bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of acupuncture in the prevention and treatment of chemotherapy-induced nausea and vomiting in patients with advanced cancer: a multi-center, single-blind, randomized, sham-controlled clinical research
Authors: Li Qi-Wei , Yu Ming-Wei , Wang Xiao-Min , Yang Guo-Wang , Wang Huan , Zhang Chen-Xi , Xue Na , Xu Wei-Ru , Zhang Yi , Cheng Pei-Yu , Yang Lin , Fu Qi , Yang Zhong 
Published: June 2020

Abstract
Background
Chemotherapy-induced nausea and vomiting (CINV) is a common and distressing side effect. We conducted this clinical trial to compare the effectiveness of true acupuncture vs. sham acupuncture in controlling chemotherapy-induced nausea and vomiting (CINV) among patients with advanced cancer.

Methods
A total of 134 participants were randomly allocated into true acupuncture (TA) (n = 68) and sham acupuncture (SA) (n = 66) groups. Participants in both groups received acupuncture session twice on the first day of chemotherapy, and once consecutively on the following 4 days. The primary outcome was using the Common Terminology Criteria for Adverse Events (CTCAE) to assess CINV. The secondary outcome measures were the Eastern Cooperative Oncology Group score (ECOG), Simplified Nutritional Appetite Questionnaire (SNAQ), and Hospital Anxiety and Depression scale (HADS).

Results
Compared to the SA group, the TA group didn’t show significant improvement in complete response rates of chemotherapy-induced nausea and vomiting (all P > 0.05). However, the TA group could modestly reduce the severity of nausea (from day-3 to day-21, P < 0.05) or vomiting (from day-4 to day-21, P < 0.05), which is notably superior to the control group. Besides, TA promoted the nutritional status of patients with a significantly higher score comparing to the SA group on day 14 (21.82 vs.20.12, P = 0.003) and day 21 (22.39 vs. 20.43, P = 0.001). No apparent differences were found in anxiety and depression assessment between these groups. Participants in both groups were well tolerant of acupuncture therapy. There was no adverse event occurs in our study.

Conclusion
Acupuncture as an adjunctive approach could alleviate the severity of chemotherapy-induced nausea and vomiting compared to the sham control, even though the effect of acupuncture in preventing CINV occurring is relatively modest.
To what degree are orphan drugs patient-centered? A review of the current state of clinical research in rare diseases
Authors: Lanar Sally , Acquadro Catherine , Seaton James , Savre Isabelle , Arnould Benoit 
Published: June 2020

AbstractBackgroundOver the past 30 years, the healthcare industry has increasingly turned its attention to rare diseases. Regulators have emphasized the need for clinical research in this area to be patient-centered. However, there is a lack of evidence concerning whether this need is actually met. In this paper, we aim to address this gap.MethodsFirst, we describe the state of patient-centricity in clinical research in rare diseases based on a targeted literature review. Second, we discuss recommendations from scientific bodies on patient-reported outcome (PRO) measures in rare diseases. Third, we analyze data collected from EMA’s and FDA’s websites concerning rare disease labeling claims and data fromClinicaltrials.govconcerning the use of PRO measures in rare disease pivotal trials. Fourth, we perform an exhaustive literature review on the use of PRO measures in the pharmaceutical industry, including all phases of clinical research, observational/registry studies, and instrument development and validation.ResultsThere is limited information on rare disease patient engagement in study design, recruitment, and retention. None of the initiatives describing methods for developing PRO measures in rare diseases provide the clear guidance clinical researchers need. Only 17.4% of orphan drug labels contain a PRO measure. Less than half of pivotal trials in orphan drugs have a PRO measure as a primary or a secondary endpoint. Although the number of publications about PRO measures in rare diseases has risen in the past fifteen years, our results indicate that substantial improvements are needed to achieve patient-centricity.ConclusionsThe nature and extent of patient engagement in rare disease research is under-documented. The current paradigm for developing and using PRO measures in clinical research is failing to meet the needs of rare disease patients. Not only are PROs rarely used as high-level endpoints in clinical trials or taken into account in labeling claims, they are also under-researched overall – there are too few measures for the multitude of rare diseases. We call for a clear guidance on patient engagement and suggest a realistic approach to the adaptation of PRO strategy to the specific context of clinical research in rare diseases.
Comparison of Streptococcus halichoeri isolates from canine and fur animal infections: biochemical patterns, molecular characteristics and genetic relatedness
Authors: Eklund Marjut , Aaltonen Kirsi , Sironen Tarja , Raunio-Saarnisto Mirja , Grönthal Thomas , Nordgren Heli , Pitkälä Anna , Vapalahti Olli , Rantala Merja 
Published: June 2020

