bluuebunny/crossref_metadata_2025_split huggingface dataset:
Willingness to pay for community based health insurance scheme and factors associated with it among households in rural community of South West Shoa Zone, Ethiopia
Authors: Negera Mebratu , Abdisa Desu 
Published: June 2022

Abstract
Background
Out-of-pocket payments are the major significant barrier in achieving universal health coverage, particularly in developing countries' rural communities. In 2011, the Ethiopian government launched a pilot community-based health insurance (CBHI) scheme with the goal of increasing access to modern health care services and providing financial security to households in the informal sector and rural areas. The main objective of this study is to estimate willingness to pay (WTP) for CBHI scheme and factors that influence it among rural households in the South West Shoa Zone.

Methods
A household-level cross-sectional study was conducted to examine the WTP for the CBHI scheme and factors associated with it in rural communities of South West Shoa Zone. The study used a sample of 400 rural households. Systematic random sampling was employed during household selection, and double-bounded contingent valuation method was used to estimate WTP for the CBHI scheme.

Results
About 65 percent of the households are willing to pay for CBHI scheme. Moreover, the study found that the households were willing to pay 255.55 Birr per year on average. The result of the study also revealed that amount of bid, household income, family size, household head's education, household health status, membership to community-based health insurance scheme, membership in any association, and awareness about the scheme are factors that are significantly associated with WTP for the scheme.

Conclusions
Households are willing to pay a higher price than the policy price. Therefore, setting a new premium that reflects households' willingness to pay is highly valuable to policymakers. Social capital and awareness about CBHI scheme play an important role in influencing WTP. Thus, the study suggests that local communities need to strengthen their social cohesion and solidarity. It is also necessary to create awareness about the CBHI’s benefits.
Evaluating the potential of third generation metagenomic sequencing for the detection of BRD pathogens and genetic determinants of antimicrobial resistance in chronically ill feedlot cattle
Authors: Freeman Claire N. , Herman Emily K. , Abi Younes Jennifer , Ramsay Dana E. , Erikson Nathan , Stothard Paul , Links Matthew G. , Otto Simon J. G. , Waldner Cheryl 
Published: June 2022

AbstractBackgroundBovine respiratory disease (BRD) is an important cause of morbidity and mortality and is responsible for most of the injectable antimicrobial use in the feedlot industry. Traditional bacterial culture can be used to diagnose BRD by confirming the presence of causative pathogens and to support antimicrobial selection. However, given that bacterial culture takes up to a week and early intervention is critical for treatment success, culture has limited utility for informing rapid therapeutic decision-making. In contrast, metagenomic sequencing has the potential to quickly resolve all nucleic acid in a sample, including pathogen biomarkers and antimicrobial resistance genes. In particular, third-generation Oxford Nanopore Technology sequencing platforms provide long reads and access to raw sequencing data in real-time as it is produced, thereby reducing the time from sample collection to diagnostic answer. The purpose of this study was to compare the performance of nanopore metagenomic sequencing to traditional culture and sensitivity methods as applied to nasopharyngeal samples from segregated groups of chronically ill feedlot cattle, previously treated with antimicrobials for nonresponsive pneumonia or lameness.ResultsBRD pathogens were isolated from most samples and a variety of different resistance profiles were observed across isolates. The sequencing data indicated the samples were dominated byMoraxella bovoculi, Mannheimia haemolytica, Mycoplasma dispar,andPasteurella multocida,and included a wide range of antimicrobial resistance genes (ARGs), encoding resistance for up to seven classes of antimicrobials. Genes conferring resistance to beta-lactams were the most commonly detected, while thetetHgene was detected in the most samples overall. Metagenomic sequencing detected the BRD pathogens of interest more often than did culture, but there was limited concordance between phenotypic resistance to antimicrobials and the presence of relevant ARGs.ConclusionsMetagenomic sequencing can reduce the time from sampling to results, detect pathogens missed by bacterial culture, and identify genetically encoded determinants of resistance. Increasing sequencing coverage of target organisms will be an essential component of improving the reliability of this technology, such that it can be better used for the surveillance of pathogens of interest, genetic determinants of resistance, and to inform diagnostic decisions.
Evaluation of the Pfs25-IMX313/Matrix-M malaria transmission-blocking candidate vaccine in endemic settings
Authors: Mulamba Charles , Williams Chris , Kreppel Katharina , Ouedraogo Jean Bosco , Olotu Ally I. 
Published: June 2022

