bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sickle Cell Disease Treatment with Arginine Therapy (STArT): study protocol for a phase 3 randomized controlled trial
Authors: Rees Chris A. , Brousseau David C. , Cohen Daniel M. , Villella Anthony , Dampier Carlton , Brown Kathleen , Campbell Andrew , Chumpitazi Corrie E. , Airewele Gladstone , Chang Todd , Denton Christopher , Ellison Angela , Thompson Alexis , Ahmad Fahd , Bakshi Nitya , Coleman Keli D. , Leibovich Sara , Leake Deborah , Hatabah Dunia , Wilkinson Hagar , Robinson Michelle , Casper T. Charles , Vichinsky Elliott , Morris Claudia R. ,   the SCD Arginine Study Group and PECARN
Published: August 2023

Abstract
Background
Despite substantial illness burden and healthcare utilization conferred by pain from vaso-occlusive episodes (VOE) in children with sickle cell disease (SCD), disease-modifying therapies to effectively treat SCD-VOE are lacking. The aim of the Sickle Cell Disease Treatment with Arginine Therapy (STArT) Trial is to provide definitive evidence regarding the efficacy of intravenous arginine as a treatment for acute SCD-VOE among children, adolescents, and young adults.

Methods
STArT is a double-blind, placebo-controlled, randomized, phase 3, multicenter trial of intravenous arginine therapy in 360 children, adolescents, and young adults who present with SCD-VOE. The STArT Trial is being conducted at 10 sites in the USA through the Pediatric Emergency Care Applied Research Network (PECARN). Enrollment began in 2021 and will continue for 5 years. Within 12 h of receiving their first dose of intravenous opioids, enrolled participants are randomized 1:1 to receive either (1) a one-time loading dose of L-arginine (200 mg/kg with a maximum of 20 g) administered intravenously followed by a standard dose of 100 mg/kg (maximum 10 g) three times a day or (2) a one-time placebo loading dose of normal saline followed by normal saline three times per day at equivalent volumes and duration as the study drug. Participants, research staff, and investigators are blinded to the participant’s randomization. All clinical care is provided in accordance with the institution-specific standard of care for SCD-VOE based on the 2014 National Heart, Lung, and Blood Institute guidelines. The primary outcome is time to SCD-VOE pain crisis resolution, defined as the time (in hours) from study drug delivery to the last dose of parenteral opioid delivery. Secondary outcomes include total parental opioid use and patient-reported outcomes. In addition, the trial will characterize alterations in the arginine metabolome and mitochondrial function in children with SCD-VOE.

Discussion
Building on the foundation of established relationships between emergency medicine providers and hematologists in a multicenter research network to ensure adequate participant accrual, the STArT Trial will provide definitive information about the efficacy of intravenous arginine for the treatment of SCD-VOE for children.

Trial registration
The STArT Trial was registered in ClinicalTrials.gov on April 9, 2021, and enrollment began on June 21, 2021 (NCT04839354).
The role of the communicated treatment rationale on treatment outcome: study protocol for a randomized controlled trial
Authors: Henrich Liv , Wilhelm Marcel , Lange Philipp , Rief Winfried 
Published: August 2023

Abstract
Background
Placebo effects are a well-established phenomenon in the treatment of depression. However, the mechanism underlying these effects are not fully understood. Treatment expectations are considered one explanation for why placebos work. Treatment expectations are likely to be affected by clinician-patient interactions. This study aims to investigate the role of the communicated treatment rationale in modulating treatment expectations and its effects on the treatment outcomes of a pharmacological and a psychological active placebo intervention for depression. In this study, treatment expectations are modulated by presenting illness models that are either congruent or incongruent with the treatment intervention that follows.

Methods
This 2 × 2 randomized controlled trial will involve patients with major depression. Participants will either receive a biological or a psychological illness model from a clinician. Following this, they are randomly assigned to receive either a pharmacological or a psychological active placebo intervention. The illness model and the treatment are either congruent or incongruent with each other, resulting in four groups. In addition, a natural course control group will be included.

