bluuebunny/crossref_metadata_2025_split huggingface dataset:
A practical measure of health facility efficiency: an innovation in the application of routine health information to determine health worker productivity in Ethiopia
Authors: Hasan Md Zabir , Dinsa Girmaye D. , Berman Peter 
Published: August 2021

AbstractBackgroundA simple indicator of technical efficiency, such as productivity of health workers, measured using routine health facility data, can be a practical approach that can inform initiatives to improve efficiency in low- and middle-income countries. This paper presents a proof of concept of using routine information from primary healthcare (PHC) facilities to measure health workers’ productivity and its application in three regions of Ethiopia.MethodsIn four steps, we constructed a productivity measure of the health workforce of Health Centers (HCs) and demonstrated its practical application: (1) developing an analytical dataset using secondary data from health management information systems (HMIS) and human resource information system (HRIS); (2) principal component analysis and factor analysis to estimate a summary measure of output from five indicators (annual service volume of outpatient visits, family planning, first antenatal care visits, facility-based deliveries by skilled birth attendants, and children [< 1 year] with three pentavalent vaccines); (3) calculating a productivity score by combining the summary measure of outputs and the total number of health workers (input), and (4) implementing regression models to identify the determinant of productivity and ranking HCs based on their adjusted productivity score.ResultsWe developed an analytical dataset of 1128 HCs; however, significant missing values and outliers were reported in the data. The principal component and factor scores developed from the five output measures were highly consistent (correlation coefficient = 0.98). We considered the factor score as the summary measure of outputs for estimating productivity. A very weak association was observed between the summary measure of output and the total number of staff. The result also highlighted a large variability in productivity across similar health facilities in Ethiopia, represented by the significant dispersion in summary measure of output occurring at similar levels of the health workers.ConclusionsWe successfully demonstrated the analytical steps to estimate health worker productivity and its practical application using HMIS and HRIS. The methodology presented in this study can be readily applied in low- and middle-income countries using widely available data—such as DHIS2—that will allow further explorations to understand the causes of technical inefficiencies in the health system.
E3 ubiquitin ligase TRIM29 promotes pancreatic cancer growth and progression via stabilizing Yes-associated protein 1
Authors: Deng Xueqiang , Fu Xiaowei , Teng Hong , Fang Lu , Liang Bo , Zeng Rengui , Chen Lian , Zou Yeqing 
Published: August 2021

Abstract
Background
Pancreatic cancer (PC) is one of the most fatal digestive system cancers. tripartite motif-29 (TRIM29) has been reported as oncogene in several human cancers. However, the precise role and underlying signal cascade of TRIM29 in PC progression remain unclear.

Methods
Western blot, qRT-PCR and immunohistochemistry were used to analyze TRIM29 and Yes-associated protein 1 (YAP1) levels. CCK8 assays, EdU assays and flow cytometry were designed to explore the function and potential mechanism of TRIM29 and YAP1 in the proliferation of PC. Next, a nude mouse model of PC was established for validating the roles of TRIM29 and YAP1 in vivo. The relationship among TRIM29 and YAP1 was explored by co-immunoprecipitation and in vitro ubiquitination assay.

Results
TRIM29 and YAP1 was significantly upregulated in PC patient samples, and TRIM29 expression was closely related to a malignant phenotype and poorer overall survival (OS) of PC patients. Functional assays revealed that TRIM29 knockdown suppresses cell growth, arrests cell cycle progression and promotes cell apoptosis of PC cells in vivo and in vitro. Furthermore, the rescue experiments demonstrated that TRIM29-induced proliferation is dependent on YAP1 in PC cells. Mechanistically, TRIM29 regulates YAP1 expression by directly binding to YAP1, and reduced its ubiquitination and degradation.