AbstractMalaria control relies heavily on the use of anti-malarial drugs and insecticides against malaria parasites and mosquito vectors. Drug and insecticide resistance threatens the effectiveness of conventional malarial interventions; alternative control approaches are, therefore, needed. The development of malaria transmission-blocking vaccines that target the sexual stages in humans or mosquito vectors is among new approaches being pursued. Here, the immunological mechanisms underlying malaria transmission blocking, status of Pfs25-based vaccines are viewed, as well as approaches and capacity for first in-human evaluation of a transmission-blocking candidate vaccine Pfs25-IMX313/Matrix-M administered to semi-immune healthy individuals in endemic settings. It is concluded that institutions in low and middle income settings should be supported to conduct first-in human vaccine trials in order to stimulate innovative research and reduce the overdependence on developed countries for research and local interventions against many diseases of public health importance.
Collective analysis of the expression and prognosis for LEM-domain proteins in prostate cancer
Authors: He Tianzhen , Zhang Yulian , Li Xueyu , Liu Caihong , Zhu Guanqun , Yin Xinbao , Zhang Zongliang , Zhao Kai , Wang Zhenlin , Zhao Peng , Wang Ke 
Published: June 2022

Abstract
Background
Mammalian LEM-domain proteins (LEMs) are encoded by seven genes, including LAP2, EMD, LEMD1, LEMD2, LEMD3, ANKLE1, and ANKLE2. Though some LEMs were involved in various tumor progression, the expression and prognostic values of LEMs in prostate adenocarcinoma (PRAD) have yet to be analyzed.

Methods
Herein, we investigated the expression, survival data, and immune infiltration levels of LEMs in PRAD patients from ATCG, TIMER, LinkedOmics, and TISIDB databases. We also further validated the mRNA and protein expression levels of ANKLE1, EMD, and LEMD2 in human prostate tumor specimens by qPCR, WB, and IHC.

Results
We found that all LEM expressions, except for that of LAP2, were markedly altered in PRAD compared to the normal samples. Among all LEMs, only the expressions of ANKLE1, EMD, and LEMD2 were correlated with advanced tumor stage and survival prognosis in PRAD. Consistent with the predicted computational results, the mRNA and protein expression levels of these genes were markedly increased in the PRAD group. We then found that ANKLE1, EMD, and LEMD2 expressions were markedly correlated with immune cell infiltration levels. High ANKLE1, EMD, and LEMD2 expressions predicted a worse prognosis in PRAD based on immune cells. DNA methylation or/and copy number variations may contribute to the abnormal upregulation of ANKLE1, EMD, and LEMD2 in PRAD.

Conclusions
Taken together, this study implied that ANKLE1, EMD, and LEMD2 were promising prognosis predictors and potential immunotherapy targets for PRAD patients.
A first-in-human phase 1/2 study of FGF401 and combination of FGF401 with spartalizumab in patients with hepatocellular carcinoma or biomarker-selected solid tumors
Authors: Chan Stephen L. , Schuler Martin , Kang Yoon-Koo , Yen Chia-Jui , Edeline Julien , Choo Su Pin , Lin Chia-Chi , Okusaka Takuji , Weiss Karl-Heinz , Macarulla Teresa , Cattan Stéphane , Blanc Jean-Frederic , Lee Kyung-Hun , Maur Michela , Pant Shubham , Kudo Masatoshi , Assenat Eric , Zhu Andrew X. , Yau Thomas , Lim Ho Yeong , Bruix Jordi , Geier Andreas , Guillén-Ponce Carmen , Fasolo Angelica , Finn Richard S. , Fan Jia , Vogel Arndt , Qin Shukui , Riester Markus , Katsanou Vasiliki , Chaudhari Monica , Kakizume Tomoyuki , Gu Yi , Porta Diana Graus , Myers Andrea , Delord Jean-Pierre 
Published: June 2022

Abstract
Background
Deregulation of FGF19-FGFR4 signaling is found in several cancers, including hepatocellular carcinoma (HCC), nominating it for therapeutic targeting. FGF401 is a potent, selective FGFR4 inhibitor with antitumor activity in preclinical models. This study was designed to determine the recommended phase 2 dose (RP2D), characterize PK/PD, and evaluate the safety and efficacy of FGF401 alone and combined with the anti-PD-1 antibody, spartalizumab.

