bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reactive, self-administered malaria treatment against asymptomatic malaria infection: results of a cluster randomized controlled trial in The Gambia
Authors: Okebe Joseph , Dabira Edgard , Jaiteh Fatou , Mohammed Nuredin , Bradley John , Drammeh Ndey-Fatou , Bah Amadou , Masunaga Yoriko , Achan Jane , Muela Ribera Joan , Yeung Shunmay , Balen Julie , Peeters Grietens Koen , D’Alessandro Umberto 
Published: June 2021

Abstract
Background
Selectively targeting and treating malaria-infected individuals may further decrease parasite carriage in low-burden settings. Using a trans-disciplinary approach, a reactive treatment strategy to reduce Plasmodium falciparum prevalence in participating communities was co-developed and tested.

Methods
This is a 2-arm, open-label, cluster-randomized trial involving villages in Central Gambia during the 2017 and 2018 malaria transmission season. Villages were randomized in a 1:1 ratio using a minimizing algorithm. In the intervention arm, trained village health workers delivered a full course of pre-packed dihydroartemisinin-piperaquine to all residents of compounds where clinical cases were reported while in the control arm, compound residents were screened for infection at the time of the index case reporting. All index cases were treated following national guidelines. The primary endpoint was malaria prevalence, determined by molecular methods, at the end of the intervention period.

Results
The trial was carried out in 50 villages: 34 in 2017 and 16 additional villages in 2018. At the end of the 2018 transmission season, malaria prevalence was 0.8% (16/1924, range 0–4%) and 1.1% (20/1814, range 0–17%) in the intervention and control arms, respectively. The odds of malaria infection were 29% lower in the intervention than in the control arm after adjustment for age (OR 0.71, 95% CI 0.27–1.84, p = 0.48). Adherence to treatment was high, with 98% (964/979) of those treated completing the 3-day treatment.
Over the course of the study, only 37 villages, 20 in the intervention and 17 in the control arm, reported at least one clinical case. The distribution of clinical cases by month in both transmission seasons was similar and the odds of new clinical malaria cases during the trial period did not vary between arms (OR 1.04, 95% CI 0.57–1.91, p = 0.893). All adverse events were classified as mild to moderate and resolved completely.

Conclusion
The systematic and timely administration of an anti-malarial treatment to residents of compounds with confirmed malaria cases did not significantly decrease malaria prevalence and incidence in communities where malaria prevalence was already low. Treatment coverage and adherence was very high. Results were strongly influenced by the lower-than-expected malaria prevalence, and by no clinical cases in villages with asymptomatic malaria-infected individuals.
Trial registration:
This study is registered with ClinicalTrials.gov, NCT02878200. Registered 25 August 2016.
https://clinicaltrials.gov/ct2/show/NCT02878200.
First Nations and Metis peoples’ access and equity challenges with early childhood oral health: a qualitative study
Authors: Kyoon-Achan Grace , Schroth Robert J. , DeMaré Daniella , Sturym Melina , Edwards Jeannette M. , Sanguins Julianne , Campbell Rhonda , Chartrand Frances , Bertone Mary , Moffatt Michael E. K. 
Published: June 2021

Abstract
Background
Inequities in early childhood oral health are evident amongst Indigenous peoples and communities in Manitoba, Canada. Early childhood caries (ECC) is decay in primary dentition in children under 6 years of age. A severe form of the disease occurs at a higher rate in Indigenous populations compared to the general population. ECC has been strongly associated with social determinants of health.

Methods
Focus groups and sharing circles were conducted with four First Nations and Metis communities in urban and rural communities in Manitoba. There were eight groups in total of purposively sampled participants (n = 59). A grounded theory approach guided thematic analysis of audio recorded and transcribed data.

Results
Indigenous participants experienced challenges similar to those found in the general population, such as encouraging and motivating parents and caregivers to establish regular oral hygiene routines for their children. However other challenges reported, disproportionately affect Indigenous communities. These include poor access to dental care, specifically no dental offices within 1 h driving radius and not having transportation to get there. Not having evidence-based oral health information to support good oral hygiene practices, preventing parents from making the best choices of oral hygiene products and oral health behaviours for their children. Poverty and food insecurity resulting in poor nutritional choices and leading to ECC. For example, feeding children sugary foods and beverages because those are more readily avialble than healthy options. Confusing or difficult encounters with dental professionals, highlighted as a factor that can erode trust, reduce compliance and impact continued attendance at dental offices.