Conclusion
Taken together, these results identify a novel mechanism used by PC growth, and provide insight regarding the role of TRIM29 in PC.
Establishing a genomic database for the medicinal plants in the Brazilian Pharmacopoeia
Authors: Zhou Guan-Ru , Liao Bao-Sheng , Li Qiu-Shi , Xu Jiang , Chen Shi-Lin 
Published: August 2021

Abstract
Background
Brazil is exceptionally abundant in medicinal plant resources and has a rich ethnopharmacological history. Brazilian Pharmacopoeia (BP) acts as a national standard that regulates drug quality and has six published editions. Recent genomic approaches have led to a resurgence of interest in herbal drugs. The genomic data of plants has been used for pharmaceutical applications, protecting natural resources, and efficiently regulating the market. However, there are few genomic databases specifically for medicinal plants, and the establishment of a database that focuses on the herbs contained in the BP is urgently required.

Methods
The medicinal plant species included in each edition of the BP were analyzed to understand the evolution of the Brazilian herbal drugs. The data of 82 plants in the BP were collected and categorized into four sections: DNA barcodes, super-barcodes, genomes, and sequencing data. A typical web server architecture pattern was used to build the database and website. Furthermore, the cp-Gs of the Aloe genus in the database were analyzed as an illustration.

Results
A new database, the Brazilian Pharmacopoeia Genomic Database (BPGD) was constructed and is now publicly accessible. A BLAST server for species identification and sequence searching with the internal transcribed spacer 2 (ITS2), the intergenic region (psbA-trnH), and the chloroplast genome (cp-G) of Brazilian medicinal plants was also embedded in the BPGD. The database has 753 ITS2 of 76 species, 553 psbA-trnH and 190 genomes (whole genome and chloroplast genome) of 57 species. In addition, it contains 37 genome sequence data sets of 24 species and 616 transcriptome sequence data sets of 34 species and also includes 187 cp-Gs representing 57 medicinal species in the BP. Analyses of the six cp-Gs of three Aloe species identified the variable regions in the cp-Gs. These can be used to identify species and understand the intraspecific relationships.

Conclusions
This study presents the first genomic database of medicinal plants listed in the latest BP. It serves as an efficient platform to obtain and analyze genomic data, accelerate studies regarding Brazilian medicinal plants and facilitate the rational development on their market regulation.
Prevalence of fibrodysplasia ossificans progressiva (FOP) in the United States: estimate from three treatment centers and a patient organization
Authors: Pignolo Robert J. , Hsiao Edward C. , Baujat Genevieve , Lapidus David , Sherman Adam , Kaplan Frederick S. 
Published: August 2021

AbstractBackgroundFibrodysplasia ossificans progressiva (FOP), an ultra-rare, progressive, and permanently disabling disorder of extraskeletal ossification, is characterized by episodic and painful flare-ups and irreversible heterotopic ossification in muscles, tendons, and ligaments. Prevalence estimates have been hindered by the rarity of FOP and the heterogeneity of disease presentation. This study aimed to provide a baseline prevalence of FOP in the United States, based on contact with one of 3 leading treatment centers for FOP (University of Pennsylvania, Mayo Clinic, or University of California San Francisco), the International Fibrodysplasia Ossificans Progressiva Association (IFOPA) membership list, or the IFOPA FOP Registry through July 22, 2020.ResultsPatient records were reviewed, collected, and deduplicated using first and last name initials, sex, state, and year of birth. A Kaplan–Meier survival curve was applied to each individual patient to estimate the probability that he or she was still alive, and a probability-weighted net prevalence estimate was calculated. After deduplication, 373 unique patients were identified in the United States, 294 of whom who were not listed as deceased in any list. The average time since last contact for 284 patients was 1.5 years. Based on the application of the survival probability, it is estimated that 279 of these patients were alive on the prevalence date (22 July 2020). An adjusted prevalence of 0.88 per million US residents was calculated using either an average survival rate estimate of 98.4% or a conservative survival rate estimate of 92.3% (based on the Kaplan–Meier survival curve from a previous study) and the US Census 2020 estimate of 329,992,681 on prevalence day.ConclusionsThis study suggests that the prevalence of FOP is higher than the often-cited value of 0.5 per million. Even so, because inclusion in this study was contingent upon treatment by the authors, IFOPA membership with confirmed clinical diagnosis, and the FOP Registry, the prevalence of FOP in the US may be higher than that identified here. Thus, it is imperative that efforts be made to identify and provide expert care for patients with this ultra-rare, significantly debilitating disease.
Feasibility of a home-based interdisciplinary rehabilitation program for patients with Post-Intensive Care Syndrome: the REACH study
Authors: Major Mel E. , Dettling-Ihnenfeldt Daniela , Ramaekers Stephan P. J. , Engelbert Raoul H. H. , van der Schaaf Marike 
Published: August 2021