Methods
Patients with HCC or other FGFR4/KLB expressing tumors were enrolled. Dose-escalation was guided by a Bayesian model. Phase 2 dose-expansion enrolled patients with HCC from Asian countries (group1), non-Asian countries (group2), and patients with other solid tumors expressing FGFR4 and KLB (group3). FGF401 and spartalizumab combination was evaluated in patients with HCC.

Results
Seventy-four patients were treated in the phase I with single-agent FGF401 at 50 to 150 mg. FGF401 displayed favorable PK characteristics and no food effect when dosed with low-fat meals. The RP2D was established as 120 mg qd. Six of 70 patients experienced grade 3 dose-limiting toxicities: increase in transaminases (n = 4) or blood bilirubin (n = 2). In phase 2, 30 patients in group 1, 36 in group 2, and 20 in group 3 received FGF401. In total, 8 patients experienced objective responses (1 CR, 7 PR; 4 each in phase I and phase II, respectively). Frequent adverse events (AEs) were diarrhea (73.8%), increased AST (47.5%), and ALT (43.8%). Increase in levels of C4, total bile acid, and circulating FGF19, confirmed effective FGFR4 inhibition.
Twelve patients received FGF401 plus spartalizumab. RP2D was established as FGF401 120 mg qd and spartalizumab 300 mg Q3W; 2 patients reported PR.

Conclusions
At biologically active doses, FGF401 alone or combined with spartalizumab was safe in patients with FGFR4/KLB-positive tumors including HCC. Preliminary clinical efficacy was observed. Further clinical evaluation of FGF401 using a refined biomarker strategy is warranted.

Trial registration
NCT02325739.
Rheumatoid arthritis patients initiating rituximab with low number of previous bDMARDs failures may effectively reduce rituximab dose and experience fewer serious adverse events than patients on full dose: a 5-year cohort study
Authors: Bertsias Antonios , Avgoustidis Nestor , Papalopoulos Ioannis , Repa Argyro , Kougkas Nikolaos , Kalogiannaki Eleni , Bertsias Georgios , Flouri Irini , Sidiropoulos Prodromos 
Published: June 2022

Abstract

Background

Rituximab is used for the treatment of active rheumatoid arthritis. In the present study, we examined the long-term flare risk and safety of reduced doses of rituximab.

Patients-methods
This was a prospective, observational, single-center study of patients starting rituximab on standard dose (SD). Patients were switched to low dose (LD) (1 g every 6 months), based on the treating rheumatologist’s decision after having achieved sustained clinical responses, while the rest of the patients continued on standard dose (SD). During a 60-month period, we assessed (Kaplan–Meier survival analysis) the relapse rate (increase ≥ 1.2 in DAS28-ESR for ≥ 6 months) and discontinuations due to treatment failure in the low dose group, and we compared the incidence of serious adverse events (SAEs) between LD and SD groups.

Results
Out of 361 patients [females 83.4%, mean age 61.9 (10.6) years, seropositive 50.3%, median total comorbidities count 4], 81 patients (22.4%) entered LD in a median time of 24 months (95% CI 18–30 months). Seropositivity (OR 1.823), more than 2 previous bDMARDs failures (OR 0.428), and DAS28 < 4.88 at 6 months (OR 2.329) predicted the odds of entering LD (p < 0.05 for all). During 60 months of follow-up, only 7.5% of patients on LD relapsed. Patients on LD had significantly less SAEs and all-cause hospitalizations as compared to the SD group (p < 0.05 for all). Linear regression analysis showed that previous hospitalization while on bDMARDs (p < 0.0001), use of prednisolone > 5 mg/day while on rituximab (p < 0.0001), and a history of ≥ 2 previous csDMARDs (p = 0.041) predicted the risk of SAEs.

Conclusion
In a cohort of patients with established RA and significant comorbidities who taper rituximab after substantial initial disease activity improvement, a low rate of relapses and lower risk of SAEs compared to SD were recorded. Seropositivity, a lower number of previous bDMARDs use, and lower DAS28 at 6 months predicted the probability of entering the LD regimen.
Honey bee venom re-challenge during specific immunotherapy: prolonged cardio-pulmonary resuscitation allowed survival in a case of near fatal anaphylaxis
Authors: Micaletto Sara , Ruetzler Kurt , Bruesch Martin , Schmid-Grendelmeier Peter 
Published: June 2022

Abstract
Background
Specific immunotherapy for patients with honey bee hypersensitivity is commonly applied. Re-challenge with venom is performed to prove protection in individual cases.