Conclusion
Closing existing early childhood oral health gaps for First Nations and Metis peoples and communities requires equity-oriented healthcare approaches to address specific problems and challenges faced by these populations. Family, community and systemic level interventions that directly implement community recommendations are needed.
Determinants of safety climate at primary care level in Ghana, Malawi and Uganda: a cross-sectional study across 138 selected primary healthcare facilities
Authors: Vallières Frédérique , Mubiri Paul , Agyemang Samuel Agyei , Amon Samuel , Gerold Jana , Martineau Tim , Nolan Ann , O’Byrne Thomasena , Sanudi Lifah , Sengooba Freddie , Prytherch Helen 
Published: June 2021

Abstract
Background
Safety climate is an essential component of achieving Universal Health Coverage, with several organisational, unit or team-level, and individual health worker factors identified as influencing safety climate. Few studies however, have investigated how these factors contribute to safety climate within health care settings in low- and middle-income countries (LMICs). The current study examines the relationship between key organisational, unit and individual-level factors and safety climate across primary health care centres in Ghana, Malawi and Uganda.

Methods
A cross-sectional, self-administered survey was conducted across 138 primary health care facilities in nine districts across Uganda, Ghana and Malawi. In total, 760 primary health workers completed the questionnaire. The relationships between individual (sex, job satisfaction), unit (teamwork climate, supportive supervision), organisational-level (district managerial support) and safety climate were tested using structural equation modelling (SEM) procedures. Post hoc analyses were also carried out to explore these relationships within each country.

Results
Our model including all countries explained 55% of the variance in safety climate. In this model, safety climate was most strongly associated with teamwork (β = 0.56, p < 0.001), supportive supervision (β = 0.34, p < 0.001), and district managerial support (β = 0.29, p < 0.001). In Ghana, safety climate was positively associated with job satisfaction (β = 0.30, p < 0.05), teamwork (β = 0.46, p < 0.001), and supportive supervision (β = 0.21, p < 0.05), whereby the model explained 43% of the variance in safety climate. In Uganda, the total variance explained by the model was 64%, with teamwork (β = 0.56, p < 0.001), supportive supervision (β = 0.43, p < 0.001), and perceived district managerial support (β = 0.35, p < 0.001) all found to be positively associated with climate. In Malawi, the total variance explained by the model was 63%, with teamwork (β = 0.39, p = 0.005) and supportive supervision (β = 0.27, p = 0.023) significantly and positively associated with safety climate.

Discussion/conclusions
Our findings highlight the importance of unit-level factors—and in specific, teamwork and supportive supervision—as particularly important contributors to perceptions of safety climate among primary health workers in LMICs. Implications for practice are discussed.
Automated tumor proportion scoring for PD-L1 expression based on multistage ensemble strategy in non-small cell lung cancer
Authors: Pan Boju , Kang Yuxin , Jin Yan , Yang Lin , Zheng Yushuang , Cui Lei , Sun Jian , Feng Jun , Li Yuan , Guo Lingchuan , Liang Zhiyong 
Published: June 2021

Abstract
Introduction
Programmed cell death ligand-1 (PD-L1) expression is a promising biomarker for identifying treatment related to non-small cell lung cancer (NSCLC). Automated image analysis served as an aided PD-L1 scoring tool for pathologists to reduce inter- and intrareader variability. We developed a novel automated tumor proportion scoring (TPS) algorithm, and evaluated the concordance of this image analysis algorithm with pathologist scores.

Methods
We included 230 NSCLC samples prepared and stained using the PD-L1(SP263) and PD-L1(22C3) antibodies separately. The scoring algorithm was based on regional segmentation and cellular detection. We used 30 PD-L1(SP263) slides for algorithm training and validation.

