bluuebunny/crossref_metadata_2025_split huggingface dataset:
TB-PRACTECAL: study protocol for a randomised, controlled, open-label, phase II–III trial to evaluate the safety and efficacy of regimens containing bedaquiline and pretomanid for the treatment of adult patients with pulmonary multidrug-resistant tuberculosis
Authors: Berry Catherine , du Cros Philipp , Fielding Katherine , Gajewski Suzanne , Kazounis Emil , McHugh Timothy D. , Merle Corinne , Motta Ilaria , Moore David A. J. , Nyang’wa Bern-Thomas 
Published: June 2022

Abstract
Background
Globally rifampicin-resistant tuberculosis disease affects around 460,000 people each year. Currently recommended regimens are 9–24 months duration, have poor efficacy and carry significant toxicity. A shorter, less toxic and more efficacious regimen would improve outcomes for people with rifampicin-resistant tuberculosis.

Methods
TB-PRACTECAL is an open-label, randomised, controlled, phase II/III non-inferiority trial evaluating the safety and efficacy of 24-week regimens containing bedaquiline and pretomanid to treat rifampicin-resistant tuberculosis. Conducted in Uzbekistan, South Africa and Belarus, patients aged 15 and above with rifampicin-resistant pulmonary tuberculosis and requiring a new course of therapy were eligible for inclusion irrespective of HIV status. In the first stage, equivalent to a phase IIB trial, patients were randomly assigned one of four regimens, stratified by site. Investigational regimens include oral bedaquiline, pretomanid and linezolid. Additionally, two of the regimens also included moxifloxacin (arm 1) and clofazimine (arm 2) respectively. Treatment was administered under direct observation for 24 weeks in investigational arms and 36 to 96 weeks in the standard of care arm. The second stage of the study was equivalent to a phase III trial, investigating the safety and efficacy of the most promising regimen/s. The primary outcome was the percentage of unfavourable outcomes at 72 weeks post-randomisation. This was a composite of early treatment discontinuation, treatment failure, recurrence, lost-to-follow-up and death. The study is being conducted in accordance with ICH-GCP and full ethical approval was obtained from Médecins sans Frontières ethical review board, London School of Hygiene and Tropical Medicine ethical review board as well as ERBs and regulatory authorities at each site.

Discussion
TB-PRACTECAL is an ambitious trial using adaptive design to accelerate regimen assessment and bring novel treatments that are effective and safe to patients quicker. The trial took a patient-centred approach, adapting to best practice guidelines throughout recruitment. The implementation faced significant challenges from the COVID-19 pandemic. The trial was terminated early for efficacy on the advice of the DSMB and will report on data collected up to the end of recruitment and, additionally, the planned final analysis at 72 weeks after the end of recruitment.

Trial registration
Clinicaltrials.gov NCT02589782. Registered on 28 October 2015.
Establishing a core outcome set for neurogenic bladder trials: study protocol for a scoping review and Delphi surveys
Authors: Zhang Yan , Chen Yamin , Niu Mingming , Li Yuanyuan , Zhang Jiaoyan , Zhang Li , Wu Fangfang , Chen Qingyun , Yu Huijin , Tian Jinhui 
Published: June 2022

AbstractBackgroundNeurogenic bladder (NGB) is a chronic and disabling condition with a high prevalence rate, which can cause economic burden on patients and their families and reduce the quality of life of patients. Researchers have carried out a large number of clinical trials on the effectiveness and safety of different interventions for the treatment of NGB. The published clinical trials of NGB generally suffered from inconsistent and irregular reporting of outcome indicators. To facilitate future research studies of NGB, a core outcome set (COS) is required, which helps translate the results into high-quality evidence.Methods and analysisThis mixed-method project has four phases instrument: in phase 1, a scoping review of the literature to identify outcomes that have been reported in clinical trials and systematic reviews of clinical trials of interventions for NGB; in phase 2, a qualitative component using interviews to obtain the views of NGB patients, families, and their caregivers; in phase 3, Delphi survey among stakeholders to prioritize the core outcomes; and in phase 4, a face-to-face consensus meeting to discuss and agree on the final NBG COS.ConclusionsWe will develop a COS that should be reported in future clinical trials of NGB.Trial registrationCore Outcome Measures in Effectiveness Trials (COMET) Initiative database registration:http://www.comet-initiative.org/studies/details/1985. Registered on 02 January 2022. INPLASY INPLASY202210007
Effect of smartphone app-based health care intervention for health management of high-risk mothers: a study protocol for a randomized controlled trial
Authors: Kim Bora , Moon Jong Youn , Shin Jae Yong , Jeon Hae Rin , Oh So Yeon , Kim Suk Young 
Published: June 2022

