+, K+ Mn2+ and Triton-X100, Tween80 increased the enzyme activity of TanHcw, whereas Zn2+, Mg2+, Hg2+, EMSO, EDTA and β-mercaptoethanol inhibited enzyme activity. Km, kcat and kcat /Km of TanHcw were 0.30 mM, 37.84 s−1, 130.67 mM−1 s−1 for EGCG, 0.33 mM, 34.59 s−1, 105.01 mM−1 s−1 for ECG and 0.82 mM, 14.64 s−1, 18.17 mM−1 s−1 for MG, respectively.

Conclusion
A novel tannase TanHcw from H. camelliae has been identified and characterized. The biological properties of TanHcw suggest that it plays a crucial role in the specific colonization of H. camelliae in tea plants. Discovery of the tannase TanHcw in this study gives us a reasonable explanation for the host specificity of H. camelliae. In addition, studying the characteristics of this enzyme offers the possibility of further defining its potential in industrial application.
Licorice extract inhibits growth of non-small cell lung cancer by down-regulating CDK4-Cyclin D1 complex and increasing CD8+ T cell infiltration
Authors: Zhu Jinglin , Huang Ruifei , Yang Ruijie , Xiao Yue , Yan Jiangna , Zheng Chunli , Xiao Wei , Huang Chao , Wang Yonghua 
Published: October 2021

Abstract
Background
Targeting tumor microenvironment (TME) may provide therapeutic activity and selectivity in treating cancers. Therefore, an improved understanding of the mechanism by which drug targeting TME would enable more informed and effective treatment measures. Glycyrrhiza uralensis Fisch (GUF, licorice), a widely used herb medicine, has shown promising immunomodulatory activity and anti-tumor activity. However, the molecular mechanism of this biological activity has not been fully elaborated.

Methods
Here, potential active compounds and specific targets of licorice that trigger the antitumor immunity were predicted with a systems pharmacology strategy. Flow cytometry technique was used to detect cell cycle profile and CD8+ T cell infiltration of licorice treatment. And anti-tumor activity of licorice was evaluated in the C57BL/6 mice.

Results
We reported the G0/G1 growth phase cycle arrest of tumor cells induced by licorice is related to the down-regulation of CDK4-Cyclin D1 complex, which subsequently led to an increased protein abundance of PD-L1. Further, in vivo studies demonstrated that mitigating the outgrowth of NSCLC tumor induced by licorice was reliant on increased antigen presentation and improved CD8+ T cell infiltration.

Conclusions
Briefly, our findings improved the understanding of the anti-tumor effects of licorice with the systems pharmacology strategy, thereby promoting the development of natural products in prevention or treatment of cancers.
Analysing malaria events from 1840 to 2020: the narrative told through postage stamps
Authors: Brabin Bernard 
Published: October 2021

AbstractThe role played by postage stamps in the history of malaria control and eradication has largely gone unrecognized. Scientific investigators of malaria, especially Nobel laureates, were commemorated with special issues, but the work of the World Health Organization (WHO), which promoted an ambitious and global philatelic initiative in 1962 to support global eradication, is generally overlooked. This review examines the philatelic programme that helped to generate international commitment to the goal of malaria eradication in 1962 and established philatelic malaria icons that had worldwide recognition. Malaria-related postage stamps have continued to be issued since then, but the initial failure of malaria eradication and the changing goals of each new malaria programme, inevitably diluted their role. After the first Global Malaria Eradication Campaign was discontinued in 1969, few Nations released philatelic issues. Since the Spirit of Dakar Call for Action in 1996 a resurgence of postage stamp releases has occurred, largely tracking global malaria control initiatives introduced between 1996 and 2020. These releases were not co-ordinated by the WHO as before, were more commercialized and targeted stamp collectors, especially with attractive miniature sheets, often produced by photomontage. Having a different purpose, they demonstrated a much wider diversity in symbolism than the earlier stylized issues and at times, have been scientifically inaccurate. Nonetheless postage stamps greatly helped to communicate the importance of malaria control programmes to a wide audience and to some extent, have supported preventive health messages.
Assessing demographic access to hip replacement surgery in the United Kingdom: a systematic review
Authors: Ryan-Ndegwa Sebastian , Zamani Reza , Akrami Mohammad 
Published: October 2021

AbstractPersisting evidence suggests significant socioeconomic and sociodemographic inequalities in access to medical treatment in the UK. Consequently, a systematic review was undertaken to examine these access inequalities in relation to hip replacement surgery. Database searches were performed using MEDLINE, PubMed and Web of Science. Studies with a focus on surgical need, access, provision and outcome were of interest. Inequalities were explored in the context of sociodemographic characteristics, socioeconomic status (SES), geographical location and hospital-related variables. Only studies in the context of the UK were included. Screening of search and extraction of data were performed and 482 articles were identified in the database search, of which 16 were eligible. Eligible studies consisted of eight cross-sectional studies, seven ecological studies and one longitudinal study. Although socioeconomic inequality has somewhat decreased, lower SES patients and ethnic minority patients demonstrate increased surgical needs, reduced access and poor outcomes. Lower SES and Black minority patients were younger and had more comorbidities. Surgical need increased with age. Women had greater surgical need and provision than men. Geographical inequality had reduced in Scotland, but a north-south divide persists in England. Rural areas received greater provision relative to need, despite increased travel for care. In all, access inequalities remain widespread and policy change driven by research is needed.
AMPK promotes antitumor immunity by downregulating PD-1 in regulatory T cells via the HMGCR/p38 signaling pathway
Authors: Pokhrel Ram Hari , Acharya Suman , Ahn Jae-Hee , Gu Ye , Pandit Mahesh , Kim Jong-Oh , Park Yun-Yong , Kang Ben , Ko Hyun-Jeong , Chang Jae-Hoon 
Published: October 2021

Abstract
Background
AMP-activated protein kinase (AMPK) is a metabolic sensor that maintains energy homeostasis. AMPK functions as a tumor suppressor in different cancers; however, its role in regulating antitumor immunity, particularly the function of regulatory T cells (Tregs), is poorly defined.