Discussion
This study will provide insights into the mechanism of expectation modulation in active placebo treatments for major depression. The results may provide insights for clinicians to improve their communication with patients by focusing on treatment expectations. By identifying the factors that contribute to placebo effects, this study has the potential to improve the effectiveness of existing depression treatments and reduce the burden of this highly prevalent mental health condition.

Trial registration
This trial has been registered prospectively at ClinicalTrials.gov under the identifier: NCT04719663. Registered on January 22, 2021.
A member of the CAP protein superfamily, Hc-CAP-15, is important for the parasitic-stage development of Haemonchus contortus
Authors: Liu Hui , Tao Zhuolin , Wang Yifan , Liu Xin , Wang Chunqun , Liu Lu , Hu Min 
Published: August 2023

Abstract
Background
The CAP superfamily proteins are distributed widely in eukaryotes and play crucial roles in various biological processes. However, very little is known about their functions in parasitic nematodes, including Haemonchus contortus, a socioeconomically important parasitic nematode. We have therefore studied a member of the CAP protein family of H. contortus, named Hc-CAP-15, with the aim to explore its roles in regulating the parasitic developmental process.

Methods
The conservation and phylogenetic relationships, spatial expression and temporal transcription profiles of Hc-CAP/cap-15, as well its biological function during parasite development were investigated using bioinformatics, immunofluorescence, real-time PCR and RNA interference (RNAi).

Results
Hc-CAP-15 was found to be a single-domain CAP protein consisting of four conserved motifs that is localized in the cuticle, intestine and oocyte of adult worms. Hc-cap-15 was transcribed at all developmental stages of H. contortus, with the highest transcription level in parasitic fourth-stage larvae (L4s). Silencing of Hc-cap-15 resulted in a significant increase in the body length of L4s.

Conclusions
The results suggested that Hc-CAP-15 is important for the development of H. contortus. Our findings provide a basis for further study of the functions of the CAP family proteins in H. contortus and related parasitic nematodes.

Graphical Abstract
The association between SGLT2 inhibitors and new-onset acute coronary syndrome in the elderly: a population-based longitudinal cohort study
Authors: Lin Tsung-Kun , Lee Mei-Chun , Cheng Yu-Han , Ma Timothy , Chen Mei-Chun , Yang Tsung-Yuan , Jong Gwo-Ping 
Published: August 2023

Abstract
Background
Several observational cohorts and meta-analytical studies on humans have shown that users of sodium-glucose cotransporter-2 inhibitors (SGLT2is) have a lower risk for new-onset acute coronary syndrome (ACS) than nonusers. However, some studies, including randomized clinical trials, reported the opposite results. This study aimed to investigate the impacts of a SGLT2i on new-onset ACS in a population.

Methods
We conducted a retrospective population-based cohort study involving 56,356 subjects who received SGLT2i therapy and 112,712 patients who did not receive SGLT2i therapy between May 1, 2016 and December 31, 2019. The outcome was the risk of new-onset ACS. Multivariable Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals for associations between SGLT2i use and ACS risk.

Results
A total of 670 and 1408 ACS events occurred in SGLT2i users and nonusers, respectively, during a follow-up of 3.7 years. SGLT2i use was associated with a nonsignificantly lower risk of ACS (adjusted HR 0.95, 95%confidence intervals (CI 0.87–1.04, P = 0.3218). We confirmed the robustness of these results through a propensity score 1:1 matching analysis. The results of the subgroup analysis of the subtype of the SGLT2i treatments were consistent with the main findings. An increased risk for the incidence of ACS in male and older (> 70 years) patients were also found.

