bluuebunny/crossref_metadata_2025_split huggingface dataset:
Process evaluation of an academic-community-government partnership to reduce liver diseases attributable to hepatitis B virus
Authors: Le Daisy , Jeon Min Jeong , Ciceron Annie Coriolan , Yang Y. Tony , Pan Jane , Juon Hee-Soon , Wallington Sherrie F. 
Published: May 2022

Abstract
Background
Racial/ethnic minorities have higher incidence and mortality rates of liver cancer, or hepatocellular carcinoma, than non-Hispanic Whites. As such, the Washington-Baltimore Metropolitan Area Hepatitis B Virus (WB-HBV) Demonstration Project, a community-based participatory research (CBPR)-driven academic-community-government (ACG) partnership, was established in 2019 to address disparities and implement strategies to improve the HBV screening and vaccination infrastructure for at-risk communities. CBPR is a partnership of community members, organizational leaders, and academic researchers with a common aim to collectively share and contribute their input at every phase of the project.
Herein, we describe the process evaluation of the WB-HBV Project and extract themes and insights to benefit future ACG partnerships and community-engaged research. The process evaluation has been conducted to determine whether CBPR-driven partnership and programmatic activities have been implemented as intended and have resulted in building expanded research capacity for future ACG partnership HBV community-level initiatives.

Methods
A WB-HBV Project Task Force was convened and comprised of eight organizations: four community organizations, three government organizations, and one academic institution. Through a mixed-methods process evaluation, an online survey and key informant interviews were conducted to provide context for program implementation barriers and facilitators. Descriptive statistics were conducted, and interviews were recorded, transcribed, and thematically coded.

Results
The survey was completed by 14 of 20 partnership members (70.0%): two academic, eight community, and four government members. Partnership members showed general agreement across 14 domains: organization and structure of meetings; trust; decisions; impact; general satisfaction; strategic planning; ACG policy impact; community-based participatory research and government; participation in meetings; assessment of participation; partnership operations and capacity; communication; challenges/limitations associated with ACG involvement; and benefits compared to challenges associated with ACG involvement. Qualitative interviews were conducted with 15 of the 20 members (75.0%): two academic, nine community, and four government members. Four themes emerged: partnership involvement, project goals and accomplishments, project challenges and barriers, and partnership involvement in government or policy.

Conclusions
The process evaluation presents insights into developing strategies to enhance partnership functioning and increase the ability of present and future ACG partnerships to improve community health outcomes.
A strategy to identify event specific hospitalizations in large health claims databases
Authors: Lambert Joshua , Sandhu Harpal , Kean Emily , Xavier Teenu , Brokman Aviv , Steckler Zachary , Park Lee , Stromberg Arnold 
Published: May 2022

Abstract
Background
Health insurance claims data offer a unique opportunity to study disease distribution on a large scale. Challenges arise in the process of accurately analyzing these raw data. One important challenge to overcome is the accurate classification of study outcomes. For example, using claims data, there is no clear way of classifying hospitalizations due to a specific event. This is because of the inherent disjointedness and lack of context that typically come with raw claims data.

Methods
In this paper, we propose a framework for classifying hospitalizations due to a specific event. We then tested this framework in a private health insurance claims database (Symphony) with approximately 4 million US adults who tested positive with COVID-19 between March and December 2020. Our claims specific COVID-19 related hospitalizations proportion is then compared to nationally reported rates from the Centers for Disease Control by age.

Results
Across all ages (18 +) the total percentage of Symphony patients who met our definition of hospitalized due to COVID-19 was 7.3% which was similar to the CDC’s estimate of 7.5%. By age group, defined by the CDC, our estimates vs. the CDC’s estimates were 18–49: 2.7% vs. 3%, 50–64: 8.2% vs. 9.2%, and 65 + : 14.6% vs. 28.1%.

