bluuebunny/crossref_metadata_2025_split huggingface dataset:
PS4DR: a multimodal workflow for identification and prioritization of drugs based on pathway signatures
Authors: Emon Mohammad Asif , Domingo-Fernández Daniel , Hoyt Charles Tapley , Hofmann-Apitius Martin 
Published: June 2020

Abstract
Background
During the last decade, there has been a surge towards computational drug repositioning owing to constantly increasing -omics data in the biomedical research field. While numerous existing methods focus on the integration of heterogeneous data to propose candidate drugs, it is still challenging to substantiate their results with mechanistic insights of these candidate drugs. Therefore, there is a need for more innovative and efficient methods which can enable better integration of data and knowledge for drug repositioning.

Results
Here, we present a customizable workflow (PS4DR) which not only integrates high-throughput data such as genome-wide association study (GWAS) data and gene expression signatures from disease and drug perturbations but also takes pathway knowledge into consideration to predict drug candidates for repositioning. We have collected and integrated publicly available GWAS data and gene expression signatures for several diseases and hundreds of FDA-approved drugs or those under clinical trial in this study. Additionally, different pathway databases were used for mechanistic knowledge integration in the workflow. Using this systematic consolidation of data and knowledge, the workflow computes pathway signatures that assist in the prediction of new indications for approved and investigational drugs.

Conclusion
We showcase PS4DR with applications demonstrating how this tool can be used for repositioning and identifying new drugs as well as proposing drugs that can simulate disease dysregulations. We were able to validate our workflow by demonstrating its capability to predict FDA-approved drugs for their known indications for several diseases. Further, PS4DR returned many potential drug candidates for repositioning that were backed up by epidemiological evidence extracted from scientific literature. Source code is freely available at https://github.com/ps4dr/ps4dr.
Skin transcriptome reveals the periodic changes in genes underlying cashmere (ground hair) follicle transition in cashmere goats
Authors: Yang Feng , Liu Zhihong , Zhao Meng , Mu Qing , Che Tianyu , Xie Yuchun , Ma Lina , Mi Lu , Li Jinquan , Zhao Yanhong 
Published: June 2020

Abstract
Background
Cashmere goats make an outstanding contribution to the livestock textile industry and their cashmere is famous for its slenderness and softness and has been extensively studied. However, there are few reports on the molecular regulatory mechanisms of the secondary hair follicle growth cycle in cashmere goats. In order to explore the regular transition through the follicle cycle and the role of key genes in this cycle, we used a transcriptome sequencing technique to sequence the skin of Inner Mongolian cashmere goats during different months. We analyzed the variation and difference in genes throughout the whole hair follicle cycle. We then verified the regulatory mechanism of the cashmere goat secondary hair follicle growth cycle using fluorescence quantitative PCR.

Results
The growth cycle of cashmere hair could be divided into three distinct periods: a growth period (March–September), a regression period (September–December), and a resting period (December–March). The results of differential gene analyses showed that March was the most significant month. Cluster analysis of gene expression throughout the whole growth cycle further supported the key nodes of the three periods of cashmere growth, and the differential gene expression of keratin corresponding to the ground haircashmere growth cycle further supported the results from tissue slices. Quantitative fluorescence analysis showed that KAP3–1, KRTAP 8–1, and KRTAP 24–1 genes had close positive correlation with the cashmere growth cycle, and their regulation was consistent with the growth cycle of cashmere.

Conclusion
The growth cycle of cashmere cashmere could be divided into three distinct periods: a growth period (March–September), a regression period (September–December) and a resting period (December–March). March was considered to be the beginning of the cycle. KAP and KRTAP showed close positive correlation with the growth cycle of secondary hair follicle cashmere growth, and their regulation was consistent with the cashmere growth cycle. But hair follicle development-related genes are expressed earlier than cashmere growth, indicating that cycle regulation could alter the temporal growth of cashmere. This study laid a theoretical foundation for the study of the cashmere development cycle and provided evidence for key genes during transition through the cashmere cycle. Our study provides a theoretical basis for cashmere goat breeding.
Source-sink modifications affect leaf senescence and grain mass in wheat as revealed by proteomic analysis
Authors: Lv Xuemei , Zhang Yan , Zhang Yunxiu , Fan Shoujin , Kong Lingan 
Published: June 2020

Abstract
Background
The grain yield of cereals is determined by the synergistic interaction between source activity and sink capacity. However, source-sink interactions are far from being fully understood. Therefore, a field experiment was performed in wheat to investigate the responses of flag leaves and grains to sink/source manipulations.