Abstract
Background
The 4th Industrial Revolution with the advent of the smart era, in which artificial intelligence, such as big data analysis and machine learning, is expected, and the provision of healthcare services using smartphones has become a reality. In particular, high-risk mothers who experience gestational diabetes, gestational hypertension, and prenatal and postpartum depression are highly likely to have adverse effects on the mother and newborn due to the disease. Therefore, continuous observation and intervention in health management are needed to prevent diseases and promote healthy behavior for a healthy life.

Methods
This randomized controlled trial will provide mothers 18 years of age or older with health care information collected based on evidence-based literature data using a smartphone app for 6 weeks. About 500 mothers will be selected in consideration of the dropout rate due to the characteristics of mothers. The study group and control group will be computer-generated in a 1:1 ratio through random assignment. The research group will receive health management items through the app, and health management information suitable for the pregnancy cycle is pushed to an alarm. The control group will receive the health management information of the paper. We also followed the procedure for developing mobile apps using the IDEAS framework.

Discussion
These results show the effectiveness of smart medical healthcare services and promote changes in health behaviors throughout pregnancy in high-risk mothers.

Trial registration
Clinical trial registration information for this study has been registered with WHO ICTRP and CRIS (Korea Clinical Research Information Service, CRIS). Clinical trial registration information is as follows:
Study of development of integrated smart health management service for the whole life cycle of high-risk mothers and newborns based on community, KCT0007193. Registered on April 14, 2022, prospectively registered. This protocol version is Version 1.0. April 14, 2022.
Efficacy of dexmedetomidine on postoperative pain in patients undergoing gastric and esophageal endoscopic submucosal dissection: a study protocol for a randomized controlled prospective trial
Authors: Luo Xin , An Li-Xin , Chen Pei-Shan , Chang Xin-Lu , Li Yang 
Published: June 2022

Abstract
Background
Endoscopic submucosal dissection (ESD) is widely used as an effective treatment of early gastric and esophageal tumors, as it is minimally invasive, safe, and convenient. Epigastric pain is a common complication of ESD. In the traditional cognition, the postoperative pain of ESD is not serious and does not attach too much attention. However, previous studies found that the incidence of moderate to severe pain after ESD can be as high as 44.9~62.8%. At present, there is no unified understanding of how to carry out good postoperative analgesia in patients undergoing ESD of stomach and esophagus. The purpose of present study is to investigate the efficacy of intraoperative dexmedetomidine (DEX) using on postoperative pain though observing the postoperative visual analog scale (VAS) score within 48 h after ESD surgery, so as to explore an effective analgesia and anesthetic method in patients undergoing gastric and esophagus ESD.

Methods/design
This study is a prospective, single-center, two-arm, randomized control trail. In total, 120 patients undergoing endoscopic submucosal dissection were stratified by type of surgery (i.e., gastric or esophagus ESD) and randomized into two treatment groups, DEX group (group D, n = 60) and control group (group C, n = 60). Patients in the experimental group (DEX group) will be administrated a loading dose of DEX at 1 μg/kg for 15 min and a continuous infusion at 0.6 μg/kg/h until 30 min before the end of operation. In control group, the same volume of normal saline was infused. The primary outcome is VAS at 2 h after ESD surgery. The secondary outcome will be VAS at 1 h, 4 h, 6 h,18 h, 24 h, and 48 h, the status of perioperative hemodynamics, the use of remedial analgesics, sedation score, shivering, postoperative nausea and vomiting (PONV), and satisfaction scores of patient and complication of ESD (such as bleeding, perforation, aspiration pneumonia).

Discussion
The results of this study will demonstrate that intraoperative application of DEX is beneficial for postoperative pain treatment in patients undergoing ESD. This study will not only confirm that postoperative pain treatment is necessary for patients undergoing ESD but also provides an effective anesthesia method for postoperative analgesia.

