bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tolerance induction through non-avoidance to prevent persistent food allergy (TINA) in children and adults with peanut or tree nut allergy: rationale, study design and methods of a randomized controlled trial and observational cohort study
Authors: Trendelenburg Valérie , Dölle-Bierke Sabine , Unterleider Nathalie , Alexiou Aikaterina , Kalb Birgit , Meixner Lara , Heller Stephanie , Lau Susanne , Lee Young- Ae , Fauchère Florent , Braun Julian , Babina Magda , Altrichter Sabine , Birkner Till , Roll Stephanie , Dobbertin-Welsch Josefine , Worm Margitta , Beyer Kirsten 
Published: March 2022

Abstract
Background
Peanuts (PN) and tree nuts (TN) are among the most frequent elicitors of food allergy and can lead to life-threatening reactions. The current advice for allergic patients is to strictly avoid the offending food independently of their individual threshold level, whereas sensitized patients without allergic symptoms should frequently consume the food to avoid (re-)development of food allergy. The aim of this trial is to investigate (I) whether the consumption of low allergen amounts below the individual threshold may support natural tolerance development and (II) to what extent regular allergen consumption in sensitized but tolerant subjects prevents the (re-)development of PN or TN allergy.

Methods
The TINA trial consisting of (part I) a randomized, controlled, open, parallel group, single-center, superiority trial (RCT), and (part II) a prospective observational exploratory cohort study. Children and adults (age 1–67 years) with suspected or known primary PN and/or TN allergy will undergo an oral food challenge (OFC) to determine their clinical reactivity and individual threshold. In the RCT, 120 PN or TN allergic patients who tolerate ≥100 mg of food protein will be randomized (1:1 ratio) to consumption of products with low amounts of PN or TN on a regular basis or strict avoidance for 1 year. The consumption group will start with 1/100 of their individual threshold, increasing the protein amount to 1/50 and 1/10 after 4 and 8 months, respectively. The primary endpoint is the clinical tolerance to PN or TN after 1 year assessed by OFC. In the cohort study, 120 subjects sensitized to PN and/or TN but tolerant are advised to regularly consume the food and observed for 1 year. The primary endpoint is the maintenance of clinical tolerance to PN and/or TN after 1 year assessed by challenging with the former tolerated cumulative dose.

Discussion
This clinical trial will help to determine the impact of allergen consumption versus avoidance on natural tolerance development and whether the current dietary advice for PN or TN allergic patients with higher threshold levels is still valid.

Trial registration
German Clinical Trials Register; ID: DRKS00016764 (RCT), DRKS00020467 (cohort study). Registered on 15 January 2020, http://www.drks.de.
The efficacy of temozolomide combined with levetiracetam for glioblastoma (GBM) after surgery: a study protocol for a double-blinded and randomized controlled trial
Authors: Sun Maoyuan , Huang Ning , Tao Yihao , Wen Rong , Zhao Guanjian , Zhang Xiang , Xie Zongyi , Cheng Yuan , Mao Jinning , Liu Guodong 
Published: March 2022

Abstract
Background
Temozolomide is applied as the standard chemotherapy agent in patients with glioblastoma (GBM) after surgery. However, the benefit of this treatment for patients is limited by the invasive growth of gliomas and drug resistance. There are indications from fundamental experimental and retrospective studies that levetiracetam has the potential to improve the survival rate of patients with GBM. However, it has yet to be determined whether the combination of temozolomide and levetiracetam is more effective than standard temozolomide chemotherapy. Therefore, we designed a randomized clinical trial to investigate the therapeutic effect of the new combined regime for treating GBM.

Methods/design
This is a double-blind and randomized clinical trial conducted in a single center. One hundred forty-two patients will be recruited and screened for the inclusion and exclusion criteria. Then, eligible participants will be randomly assigned to an experimental group or a control group in a 1:1 ratio. Based on the administration of radiation therapy (RT), participants in the experimental group will be prescribed levetiracetam plus temozolomide chemotherapy for 34 weeks while participants in the control group will receive placebo tablets plus temozolomide for the same duration. A 3-year follow-up will be conducted on all patients after intervention. Accordingly, the primary outcome will be progression-free survival (PFS). The secondary endpoints include overall survival (OS), the Karnofsky Performance Status (KPS), the objective response rate (ORR), and adverse event incidence.