Results
Half-degraining delayed but partial defoliation enhanced leaf senescence. Sink/source manipulations influenced the content of reactive oxygen species in the flag leaf and the concentration of phytohormones, including cytokinins, indoleacetic 3-acid and jasmonic acid, in the flag leaves (LDef) and grains (GDef) in defoliated plants and flag leaves (LDG) and grain (GDG) in de-grained plants. Isobaric tag for relative and absolute quantitation (iTRAQ)-based quantitative proteomic analysis indicated that at 16 days after manipulation, a total of 97 and 59 differentially expressed proteins (DEPs) from various functional categories were observed in the LDG and LDef groups, respectively, compared with the control, and 115 and 121 DEPs were observed in the GDG and GDef groups, respectively. The gene ontology annotation terms of the DEPs mainly included carbon fixation, hydrogen peroxide catabolic process, chloroplast and cytoplasm, oxidoreductase activity and glutamate synthase activity in the flag leaves of manipulated plants and organonitrogen compound metabolic process, cytoplasm, vacuolar membrane, CoA carboxylase activity, starch synthase activity and nutrient reservoir activity in the grains of manipulated plants. KEGG pathway enrichment analysis revealed that photosynthesis, carbon, nitrogen and pyruvate metabolism and glycolysis/gluconeogenesis were the processes most affected by sink/source manipulations. Sink/source manipulations affected the activities of amylase and proteinases and, ultimately, changed the mass per grain.

Conclusions
Manipulations to change the sink/source ratio affect hormone levels; hydrolytic enzyme activities; metabolism of carbon, nitrogen and other main compounds; stress resistance; and leaf senescence and thus influence grain mass.
Bayesian alternatives to null hypothesis significance testing in biomedical research: a non-technical introduction to Bayesian inference with JASP
Authors: Kelter Riko 
Published: June 2020

Abstract
Background
Although null hypothesis significance testing (NHST) is the agreed gold standard in medical decision making and the most widespread inferential framework used in medical research, it has several drawbacks. Bayesian methods can complement or even replace frequentist NHST, but these methods have been underutilised mainly due to a lack of easy-to-use software. JASP is an open-source software for common operating systems, which has recently been developed to make Bayesian inference more accessible to researchers, including the most common tests, an intuitive graphical user interface and publication-ready output plots. This article provides a non-technical introduction to Bayesian hypothesis testing in JASP by comparing traditional tests and statistical methods with their Bayesian counterparts.

Results
The comparison shows the strengths and limitations of JASP for frequentist NHST and Bayesian inference. Specifically, Bayesian hypothesis testing via Bayes factors can complement and even replace NHST in most situations in JASP. While p-values can only reject the null hypothesis, the Bayes factor can state evidence for both the null and the alternative hypothesis, making confirmation of hypotheses possible. Also, effect sizes can be precisely estimated in the Bayesian paradigm via JASP.