AbstractBackgroundSurvivors of critical illness experience long-term functional challenges, which are complex, heterogeneous, and multifactorial in nature. Although the importance of rehabilitation interventions after intensive care unit (ICU) discharge is universally recognized, evidence on feasibility and effectiveness of home-based rehabilitation programs is scarce and ambiguous. This study investigates the feasibility of an interdisciplinary rehabilitation program designed for patients with Post-Intensive Care Syndrome (PICS) who are discharged home.MethodsA mixed method, non-randomized, prospective pilot feasibility study was performed with a 6-month follow-up, comparing the intervention (REACH) with usual care. REACH was provided by trained professionals and included a patient-centered, interdisciplinary approach starting directly after hospital discharge. Primary outcomes were patient safety, satisfaction, adherence, referral need and health care usage. Secondary outcomes, measured at 3 timepoints, were functional exercise capacity, self-perceived health status, health-related quality of life (HRQoL), return to work and psychotrauma. Risk of undernutrition was assessed at baseline.Results43 patients with a median mechanical ventilation duration of 8 (IQR:10) days, were included in the study and 79.1% completed 6-month follow-up. 19 patients received the intervention, 23 received usual care. Groups were similar for gender distribution and ICU length of stay. No adverse events occurred. REACH participants showed higher satisfaction with treatment and reported more allied health professional visits, while the usual care group reported more visits to medical specialists. Qualitative analysis identified positive experiences among REACH-professionals related to providing state-of-the-art interventions and sharing knowledge and expertise within an interprofessional network. Similar recovery was seen between groups on all secondary outcomes, but neither group reached reference values for HRQoL at 6 months. Larger return to work rates were seen in the REACH group. Prevalence of undernutrition at hospital discharge was high in both groups (> 80%), warranting the need for careful tuning of physical therapy and nutritional interventions.ConclusionsThis study shows that providing early, home-based rehabilitation interventions for patients with PICS-related symptoms is feasible and perceived positively by patients and professionals. When provided in an interdisciplinary collaborative network state of the art, person-centered interventions can be tailored to individual needs potentially increasing patient satisfaction, adherence, and efficacy.Registered in the Dutch Trial register: NL7792:https://www.trialregister.nl/trial/7792, registered 7-06-2019.
Course and predictors of posttraumatic stress-related symptoms among family members of deceased ICU patients during the first year of bereavement
Authors: Tang Siew Tzuh , Huang Chung-Chi , Hu Tsung-Hui , Chou Wen-Chi , Chuang Li-Pang , Chiang Ming Chu 
Published: August 2021

AbstractBackground/ObjectiveDeath in intensive care units (ICUs) may increase bereaved family members’ risk for posttraumatic stress disorder (PTSD). However, posttraumatic stress-related symptoms (hereafter as PTSD symptoms) and their precipitating factors were seldom examined among bereaved family members and primarily focused on associations between PTSD symptoms and patient/family characteristics. We aimed to investigate the course and predictors of clinically significant PTSD symptoms among family members of deceased ICU patients by focusing on modifiable quality indicators for end-of-life ICU care.MethodIn this longitudinal observational study, 319 family members of deceased ICU patients were consecutively recruited from medical ICUs from two Taiwanese medical centers. PTSD symptoms were assessed at 1, 3, 6, and 13 months post-loss using the Impact of Event Scale-Revised (IES-R). Family satisfaction with end-of-life care in ICUs was assessed at 1 month post-loss. End-of-life care received in ICUs was documented over the patient’s ICU stay. Predictors for developing clinically significant PTSD symptoms (IES-R score ≥ 33) were identified by multivariate logistic regression with generalized estimating equation modeling.ResultsThe prevalence of clinically significant PTSD symptoms decreased significantly over time (from 11.0% at 1 month to 1.6% at 13 months post-loss). Longer ICU stays (adjusted odds ratio [95% confidence interval] = 1.036 [1.006, 1.066]), financial insufficiency (3.166 [1.159, 8.647]), and reported use of pain medications (3.408 [1.230, 9.441]) by family members were associated with a higher likelihood of clinically significant PTSD symptoms among family members during bereavement. Stronger perceived social support (0.937 [0.911, 0.965]) and having a Do-Not-Resuscitate (DNR) order issued before the patient’s death (0.073 [0.011, 0.490]) were associated with a lower likelihood of clinically significant PTSD symptoms. No significant association was observed for family members’ satisfaction with end-of-life care (0.988 [0.944, 1.034]) or decision-making in ICUs (0.980 [0.944, 1.018]).ConclusionsThe likelihood of clinically significant PTSD symptoms among family members decreased significantly over the first bereavement year and was lower when a DNR order was issued before death. Enhancing social support and facilitating a DNR order may reduce the trauma of ICU death of a beloved for family members at risk for developing clinically significant PTSD symptoms.
Specific splice junction detection in single cells with SICILIAN
Authors: Dehghannasiri Roozbeh , Olivieri Julia Eve , Damljanovic Ana , Salzman Julia 
Published: August 2021