Abstract
Background
Streptococcus halichoeri infections have been reported in grey seals, a European badger, a Stellar sea lion and humans, but its presence in companion and fur animals is unknown. Since 2010, S. halichoeri-like bacteria (SHL) have been isolated from fur animals and dogs in Finland. Our aim was to retrospectively investigate laboratory records for SHL from canine and fur animal infections, characterize the isolates and compare their genetic relatedness in relation to three reference strains: CCUG 48324T, originating from a grey seal, and strains 67100 and 61265, originally isolated from humans.

Results
A total of 138 and 36 SHLs from canine and fur animal infections, respectively, were identified in the laboratory records. SHL was commonly associated with skin infections, but rarely as the only species. A set of 49 canine and 23 fur animal SHLs were further characterized. MALDI-TOF confirmed them as being S. halichoeri. The growth characteristics were consistent with the original findings, but isolates were catalase positive. In total, 17 distinct API 20 Strep patterns were recorded among all 75 isolates tested, of which pattern 5563100 was the most common (n = 30). Antimicrobial resistance to erythromycin and clindamycin was common in canine isolates, but rare in fur animal isolates. Three clusters were observed by PFGE, and 16S rRNA sequencing revealed 98.1–100% similarities with the human strains and 98.1–99.5% with the seal strain. A phylogenetic tree of concatenated 16S rRNA and rpoB revealed closely related isolates with two clades. Fifteen canine isolates were identical to the human strains based on concatenated 16S rRNA and rpoB sequencing.

Conclusions
Streptococcus halichoeri appears to be quite a common bacterial species in the skin of dogs and fur animals. The clinical significance of S. halichoeri is uncertain, as it was rarely isolated as a monoculture. No apparent temporal or spatial clustering was detected, but isolates from different sources were genetically very similar. Because many canine isolates were genetically similar to the human reference strains, transmission between dogs and humans may be possible. WGS sequencing of strains from different sources is needed to further investigate the epidemiology and virulence of S. halichoeri.
Championing survival: connecting the unknown network of responders to address out-of-hospital cardiac arrest
Authors: McBride Ronan , Ski Chantal F. , Thompson David R. , Quinn Tom , Wilson Mark H. 
Published: June 2020

AbstractEarly intervention for out-of-hospital cardiac arrest (OHCA) presents a challenge for Emergency Medical Services (EMS) across Europe. Strategies designed to address this include education and training initiatives for citizens and building CPR skills capacity and awareness amongst health care professionals. However, there is a need to improve access to volunteer first responders who can commence CPR and defibrillate before the arrival of EMS. In the UK, initiatives such GoodSAM have integrated crowdsourcing technology with ambulance services to allow them autonomy in alerting responders to OHCAs which is parallel to an EMS dispatch. These services are building capacity to improve the initial ‘call for help’ and time to commence CPR and defibrillation if indicated. The next step is to identify and implement appropriate methods for public engagement, involvement and eventual networking of resources with statutory bodies such as local EMS. As crowdsourcing volunteer responders is at an early stage, there is a need to determine whether crowdsourcing is associated with patient outcomes, what its impact is on those responding to OHCA, whether it facilitates or impedes current services, and whether it is a safe and cost effective way to involve citizens to intervene in the community during cardiac arrest or other medical emergencies? Addressing such issues is likely to provide further insight into the role and effectiveness of new technologies and their potential impact on the wider community.
Changes to aspects of ongoing randomised controlled trials with fixed designs
Authors: Coskinas Xanthi , Simes John , Schou Manjula , Martin Andrew James 
Published: June 2020

Abstract
Background
Despite careful planning, changes to some aspects of an ongoing randomised clinical trial (RCT), with a fixed design, may be warranted. We sought to elucidate the distinction between legitimate versus illegitimate changes to serve as a guide for less experienced clinical trialists and other stakeholders.