Discussion
It is expected that the results of this trial will provide high-level evidence regarding the clinical benefits of levetiracetam and temozolomide combined in the treatment of GBM.

Trial registration
Chinese Clinical Trial Registry, ChiCTR2100049941. Registered on 14 August 2021
The application of augmented reality in craniofacial bone fracture reduction: study protocol for a randomized controlled trial
Authors: Lin Li , Liu Xiangqi , Gao Yuan , Aung Zin Mar , Xu Haisong , Wang Bingshun , Xie Le , Yang Xianxian , Chai Gang 
Published: March 2022

Abstract
Background
Augmented reality (AR) is a new technology that increases users’ perception of the real world. The purpose of this study is to evaluate the efficacy and safety of augmented reality navigation system in treatment with craniofacial fracture reduction.

Methods
This will be a single-center prospective randomized controlled trial. Twenty-two patients will be assigned to two groups of 11, and those with zygomaticomaxillary complex fractures will undergo preoperative three-dimensional CT modeling and have operational plans designed. The control team will use traditional optical navigation to perform the surgery, and the experimental team will use an AR navigation system. The primary outcome measures will be the accuracy of the key points of surgical area between the preoperational surgical plan and post-operation. The secondary outcome measures will be the blood loss, operation time, bone reduction time, hospital time, and complication rate. The findings obtained through this study are expected to evaluate efficacy and safety of the augmented reality navigation system in the treatment of zygomaticomaxillary complex fractures.

Discussion
This controlled trial of augmented reality navigation system in treatment with zygomaticomaxillary complex fracture reduction will clarify the efficacy and safety of this technology by measuring the accuracy of the key points of surgical area and blood loss, operation and bone reduction times, hospital stay duration, and complication rates. This is a single-center study, and the results are expected to promote the application of augmented reality in craniofacial fracture reduction to improve surgery accuracy and efficacy.

Trial registration
Chinese Clinical Trial Registry ChiCTR1900022626. Registered on April 19, 2019.
Randomized Evaluation of Surgery in Elderly with Traumatic Acute SubDural Hematoma (RESET-ASDH trial): study protocol for a pragmatic randomized controlled trial with multicenter parallel group design
Authors: Singh Ranjit D. , van Dijck Jeroen T. J. M. , van Essen Thomas A. , Lingsma Hester F. , Polinder Suzanne S. , Kompanje Erwin J. O. , van Zwet Erik W. , Steyerberg Ewout W. , de Ruiter Godard C. W. , Depreitere Bart , Peul Wilco C. 
Published: March 2022

Abstract
Background
The rapidly increasing number of elderly (≥ 65 years old) with TBI is accompanied by substantial medical and economic consequences. An ASDH is the most common injury in elderly with TBI and the surgical versus conservative treatment of this patient group remains an important clinical dilemma. Current BTF guidelines are not based on high-quality evidence and compliance is low, allowing for large international treatment variation. The RESET-ASDH trial is an international multicenter RCT on the (cost-)effectiveness of early neurosurgical hematoma evacuation versus initial conservative treatment in elderly with a t-ASDH

Methods
In total, 300 patients will be recruited from 17 Belgian and Dutch trauma centers. Patients ≥ 65 years with at first presentation a GCS ≥ 9 and a t-ASDH > 10 mm or a t-ASDH < 10 mm and a midline shift > 5 mm, or a GCS < 9 with a traumatic ASDH < 10 mm and a midline shift < 5 mm without extracranial explanation for the comatose state, for whom clinical equipoise exists will be randomized to early surgical hematoma evacuation or initial conservative management with the possibility of delayed secondary surgery. When possible, patients or their legal representatives will be asked for consent before inclusion. When obtaining patient or proxy consent is impossible within the therapeutic time window, patients are enrolled using the deferred consent procedure. Medical-ethical approval was obtained in the Netherlands and Belgium. The choice of neurosurgical techniques will be left to the discretion of the neurosurgeon. Patients will be analyzed according to an intention-to-treat design. The primary endpoint will be functional outcome on the GOS-E after 1 year. Patient recruitment starts in 2022 with the exact timing depending on the current COVID-19 crisis and is expected to end in 2024.

