bluuebunny/crossref_metadata_2025_split huggingface dataset:
A comparative study of international and Chinese public health emergency management from the perspective of knowledge domains mapping
Authors: Li Juan , Zhu Yuhang , Feng Jianing , Meng Weijing , Begma Kseniia , Zhu Gaopei , Wang Xiaoxuan , Wu Di , Shi Fuyan , Wang Suzhen 
Published: October 2020

AbstractBackgroundAt the end of 2019, the outbreak of coronavirus disease 2019 (COVID-19) severely damaged and endangered people’s lives. The public health emergency management system in China has played an essential role in handling the response to the outbreak, which has been appreciated by the World Health Organization and some countries. Hence, it is necessary to conduct an overall analysis of the development of the health emergency management system in China. This can provide a reference for scholars to aid in understanding the current situation and to reveal new research topics.MethodsWe collected 2247 international articles from the Web of Science database and 959 Chinese articles from the China National Knowledge Infrastructure database. Bibliometric and mapping knowledge domain analysis methods were used in this study for temporal distribution analysis, cooperation network analysis, and co-word network analysis.ResultsThe first international article in this field was published in 1991, while the first Chinese article was published in 2005. The research institutions producing these studies mainly existed in universities and health organizations. Developed countries and European countries published the most articles overall, while eastern China published the most articles within China. There were 52 burst words for international articles published from 1999–2018 and 18 burst words for Chinese articles published from 2003–2018. International top-ranked articles according to the number of citations appeared in 2005, 2007, 2009, 2014, 2015, and 2016, while the corresponding Chinese articles appeared in 2003, 2004, 2009, and 2011.ConclusionsThere are differences in the regional and economic distribution of international and Chinese cooperation networks. International research is often related to timely issues mainly by focusing on emergency preparedness and monitoring of public health events, while China has focused on public health emergencies and their disposition. International research began on terrorism and bioterrorism, followed by disaster planning and emergency preparedness, epidemics, and infectious diseases. China considered severe acute respiratory syndrome as the starting research background and the legal system construction as the research starting point, which was followed by the mechanism, structure, system, and training abroad for public health emergency management.
PALMER: improving pathway annotation based on the biomedical literature mining with a constrained latent block model
Authors: Nam Jin Hyun , Couch Daniel , da Silveira Willian A. , Yu Zhenning , Chung Dongjun 
Published: October 2020

AbstractBackgroundIn systems biology, it is of great interest to identify previously unreported associations between genes. Recently, biomedical literature has been considered as a valuable resource for this purpose. While classical clustering algorithms have popularly been used to investigate associations among genes, they are not tuned for the literature mining data and are also based on strong assumptions, which are often violated in this type of data. For example, these approaches often assume homogeneity and independence among observations. However, these assumptions are often violated due to both redundancies in functional descriptions and biological functions shared among genes. Latent block models can be alternatives in this case but they also often show suboptimal performances, especially when signals are weak. In addition, they do not allow to utilize valuable prior biological knowledge, such as those available in existing databases.ResultsIn order to address these limitations, here we propose PALMER, a constrained latent block model that allows to identify indirect relationships among genes based on the biomedical literature mining data. By automatically associating relevant Gene Ontology terms, PALMER facilitates biological interpretation of novel findings without laborious downstream analyses. PALMER also allows researchers to utilize prior biological knowledge about known gene-pathway relationships to guide identification of gene–gene associations. We evaluated PALMER with simulation studies and applications to studies of pathway-modulating genes relevant to cancer signaling pathways, while utilizing biological pathway annotations available in the KEGG database as prior knowledge.ConclusionsWe showed that PALMER outperforms traditional latent block models and it provides reliable identification of novel gene–gene associations by utilizing prior biological knowledge, especially when signals are weak in the biomedical literature mining dataset. We believe that PALMER and its relevant user-friendly software will be powerful tools that can be used to improve existing pathway annotations and identify novel pathway-modulating genes.
Single cell transcriptomes reveal expression patterns of chemoreceptor genes in olfactory sensory neurons of the Caribbean spiny lobster, Panulirus argus
Authors: Kozma Mihika T. , Ngo-Vu Hanh , Rump Matthew T. , Bobkov Yuriy V. , Ache Barry W. , Derby Charles D. 
Published: October 2020