Methods
Using data from a large trial of statin therapy for secondary prevention, we generated a set of simulated trial datasets under the null hypothesis (H0) and a set under an alternative hypothesis (H1). Through analysis of these simulated trials, we assessed the performance of the strategy of changing aspects of the design/analysis with knowledge of treatment allocation (illegitimate) versus the strategy of making changes without knowledge of treatment allocation (legitimate). Performance was assessed using the type 1 error, as well as measures of absolute and relative bias in the treatment effect.

Results
Illegitimate changes led to a relative bias of 61% under H1, and a type 1 error rate under H0 of 23%—well in excess of the 5% significance level targeted. Legitimate changes produced unbiased estimates under H1 and did not inflate the type 1 error rate under H0.

Conclusions
Changes to pre-specified aspects of the design and analysis of an ongoing RCT may be a necessary response to unforeseen circumstances. Such changes risk introducing a bias if undertaken with knowledge of treatment allocation. Legitimate changes need to be adequately documented to provide assurance to all stakeholders of their validity.
MOdified DIagnostic strateGy to safely ruLe-out pulmonary embolism In the emergency depArtment: study protocol for the Non-Inferiority MODIGLIANI cluster cross-over randomized trial
Authors: Philippon Anne-Laure , Dumont Margaux , Jimenez Sonia , Salhi Sarah , Cachanado Marine , Durand-Zaleski Isabelle , Simon Tabassome , Freund Yonathan 
Published: June 2020

Abstract
Introduction
In the work-up strategy for pulmonary embolism (PE) in the ED, the recently introduced YEARS rule allows the raising of the D-dimer threshold to 1000 ng/ml in patients with no signs of deep venous thrombosis and no hemoptysis and in whom PE is not the most likely diagnosis. However, this decision rule has never been prospectively compared to the usual strategy. Furthermore, it is unclear if the YEARS rule can be used on top of the Pulmonary Embolism Rule-out Criteria (PERC). We aim to assess the non-inferiority of YEARS compared to current guidelines to rule out PE among PERC-positive ED patients with suspicion of PE.

Methods/design
The MODIGLIANI study is a multicenter, European, non-inferiority, cluster-randomized, two periods cross-over, controlled trial. Each center will be randomized for the sequence of two 4-month periods: intervention (MOdified Diagnostic Strategy: MODS) followed by control (usual care), or control followed by intervention with 1 month of “wash-out” between the two periods. In the control period, the threshold will be as usual (500 ng/ml for patients aged 50 years or younger and age × 10 for older patients). In the MODS period, the threshold of D-dimers to rule out PE will be raised to 1000 ng/ml if no item of the YEARS score is present or will remain unchanged otherwise. Patients will be included if they have a suspicion of PE, defined as chest pain, dyspnea, or syncope. Non-inclusion criteria comprise a high clinical probability of PE or PERC-negative patients with low clinical probability.

Ethics and dissemination
The study has received the following approvals: Comité de protection des personnes Ile de France XI (France) and Comité de Ética de la Investigación con medicamentos del Hospital Clínic de Barcelona (Spain). Results will be made available to all included participants and other researchers.