Discussion
The study results will be implemented after publication and presented on international conferences. Depending on the trial results, the current Brain Trauma Foundation guidelines will either be substantiated by high-quality evidence or will have to be altered.

Trial registration
Nederlands Trial Register (NTR), Trial NL9012. ClinicalTrials.gov, Trial NCT04648436.
Social network-based group intervention to promote HIV prevention in Uganda: study protocol for a cluster randomized controlled trial of Game Changers
Authors: Wagner Glenn J. , Bogart Laura M. , Green Harold D. , Storholm Erik D. , Klein David J. , McBain Ryan K. , Serunkuuma Richard , Mubiru Kuraish , Matovu Joseph K. B. , Okoboi Stephen 
Published: March 2022

AbstractIntroductionInnovative strategies are needed to disseminate HIV prevention messages across communities efficiently, as well as reduce HIV stigma while promoting HIV prevention. This randomized controlled trial will evaluate the efficacy of a social network-based group intervention,Game Changers, which trains persons living with HIV (PLWH) to encourage members of their social network to use HIV protective behaviorsMethodsPLWH in HIV care for at least 1 year will be randomly assigned to receive the 8-session group advocacy training intervention or no-intervention control group. Each enrolled PLWH (index participant) will be asked to recruit up to four social network members (alter participant). Assessments will be administered at baseline and months 6, 12, and 18 to both index and alter participants. The primary outcomes are HIV testing and condom use among alter participants; secondary outcomes are engagement in HIV prevention advocacy and internalized HIV stigma among index participants. Repeated-measures multivariable regression analyses will be conducted to compare outcomes between the intervention and control arms, in addition to a cost-effectiveness evaluation.DiscussionThis social network-based approach to HIV prevention is particularly timely in the era of biomedical interventions, which require widespread penetration of effective HIV prevention and care messaging into communities. Positioning PLWH as central to the solution for controlling (vs. causing) the HIV epidemic has the potential to reduce HIV stigma and improve prevention outcomes at the individual and network levels.Trial registrationClinicalTrials.govNIH Clinical Trial Registry NCT05098015. Registered on October 18, 2021.
Transgenesis in parasitic helminths: a brief history and prospects for the future
Authors: Quinzo M. J. , Perteguer M. J. , Brindley P. J. , Loukas A. , Sotillo J. 
Published: March 2022

AbstractHelminth infections impact the health of hundreds of millions of persons globally and also cause important economic losses in livestock farming. Methodological limitations as well as the low attention given to the study of helminths have impacted biological research and, thus, the procurement of accurate diagnosis and effective treatments. Understanding the biology of helminths using genomic and proteomic approaches could contribute to advances in understanding host–helminth interactions and lead to new vaccines, drugs and diagnostics. Despite the significant advances in genomics in the last decade, the lack of methodological adaptation of current transgenesis techniques has hampered the progression of post-genomic research in helminthology. However, the application of new techniques, such as CRISPR, to the study of trematodes and nematodes has opened new avenues for genome editing-powered functional genomics for these pathogens. This review summarises the historical advances in functional genomics in parasitic helminths and highlights pending limitations that will need to be overcome to deploy transgenesis tools.
Graphical Abstract
Lessons from the Winter Paralympic Games disclosing the epidemiology of winter sports injury in paralytic athletes: a meta-analysis
Authors: Wu Fengyu , Liu Yitong , Zhuang Maohua 
Published: March 2022

Abstract
Background
In this study, the incidence rate of the injury in Winter Paralympic Games was summarized. Besides, to testify the underlying factors of injury incidence heterogeneity, the difference of these events incidence between different Paralympic Winter Games was investigated by meta regression analysis.

Methods
Electronic databases were searched for full-text publications on sports related injury in Winter Paralympic Games. And meta-regression was used to analyze the heterogeneity.