Case presenation
We report a case of near fatal anaphylaxis with asystole for 24 min in a 35-years-old patient with mastocytosis after honey bee sting challenge, despite 5-years of specific immunotherapy. Successful cardio-pulmonary resuscitation was applied for 32 min.

Conclusion
This intervention demonstrates, that in anaphylaxis with cardio-vascular arrest, prolonged cardio-pulmonary resuscitation for up to 40 min may be appropriate to overcome the half-life of massively released histamine. Failure of specific immunotherapy was possibly due to sensitization to the allergen Api m10, potentially underrepresented in commercial honey bee venom extracts. Molecular analyses may provide additional clues to the potentially unsuccessful outcome of venom specific immunotherapy, especially in high-risk patients such as mastocytosis.
Flow cytometry optimizing the diagnostic approach in inborn errors of immunity: experience from Egypt
Authors: Meshaal Safa , EI Hawary Rabab , Eldash Alia , Erfan Aya , Abd Elaziz Dalia , Alkady Radwa , Lotfy Sohilla , Galal Nermeen , Boutros Jeannette , Elmarsafy Aisha 
Published: June 2022

Abstract
Background
Human inborn errors of immunity (IEI) are a group of inherited genetic disorders of the immune system. IEI Patients suffer from severe repeated infections, autoimmunity, lymphadenopathy and/or increased susceptibility to malignancies. IEI are due to absence, disproportion, or loss of function of immune cells; mostly inherited in autosomal recessive manner, hence are more common in countries with high rate of consanguinity. Definite diagnosis of IEI is achieved by genetic analysis, however it is not always available. Aim: to report on different IEI categories and impact of expanding the use of flow cytometry (FCM) in diagnosis, categorization and follow up of IEI patients in a highly consanguineous population.

Methods
Retrospective chart review on different IEI categories diagnosed at the primary immunodeficiency center in Cairo University Specialized Pediatric hospital from 2011 to 2021 based on expanding the use of FCM.

Results
1510 IEI patients were diagnosed; 480 were diagnosed genetically with FMF, 11 with cystic fibrosis and 1019 patients were diagnosed with other IEI disorders. Phagocytic defects were the commonest (30%) followed by severe combined immunodeficiency (22%) and combined immunodeficiency (18.3%). FCM testing properly diagnosed and categorized 73% of the cases.

Conclusion
Using multi-color FCM to evaluate immune cells populations, subpopulations, functions, and intracellular proteins expression is proved a useful cost-effective method for screening, categorization and follow up of IEI patients. FCM can improve the diagnosis of IEI significantly when tests are properly targeted and well designed. This study presents a 10-year experience in diagnosis of IEI using FCM at a tertiary referral center in a setting of limited resources and yet high prevalence of IEI.
Health diplomacy to promote multisectoral participation in fighting against fragmentation and increasing budget for internalization of the health financing progress matrix in Burundi
Authors: Nimubona Alexandre 
Published: June 2022

Abstract
Background
Regardless of its form, financing health in isolation will never raise sufficient funds to lead to universal health coverage. Achieving this goal which is not a pure health policy, requires multisectoral collaboration to support financing mechanisms. Within this framework, the World Health Organization has created the Health Financing Progress Matrix to assess a country’s progress in health financing. The World Health Organization calls for multisectoral support for health financing systems to achieve universal health coverage. This paper aims to explain how health diplomacy can be defined and implemented to influence and facilitate multisectoral participation in fighting against fragmentation and increase necessary budget to internalize the health financing progress matrix in Burundi.

Main text
Burundi’s health financing system is characterized by multiple fragmentation of resources and services, which reinforces economic and health inequities, referred to as de-universalization of universal health coverage. The health financing system in Burundi is inadequate to meet the health needs of the population. Different people with different needs form different segments, and coverage may be inconsistent, duplicative, or incomplete. Health diplomacy can alleviate this situation by appointing health finance attachés in each of the 19 sectors that make up the life of the country. Health finance attachés may have three main tasks:1) promoting confidence building, 2) seeking consensus, and 3) building solidarity for universal health coverage. The practices of health finance attachés can help to improve budget for more coverage. Following the World Health Organization’s progress matrix on health financing, internalization can be achieved in four ways: (i) raising the profile of health diplomats to be accredited in non-health sectors, (ii) establishing offices of health finance attachés in each sector, (iii) creating means by which sectors benefiting from internalization act, (iv) operationalizing proportionate universal health coverage.