Conclusions
In this population-based cohort study, we found that SGLT2i use is associated with a nonsignificantly decreased risk of ACS. No difference in the SGLT2i subtype was observed in subgroup analyses. However, the results of this study indicated an increased risk for the incidence of ACS in male and older (> 70 years) patients.
Draft genome sequence of two “Candidatus Intestinicoccus colisanans” strains isolated from faeces of healthy humans
Authors: Zhou Joyce , Boyd Joel A , Nyeverecz Bozica , Vivian Charlotte , Angel Nicola , Wood David L A , Hugenholtz Philip , Tyson Gene W , Krause Lutz , Ó Cuív Páraic 
Published: August 2023

Abstract
Objectives
In order to provide a better insight into the functional capacity of the human gut microbiome, we isolated a novel bacterium, “Candidatus Intestinicoccus colisanans” gen. nov. sp. nov., and performed whole genome sequencing. This study will provide new insights into the functional potential of this bacterium and its role in modulating host health and well-being. We expect that this data resource will be useful in providing additional insight into the diversity and functional potential of the human microbiome.

Data description
Here, we report the first draft genome sequences of “Candidatus Intestinicoccus colisanans” strains MH27-1 and MH27-2, recovered from faeces collected from healthy human donors. The genomes were sequenced using short-read Illumina technology and whole-genome-based comparisons and phylogenomics reconstruction indicate that “Candidatus Intestinicoccus colisanans” represents a novel genus and species within the family Acutalibacteraceae. Both genomes were estimated to be > 98% completed and to range in size from 2.9 to 3.3 Mb with a G + C content of approximately 51%. The gene repertoire of “Candidatus Intestinicoccus colisanans” indicate it is likely a saccharolytic gut bacterium.
On the qualitative evaluation of the variable-order coupled boundary value problems with a fractional delay
Authors: Hammad Hasanen A. , Aydi Hassen , Zayed Mohra 
Published: August 2023

AbstractThe logical progression from the constant order differential equations is the field of variable-order differential equations. Such equations can frequently give a more succinct description of problems in the real world. In light of this, we therefore take into account a class of coupled boundary value problems under variable-order differentiation. By utilizing the fixed-point techniques of Banach and Schauder, we investigate the existence and uniqueness of solutions to the proposed problem. Also, sufficient results are documented for the necessary needs. Furthermore, some stability results based on the ideas of Ulam, Hyers, and Rassias are elaborated upon. Ultimately, appropriate examples and in-depth analysis are presented to support our results.
Prevalence of epilepsy in the onchocerciasis endemic middle belt of Ghana after 27 years of mass drug administration with ivermectin
Authors: Otabil Kenneth Bentum , Ankrah Blessing , Bart-Plange Emmanuel John , Donkoh Emmanuel Sam , Avarikame Fiona Amoabil , Ofori-Appiah Fredrick Obeng , Babae Theophilus Nti , Kudzordzi Prince-Charles , Darko Vera Achiaa , Ameyaw Joseph , Bamfo Joseph Gyekye , Sakibu Raji Abdul , Antwi-Berko Daniel , Fodjo Joseph Nelson Siewe , Basáñez María-Gloria , Schallig Henk D. F. H. , Colebunders Robert 
Published: August 2023

Abstract
Background
In onchocerciasis-endemic areas with high ongoing Onchocerca volvulus transmission, a high prevalence of epilepsy has been reported. This study aimed to determine the prevalence and clinical characteristics of epilepsy in the Bono Region of Ghana following 27 years of implementation of ivermectin mass drug administration (MDA).

Methods
Between October 2020 and August 2021, cross-sectional surveys were conducted in nine communities in the Tain District and Wenchi Municipality of the Bono Region of Ghana. In the first stage, a random door-to-door approach was used to screen the population for epilepsy using a pre-tested questionnaire. Persons suspected of having epilepsy were invited for a second-stage neurological examination for case verification. Community O. volvulus microfilarial infection status and Ov16 seropositivity were also determined. Ninety-five confidence intervals (95% CI) for prevalence values were calculated using the Wilson Score Interval.

Results
Of the 971 participants, 500 (51.5%) were females, and the median age (interquartile range) was 26 (15‒43) years. Fourteen participants (1.4%, 95% CI: 1.0‒2.0) were diagnosed as having epilepsy with generalized seizures being the most frequent seizure type (85.7%, 12/14). The overall microfilarial prevalence of O. volvulus was 10.3% (November 2020) and 9.9% (August 2021); the Ov16 seroprevalence was 22.2% (June 2021). Only 63.2% took ivermectin in the last round of MDA distribution in March 2021.