Results
Four studies were included. The incidence of sports related injury was 0.21 (95% CI 0.15–0.31) in all items, 0.22 in female athletes (95% CI 0.12–0.32), and 0.21 in male athletes (95% CI 0.11–0.30), respectively. The incidence of sports related injury was 0.10 (95% CI 0.08–0.12) in alpine skiing, 0.01 (95% CI 0–0.02) in Nordic skiing, and 0.22 in sledge hockey (95% CI 0.05–0.40). Meta-regression suggested the year and the host country couldn’t influence the injury incidence.

Conclusion
The present study summarized the incidence of sports related injury in Winter Paralympic Games, indicated similar injury risk between female athletes and male athletes, and accentuated the careful protection on sledge hockey. This study pointed out that sledge hockey with the highest risk of sports related injury should draw great attention to improve the corresponding protective measures to decrease its injury probability.
Establishment of a novel assessment of the quality of human spermatozoa measuring mitochondrial oxygen metabolism
Authors: Taniguchi Hisanori , Matsuo Yoshiyuki , Shimoi Kayo , Yoshimura Masahiro , Hirota Kiichi , Kinoshita Hidefumi 
Published: March 2022

Abstract
Objective
We aimed to establish a novel sperm quality evaluation technology by measuring mitochondrial oxygen metabolism in human spermatozoa.

Results
Normozoospermic human sperm samples were used. After establishing the optimal parameters for measuring the oxygen metabolism of human sperm cells using the extracellular flux analyzer, we measured the oxygen consumption rate (OCR) of human spermatozoa exposed to different storage temperatures. Although sperm motility was significantly lower at 4 °C when compared with sperm motility at 37 °C, there were no significant differences in sperm vitality and the OCR under both conditions. The present study established a methodology for human sperm quality evaluation using extracellular flux analysis technology. The OCR evaluation could be a reliable measurement tool for assessing human sperm quality.
VALCOR: a protocol for the validation of SARS-corona virus-2 assays
Authors: Arbyn Marc , Dhillon Sharonjit Kaur , Martinelli Marianna , Simoens Cindy , Cuypers Lize , Bode Jannes , Van Ranst Marc , Corbisier Philippe , Bonde Jesper , Cocuzza Clementina 
Published: March 2022

Abstract
Background
Testing for SARS-CoV-2, together with vaccination, is one of the most vital strategies in curbing the current COVID-19 pandemic. The pandemic has led to an unprecedented need for diagnostic testing and the rapid emergence of an abundance of commercial assays on the market. Due to the nature of the pandemic and in the interest of health protection, many of these assays received provisional authorisation for emergency use without thorough validation. To limit false negative and false positive results, it is key to define common criteria that SARS-CoV-2 assays need to fulfil. VALCOR or “VALidation of SARS-CORona Virus-2 assays” is a protocol designed to set up a framework for test validation of SARS-CoV-2 virus assays.

Objectives
VALCOR is a study protocol for the validation of assays used for confirmation of the presence of SARS-CoV-2 in patients with COVID-19 disease or the screening of carriers of SARS-CoV-2 virus by the identification of viral RNA in oropharyngeal and/or nasopharyngeal specimens or other specimens from the human respiratory tract.

Methods
The VALCOR panel of samples will contain clinical human specimens and standardised artificial specimens. The collection of clinical specimens will include nasopharyngeal or oropharyngeal specimens or other specimens from the respiratory tract obtained from COVID-19 patients and healthy carriers of SARS-CoV-2 as well as specimens from subjects not carrying SARS-CoV-2. Artificial specimens include calibrated amounts of viral RNA of SARS-CoV-2 sequences provided by established competent agencies that produce reference materials for the assessment of the limit of detection of each assay. The panel of samples are sent from a central reference laboratory (having access to biobanks of clinical specimens tested already for SARS-CoV-2 with a reference comparator assay) to participating laboratories for testing with a SARS-CoV-2 index assay that requires evaluation.