Trial registration
Chinese Clinical Trial Registry, ID: ChiCTR2100043837, registered on March 4, 2021, http://www.chictr.org.cn.
Influence on study outcomes of an inpatient study by the behavior of the study staff (PINgPOng): study protocol for a randomized clinical trial
Authors: Coenen Martin , Bingel Ulrike , Zunhammer Matthias , Berdaguer Maria Soledad , Fuhrmann Christine , Fimmers Rolf , Rengelshausen Jens , Hartmann Gunther , Schedlowski Manfred , Coch Christoph 
Published: June 2022

Abstract
Background
The placebo effect as the symptom improvement following inert treatments is a fixed component of RCTs to differentiate between specific effects of the tested pharmacological substance from other unspecific effects. The PINgPOng study was set up to analyze the influence of a study team trained to either minimize the placebo response and optimize drug-placebo differences or to maximize the placebo response to increase drug efficacy by unspecific factors on the study results of a RCT in a classical early clinical trial setting.

Methods/design
PINgPOng is a single-center, prospective, randomized, double-blind, placebo-controlled study in a 3-group, 2-sequence, 2-period cross-over design. The study is conducted according to the principles of ICH-GCP and the Declaration of Helsinki on the Phase I-Unit of the University Hospital Bonn. The primary endpoint is the pain intensity in the cold pressor test before and after the administration of 15 mg oxycodone or placebo. The pain intensity is compared between three study conditions: 32 healthy volunteers in each study arm will be treated either by an untrained study team (arm A), by a study team trained to maximize (arm B), or to minimize placebo responses (arm C). Neuroendocrine factors (alpha-amylase activity, salivary cortisol), characteristic traits (anxiety, depression, stress), and somatic reactions are analyzed as covariates of the pain perception.

Discussion
The PINgPOng study will allow to answer the question whether and to what extent the behavior of a trained study team (neutral vs. maximize vs. minimize placebo responses) will differentially affect placebo responses in a setting of a highly standardized early clinical trial. The results will help to control the placebo effects by education of the clinical study team and to avoid unnecessary high placebo effects in clinical development.

Trial registration
German Clinical Trials Register DRKS00013586. Registered on December 22, 2017.
Amplification of LTRs of extrachromosomal linear DNAs (ALE-seq) identifies two active Oryco LTR retrotransposons in the rice cultivar Dongjin
Authors: Koo Hyunjin , Kim Soomin , Park Hyun-Seung , Lee Sang-Ji , Paek Nam-Chon , Cho Jungnam , Yang Tae-Jin 
Published: June 2022

AbstractLong terminal repeat retrotransposons (LTR-RTs) make up a considerable portion of plant genomes. New insertions of these active LTR-RTs modify gene structures and functions and play an important role in genome evolution. Therefore, identifying active forms of LTR-RTs could uncover the effects of these elements in plants. Extrachromosomal linear DNA (eclDNA) forms during LTR-RT replication; therefore, amplification LTRs of eclDNAs followed by sequencing (ALE-seq) uncover the current transpositional potential of the LTR-RTs. The ALE-seq protocol was validated by identification of Tos17 in callus of Nipponbare cultivar. Here, we identified two active LTR-RTs belonging to the Oryco family on chromosomes 6 and 9 in rice cultivar Dongjin callus based on the ALE-seq technology. Each Oryco family member has paired LTRs with identical sequences and internal domain regions. Comparison of the two LTR-RTs revealed 97% sequence identity in their internal domains and 65% sequence identity in their LTRs. These two putatively active Oryco LTR-RT family members could be used to expand our knowledge of retrotransposition mechanisms and the effects of LTR-RTs on the rice genome.
KNIME workflow for retrieving causal drug and protein interactions, building networks, and performing topological enrichment analysis demonstrated by a DILI case study
Authors: Füzi Barbara , Malik-Sheriff Rahuman S. , Manners Emma J. , Hermjakob Henning , Ecker Gerhard F. 
Published: June 2022