Conclusions
Bayesian inference has not been widely used by now due to the dearth of accessible software. Medical decision making can be complemented by Bayesian hypothesis testing in JASP, providing richer information than single p-values and thus strengthening the credibility of an analysis. Through an easy point-and-click interface researchers used to other graphical statistical packages like SPSS can seemlessly transition to JASP and benefit from the listed advantages with only few limitations.
Portal hypertension as a result of the incomplete surgically treated advanced alveolar echinococcosis: a case description
Authors: Pielok Ł. , Karczewski M. , Cierach W. , Zmora P. , Lenartowicz E. , Stefaniak J. 
Published: June 2020

Abstract
Background
Infection of Echinococcus multilocularis causes in humans the alveolar echinococcosis. Although the infection has world-wide distribution it is rarely detected. Diagnosis of alveococcosis is difficult because of not typical clinical picture and irregular results of radiological examinations suggesting neoplasmatic process which begins in the liver tissue or in the biliary tracts. The parasitic growth is slow, so the illness is quite often established in late invasion period. Treatment of long-lasting and late diagnosed infection is difficult and requires cooperation of parasitologists together with surgeons to avoid life-threatening organ dysfunction.

Case presentation
We describe a young male patient, diagnosed, according to the radiological, immunological and histological examination results, infection of Echinococcus multilocularis, who was treated with not radical resection of pathologic mass together with persistent albendazole intake. The right hepatectomy was performed. In addition, visible cysts were removed from the left lobe of the liver in nonanatomical resection and suspicious calcified lesions in hepatoduodenal ligament were also removed. After the operation portal hypertension, with splenomegaly and symptoms of the liver cirrhosis occurred (thrombocytopenia, collateral venous circulation, first degree varices oesophagii). The portal hypertension probably could be a result of incomplete surgery due to extended parasitic infection and liver anathomical changes due to performed procedures, because the portal hypertension and it’s further complications had not been observed before the operation.

Conclusions
Echinococcus multilocularis should be taken under consideration in differential diagnosis of irregular lesions within the liver. Lon-lasting invasion could be responsible for the irreversible secondary liver changes such as cirrhosis and portal hypertension. The surgery treatment (treatment of choice) is difficult and it’s results depends on the invasion period the patient is operated on. After the surgery the patient requires careful follow – up, to detect early complications.
A comprehensive assessment for community-based, person-centered care for older adults
Authors: Aronoff-Spencer Eliah , Asgari Padideh , Finlayson Tracy L. , Gavin Joseph , Forstey Melinda , Norman Gregory J. , Pierce Ian , Ochoa Carlos , Downey Paul , Becerra Karen , Agha Zia 
Published: June 2020

AbstractBackgroundMany health and social needs can be assessed and met in community settings, where lower-cost, person-centered, preventative and proactive services predominate. This study reports on the development and implementation of a person-centered care model integrating dental, social, and health services for low-income older adults at a community dental clinic co-located within a senior wellness center.MethodsA digital comprehensive geriatric assessment (CGA) and referral system linking medical, dental, and psychosocial needs by real-time CGA-derived metrics for 996 older adults (age ≥ 60) was implemented in 2016–2018 as part of a continuous quality improvement project. This study aims to describe: 1) the development and content of a new CGA; 2) CGA implementation, workflows, triage, referrals; 3) correlations between CGA domains, and adjusted regression models, assessing associations with self-reported recent hospitalizations, emergency department (ED) visits, and clinically-assessed dental urgency.ResultsThe multidisciplinary team from the senior wellness and dental centers planned and implemented a CGA that included standard medical history along with validated instruments for functional status, mental health and social determinants, and added oral health. Care navigators employed the CGA with 996 older adults, and made 1139 referrals (dental = 797, care coordination = 163, social work = 90, mental health = 32). CGA dimensions correlated between oral health, medical status, depressive symptoms, isolation, and reduced quality of life (QoL). Pain, medical symptoms, isolation and depressive symptoms were associated with poorer self-reported health, while general health was most strongly correlated with lower depressive symptoms, and higher functional status and QoL. Isolation was the strongest correlate of lower QoL.Adjusted odds ratios identified social and medical factors associated with recent hospitalization and ED visits. General and oral health were associated with dental urgency. Dental urgency was most strongly associated with general health (AOR = 1.78,95%CI [1.31, 2.43]), dental symptoms (AOR = 2.39,95%CI [1.78, 3.20]), dental pain (AOR = 2.06,95%CI [1.55–2.74]), and difficulty chewing (AOR = 2.80, 95%CI [2.09–3.76]). Dental symptoms were associated with recent ED visits (AOR = 1.61, 95%CI [1.12–2.30]) or hospitalizations (AOR = 1.47, 95%CI [1.04–2.10]).ConclusionCommunity-based inter-professional care is feasible with CGAs that include medical, dental, and social factors. A person-centered care model requires coordination supported by new workflows. Real-time metrics-based triage process provided efficient means for client review and a robust process to surface needs in complex cases.
Measles outbreak amplified in a pediatric ward: Lyantonde District, Uganda, August 2017
Authors: Biribawa Claire , Atuhairwe Joselyn Annet , Bulage Lilian , Okethwangu Denis Othuba , Kwesiga Benon , Ario Alex Riolexus , Zhu Bao-Ping 
Published: June 2020