Trial registration
ClinicalTrials.gov, NCT04032769. Registered on 24 July 2019.
Umbilical cord blood therapy to prevent progression of COVID-19 related pneumonia: a structured summary of a study protocol for a pilot randomised controlled trial
Authors: Malhotra Atul , Ernest David , Rogers Benjamin A. , Haylock David , Watt Ashalyn , Moeneclaey Guy , Jenkin Graham 
Published: June 2020

Abstract
Objectives
Objective: To undertake a pilot, feasibility RCT of umbilical cord blood derived cell therapy for treatment of adult patients infected with SARS-CoV-2 virus related moderate-to-severe pneumonia to prevent progression to severe ARDS.
Hypothesis: Expanded cord blood derived cell therapy will be feasible, well tolerated and show potential efficacy in the treatment of acute COVID-19 related moderate to severe pneumonia in adult patients because of their powerful anti-inflammatory and immunomodulatory properties.

Trial design
Pilot, parallel design randomised controlled trial.

Participants
The trial will recruit 24 hospitalised patients with confirmed SARS-CoV-2 infection and pneumonia from July to December 2020 at Monash Medical Centre in Melbourne, Australia.

Intervention and comparator
Intervention: Intravenous injection of expanded umbilical cord blood cells at a dose of 5 million cells/kg (maximum dose - 500 million cells). Cell infusion will occur over 30-60 minutes through a peripheral intravenous cannula. Standard supportive care will continue as needed.
Comparator: Standard supportive care.

Main outcomes
Safety and tolerability of cell administration within first 24 hours of administration; clinical improvement on a seven-category clinical improvement ordinal scale.

Randomisation
Randomisation will be done using computer generated allocation to intervention/ control groups in a 1:1 ratio (in blocks of 6) using sealed opaque envelopes.

Blinding (masking)
This will be an unblinded study, given that it is the first study using expanded cord blood cells in COVID-19 patients. There will be no placebo infusion.

Numbers to be randomised (sample size)
Twelve participants in each group. Total n=24.

Trial Status
CBC-19 protocol v2, dated 23rd April 2020. Recruitment has not started yet. Estimated recruitment timeline is between 1st July – 31st December 2020.

Trial registration
Australian New Zealand Clinical Trials Registry, ACTRN12620000478910, registered 16th April 2020.

Full protocol
The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.
Effect of transcranial direct current stimulation on sports performance for two profiles of athletes (power and endurance) (COMPETE): a protocol for a randomised, crossover, double blind, controlled exploratory trial
Authors: Grandperrin Yohan , Grosprêtre Sidney , Nicolier Magali , Gimenez Philippe , Vidal Chrystelle , Haffen Emmanuel , Bennabi Djamila 
Published: June 2020

AbstractBackgroundTranscranial direct current stimulation (tDCS) is promising for improving motor and cognitive performance. Nevertheless, its mechanisms of action are unclear and need to be better characterised according to the stimulated brain area and the type of exercise performed.Methods/designThis is a double-blind crossover study, organised into two parts: the first is to assess the effects of tDCS on explosive performance (jump task) and the second is to assess the effects on endurance performance (cycling time trial task). Participants, who are recreationally active or athletes (parkour practitioners, cyclists), will receive two active tDCS sessions (over the left dorsolateral prefrontal cortex and right motor cortex) and one sham tDCS session (part A), or two sequences (one active and one sham) of two daily tDCS sessions over 5 days (part B). Motor and cognitive performance will be compared before and after tDCS sessions (part A), and before and after the first session, after the last session and at day 12 and day 30 of each tDCS sequence (part B).DiscussionThis study investigates the acute and repeated effects of tDCS on the motor and cognitive performance of healthy subjects. It will try to evaluate if tDCS could be considered as a neuroenhancement technology according to the physical task investigated (endurance versus explosive).Trial registrationClinicalTrials.gov,NCT03937115. Registered on 3 May 2019; retrospectively registered.
Purification and immobilization of engineered glucose dehydrogenase: a new approach to producing gluconic acid from breadwaste
Authors: Karagoz Pinar , Mandair Ravneet , Manayil Jinesh Cherukkattu , Lad Jai , Chong Katie , Kyriakou Georgios , Lee Adam F. , Wilson Karen , Bill Roslyn M. 
Published: June 2020

Abstract
Background
Platform chemicals are essential to industrial processes. Used as starting materials for the manufacture of diverse products, their cheap availability and efficient sourcing are an industrial requirement. Increasing concerns about the depletion of natural resources and growing environmental consciousness have led to a focus on the economics and ecological viability of bio-based platform chemical production. Contemporary approaches include the use of immobilized enzymes that can be harnessed to produce high-value chemicals from waste.