AbstractPrecise splice junction calls are currently unavailable in scRNA-seq pipelines such as the 10x Chromium platform but are critical for understanding single-cell biology. Here, we introduce SICILIAN, a new method that assigns statistical confidence to splice junctions from a spliced aligner to improve precision. SICILIAN is a general method that can be applied to bulk or single-cell data, but has particular utility for single-cell analysis due to that data’s unique challenges and opportunities for discovery. SICILIAN’s precise splice detection achieves high accuracy on simulated data, improves concordance between matched single-cell and bulk datasets, and increases agreement between biological replicates. SICILIAN detects unannotated splicing in single cells, enabling the discovery of novel splicing regulation through single-cell analysis workflows.
Expression of Sonic Hedgehog and pathway components in the embryonic mouse head: anatomical relationships between regulators of positive and negative feedback
Authors: Sigulinsky Crystal L. , Li Xiaodong , Levine Edward M. 
Published: August 2021

Abstract
Objective
The Hedgehog pathway is a fundamental signaling pathway in organogenesis. The expression patterns of the ligand Sonic Hedgehog (Shh) and key pathway components have been studied in many tissues but direct spatial comparisons across tissues with different cell compositions and structural organization are not common and could reveal tissue-specific differences in pathway dynamics.

Results
We directly compared the expression characteristics of Shh, and four genes with functional roles in signaling and whose expression levels serve as readouts of pathway activity in multiple tissues of the embryonic mouse head at embryonic day 15.5 by serial in situ hybridization. The four readout genes were the positive feedback regulator Gli1, and three negative feedback regulators, Patched1, Patched2, and Hedgehog Interacting Protein. While the relative abundance of Gli1 was similar across tissues, the relative expression levels and spatial distribution of Shh and the negative feedback regulators differed, suggesting that feedback regulation of hedgehog signaling is context dependent. This comparative analysis offers insight into how consistent pathway activity could be achieved in tissues with different morphologies and characteristics of ligand expression.
Examination of social determinants of health among patients with limited English proficiency
Authors: Fischer Austin , Conigliaro Joseph , Allicock Shaun , Kim Eun Ji 
Published: August 2021

Abstract
Objectives
The purpose of this study is to examine the prevalence of social needs by English proficiency using data from Northwell Health’s social determinants of health screening program. The screening program evaluates 12 domains of social needs: material need, employment, medical-legal assistance, health insurance, public benefits, health literacy, transportation, medical care, utilities, housing quality, food security, and housing insecurity. We have identified patients to have limited English proficiency if they have selected a language other than English as their primary language.