Abstract
Background
Measles is a highly infectious viral disease. In August 2017, Lyantonde District, Uganda reported a measles outbreak to Uganda Ministry of Health. We investigated the outbreak to assess the scope, factors facilitating transmission, and recommend control measures.

Methods
We defined a probable case as sudden onset of fever and generalized rash in a resident of Lyantonde, Lwengo, or Rakai Districts from 1 June-30 September 2017, plus ≥1 of the following: coryza, conjunctivitis, or cough. A confirmed case was a probable case with serum positivity of measles-specific IgM. We conducted a neighborhood- and age-matched case-control study to identified exposure factors, and used conditional logistic regression to analyze the data. We estimated vaccine effectiveness and vaccination coverage.

Results
We identified 81 cases (75 probable, 6 confirmed); 4 patients (4.9%) died. In the case-control study, 47% of case-patients and 2.3% of controls were hospitalized at Lyantonde Hospital pediatric department for non-measles conditions 7–21 days before case-patient’s onset (ORadj = 34, 95%CI: 5.1–225). Estimated vaccine effectiveness was 95% (95%CI: 75–99%) and vaccination coverage was 76% (95%CI: 68–82%). During the outbreak, an “isolation” ward was established inside the general pediatric ward where there was mixing of both measles and non-measles patients.

Conclusions
This outbreak was amplified by nosocomial transmission and facilitated by low vaccination coverage. We recommended moving the isolation ward outside of the building, supplemental vaccination, and vaccinating pediatric patients during measles outbreaks.
Identification of a novel WAS mutation in a South African patient presenting with atypical Wiskott-Aldrich syndrome: a case report
Authors: Glanzmann Brigitte , Möller Marlo , Schoeman Mardelle , Urban Michael , van Helden Paul D. , Frigati Lisa , Grewal Ravnit , Pieters Hermanus , Loos Ben , Hoal Eileen G. , Glashoff Richard H. , Cornelissen Helena , Rabie Helena , Esser Monika M. , Kinnear Craig J. 
Published: June 2020

AbstractBackgroundThe X-linked recessive primary immunodeficiency disease (PIDD) Wiskott-Aldrich syndrome (WAS) is identified by an extreme susceptibility to infections, eczema and thrombocytopenia with microplatelets. The syndrome, the result of mutations in theWASgene which encodes the Wiskott-Aldrich protein (WASp), has wide clinical phenotype variation, ranging from classical WAS to X-linked thrombocytopaenia and X-linked neutropaenia. In many cases, the diagnosis of WAS in first affected males is delayed, because patients may not present with the classic signs and symptoms, which may intersect with other thrombocytopenia causes.Case presentationHere, we describe a three-year-old HIV negative boy presenting with recurrent infections, skin rashes, features of autoimmunity and atopy. However, platelets were initially reported as normal in numbers and morphology as were baseline immune investigations. An older male sibling had died in infancy from suspected immunodeficiency. Uncertainty of diagnosis and suspected severe PIDD prompted urgent further molecular investigation. Whole exome sequencing identifiedc. 397 G > Aas a novel hemizygous missense mutation located in exon 4 ofWAS.ConclusionWith definitive molecular diagnosis, we could target treatment and offer genetic counselling and prenatal diagnostic testing to the family. The identification of novel variants is important to confirm phenotype variations of a syndrome.
Adenocarcinomatous-predominant subtype associated with a better prognosis in adenosquamous lung carcinoma
Authors: Liu Yangli , Zhu Ying , Bai Lihong , Chen Fengjia , Wang Jue , Guo Yubiao 
Published: June 2020