Results
Overall, 192 SP263 samples and 117 22C3 samples were amenable to image analysis scoring. Automated image analysis and pathologist scores were highly concordant [intraclass correlation coefficient (ICC) = 0.873 and 0.737]. Concordances at moderate and high cutoff values were better than at low cutoff values significantly. For SP263 and 22C3, the concordances in squamous cell carcinomas were better than adenocarcinomas (SP263 ICC = 0.884 vs 0.783; 22C3 ICC = 0.782 vs 0.500). In addition, our automated immune cell proportion scoring (IPS) scores achieved high positive correlation with the pathologists TPS scores.

Conclusions
The novel automated image analysis scoring algorithm permitted quantitative comparison with existing PD-L1 diagnostic assays and demonstrated effectiveness by combining cellular and regional information for image algorithm training. Meanwhile, the fact that concordances vary in different subtypes of NSCLC samples, which should be considered in algorithm development.
Characterization of terminal-ileal and colonic Crohn’s disease in treatment-naïve paediatric patients based on transcriptomic profile using logistic regression
Authors: Park Ilkyu , Jung Jaeeun , Lee Sugi , Park Kunhyang , Ryu Jea-Woon , Son Mi-Young , Cho Hyun-Soo , Kim Dae-Soo 
Published: June 2021

Abstract
Background
Inflammatory bowel disease (IBD) is a chronic and idiopathic inflammatory disorder of the gastrointestinal tract and comprises ulcerative colitis (UC) and Crohn’s disease (CD). Crohn’s disease can affect any part of the gastrointestinal tract, but mainly the terminal ileum and colon. In the present study, we aimed to characterize terminal-ileal CD (ICD) and colonic CD (CCD) at the molecular level, which might enable a more optimized approach for the clinical care and scientific research of CD.

Methods
We analyzed differentially expressed genes in samples from 23 treatment-naïve paediatric patients with CD and 25 non-IBD controls, and compared the data with previously published RNA-Seq data using multi-statistical tests and confidence intervals. We implemented functional profiling and proposed statistical methods for feature selection using a logistic regression model to identify genes that are highly associated in ICD or CCD. We also validated our final candidate genes in independent paediatric and adult cohorts.

Results
We identified 550 genes specifically expressed in patients with CD compared with those in healthy controls (p < 0.05). Among these DEGs, 240 from patients with CCD were mainly involved in mitochondrial dysfunction, whereas 310 from patients with ICD were enriched in the ileum functions such as digestion, absorption, and metabolism. To choose the most effective gene set, we selected the most powerful genes (p-value ≤ 0.05, accuracy ≥ 0.8, and AUC ≥ 0.8) using logistic regression. Consequently, 33 genes were identified as useful for discriminating CD location; the accuracy and AUC were 0.86 and 0.83, respectively. We then validated the 33 genes with data from another independent paediatric cohort (accuracy = 0.93, AUC = 0.92) and adult cohort (accuracy = 0.88, AUC = 0.72).

Conclusions
In summary, we identified DEGs that are specifically expressed in CCD and ICD compared with those in healthy controls and patients with UC. Based on the feature selection analysis, 33 genes were identified as useful for discriminating CCD and ICD with high accuracy and AUC, for not only paediatric patients but also independent cohorts. We propose that our approach and the final gene set are useful for the molecular classification of patients with CD, and it could be beneficial in treatments based on disease location.
A comprehensive review on clinical and mechanistic pathophysiological aspects of COVID-19 Malady: How far have we come?
Authors: Shakaib Baila , Zohra Tanzeel , Ikram Aamer , Shakaib Muhammad Bin , Ali Amna , Bashir Adnan , Salman Muhammad , khan Mumtaz Ali , Ansari Jamil 
Published: June 2021