Methods
AMPKα1fl/flFoxp3YFP-Cre, Foxp3YFP-Cre, Rag1−/−, and C57BL/6 J mice were used for our research. Flow cytometry and cell sorting, western blotting, immuno-precipitation, immuno-fluorescence, glycolysis assay, and qRT-PCR were used to investigate the role of AMPK in suppressing programmed cell death 1 (PD-1) expression and for mechanistic investigation.

Results
The deletion of the AMPKα1 subunit in Tregs accelerates tumor growth by increasing the expression of PD-1. Metabolically, loss of AMPK in Tregs promotes glycolysis and the expression of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), a key enzyme of the mevalonate pathway. Mechanistically, AMPK activates the p38 mitogen-activated protein kinase (MAPK) that phosphorylates glycogen synthase kinase-3β (GSK-3β), inhibiting the expression of PD-1 in Tregs.

Conclusion
Our study identified an AMPK regulatory mechanism of PD-1 expression via the HMGCR/p38 MAPK/GSK3β signaling pathway. We propose that the AMPK activator can display synergic antitumor effect in murine tumor models, supporting their potential clinical use when combined with anti-PD-1 antibody, anti-CTLA-4 antibody, or a HMGCR inhibitor.
Community health workers at the dawn of a new era: 8. Incentives and remuneration
Authors: Colvin Christopher J. , Hodgins Steve , Perry Henry B. 
Published: October 2021

Abstract
Background
This is the eighth in our series of 11 papers on “CHWs at the Dawn of a New Era”. Community health worker (CHW) incentives and remuneration are core issues that affect the performance of individual CHWs and the performance of the overall CHW programme. A better understanding of what motivates CHWs and a stronger awareness of the social justice dimensions of remuneration are essential in order to build stronger CHW programmes and to support the professionalization of the CHW workforce.

Methods
We provide examples of incentives that have been provided to CHWs and identify factors that motivate and demotivate CHWs. We developed our findings in this paper by synthesizing the findings of a recent review of CHW motivation and incentives in a wide variety of CHW programmes with detailed case study data about CHW compensation and incentives in 29 national CHW programmes.

Results
Incentives can be direct or indirect, and they can be complementary/demand-side incentives. Direct incentives can be financial or nonfinancial. Indirect incentives can be available through the health system or from the community, as can complementary, demand-side incentives. Motivation is sustained when CHWs feel they are a valued member of the health system and have a clear role and set of responsibilities within it. A sense of the “do-ability” of the CHW role is critical in maintaining CHW motivation. CHWs are best motivated by work that provides opportunities for personal growth and professional development, irrespective of the direct remuneration and technical skills obtained. Working and social relationships among CHWs themselves and between CHWs and other healthcare professionals and community members strongly shape CHW motivation.

Conclusion
Our findings support the recent guidelines for CHWs released by WHO in 2018 that call for CHWs to receive a financial package that corresponds to their job demands, complexity, number of hours worked, training, and the roles they undertake. The guidelines also call for written agreements that specify the CHW’s role and responsibilities, working conditions, remuneration, and workers’ rights.
Community health workers at the dawn of a new era: 1. Introduction: tensions confronting large-scale CHW programmes
Authors: Hodgins Stephen , Kok Maryse , Musoke David , Lewin Simon , Crigler Lauren , LeBan Karen , Perry Henry B. 
Published: October 2021

Abstract
Background
Community health worker (CHW) programmes are again receiving more attention in global health, as reflected in important recent WHO guidance. However, there is a risk that current CHW programme efforts may result in disappointing performance if those promoting and delivering them fail to learn from past efforts. This is the first of a series of 11 articles for a supplement entitled “Community Health Workers at the Dawn of a New Era”.

Methods
Drawing on lessons from case studies of large well-established CHW programmes, published literature, and the authors’ experience, the paper highlights major issues that need to be acknowledged to design and deliver effective CHW programmes at large scale. The paper also serves as an introduction to a set of articles addressing these issues in detail.

Results
The article highlights the diversity and complexity of CHW programmes, and offers insights to programme planners, policymakers, donors, and others to inform development of more effective programmes. The article proposes that be understood as actors within community health system(s) and examines five tensions confronting large-scale CHW programmes; the first two tensions concern the role of the CHW, and the remaining three, broader strategic issues:

What kind of an actor is the CHW? A lackey or a liberator? Provider of clinical services or health promoter?

Lay versus professional?

Government programme at scale or nongovernmental organization-led demonstration project?

Standardized versus tailored to context?

Vertical versus horizontal?

Conclusion
CHWs can play a vital role in primary healthcare, but multiple conditions need to be met for them to reach their full potential.