Conclusions
The proposed methodology is a rigorous way to define event specific hospitalizations in claims data. This methodology can be extended to many different types of events and used on a variety of different types of claims databases.
Associations of maternal iron deficiency with malaria infection in a cohort of pregnant Papua New Guinean women
Authors: Unger Holger W. , Bleicher Andie , Ome-Kaius Maria , Aitken Elizabeth H. , Rogerson Stephen J. 
Published: May 2022

AbstractBackgroundIron deficiency (ID) is common in malaria-endemic settings. Intermittent preventative treatment of malaria in pregnancy (IPTp) and iron supplementation are core components of antenatal care in endemic regions to prevent adverse pregnancy outcomes. ID has been associated with reduced risk of malaria infection, and correspondingly, iron supplementation with increased risk of malaria infection, in some studies.MethodsA secondary analysis was conducted amongst 1888 pregnant women enrolled in a malaria prevention trial in Papua New Guinea. Maternal ID was defined as inflammation-corrected plasma ferritin levels < 15 μg/L at antenatal enrolment. Malaria burden (Plasmodium falciparum,Plasmodium vivax) was determined by light microscopy, polymerase chain reaction, and placental histology. Multiple logistic and linear regression analyses explored the relationship of ID or ferritin levels with indicators of malaria infection. Models were fitted with interaction terms to assess for modification of iron-malaria relationships by gravidity or treatment arm.ResultsTwo-thirds (n = 1226) and 13.7% (n = 258) of women had ID and peripheral parasitaemia, respectively, at antenatal enrolment (median gestational age: 22 weeks), and 18.7% (120/1,356) had evidence of malaria infection on placental histology. Overall, ID was associated with reduced odds of peripheral parasitaemia at enrolment (adjusted odds ratio [aOR] 0.50; 95% confidence interval [95% CI] 0.38, 0.66, P < 0.001); peripheral parasitaemia at delivery (aOR 0.68, 95% CI 0.46, 1.00; P = 0.050); and past placental infection (aOR 0.35, 95% CI 0.24, 0.50; P < 0.001). Corresponding increases in the odds of infection were observed with two-fold increases in ferritin levels. There was effect modification of iron-malaria relationships by gravidity. At delivery, ID was associated with reduced odds of peripheral parasitaemia amongst primigravid (AOR 0.44, 95% CI 0.25, 0.76; P = 0.003), but not multigravid women (AOR 1.12, 95% CI 0.61, 2.05; P = 0.720). A two-fold increase in ferritin associated with increased odds of placental blood infection (1.44, 95% CI 1.06, 1.96; P = 0.019) and active placental infection on histology amongst primigravid women only (1.24, 95% CI 1.00, 1.54; P = 0.052).ConclusionsLow maternal ferritin at first antenatal visit was associated with a lower risk of malaria infection during pregnancy, most notably in primigravid women. The mechanisms by which maternal iron stores influence susceptibility to infection withPlasmodiumspecies require further investigation.Trial registration
PIK3CA mutations-mediated downregulation of circLHFPL2 inhibits colorectal cancer progression via upregulating PTEN
Authors: Chong Xiaodan , Chen Jingde , Zheng Nanxin , Zhou Zhuqing , Hai Yanan , Chen Shiqing , Zhang Yu , Yu Qingzhuo , Yu Shijun , Chen Zhiqin , Bao Wenfang , Quan Ming , Chen Zhe-Sheng , Zhan Yangyang , Gao Yong 
Published: May 2022

Abstract
Background
PIK3CA mutation and PTEN suppression lead to tumorigenesis and drug resistance in colorectal cancer (CRC). There is no research on the role of circular RNAs (circRNAs) in regulating PIK3CA mutation and MEK inhibitor resistance in CRC.

Methods
The expression of circLHFPL2 in PIK3CA-mutant and wild-type cells and tissues was quantified by RNA-sequencing and qRT-PCR. CCK-8 assay and colony formation assay were used to evaluate cell viability. Annexin V/PI staining was implemented to assess cell apoptosis. Luciferase assay, biotin-coupled microRNA capture, and RIP assay were used to validate the interaction among potential targets. Western blotting and qRT-PCR assays were used to evaluate the expression of involved targets. Xenograft tumor in a nude mouse model was used to explore the role of circRNAs in vivo.

Results
RNA sequencing defined downregulated expression of circLHFPL2 in both PIK3CAH1047R (HCT116) and PIK3CAE545K (DLD1) cells. CircLHFPL2 was also downregulated in PIK3CA-mutant CRC primary cells and tissues, which was correlated with poor prognosis. CircLHFPL2 was mainly localized in the cytoplasm and its downregulation was attributed to the PI3K/AKT signaling pathway activated by phosphorylating Foxo3a. CircLHFPL2 inhibited PI3KCA-Mut CRC progression both in vitro and in vivo. Furthermore, our work indicated that circLHFPL2 acts as a ceRNA to sponge miR-556-5p and miR-1322 in CRC cells and in turn modulate the expression of PTEN. Importantly, circLHFPL2 was able to overcome PIK3CA-mediated MEK inhibitor resistance in CRC cells.