Conclusions
The 1.4% prevalence of epilepsy in the Bono region is similar to the median epilepsy prevalence in sub-Saharan Africa. However, the persistent microfilarial prevalence and low ivermectin study coverage call for the Ghana Onchocerciasis Elimination Programme to step up its efforts to ensure that the gains achieved are consolidated and improved to achieve the elimination of onchocerciasis by 2030.

Graphical Abstract
Metamizole-induced agranulocytosis (MIA): a mini review
Authors: Tomidis Chatzimanouil Markos K. , Goppelt Ines , Zeissig Yvonne , Sachs Ulrich J. , Laass Martin W. 
Published: August 2023

AbstractMetamizole is an analgesic, antipyretic, and spasmolytic drug in Germany only approved for the treatment of severe pain or high fever that does not respond to other measures. In recent years, an increased use has been described among both adults and children, often against the approved indication. The most important side effect of metamizole is the development of agranulocytosis (neutrophil count < 500/µL). Incidence of metamizole-induced agranulocytosis (MIA) ranges depending on the study from 0.96 cases per million per year to 1:1602 per patient and metamizole prescription. The risk of agranulocytosis in children remains unclear, but is probably lower than in adults. Female gender and older age are associated with higher incidence, reflecting prescription distribution. MIA is dose-independent and risk seems to increase with duration of intake. In patients with past exposure, re-exposure may lead to rapid onset. MIA is believed to be induced either through immunologic or toxic mechanisms. MIA presents with fever, sore throat, fatigue, and mucosal inflammation, up to ulceration. Even in the case of suspected MIA, treatment with metamizole should be immediately paused and an examination of the blood cell count is required. In case of local or systemic infections, empirical therapy with broad-spectrum antibiotics should be administered. G-CSF therapy should be limited to patients with poor prognostic factors. The patient should be monitored closely until the neutrophil count returns to normal. Re-exposure to metamizole must be avoided.
Distinct host-response signatures in circulatory shock: a narrative review
Authors: Soussi Sabri , dos Santos Claudia , Jentzer Jacob C. , Mebazaa Alexandre , Gayat Etienne , Pöss Janine , Schaubroeck Hannah , Billia Filio , Marshall John C. , Lawler Patrick R. 
Published: August 2023

AbstractCirculatory shock is defined syndromically as hypotension associated with tissue hypoperfusion and often subcategorized according to hemodynamic profile (e.g., distributive, cardiogenic, hypovolemic) and etiology (e.g., infection, myocardial infarction, trauma, among others). These shock subgroups are generally considered homogeneous entities in research and clinical practice. This current definition fails to consider the complex pathophysiology of shock and the influence of patient heterogeneity. Recent translational evidence highlights previously under-appreciated heterogeneity regarding the underlying pathways with distinct host-response patterns in circulatory shock syndromes. This heterogeneity may confound the interpretation of trial results as a given treatment may preferentially impact distinct subgroups. Re-analyzing results of major ‘neutral’ treatment trials from the perspective of biological mechanisms (i.e., host-response signatures) may reveal treatment effects in subgroups of patients that share treatable traits (i.e., specific biological signatures that portend a predictable response to a given treatment). In this review, we discuss the emerging literature suggesting the existence of distinct biomarker-based host-response patterns of circulatory shock syndrome independent of etiology or hemodynamic profile. We further review responses to newly prescribed treatments in the intensive care unit designed to personalize treatments (biomarker-driven or endotype-driven patient selection in support of future clinical trials).
The relationship between the intake of fruits, vegetables, and dairy products with hypertension: findings from the STEPS study
Authors: Nouri Mehran , Shateri Zainab , Vali Mohebat , Faghih Shiva 
Published: August 2023

Abstract
Background
The current research aimed to evaluate the relationship between fruit, vegetable (FV), and dairy consumption with the odds of developing hypertension based on nationwide Stepwise approach to surveillance (STEPS) data in Iran.