Abstract
Background
According to the proportion of glandular and squamous pathological components, adenosquamous carcinoma (ASC) could be divided into adenocarcinoma (AC) and squamous cell carcinoma (SCC) predominant subtypes. Due to its rarity, no study investigating the impact of different subtypes on the clinical features, radiologic findings and prognosis characteristics of ASC has been reported.

Methods
Sixty eight patients who underwent surgical resection for lung adenosquamous carcinoma in our institute between January 2006 and March 2017 were retrospectively reviewed. Data regarding the clinical features, radiologic findings and prognosis characteristics were collected.

Results
Thirty nine patients of the study cohort were with AC-predominant ASC and 29 with SCC-predominant ASC. There was no significant difference between the two subgroups in age, gender, smoking history, serum carcinoembryonic antigen (CEA) level and T,N classification. Air bronchogram was found more frequently in AC-predominant ASC than in SCC-predominant ASC (P = 0.046). Multivariate analysis identified pathological subtype (P = 0.022) and CT findings of peripheral location (P = 0.009) to be independent prognostic factors.

Conclusions
AC-predominant ASC were more commonly presented with air bronchogram, and were with a better prognosis than SCC-predominant ASC.
The patient-level effect of the cost of Cancer care – financial burden in German Cancer patients
Authors: Mehlis Katja , Witte Julian , Surmann Bastian , Kudlich Matthias , Apostolidis Leonidas , Walther Jürgen , Jäger Dirk , Greiner Wolfgang , Winkler Eva C. 
Published: June 2020

Abstract
Background
Financial toxicity of cancer has so far been discussed primarily in the US health care system and is associated with higher morbidity and mortality. In European health care systems, the socio-economic impact of cancer is poorly understood. This study investigates the financial burden and patient-reported outcomes of neuroendocrine (NET) or colorectal (CRC) cancer patients at a German Comprehensive Cancer Center.

Methods
This prospective cross-sectional study surveyed 247 advanced stage patients (n = 122 NET/n = 125 CRC) at the National Center for Tumor Diseases, in Germany about cancer-related out-of-pocket costs, income loss, distress, and quality of life. Multiple linear regression analysis was performed to demonstrate the effects of economic deterioration on patients’ quality of life and distress.

Results
81% (n = 199) of the patients reported out-of-pocket costs, and 37% (n = 92) income loss as a consequence of their disease. While monthly out-of-pocket costs did not exceed 200€ in 77% of affected patients, 24% of those with income losses reported losing more than 1.200€ per month. High financial loss relative to income was significantly associated with patients’ reporting a worse quality of life (p < .05) and more distress (p < .05).

Conclusions
Financial toxicity in third-party payer health care systems like Germany is caused rather by income loss than by co-payments. Distress and reduced quality of life due to financial problems seem to amplify the burden that already results from a cancer diagnosis and treatment. If confirmed at a broader scale, there is a need for targeted support measures at the individual and system level.
Clozapine rechallenge and initiation despite neutropenia- a practical, step-by-step guide
Authors: Silva Edward , Higgins Melanie , Hammer Barbara , Stephenson Paul 
Published: June 2020

AbstractClozapine remains the only drug treatment likely to benefit patients with treatment resistant schizophrenia. Its use is complicated by an increased risk of neutropenia and so there are stringent monitoring requirements and restrictions in those with previous neutropenia from any cause or from clozapine in particular. Despite these difficulties clozapine may yet be used following neutropenia, albeit with caution. Having had involvement with 14 cases of clozapine use in these circumstances we set out our approach to the assessment of risks and benefits, risk mitigation and monitoring with a practical guide.