AbstractSince its outbreak in 2019, the coronavirus disease (COVID-19) has become a pandemic, affecting more than 52 million people and causing more than 1 million mortalities globally till date. Current research reveals a wide array of disease manifestations and behaviors encompassing multiple organ systems in body and immense systemic inflammation, which have been summarized in this review. Data from a number of scientific reviews, research articles, case series, observational studies, and case reports were retrieved by utilizing online search engines such as Cochrane, PubMed, and Scopus from December 2019 to November 2020. The data for prevalence of signs and symptoms, underlying disease mechanisms and comorbidities were analyzed using SPSS version 25. This review will discuss a wide range of COVID-19 clinical presentations recorded till date, and the current understanding of both the underlying general as well as system specific pathophysiologic, and pathogenetic pathways. These include direct viral penetration into host cells through ACE2 receptors, induction of inflammosomes and immune response through viral proteins, and the initiation of system-wide inflammation and cytokine production. Moreover, peripheral organ damage and underlying comorbid diseases which can lead to short term and long term, reversible and irreversible damage to the body have also been studied. We concluded that underlying comorbidities and their pathological effects on the body contributed immensely and determine the resultant disease severity and mortality of the patients. Presently there is no drug approved for treatment of COVID-19, however multiple vaccines are now in use and research for more is underway.
The deletion of glucagon-like peptide-1 receptors expressing neurons in the dorsomedial hypothalamic nucleus disrupts the diurnal feeding pattern and induces hyperphagia and obesity
Authors: Maejima Yuko , Yokota Shoko , Shimizu Masaru , Horita Shoichiro , Kobayashi Daisuke , Hazama Akihiro , Shimomura Kenju 
Published: June 2021

Abstract
Background
Feeding rhythm disruption contributes to the development of obesity. The receptors of glucagon-like peptide-1 (GLP-1) are distributed in the wide regions of the brain. Among these regions, GLP-1 receptors (GLP-1R) are expressed in the dorsomedial hypothalamic nucleus (DMH) which are known to be associated with thermogenesis and circadian rhythm development. However, the physiological roles of GLP-1R expressing neurons in the DMH remain elusive.

Methods
To examine the physiological role of GLP-1R expressing neurons in the DMH, saporin-conjugated exenatide4 was injected into rat brain DMH to delete GLP-1R-positive neurons. Subsequently, locomotor activity, diurnal feeding pattern, amount of food intake and body weight were measured.

Results
This deletion of GLP-1R-positive neurons in the DMH induced hyperphagia, the disruption of diurnal feeding pattern, and obesity. The deletion of GLP-1R expressing neurons also reduced glutamic acid decarboxylase 67 and cholecystokinin A receptor mRNA levels in the DMH. Also, it reduced the c-fos expression after refeeding in the suprachiasmatic nucleus (SCN). Thirty percent of DMH neurons projecting to the SCN expressed GLP-1R. Functionally, refeeding after fasting induced c-fos expression in the SCN projecting neurons in the DMH. As for the projection to the DMH, neurons in the nucleus tractus solitarius (NTS) were found to be projecting to the DMH, with 33% of those neurons being GLP-1-positive. Refeeding induced c-fos expression in the DMH projecting neurons in the NTS.

Conclusion
These findings suggest that GLP-1R expressing neurons in the DMH may mediate feeding termination. In addition, this meal signal may be transmitted to SCN neurons and change the neural activities.
Accuracy of institutional orthopedic trauma databases: a retrospective chart review
Authors: Chopra Aman , Cortez Abigail C. , El Naga Ashraf , Ding Anthony , Morshed Saam 
Published: June 2021

Abstract
Introduction
Academic trauma institutions rely on fracture databases as research and quality control tools. Frequently, these databases are populated by trainees, but the completeness and accuracy of such databases has not yet been evaluated. The purpose of this study is to determine the capture rate of a resident-populated database in collecting extremity fractures and to determine the accuracy of assigned Orthopaedic Trauma Association (OTA) classifications.

Materials and methods
A retrospective study was performed at a level 1 trauma center of all adult patients who underwent treatment for extremity fractures after an emergency department or inpatient consultation. A 20% random sample was taken from these entries and compared to a resident-populated fracture database designed to capture the same patients. For all matching records containing a resident-assigned OTA classification, relevant imaging was blindly reviewed by a trauma fellowship-trained orthopedic attending surgeon for fracture pattern classification. Resident OTA classifications were compared to this gold standard to determine overall accuracy rate.