Conclusion
Health diplomacy holds an ethical practice (representation approach) for internalizing the matrix. Measuring the size of the health gap and the steepness of the health gradient determines the degree of matrix internalization. Health diplomacy needs to be included in all health financing agendas to achieve proportionate universal health coverage in poor countries like Burundi.
Anticancer effects of disulfiram: a systematic review of in vitro, animal, and human studies
Authors: Wang Ling , Yu Yang , Zhou Cong , Wan Run , Li Yumin 
Published: June 2022

Abstract
Background and objectives
Cancer morbidity and mortality rates remain high, and thus, at present, considerable efforts are focused on finding drugs with higher sensitivity against tumor cells and fewer side effects. Disulfiram (DSF), as an anti-alcoholic drug, kills the cancer cells by inducing apoptosis. Several preclinical and clinical studies have examined the potential of repurposing DSF as an anticancer treatment. This systematic review aimed to assess evidence regarding the antineoplastic activity of DSF in in vitro and in vivo models, as well as in humans.

Methods
Two authors independently conducted this systematic review of English and Chinese articles from the PubMed, Embase, and the Cochrane Library databases up to July 2019. Eligible in vitro studies needed to include assessments of the apoptosis rate by flow cytometry using annexin V/propidium iodide, and studies in animal models and clinical trials needed to examine tumor inhibition rates, and progression-free survival (PFS) and overall survival (OS), respectively. Data were analyzed using descriptive statistics.

Results
Overall, 35 studies, i.e., 21 performed in vitro, 11 based on animal models, and three clinical trials, were finally included. In vitro and animal studies indicated that DSF was associated with enhanced apoptosis and tumor inhibition rates, separately. Human studies showed that DSF prolongs PFS and OS. The greatest anti-tumor activity was observed when DSF was used as combination therapy or as a nanoparticle-encapsulated molecule. There was no noticeable body weight loss after DSF treatment, which indicated that there was no major toxicity of DSF.

Conclusions
This systematic review provides evidence regarding the anti-tumor activity of DSF in vitro, in animals, and in humans and indicates the optimal forms of treatment to be evaluated in future research.
Fixed point results via extended $\mathcal{FZ}$-simulation functions in fuzzy metric spaces
Authors: Moussaoui Abdelhamid , Hussain Nawab , Melliani Said , Nasr Hayel , Imdad Mohammad 
Published: June 2022

AbstractIn this paper, we introduce a new class of control functions, namely extended$\mathcal{FZ}$FZ-simulation functions, and employ it to define a new contractive condition. We also prove some new fixed and best proximity point results in the context of anM-complete fuzzy metric space. The presented theorems unify, generalize, and improve several existing results in the literature.
Experience and perspectives of infection prevention staff of the COVID-19 response in Australian hospitals
Authors: Baswa Alisha , Russo Philip L. , Doyle Joseph S. , Ayton Darshini , Stewardson Andrew J. 
Published: June 2022

Abstract
Background
Hospital infection prevention and control (IPC) staff have played a key role in adapting and implementing jurisdictional COVID-19 policy during the current pandemic. We aimed to describe the experiences of IPC staff in Australian hospitals during the COVID-19 pandemic to inform future pandemic preparedness plans.

Methods
A cross-sectional study involving an online survey distributed to IPC practitioners employed in Australian hospitals. Survey content was informed by in-depth interviews, and addressed work conditions, redeployed workforce, personal protective equipment, communication, and guidelines. Participants were recruited through the mailing lists of Australasian College of Infection Prevention and Control and the Australasian Society of Infectious Diseases.

Results
We received fully or partially completed responses from 160 participants, including 38 (24%) and 122 (76%) with nursing and medical backgrounds, respectively. Respondents reported access to sufficient information about PPE (75%, 114/152), PPE was of sufficient quantity (77%, 117/152) and was of sufficient quality (70%, 106/152). Barriers to infection prevention guideline implementation included frequently changing guidelines (57%, 84/148), timing of updates (65%, 96/148) and contradictory sources of information (64%, 95/148). Respondents described a need for better communication channels from government authorities to hospital IPC teams. All respondents described an increase in workload leading to difficulty completing work (63%, 97/154) and feeling burnt out (48%, 74/154).

Conclusions
These data identify avoidable barriers to implementation of COVID-19 infection prevention guidance in Australian hospitals. These findings can inform future national preparedness strategies.