Abstract
Background
Crustaceans express several classes of receptor genes in their antennules, which house olfactory sensory neurons (OSNs) and non-olfactory chemosensory neurons. Transcriptomics studies reveal that candidate chemoreceptor proteins include variant Ionotropic Receptors (IRs) including both co-receptor IRs and tuning IRs, Transient Receptor Potential (TRP) channels, Gustatory Receptors, epithelial sodium channels, and class A G-protein coupled receptors (GPCRs). The Caribbean spiny lobster, Panulirus argus, expresses in its antennules nearly 600 IRs, 17 TRP channels, 1 Gustatory Receptor, 7 epithelial sodium channels, 81 GPCRs, 6 G proteins, and dozens of enzymes in signaling pathways. However, the specific combinatorial expression patterns of these proteins in single sensory neurons are not known for any crustacean, limiting our understanding of how their chemosensory systems encode chemical quality.

Results
The goal of this study was to use transcriptomics to describe expression patterns of chemoreceptor genes in OSNs of P. argus. We generated and analyzed transcriptomes from 7 single OSNs, some of which were shown to respond to a food odor, as well as an additional 7 multicell transcriptomes from preparations containing few (2–4), several (ca. 15), or many (ca. 400) OSNs. We found that each OSN expressed the same 2 co-receptor IRs (IR25a, IR93a) but not the other 2 antennular coIRs (IR8a, IR76b), 9–53 tuning IRs but only one to a few in high abundance, the same 5 TRP channels plus up to 5 additional TRPs, 12–17 GPCRs including the same 5 expressed in every single cell transcriptome, the same 3 G proteins plus others, many enzymes in the signaling pathways, but no Gustatory Receptors or epithelial sodium channels. The greatest difference in receptor expression among the OSNs was the identity of the tuning IRs.

Conclusions
Our results provide an initial view of the combinatorial expression patterns of receptor molecules in single OSNs in one species of decapod crustacean, including receptors directly involved in olfactory transduction and others likely involved in modulation. Our results also suggest differences in receptor expression in OSNs vs. other chemosensory neurons.
Differential network analysis of bovine muscle reveals changes in gene coexpression patterns in response to changes in maternal nutrition
Authors: Liu Lihe , Amorín Rocío , Moriel Philipe , DiLorenzo Nicolás , Lancaster Phillip A. , Peñagaricano Francisco 
Published: October 2020

Abstract
Background
Coexpression network analysis is a powerful tool to reveal transcriptional regulatory mechanisms, identify transcription factors, and discover gene functions. It can also be used to investigate changes in coexpression patterns in response to environmental insults or changes in experimental conditions. Maternal nutrition is considered a major intrauterine regulator of fetal developmental programming. The objective of this study was to investigate structural changes in gene coexpression networks in the muscle of bull beef calves gestated under diets with or without methionine supplementation. Both muscle transcriptome and methylome were evaluated using next generation sequencing.

Results
Maternal methionine supplementation significantly perturbed coexpression patterns in the offspring’s muscle. Indeed, we found that neither the connection strength nor the connectivity pattern of six modules (subnetworks) detected in the control diet were preserved in the methionine-rich diet. Functional characterization revealed that some of the unpreserved modules are implicated in myogenesis, adipogenesis, fibrogenesis, canonical Wnt/β-catenin pathway, ribosome structure, rRNA binding and processing, mitochondrial activities, ATP synthesis and NAD(P) H oxidoreductases, among other functions. The bisulfite sequencing analysis showed that nearly 2% of all evaluated cytosines were differentially methylated between maternal diets. Interestingly, there were significant differences in the levels of gene body DNA methylation between preserved and unpreserved modules.