Results
Three hundred eighteen (80%) out of 400 entries were captured by the resident-populated database. Two hundred thirty-one of these 318 entries contained an OTA classification. One hundred fifty-three (66%) of these 231 entries demonstrated concordance between resident and attending assigned OTA classifications. On subgroup analysis, 133 (70%) of the 190 lower extremity classifications were accurately identified as compared to just 20 (49%) of the 41 upper extremity classifications (p = 0.009). Seventy-nine (65%) of the 121 end segment fractures showed agreement versus 42 (67%) of the 63 diaphyseal injury patterns (p = 0.85). Accuracy of classification did not significantly vary by resident year of training (p = 0.142).

Conclusion
Trainee generated databases at academic institutions may be subject to incomplete data entry and inaccurate fracture classifications. Quality control measures should be instituted to ensure accuracy in such databases if efforts are invested with the expectation of useful information.
Pulmonary hydatidosis genotypes isolates from human clinical surgery based on sequencing of mitochondrial genes in Fars, Iran
Authors: Mardani Parviz , Ezabadi Ali Talebi , Sedaghat Bahareh , Sadjjadi Seyed Mahmoud 
Published: June 2021

Abstract
Background
Cystic echinococcosis (CE)/hydatidosis is an important neglected parasitic zoonotic disease caused by the metacestode of Echinococcus granulosus s.l. The present study was designed to identify the pulmonary CE species/genotypes in isolated human underwent to surgery in our center in Southern Iran.

Methods
The study population of this study were all patients in Fars province who were admitted to Namazi Hospitals for pulmonary hydatid cyst surgery. Thoracic surgery was performed in the thoracic ward and the cyst/s was removed by open surgery via posterolateral or lateral thoracotomy. DNA was extracted from the germinal layer or the protoscoleces. PCR technique was performed using the cytochrome C oxidase subunit1 (cox1) gene, and the products were sequenced.

Results
A total of 32 pulmonary hydatid cyst samples were collected from 9 (28%) female and 23 (72%) male aged from 4 to 74 years old. A total of 18(56%) cyst/s were in the left lobe and 14 (44%) cysts in the right lobe. Sequence analysis of the cysts showed that 24 samples (75%) were E. granulosus s.s (G1-G3) genotype and 8 (25%) were E. canadensis (G6/G7) genotype.

Conclusion
E.granulosus s.s genotype was the most prevalent genotype followed by E. canadensis (G6/G7) genotype. There was no significant statistical correlation between cysts’ size, location, genotype strain, and patients’ age and gender.
The three syndromes and six Chinese patent medicine study during the recovery phase of COVID-19
Authors: An Xuedong , Duan Liyun , Zhang Yue Hong , Jin De , Zhao Shenghui , Zhou Rong Rong , Duan Yingying , Lian Fengmei , Tong Xiaolin 
Published: June 2021

AbstractThe coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), first broke out in Wuhan, China, in 2019. SARS-CoV-2 develops many types of mutations (such as B.1.1.7), making diagnosis and treatment challenging. Although we now have a preliminary understanding of COVID-19, including pathological changes, clinical manifestations, and treatment measures, we also face new difficulties. The biggest problem is that most COVID-19 patients might face sequelae (e.g., fatigue, sleep disturbance, pulmonary fibrosis) during the recovery phase. We aimed to test six Chinese patent medicines to treat three major abnormal symptoms in COVID-19 patients during the recovery phase, including cardiopulmonary function, sleep disturbance, and digestive function. We launched the “three syndromes and six Chinese patent medicines” randomized, double-blind, placebo-controlled, multicenter clinical trial on April 10, 2020. The results showed that Jinshuibao tablets and Shengmaiyin oral liquid significantly improved the cardiopulmonary function of recovering COVID-19 patients. Shumian capsules, but not Xiaoyao capsules, significantly improved patients’ sleep disorders. This might be because the indication of Xiaoyao capsules is liver qi stagnation rather than psychological or emotional problems. Xiangsha Liujun pills and Ludangshen oral liquid significantly improved digestive function. Our research provides a guideline for treating COVID-19 sequelae in patients during the recovery period based on high-quality evidence.