Results
The study population includes 92,958 individuals; of these, 83,445 (89.8%) patients are English proficient, and 9513 (10.2%) patients have limited English proficiency. A higher percentage of patients with limited English proficiency has social needs, including material need, employment, medical-legal assistance, health insurance, public benefit, health literacy, medical care, utility bill, poor housing quality, and food insecurity (all p-values < 0.05). In multivariable logistic regression models adjusting for sociodemographic information, LEP status (odds ratio = 1.36 [1.25–1.49]) has been associated with having social needs. These findings suggest that system-wide SDH screening and referral programs should identify ways to ensure capturing social needs among patients with limited English proficiency.
Perivascular spaces are associated with tau pathophysiology and synaptic dysfunction in early Alzheimer’s continuum
Authors: Vilor-Tejedor Natalia , Ciampa Iacopo , Operto Grégory , Falcón Carles , Suárez-Calvet Marc , Crous-Bou Marta , Shekari Mahnaz , Arenaza-Urquijo Eider M. , Milà-Alomà Marta , Grau-Rivera Oriol , Minguillon Carolina , Kollmorgen Gwendlyn , Zetterberg Henrik , Blennow Kaj , Guigo Roderic , Molinuevo José Luis , Gispert Juan Domingo ,   for the ALFA study, Beteta Annabella , Brugulat Anna , Cacciaglia Raffaele , Cañas Alba , Deulofeu Carme , Cumplido Irene , Dominguez Ruth , Emilio Maria , Fauria Karine , Fuentes Sherezade , Hernandez Laura , Huesa Gema , Huguet Jordi , Marne Paula , Menchón Tania , Polo Albina , Pradas Sandra , Rodriguez-Fernandez Blanca , Sala-Vila Aleix , Sánchez-Benavides Gonzalo , Salvadó Gemma , Soteras Anna , Vilanova Marc 
Published: August 2021

Abstract
Background
Perivascular spaces (PVS) have an important role in the elimination of metabolic waste from the brain. It has been hypothesized that the enlargement of PVS (ePVS) could be affected by pathophysiological mechanisms involved in Alzheimer’s disease (AD), such as abnormal levels of CSF biomarkers. However, the relationship between ePVS and these pathophysiological mechanisms remains unknown.

Objective
We aimed to investigate the association between ePVS and CSF biomarkers of several pathophysiological mechanisms for AD. We hypothesized that ePVS will be associated to CSF biomarkers early in the AD continuum (i.e., amyloid positive cognitively unimpaired individuals). Besides, we explored associations between ePVS and demographic and cardiovascular risk factors.

Methods
The study included 322 middle-aged cognitively unimpaired participants from the ALFA + study, many within the Alzheimer’s continuum. NeuroToolKit and Elecsys® immunoassays were used to measure CSF Aβ42, Aβ40, p-tau and t-tau, NfL, neurogranin, TREM2, YKL40, GFAP, IL6, S100, and α-synuclein. PVS in the basal ganglia (BG) and centrum semiovale (CS) were assessed based on a validated 4-point visual rating scale. Odds ratios were calculated for associations of cardiovascular and AD risk factors with ePVS using logistic and multinomial models adjusted for relevant confounders. Models were stratified by Aβ status (positivity defined as Aβ42/40 < 0.071).

Results
The degree of PVS significantly increased with age in both, BG and CS regions independently of cardiovascular risk factors. Higher levels of p-tau, t-tau, and neurogranin were significantly associated with ePVS in the CS of Aβ positive individuals, after accounting for relevant confounders. No associations were detected in the BG neither in Aβ negative participants.

Conclusions
Our results support that ePVS in the CS are specifically associated with tau pathophysiology, neurodegeneration, and synaptic dysfunction in asymptomatic stages of the Alzheimer’s continuum.
Canadian food ladders for dietary advancement in children with IgE-mediated allergy to milk and/or egg
Authors: Chomyn Alanna , Chan Edmond S. , Yeung Joanne , Vander Leek Timothy K. , Williams Brock A. , Soller Lianne , Abrams Elissa M. , Mak Raymond , Wong Tiffany 
Published: August 2021

AbstractFood ladders are clinical tools already widely used in Europe for food reintroduction in milk- and egg-allergic children. Previously developed milk and egg ladders have limited applicability to Canadian children due to dietary differences and product availability. Herein we propose a Canadian version of cow’s milk and egg food ladders and discuss the potential role that food ladders may have in the care of children with IgE-mediated allergies to cow’s milk and/or egg, as either a method of accelerating the acquisition of tolerance in those who would outgrow on their own, or as a form of modified oral immunotherapy in those with otherwise persistent allergy.