Conclusions
Overall, our findings provide evidence that maternal nutrition can significantly alter gene coexpression patterns in the offspring, and some of these perturbations are mediated by changes in DNA methylation.
Comparison of real-time PCR and the Kato-Katz method for the diagnosis of soil-transmitted helminthiasis and assessment of cure in a randomized controlled trial
Authors: Barda Beatrice , Schindler Christian , Wampfler Rahel , Ame Shaali , Ali Said M. , Keiser Jennifer 
Published: October 2020

Abstract
Background
Diagnosis of soil-transmitted helminths (STHs) in developing countries is commonly based on microscopic detection of eggs in stool samples, using the Kato-Katz (KK) method, which has a poor sensitivity for detecting light intensity infections. We compared the performance of the KK method and real-time PCR in the framework of a randomized trial, which evaluated four novel treatments against Trichuris trichiura and concomitant STH infections.

Results
Two stool samples obtained from 320 participants were examined at baseline and follow-up with quadruplicate KK and PCR analyses of one of the two samples using “bead-beating” for DNA extraction. At follow-up, 80 samples were negative according to both PCR and KK and 173 were positive with both methods for any of the STHs. Relative to PCR, the calculated sensitivity of KK at follow-up was 83.6%, 43.0% and 53.8% for T. trichiura, for hookworm and for Ascaris lumbricoides, respectively. The sensitivity of PCR compared with KK at this time point was 89.1% for T. trichiura, 72.7% for hookworm and 87.5% for A. lumbricoides. Cure rates (CRs) for T. trichiura and A. lumbricoides were slightly lower with the PCR method. For hookworm CRs with KK were mostly significantly lower, namely 36.7%, 91.1%, 72.2% and 77.8% for moxidectin, moxidectin in combination with tribendimidine, moxidectin in combination with albendazole and albendazole in combination with oxantel pamoate, respectively, whereas with PCR the CRs were 8.3%, 82.6%, 37.1% and 57.1%, respectively.

Conclusions
In conclusion, a single real-time PCR is as sensitive as quadruplicate KK for T. trichiura and A. lumbricoides detection but more sensitive for hookworm, which has an influence on the estimated treatment efficacy. PCR method with DNA extraction using the “bead-beating protocol” should be further promoted in endemic areas and laboratories that can afford the needed equipment.
The study is registered at ISRCTN (no. 20398469).
Impact of investigator initiated trials and industry sponsored trials on medical practice (IMPACT): rationale and study design
Authors: Nury E. , Bischoff K. , Wollmann K. , Nitschke K. , Lohner S. , Schumacher M. , Rücker G. , Blümle A. 
Published: October 2020

Abstract
Background
The German Research Foundation (DFG) and the Federal Ministry of Education and Research (BMBF) initiated large research programs to foster high quality clinical research in the academic area. These investigator initiated trials (IITs) cover important areas of medical research and often go beyond the scope of industry sponsored trials (ISTs). The purpose of this project was to understand to what extent results of randomized controlled IITs and ISTs have an impact on medical practice, measured by their availability for decisions in healthcare and their implementation in clinical practice. We aimed to determine study characteristics influencing a trial’s impact such as type of sponsor and place of conduct. In this article, we describe the rationale and design of this project and present the characteristics of the trials included in our study cohort.

Methods
The research impact of the following sub-cohorts was compared: German IITs (funded by DFG and BMBF or by other German non-commercial organizations), international IITs (without German contribution), German ISTs, and international ISTs. Trials included were drawn from the DFG−/BMBF-Websites, the German Clinical Trials Register, and from ClinicalTrials.gov. Research impact was measured as follows: 1) proportion of published trials, 2) time to publication, 3) proportion of publications appropriately indexed in biomedical databases, 4) proportion of openly accessible publications, 5) broadness of publication’s target group, 6) citation of publications by systematic reviews or meta-analyses, and 7) appearance of publications or citing systematic reviews or meta-analyses in clinical practice guidelines. We also aimed to identify study characteristics associated with the impact of trials.

Results
We included 691 trials: 120 German IITs, 200 International IITs, 171 German ISTs and 200 International ISTs. The median number of participants was 150, 30% were international trials and 70% national trials, 48% drug-trials and 52% non-drug trials. Overall, 72% of the trials had one pre-defined primary endpoint, 28% two or more (max. 36).