Methods
This cross-sectional study was accomplished by the research center of non-communicable diseases (NCDs) in Tehran. In total, 29,378 individuals’ data were analyzed. Participants were classified into normal, elevated BP, stage I, and stage II hypertension according to systolic blood pressure (SBP) and diastolic blood pressure (DBP) examinations. Based on the STEPS questionnaire, the consumption of FVs and dairy products was evaluated. Multinomial logistic regression was applied to assess the relationship between the consumption of FVs and dairy products with hypertension.

Results
The findings revealed that only fruit consumption (≥ 2 servings/day) was negatively related to stage I hypertension (odds ratio (OR) = 0.81; 95% confidence interval (CI): 0.69–0.95) in two servings per day and OR = 0.81; 95% CI: 0.68–0.96 in > two servings per day) in the adjusted model. There was no significant relationship between consuming vegetables and dairy products with elevated BP and hypertension.

Conclusion
Our study showed that increasing fruit consumption was related to reducing hypertension odds. Regarding the consumption of dairy products and vegetables, no significant relationship was found with the odds of hypertension. More studies, especially cohorts, are needed to evaluate the impacts of FV and dairy products on the risk of hypertension.
In-between duty and hope for recognition, the experience of physiotherapists working in a university hospital during the COVID-19 first wave in Switzerland: a qualitative study based on focus groups
Authors: Pichonnaz Claude , Foley Rose-Anna 
Published: August 2023

Abstract
Background
Learning more about the physiotherapists’ experience, perceived role and perception of events during the COVID-19 crisis, as well as their recovery and projection into the post-crisis future, may be useful to inform stakeholders about the impact of the crisis.
The objective of this study was to investigate the experience of physiotherapists working in a university hospital in Switzerland during the 1st wave of the COVID-19 crisis, more specifically their subjective experience, professional involvement, perception of management and perceived implications for the future.

Methods
This interpretative qualitative study investigated the subjective experience of a purposeful sample of 12 physiotherapists using two 2 h semi-directive focus group interviews conducted by a physiotherapist in June 2020. Data were recorded, transcribed, and analysed using a thematic analysis approach. The report was approved by participants and the study was audited by a health anthropologist.

Results
The most impressive points were the unprecedented nature of the crisis, the health threat, the hospital's capacity to reorganise on a large scale and the solidarity between colleagues. Participants expressed a high level of commitment to their role despite the potentially serious repercussions at an individual level. Pride and stress coexisted for those directly involved in the crisis, while those working in a reduced activity department felt anxious and idle. The need for immediacy in decision-making and action led to a flattening of hierarchies and an increase of uncertainties. Communication management was seen as the main area for improvement. Physiotherapists hoped that their involvement would improve recognition of the profession but feared that working conditions would deteriorate after the crisis.

Conclusions
The physiotherapists expressed high dedication to their profession and pride to be part of the “war effort” during the crisis. The stress level was partly tempered by the solidarity amongst health professionals and distraction by engaging in action. Despite the mental load, this situation was also seen as an opportunity to grow at a personal and professional level. The healthcare system capacity having not been exceeded in Switzerland, less distress related to death and powerlessness were expressed than in other studies investigating healthcare professionals’ experience of the COVID-19 crisis.
Stationary transport above the critical velocity in a one-dimensional superflow past an obstacle
Authors: Huynh J. , Hébert F. , Larré P.-É. , Albert M. 
Published: August 2023

Abstract
We consider in this work the different possible stationary flows of a one-dimensional quantum fluid in the mean-field regime. We focus on the supersonic regime where a transition from a time-dependent flow to a stationary diffractive flow occurs at a given critical velocity. We give nonperturbative results for this critical velocity in the presence of a localised obstacle of arbitrary size and strength. In addition, we discuss the existence of superfluid-like solution in the supersonic regime due to resonant transport and provide a complete map of the different regimes of stationary transport of a quantum fluid.