AbstractAs an alternative to one drug-one target approaches, systems biology methods can provide a deeper insight into the holistic effects of drugs. Network-based approaches are tools of systems biology, that can represent valuable methods for visualizing and analysing drug-protein and protein–protein interactions. In this study, a KNIME workflow is presented which connects drugs to causal target proteins and target proteins to their causal protein interactors. With the collected data, networks can be constructed for visualizing and interpreting the connections. The last part of the workflow provides a topological enrichment test for identifying relevant pathways and processes connected to the submitted data. The workflow is based on openly available databases and their web services. As a case study, compounds of DILIRank were analysed. DILIRank is the benchmark dataset for Drug-Induced Liver Injury by the FDA, where compounds are categorized by their likeliness of causing DILI. The study includes the drugs that are most likely to cause DILI (“mostDILI”) and the ones that are not likely to cause DILI (“noDILI”). After selecting the compounds of interest, down- and upregulated proteins connected to the mostDILI group were identified; furthermore, a liver-specific subset of those was created. The downregulated sub-list had considerably more entries, therefore, network and causal interactome were constructed and topological pathway enrichment analysis was performed with this list. The workflow identified proteins such as Prostaglandin G7H synthase 1 and UDP-glucuronosyltransferase 1A9 as key participants in the potential toxic events disclosing the possible mode of action. The topological network analysis resulted in pathways such as recycling of bile acids and salts and glucuronidation, indicating their involvement in DILI. The KNIME pipeline was built to support target and network-based approaches to analyse any sets of drug data and identify their target proteins, mode of actions and processes they are involved in. The fragments of the pipeline can be used separately or can be combined as required.
Commentary: the first twelve years of the Journal of Cheminformatics
Authors: Willett Peter 
Published: June 2022

AbstractThis commentary provides an overview of the publications in, and the citations to, the first twelve volumes of the Journal of Cheminformatics, covering the period 2009–2020. The analysis is based on the 622 articles that have appeared in the journal during that time and that have been indexed in the Clarivate Web of Science Core Collection database. It is clear that the journal has established itself as one of the most important publications in the field of cheminformatics: it attracts citations not only from other journals in its specialist field but also from biological and chemical journals more widely, and moreover from journals that are far removed in focus from it but that are still able to benefit from the articles that it publishes.
Gastric Helicobacter species associated with dogs, cats and pigs: significance for public and animal health
Authors: Taillieu Emily , Chiers Koen , Amorim Irina , Gärtner Fátima , Maes Dominiek , Van Steenkiste Christophe , Haesebrouck Freddy 
Published: June 2022

AbstractThis article focuses on the pathogenic significance ofHelicobacterspecies naturally colonizing the stomach of dogs, cats and pigs. These gastric “non-Helicobacter(H.)pylori Helicobacterspecies” (NHPH) are less well-known than the human adaptedH. pylori.Helicobacter suishas been associated with gastritis and decreased daily weight gain in pigs. Several studies also attribute a role to this pathogen in the development of hyperkeratosis and ulceration of the non-glandular stratified squamous epithelium of thepars oesophageaof the porcine stomach.The stomach of dogs and cats can be colonized by severalHelicobacterspecies but their pathogenic significance for these animals is probably low.Helicobacter suisas well as several canine and feline gastricHelicobacterspecies may also infect humans, resulting in gastritis, peptic and duodenal ulcers, and low-grade mucosa-associated lymphoid tissue lymphoma. These agents may be transmitted to humans most likely through direct or indirect contact with dogs, cats and pigs. Additional possible transmission routes include consumption of water and, forH. suis, also consumption of contaminated pork. It has been described that standardH. pylorieradication therapy is usually also effective to eradicate the NHPH in human patients, although acquired antimicrobial resistance may occasionally occur and porcineH. suisstrains are intrinsically less susceptible to aminopenicillins than non-human primateH. suisstrains and other gastricHelicobacterspecies. Virulence factors ofH. suisand the canine and feline gastricHelicobacterspecies include urease activity, motility, chemotaxis, adhesins and gamma-glutamyl transpeptidase. These NHPH, however, lack orthologs of cytotoxin-associated gene pathogenicity island and vacuolating cytotoxin A, which are major virulence factors inH. pylori.It can be concluded that besidesH. pylori, gastricHelicobacterspecies associated with dogs, cats and pigs are also clinically relevant in humans. Although recent research has provided better insights regarding pathogenic mechanisms and treatment strategies, a lot remains to be investigated, including true prevalence rates, exact modes of transmission and molecular pathways underlying disease development and progression.
Loop diuretics in adult intensive care patients with fluid overload: a systematic review of randomised clinical trials with meta-analysis and trial sequential analysis
Authors: Wichmann Sine , Barbateskovic Marija , Liang Ning , Itenov Theis Skovsgaard , Berthelsen Rasmus Ehrenfried , Lindschou Jane , Perner Anders , Gluud Christian , Bestle Morten Heiberg 
Published: June 2022