Conclusions
The results of this project deepen our understanding of the impact of biomedical research on clinical practice and healthcare policy, add important insights for the efficient allocation of scarce research resources and may facilitate providing accountability to the different stakeholders involved.
When complexity matters: a step-by-step guide to incorporating a complexity perspective in guideline development for public health and health system interventions
Authors: Movsisyan A. , Rehfuess E. , Norris S. L. 
Published: October 2020

Abstract
Background
Guidelines on public health and health system interventions often involve considerations beyond effectiveness and safety to account for the impact that these interventions have on the wider systems in which they are implemented. This paper describes how a complexity perspective may be adopted in guideline development to facilitate a more nuanced consideration of a range of factors pertinent to decisions regarding public health and health system interventions. These factors include acceptability and feasibility, and societal, economic, and equity and equality implications of interventions.

Main message
A 5-step process describes how to incorporate a complexity perspective in guideline development with examples to illustrate each step. The steps include: (i) guideline scoping, (ii) formulating questions, (iii) retrieving and synthesising evidence, (iv) assessing the evidence, and (v) developing recommendations. Guideline scoping using stakeholder consultations, complexity features, evidence mapping, logic modelling, and explicit decision criteria is emphasised as a key step that informs all subsequent steps.

Conclusions
Through explicit consideration of a range of factors and enhanced understanding of the specific circumstances in which interventions work, a complexity perspective can yield guidelines with better informed recommendations and facilitate local adaptation and implementation. Further work will need to look into the methods of collecting and assessing different types of evidence beyond effectiveness and develop procedural guidance for prioritising across a range of decision criteria.
Discovery and validation of mucosal TNF expression combined with histological score - a biomarker for personalized treatment in ulcerative colitis
Authors: Florholmen Jon R. , Johnsen Kay-Martin , Meyer Renate , Olsen Trine , Moe Øystein K. , Tandberg Petter , Gundersen Mona D. , Kvamme Jan-Magnus , Johnsen Knut , Løitegård Terje , Raschpichler Gabriele , Vold Cecilia , Sørbye Sveinung W. , Goll Rasmus 
Published: October 2020

Abstract
Background
There are no accurate markers that can predict clinical outcome in ulcerative colitis at time of diagnosis. The aim of this study was to explore a comprehensive data set to identify and validate predictors of clinical outcome in the first year following diagnosis.

Methods
Treatment naive-patients with ulcerative colitis were included at time of initial diagnosis from 2004 to 2014, followed by a validation study from 2014 to 2018. Patients were treated according to clinical guidelines following a standard step-up regime. Patients were categorized according to the treatment level necessary to achieve clinical remission: mild, moderate and severe. The biopsies were assessed by Robarts histopathology index (RHI) and TNF gene transcripts.

Results
We included 66 patients in the calibration cohort and 89 patients in the validation. Mucosal TNF transcripts showed high test reliability for predicting severe outcome in UC. When combined with histological activity (RHI) scores the test improved its diagnostic reliability. Based on the cut-off values of mucosal TNF and RHI scores from the calibration cohort, the combined test had still high reliability in the validation cohort (specificity 0.99, sensitivity 0.44, PPV 0.89, NPV 0.87) and a diagnostic odds-ratio (DOR) of 54.

Conclusions
The combined test using TNF transcript and histological score at debut of UC can predict severe outcome and the need for anti-TNF therapy with a high level of precision. These validated data may be of great clinical utility and contribute to a personalized medical approach with the possibility of top-down treatment for selected patients.
Peptide receptor radionuclide therapy controls inappropriate calcitriol secretion in a pancreatic neuro-endocrine tumor: a case report
Authors: Haemels Maarten , Delaunoit Thierry , Van Laere Koen , Van Cutsem Eric , Verslype Chris , Deroose Christophe M. 
Published: October 2020

Abstract
Background
Hypercalcemia of malignancy is not uncommon in patients with advanced stage cancer. In rare cases the cause of the hypercalcemia is excessive production of calcitriol, the active form of vitamin D. Although inappropriate tumoral secretion of calcitriol is typically associated with lymphomas and some ovarian germ cell tumors, we present a case of calcitriol overproduction-induced hypercalcemia due to a pancreatic neuroendocrine tumor. The high expression of somatostatin receptors on this neuroendocrine neoplasm opened up the opportunity to treat the patient with radiolabelled somatostatin analogs, which successfully controlled the refractory hypercalcaemia and calcitriol levels. This case documents a rare finding of refractory hypercalcaemia of underlying malignancy due to a calcitriol-producing pancreatic neuroendocrine tumor, responding to peptide receptor radionuclide therapy (PRRT).