Results
In this study, an engineered glucose dehydrogenase (GDH) was optimized for gluconic acid (GA) production. Sulfolobus solfataricus GDH was expressed in Escherichia coli. The Km and Vmax values for recombinant GDH were calculated as 0.87 mM and 5.91 U/mg, respectively. Recombinant GDH was immobilized on a hierarchically porous silica support (MM-SBA-15) and its activity was compared with GDH immobilized on three commercially available supports. MM-SBA-15 showed significantly higher immobilization efficiency (> 98%) than the commercial supports. After 5 cycles, GDH activity was at least 14% greater than the remaining activity on commercial supports. Glucose in bread waste hydrolysate was converted to GA by free-state and immobilized GDH. After the 10th reuse cycle on MM-SBA-15, a 22% conversion yield was observed, generating 25 gGA/gGDH. The highest GA production efficiency was 47 gGA/gGDH using free-state GDH.

Conclusions
This study demonstrates the feasibility of enzymatically converting BWH to GA: immobilizing GDH on MM-SBA-15 renders the enzyme more stable and permits its multiple reuse.
Protist enteroparasites in wild boar (Sus scrofa ferus) and black Iberian pig (Sus scrofa domesticus) in southern Spain: a protective effect on hepatitis E acquisition?
Authors: Rivero-Juarez Antonio , Dashti Alejandro , López-López Pedro , Muadica Aly Salimo , Risalde Maria de los Angeles , Köster Pamela C. , Machuca Isabel , Bailo Begoña , de Mingo Marta Hernández , Dacal Elena , García-Bocanegra Ignacio , Saugar José M. , Calero-Bernal Rafael , González-Barrio David , Rivero Antonio , Briz Verónica , Carmena David 
Published: June 2020

Abstract
Background
Several studies have independently evaluated the occurrence of hepatitis E virus (HEV) and enteroparasites in swine, but no surveys have been conducted to jointly assess the prevalence and genetic diversity of enteroparasites in pigs and wild boars, their sympatric transmission between hosts, and their potential interaction with HEV.

Methods
We prospectively collected serum and faecal samples from black Iberian domestic pigs and wild boars from southern Spain between 2015‒2016. We evaluated for HEV in serum and faeces, and for the presence of enteroparasites (Giardia duodenalis, Cryptosporidium spp., Blastocystis sp., Neobalantidium coli and Strongyloides spp.) in the same faecal samples. The prevalence of each intestinal parasite species was calculated.

Results
A total of 328 animals (56.7% black Iberian pigs and 43.3% wild boars) were included in the study. The overall global prevalence of HEV in serum was 16.8%. The overall global prevalence of each enteroparasite species was 19.5% for G. duodenalis, 8.2% for Cryptosporidium spp., 41.8% for Blastocystis sp., 31.4% for N. coli, and 8.8% for Strongyloides spp. HEV-infected animals showed a significantly lower prevalence of G. duodenalis (3.2 vs 20%; P = 0.002) and Blastocystis sp. (38.7 vs 80%; P < 0.001) than those uninfected by HEV. Animals carrying G. duodenalis and Blastocystis sp. infections showed a significantly lower rate of HEV infection than those not harbouring these enteroparasites (P < 0.001).

Conclusions
Our study found a high prevalence of enteroparasites in black Iberian pigs and wild boars in southern Spain, suggesting a sympatric co-transmission of some of the species investigated. It is suggested that extracellular G. duodenalis and Blastocystis sp. might have a protective effect on HEV acquisition in swine.