Abstract
Background
Fluid overload is a risk factor for organ dysfunction and death in intensive care unit (ICU) patients, but no guidelines exist for its management. We systematically reviewed benefits and harms of a single loop diuretic, the predominant treatment used for fluid overload in these patients.

Methods
We conducted a systematic review with meta-analysis and Trial Sequential Analysis (TSA) of a single loop diuretic vs. other interventions reported in randomised clinical trials, adhering to our published protocol, the Cochrane Handbook, and PRISMA statement. We assessed the risks of bias with the ROB2-tool and certainty of evidence with GRADE. This study was registered in the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42020184799).

Results
We included 10 trials (804 participants), all at overall high risk of bias. For loop diuretics vs. placebo/no intervention, we found no difference in all-cause mortality (relative risk (RR) 0.72, 95% confidence interval (CI) 0.49–1.06; 4 trials; 359 participants; I2 = 0%; TSA-adjusted CI 0.15–3.48; very low certainty of evidence). Fewer serious adverse events were registered in the group treated with loop diuretics (RR 0.81, 95% CI 0.66–0.99; 6 trials; 476 participants; I2 = 0%; very low certainty of evidence), though contested by TSA (TSA-adjusted CI 0.55–1.20).

Conclusions
The evidence is very uncertain about the effect of loop diuretics on mortality and serious adverse events in adult ICU patients with fluid overload. Loop diuretics may reduce the occurrence of these outcomes, but large randomised placebo-controlled trials at low risk of bias are needed.
Joint high-dimensional soft bit estimation and quantization using deep learning
Authors: Arvinte Marius , Vishwanath Sriram , Tewfik Ahmed H. , Tamir Jonathan I. 
Published: June 2022

AbstractForward error correction using soft probability estimates is a central component in modern digital communication receivers and impacts end-to-end system performance. In this work, we introduce EQ-Net: a deep learning approach for joint soft bit estimation (E) and quantization (Q) in high-dimensional multiple-input multiple-output (MIMO) systems. We propose a two-stage algorithm that uses soft bit quantization as pretraining for estimation and is motivated by a theoretical analysis of soft bit representation sizes in MIMO channels. Our experiments demonstrate that a single deep learning model achieves competitive results on both tasks when compared to previous methods, with gains in quantization efficiency as high as$$20\%$$20%and reduced estimation latency by at least$$21\%$$21%compared to other deep learning approaches that achieve the same end-to-end performance. We also demonstrate that the quantization approach is feasible in single-user MIMO scenarios of up to$$64 \times 64$$64×64and can be used with different soft bit estimation algorithms than the ones during training. We investigate the robustness of the proposed approach and demonstrate that the model is robust to distributional shifts when used for soft bit quantization and is competitive with state-of-the-art deep learning approaches when faced with channel estimation errors in soft bit estimation.
Existence and stability results for non-hybrid single-valued and fully hybrid multi-valued problems with multipoint-multistrip conditions
Authors: Rezapour Shahram , Ahmad Bashir , Boutiara Abdellatif , Nonlaopon Kamsing , Etemad Sina 
Published: June 2022

AbstractIn this paper, we study a new class of non-hybrid single-valued fractional boundary value problems equipped with integro-non-hybrid-multiterm-multipoint-multistrip conditions and a fully hybrid integro-multi-valued fractional boundary value problem by some new methods including the Kuratowski measures based on Sadovskii’s theorem, Krasnoselskii–Zabreiko criterion, and Dhage’s technique. We generalize the Gronwall inequality in relation to a non-hybrid single-valued fractional boundary value problem, and then we investigate the stability notions in two versions. To examine the correctness of the results, we provide some examples.