Discussion
VALCOR provides a harmonised and standard framework to benchmark the testing performance of SARS-CoV-2 assays that are rapidly evolving. As the pandemic incited an urgent need for testing capacity, there is a gap in the comprehensive validation of SARS-CoV-2 assays. This study will generate comprehensive validation data for assays used for the diagnosis of SARS-CoV-2 and may serve as a basis for other validation protocols.
How to improve the COVID-19 health education strategy in impoverished regions: a pilot study
Authors: Wang Huimin , Liao Rujun , Chen Xin , Yu Jie , Zhu Tianyu , Liao Qiang , Zhang Tao 
Published: March 2022

Abstract
Background
It is of great challenge to raise the public coronavirus disease 2019 (COVID-19) related health literacy (CRHL) in impoverished regions due to the limits of poor infrastructure, large proportion of vulnerable groups, etc. However, those limits cannot be solved in the short term. Therefore, this study chose Liangshan Yi Autonomous Prefecture, one of the poorest areas in China, as a pilot, to reveal the quantitative relationships among different dimensions under the COVID-19 health education framework, clarify the key points for health promotion, and provide specific suggestions for COVID-19 health education strategy in impoverished regions.

Methods
A cross-sectional questionnaire survey was conducted in five regions of Liangshan Yi Autonomous Prefecture in 2020. There were 2,100 individuals sampled by multi-stage method. This survey mainly measured the four dimensions: CRHL, COVID-19 related tense psychological reactions (CRTPR), COVID-19 related information report acquisition (CRIRA), and general health literacy (GHL). The multivariate logistic regression was used to explore the influence of demographic characteristics on each dimension. Furthermore, to quantify the relationships among different dimensions, this study employed the structural equation model (SEM), and analyzed the mediating effects of CRHL and CRIRA as well as the moderating effects of regional characteristic variables.

Results
The CRHL played an important role in promoting COVID-19 health education, reaching 52.5% in Liangshan Yi Autonomous Prefecture. The GHL (β = 0.336) and age (β = 0.136) had statistically positive impacts on CRHL. The CRHL affected CRTPR negatively (β = − 0.198) and CRIRA positively (β = 0.052). The CRHL played significant mediating roles among the four dimensions (P < 0.05). Effectiveness of government prevention and control as well as the ethnicity moderated not only the relationships between CRHL and other dimensions, but also the mediating effect of CRHL (P < 0.05). People with lower income and education levels had lower GHL (β = 0.286, 1.292). The youth were more likely to show CRTPR (β = − 0.080).

Conclusions
By proposing and verifying the theoretical framework, this study put forward specific suggestions on how to improve COVID-19 health education strategies in impoverished regions via implementation methods, key groups and effect evaluation, which also provided references about future public health emergencies for other impoverished regions of the world.

Graphical Abstract
Voriconazole injection may induce delayed methotrexate excretion: a case report and experimental study
Authors: Watahiki Daisuke , Saito Daisuke , Nishida Naonori , Tsuri Hiroyuki , Nomura Keiko , Adachi Yuichi , Taguchi Masato 
Published: March 2022

Abstract
Background
We report a case of delayed excretion of methotrexate (MTX) in a pediatric patient on high-dose MTX therapy in response to a change in the concomitant dosage of voriconazole from oral to intravenous. As the intravenous, but not the oral formulation of voriconazole includes sulfobutylether-β-cyclodextrin (SBECD), which has an anionic residue, we hypothesized that SBECD inhibits the renal excretion of anionic compounds.

Methods
We evaluated the inhibitory effects of SBECD on renal excretion of phenolsulfonphthalein (PSP), which is eliminated in urine via organic anion transport systems. PSP was administered intravenously to rats at 2.5 and 25 mg/kg with or without SBECD pretreatment (320 mg/kg).

Results
The plasma concentration of PSP at the dosage of 2.5 mg/kg were comparable between control and SBECD groups. On the other hand, at 25 mg/kg the elimination of PSP was delayed. The clearance of PSP at the dosage of 25 mg/kg was 9.71 ± 1.65 and 4.13 ± 0.76 mL/min/kg in control and SBECD groups, respectively (p < 0.05). This suggested that SBECD partly inhibits the renal excretion of anionic drugs.

Conclusion
The present case report discusses the delayed elimination of MTX in high dose therapy and possible mechanism involving SBECD as an excipient in concomitant drugs. It seems better to avoid choosing injection containing SBECD for patients undergoing HD-MTX treatment. Further studies are needed to confirm the inhibitory effects of SBECD on the renal excretion of MTX, especially in high-dose regimens.