Conclusions
Downregulation of circLHFPL2 sustains the activation of the PI3K/AKT signaling pathway via a positive feedback loop in PIK3CA-mutant CRC. In addition, downregulation of circLHFPL2 leads to MEK inhibitor resistance in CRC. Therefore, targeting circLHFPL2 could be an effective approach for the treatment of CRC patients harboring oncogenic PIK3CA mutations.
What do Iranian physicians value most when choosing a specialty? Evidence from a discrete choice experiment
Authors: Sarikhani Yaser , Ghahramani Sulmaz , Edirippulige Sisira , Fujisawa Yoshikazu , Bambling Matthew , Bastani Peivand 
Published: May 2022

Abstract
Background
Choosing a specialty by physicians is fundamentally linked to the performance of health systems and public health outcomes. Identifying the determinants of specialty selection is important to health policy for targeting resources and planning the development of services. This study examined preferences of Iranian physicians for medical specialty using a discrete choice experiment (DCE) method.

Methods
In this study, the attributes of the DCE were determined using rigorous qualitative approach. Then we applied D-efficiency criteria to design the DCE and validated it at a pilot study. In the final survey, we recruited participants from six Iranian provinces and analyzed data using conditional logit model. We estimated willingness to pay (WTP) for non-monetary attributes.

Results
The WTP analysis revealed that the most important non-monetary attributes in the selection of a specialty were job burnout, opportunity for procedural activities, and job prestige. The results imply that the attributes that were related to the quality of personal life was more important only for physicians who preferred to choose non-surgical specialties.

Conclusions
The findings demonstrate that traditional gender patterns of specialty selection are changing and quality of personal life characteristics might be the most important factor when developing policies to recruit physicians into non-surgical specialties.
Synergistic effect of the commonest residual risk factors, remnant cholesterol, lipoprotein(a), and inflammation, on prognosis of statin-treated patients with chronic coronary syndrome
Authors: Liu Hui-Hui , Guo Yuan-Lin , Zhu Cheng-Gang , Wu Na-Qiong , Gao Ying , Xu Rui-Xia , Dong Qian , Qian Jie , Dou Ke-Fei , Li Jian-Jun 
Published: May 2022

AbstractBackgroundCurrently, remnant cholesterol (RC), lipoprotein(a) [Lp(a)], and inflammation are considered the principal residual cardiovascular risk (RCVR) factors. This study sought to evaluate the combined impact of RC, Lp(a), and inflammation on prognosis of statin-treated patients with chronic coronary syndrome (CCS), which has not been investigated.MethodsA total of 6839 patients with CCS were consecutively enrolled. Baseline RC, Lp(a), and high-sensitivity C-reactive protein (hsCRP) concentrations were measured and their medians were used for categorizations. All patients were followed for the major adverse cardiovascular events (MACEs), including cardiovascular death, non-fatal myocardial infarction, and stroke. The individual and combined effects of RC, Lp(a), and hsCRP on MACEs were examined and stratification analysis according to low-density lipoprotein cholesterol (LDL-C) was performed.ResultsOver an average of 54.93 ± 18.59 months follow-up, 462 MACEs were recorded. Multivariate Cox analysis showed that elevated RC and Lp(a) levels were significantly associated with an increased risk of MACEs, while high hsCRP levels were related to a slightly but non-significantly increased MACEs risk. Moreover, when participants were subgrouped according to RC, Lp(a), and hsCRP levels together, only High RC-High Lp(a)-High hsCRP group had significantly higher risk of MACEs [hazard ratio (HR) 1.99, 95% confidence interval (CI) 1.15–3.47] compared with the reference group (Low RC-Low Lp(a)-Low hsCRP), especially in patients with LDL-C < 2.6 mmol/L.ConclusionsThe combination of elevated levels of RC, Lp(a), and hsCRP potentiated the adverse effect on MACEs among statin-treated patients with CCS, suggesting that multiple RCVR factors assessment may be a better strategy to improve stratification in very-high risk population.
Association between mitochondrial DNA haplogroups J and K, serum branched-chain amino acids and lowered capability for endurance exercise
Authors: Kiiskilä Jukka M. , Hassinen Ilmo E. , Kettunen Johannes , Kytövuori Laura , Mikkola Ilona , Härkönen Pirjo , Jokelainen Jari J. , Keinänen-Kiukaanniemi Sirkka , Perola Markus , Majamaa Kari 
Published: May 2022