Case presentation
A 57 years-old patient presented with back pain, general discomfort, polydipsia, polyuria, fatigue and recent weight loss of 10 kg. Clinical examination was normal and there was no relevant medical history. Biochemical evaluation showed hypercalcemia with markedly increased calcitriol levels. CT-thorax-abdomen and ultrasound guided biopsy revealed a pancreatic neuroendocrine tumor with multifocal liver metastases, suggesting that excessive overproduction of calcitriol by this neuroendocrine tumor was the cause of the refractory hypercalcemia. The patient was eligible for PRRT. Four cycles of 177Lu-DOTATATE PRRT resulted in a morphological response and a normalization of serum calcium levels, confirming the hypothesis of a calcitriol producing pancreatic neuroendocrine tumor. Progression of liver metastases warranted further therapy and temozolomide-capecitabine was started with morphological and biochemical (serum calcium, calcitriol) stabilization.

Conclusion
Although up to 30–40% of gastroenteropancreatic neuroendocrine tumors are known to be functional (i.e. producing symptoms associated with the predominant hormone/peptide secreted), calcitriol secreting pancreatic neuroendocrine tumors are very rare. However, treatment with PRRT resulted in normalization of calcium and calcitriol levels, strongly supporting the hypothesis of a calcitriol-producing pancreatic neuroendocrine tumor.
Accelerometry assessed physical activity of older adults hospitalized with acute medical illness - an observational study
Authors: Tasheva Plamena , Kraege Vanessa , Vollenweider Peter , Roulet Guillaume , Méan Marie , Marques-Vidal Pedro 
Published: October 2020

Abstract
Background
In a hospital setting and among older patients, inactivity and bedrest are associated with a wide range of negative outcomes such as functional decline, increased risk of falls, longer hospitalization and institutionalization. Our aim was to assess the distribution, determinants and predictors of physical activity (PA) levels using wrist-worn accelerometers in older patients hospitalized with acute medical illness.

Methods
Observational study conducted from February to November 2018 at an acute internal medicine unit in the University hospital of Lausanne, Switzerland. We enrolled 177 patients aged ≥65 years, able to walk prior to admission. PA during acute hospital stay was continuously recorded via a 3D wrist accelerometer. Clinical data was collected from medical records or by interview. Autonomy level prior to inclusion was assessed using Barthel Index score. PA levels were defined as < 30 mg for inactivity, 30–99 mg for light and ≥ 100 for moderate PA. Physically active patients were defined as 1) being in the highest quartile of time spent in light and moderate PA or 2) spending ≥20 min/day in moderate PA.

Results
Median [interquartile range - IQR] age was 83 [74–87] years and 60% of participants were male. The median [IQR] time spent inactive and in light PA was 613 [518–663] and 63 [30–97] minutes/day, respectively. PA peaked between 8 and 10 am, at 12 am and at 6 pm. Less than 10% of patients were considered physically active according to definition 2. For both definitions, active patients had a lower prevalence of walking aids and a lower dependency level according to Barthel Index score. For definition 1, use of medical equipment was associated with a 70% reduction in the likelihood of being active: odds ratio (OR) 0.30 [0.10–0.92] p = 0.034; for definition 2, use of walking aids was associated with a 75% reduction in the likelihood of being active: OR = 0.24 [0.06–0.89], p = 0.032.

Conclusion
Older hospitalized patients are physically active only 10% of daily time and concentrate their PA around eating periods. Whether a Barthel Index below 95 prior to admission may be used to identify patients at risk of inactivity during hospital stay remains to be proven.