Abstract
Background
Endurance exercise training promotes the catabolism of branched-chain amino acids (BCAAs) in skeletal muscles. We have previously shown that mitochondrial DNA (mtDNA) haplogroups J and K are markers of low responders in endurance training. In this paper, we hypothesize that BCAA catabolism is a surrogate marker of lower respiratory chain activity attributed to these haplogroups. We evaluated whether exercise-induced changes in amino acid concentrations differ between subjects harbouring mtDNA haplogroups J or K and those with non-JK haplogroups.

Methods
Finnish male conscripts (N = 633) undertook the 12-min Cooper running test at the beginning and end of their military service. The intervention during the service mainly included endurance aerobic exercise and sports-related muscle training. Concentrations of seven amino acids were analysed in the serum using a high-throughput 1H NMR metabolomics platform. Total DNA was extracted from whole blood, and restriction fragment analysis was used to determine mtDNA haplogroups J and K.

Results
The concentrations of the seven amino acids were higher following the intervention, with the exception of phenylalanine; interestingly, the increase in the concentrations of three BCAAs was larger in subjects with haplogroup J or K than in subjects with non-JK haplogroups (p = 0.029). MtDNA haplogroups J and K share two common nonsynonymous variants. Structural analysis based on crystallographic data on bovine complexes I and III revealed that the Leu18 variant in cytochrome b encoded by m.14798T > C may interfere with ubiquinone binding at the Qi site in complex III.

Conclusions
The increase in the concentrations of serum BCAAs following exercise intervention differs between subjects harbouring mtDNA haplogroup J or K and those harbouring non-JK haplogroups. Lower response in endurance training and difference in exercise-induced increase in the concentrations of serum BCAAs suggest decreased respiratory chain activity. Haplogroups J and K share m.14798T > C in MT-CYB, which may hamper the function of complex III.
A randomized controlled clinical trial of the effects of range of motion exercises and massage on muscle strength in critically ill patients
Authors: Rahiminezhad Elham , Sadeghi Mehdi , Ahmadinejad Mehdi , Mirzadi Gohari Seyed Iman , Dehghan Mahlagha 
Published: May 2022

AbstractBackgroundAtrophy and muscle weakness is a common problem in critically ill patients admitted to the intensive care unit (ICU). Muscle weakness in severe cases can lead to tetraplegia, reduced or lost tendon reflexes, delayed weaning from mechanical ventilation, physical disability, and increased mortality. The aim of this study was to compare the effects of range of motion exercises (ROM) and massage on muscle strength of the patients admitted to ICUs.MethodsThis study was a single-blinded randomized controlled trial conducted in ICUs of Afzalipour hospital in Kerman, southeastern Iran. Ninety conscious ICU patients were randomly divided into three groups (massage, ROM exercises and control). The researcher/co-researcher massaged or did ROM exercises on the patients’ extremities once a day for seven consecutive days. Using a hand-held dynamometer, the co-researcher, rated the muscle strength before, on the fourth and seventh days of intervention at 8 p.m.ResultsThe mean muscles strength of the right arm in the ROM exercise and massage groups increased by 0.63 kg, and 0.29 kg, respectively after the intervention compared with before the intervention. The muscle strength of the right arm in the control group reduced by 0.55 kg. The mean muscles strength of the left arm in the ROM exercise and massage groups increased by 0.61 kg and 0.28 kg after the intervention, respectively while it reduced by 0.56 kg in the control group. The mean muscles strength of the right leg in the ROM exercise and massage groups increased by 0.53 kg and 0.27 kg after the intervention compared with before the intervention while it reduced by 0.70 kg in the control group. The mean muscles strength of the left leg in the ROM exercise and massage groups increased by 0.54 kg and 0.26 kg after the intervention compared with before the intervention while it reduced by 0.71 kg in the control group.ConclusionThe results of the present study showed that ROM exercises and massage were effective interventions in increasing muscle strength of the critically ill patients admitted to intensive care units.
Nebulized exosomes derived from allogenic adipose tissue mesenchymal stromal cells in patients with severe COVID-19: a pilot study
Authors: Zhu Ying-Gang , Shi Meng-meng , Monsel Antoine , Dai Cheng-xiang , Dong Xuan , Shen Hong , Li Su-ke , Chang Jing , Xu Cui-li , Li Ping , Wang Jing , Shen Mei-ping , Ren Cheng-jie , Chen De-chang , Qu Jie-Ming 
Published: May 2022

Abstract
Background
Existing clinical studies supported the potential efficacy of mesenchymal stromal cells as well as derived exosomes in the treatment of COVID-19. We aimed to explore the safety and efficiency of aerosol inhalation of the exosomes derived from human adipose-derived MSCs (haMSC-Exos) in patients with COVID-19.

Methods
The MEXCOVID trial is a phase 2a single-arm, open-labelled, interventional trial and patients were enrolled in Jinyintan Hospital, Wuhan, China. Eligible 7 patients were assigned to receive the daily dose of haMSCs-Exos (2.0 × 108 nano vesicles) for consecutively 5 days. The primary outcomes included the incidence of prespecified inhalation-associated events and serious adverse events. We also observed the demographic data, clinical characteristics, laboratory results including lymphocyte count, levels of D-dimer and IL-6 as well as chest imaging.

Results
Seven severe COVID-19 related pneumonia patients (4 males and 3 females) were enrolled and received nebulized haMSC-Exos. The median age was 57 year (interquartile range (IQR), 43 year to 70 year). The median time from onset of symptoms to hospital admission and administration of nebulized haMSC-Exos was 30 days (IQR, 15 days to 40 days) and 54 d (IQR, 34 d to 69 d), respectively. All COVID-19 patients tolerated the haMSC-Exos nebulization well, with no evidence of prespecified adverse events or clinical instability during the nebulization or during the immediate post-nebulization period. All patients presented a slight increase of serum lymphocyte counts (median as 1.61 × 109/L vs. 1.78 × 109/L). Different degrees of resolution of pulmonary lesions after aerosol inhalation of haMSC-Exos were observed among all patients, more obviously in 4 of 7 patients.

Conclusions
Our trial shows that a consecutive 5 days inhalation dose of clinical grade haMSC-Exos up to a total amount of 2.0 × 109 nano vesicles was feasible and well tolerated in seven COVID-19 patients, with no evidence of prespecified adverse events, immediate clinical instability, or dose-relevant toxicity at any of the doses tested. This safety profile is seemingly followed by CT imaging improvement within 7 days. Further trials will have to confirm the long-term safety or efficacy in larger population.
Trial Registration: MEXCOVID, NCT04276987.
Assay establishment and validation of a high-throughput organoid-based drug screening platform
Authors: Li Xiaomeng , Fu Guoxiang , Zhang Long , Guan Ruoyu , Tang Peiyuan , Zhang Jialing , Rao Xinxin , Chen Shengzhi , Xu Xiaoya , Zhou Yi , Deng Yun , Lv Tao , He Xingfeng , Mo Shaobo , Mu Peiyuan , Gao Jianjun , Hua Guoqiang 
Published: May 2022

Abstract
Background
Organoids are three-dimensional structures that closely recapitulate tissue architecture and cellular composition, thereby holding great promise for organoid-based drug screening. Although growing in three-dimensional provides the possibility for organoids to recapitulate main features of corresponding tissues, it makes it incommodious for imaging organoids in two-dimensional and identifying surviving organoids from surrounding dead cells after organoids being treated by irradiation or chemotherapy. Therefore, significant work remains to establish high-quality controls to standardize organoid analyses and make organoid models more reproducible.

Methods
In this study, the Z-stack imaging technique was used for the imaging of three-dimensional organoids to gather all the organoids’ maximum cross sections in one imaging. The combination of live cell staining fluorescent dye Calcein-AM and ImageJ assessment was used to analyze the survival of organoids treated by irradiation or chemotherapy.

Results
We have established a novel quantitative high-throughput imaging assay that harnesses the scalability of organoid cultures. Using this assay, we can capture organoid growth over time, measure multiple whole-well organoid readouts, and show the different responses to drug treatments.

Conclusions
In summary, combining the Z-stack imaging technique and fluorescent labeling methods, we established an assay for the imaging and analysis of three-dimensional organoids. Our data demonstrated the feasibility of using organoid-based platforms for high-throughput drug screening assays.

Graphical Abstract