bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and tolerability of a 12-week combination chemotherapy followed by lomustine consolidation treatment in canine B- and T-cell lymphoma
Authors: Limmer Stefanie , Nerschbach Verena , Eberle Nina , Teske Erik , Simon Betz Daniela 
Published: December 2022

AbstractBackgroundHigh-grade lymphoma in dogs is a chemotherapy-responsive neoplasia with remission rates exceeding 80% under combination chemotherapy protocols. Usually these protocols are intensive and 24 + weeks. The objective of the present study was to investigate if a shorter protocol combined with an oral lomustine maintenance treatment (3 × in 8 weeks) would present an acceptable result, both for B- and T-cell lymphomas, and for the different types of lymphomas normally encountered in private veterinary practice.Results144 dogs entered the study. Lymphoma types included multicentric (n = 123), alimentary (n = 13), miscellaneous (n = 7), and mediastinal lymphoma (n = 1). Overall response rate was 83.3% (B-cell: 86.6%, T-cell: 79.4%). Complete remission (CR) was achieved in 72.2% (B-cell: 77.3%, T-cell: 67.6%) and partial remission (PR) in 11.1% (B-cell: 9.3%, T-cell: 11.8%) of the dogs. Median duration of first CR amounted to 242 days (B-cell: 263 d, T-cell: 161 d). Median survival in dogs with CR was 374 days (B-cell: 436 d, T-cell: 252 d), and median overall survival time was 291 days (B-cell: 357d, T-cell: 210d). Immunophenotype demonstrated an independent significant influence on duration of remission and survival in the whole group. Findings of splenic and hepatic cytology were not significant associated with patient outcome. Treatment was well tolerated; the majority of adverse events were classified as grade 1 or 2.ConclusionsShort-term chemotherapy followed by lomustine consolidation leads to compara-ble remission and survival times compared to conventional protocols with cyclophosphamide, doxorubicin, vincristine and prednisolone with acceptable toxicosis in dogs with both B-cell and T-cell lymphoma.
Surrogate endpoints in trials: a call for better reporting
Authors: Ciani Oriana , Manyara Anthony M. , Chan An-Wen , Taylor Rod S. ,   on behalf of the SPIRIT-SURROGATE/CONSORT-SURROGATE project group
Published: December 2022

AbstractUsing a surrogate endpoint as a substitute for a patient-relevant final outcome enables randomised controlled trials (RCTs) to be conducted more efficiently. However, the use of surrogates remains controversial and there is currently no guideline for the reporting of RCTs using surrogate endpoints; therefore, we seek to develop SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) and CONSORT (Consolidated Standards of Reporting Trials) extensions to improve the reporting of these trials. We would like to invite interested individuals (trial methodologists, journal editors, healthcare industry, regulators and payers, and patient/public representative groups), particularly those with experience in the use of surrogate endpoints in trials.
Evaluation of a web-based randomized controlled trial educational intervention based on media literacy on preventing substance abuse among college students, applying the integrated social marketing approach: a study protocol
Authors: Jormand Hanieh , Bashirian Saeed , Barati Majid , Rezapur-Shahkolai Forouzan , Babamiri Mohammad 
Published: December 2022

AbstractBackgroundSubstance abuse is the actual psychosocial harm, especially in young people confronted with content marketing in nowadays media environment, a risk factor for experiencing substance abuse. Based on the literature review, education designed based on the cognitive-behavioral model and planning models, such as using a social marketing framework, is the most effective method to prevent addictive substance abuse. Also, media literacy related to substance abuse and the prototype willingness model is considered a new integrated approach to present the intervention measures’ desired results.MethodsThe present study evaluates an intervention program based on media literacy on substance abuse prevention among students using an integrated social marketing approach. This study aims to complete the SMART model’s sixth and seventh stages, implementing intervention and evaluation. Participants will be students of Hamadan University, Iran. Randomization will occur at the university and school levels, and gathered data will appear at two-time (i.e., pre-test and three months follow-up). Intervention group students will obtain both substance abuse prevention education and substance abuse media literacy (SAML) education between pre-test and 3 months post-test. Students in the delayed intervention will be given this education after study accomplishment; this group will receive their regular courses except for substance abuse prevention and media literacy titles during education intervention. The outcome variables are intentions and substance abuse behavior based on prototype willingness and substance abuse media literacy.DiscussionEvaluation of Substance abuse prevention and substance abuse media literacy education must be careful to ensure that they effectively enable people, especially in youth in the new media ecology and unique “Infomedia” ecosystems, in the current digital society. The SAML education plan’s evaluation has the first web-based education program in universities. No prior research has psychometrically considered SAML in students in the SMART model’s sixth and seventh stages.Trial registrationIRCT20200914048719N1. Registered on June 30, 2021.
Approaches to prioritising research for clinical trial networks: a scoping review
Authors: Morton Rachael L. , Tuffaha Haitham , Blaya-Novakova Vendula , Spencer Jenean , Hawley Carmel M. , Peyton Phil , Higgins Alisa , Marsh Julie , Taylor William J. , Huckson Sue , Sillett Amy , Schneemann Kieran , Balagurunanthan Anitha , Cumpston Miranda , Scuffham Paul A. , Glasziou Paul , Simes Robert J. 
Published: December 2022

Abstract
Background
Prioritisation of clinical trials ensures that the research conducted meets the needs of stakeholders, makes the best use of resources and avoids duplication. The aim of this review was to identify and critically appraise approaches to research prioritisation applicable to clinical trials, to inform best practice guidelines for clinical trial networks and funders.

Methods
A scoping review of English-language published literature and research organisation websites (January 2000 to January 2020) was undertaken to identify primary studies, approaches and criteria for research prioritisation. Data were extracted and tabulated, and a narrative synthesis was employed.

Results
Seventy-eight primary studies and 18 websites were included. The majority of research prioritisation occurred in oncology and neurology disciplines. The main reasons for prioritisation were to address a knowledge gap (51 of 78 studies [65%]) and to define patient-important topics (28 studies, [35%]). In addition, research organisations prioritised in order to support their institution’s mission, invest strategically, and identify best return on investment. Fifty-seven of 78 (73%) studies used interpretative prioritisation approaches (including Delphi surveys, James Lind Alliance and consensus workshops); six studies used quantitative approaches (8%) such as prospective payback or value of information (VOI) analyses; and 14 studies used blended approaches (18%) such as nominal group technique and Child Health Nutritional Research Initiative. Main criteria for prioritisation included relevance, appropriateness, significance, feasibility and cost-effectiveness.

Conclusion
Current research prioritisation approaches for groups conducting and funding clinical trials are largely interpretative. There is an opportunity to improve the transparency of prioritisation through the inclusion of quantitative approaches.
Efficacy of the Digital Therapeutic sinCephalea in the prophylaxis of migraine in patients with episodic migraine: study protocol for a digital, randomized, open-label, standard treatment controlled trial
Authors: Schröder Torsten , Brudermann Hanna C. B. , Kühn Gianna , Sina Christian , Thaçi Diamant , Nitschke Matthias , König Inke R. 
Published: December 2022

Abstract
Background
The German government implemented the Digital Healthcare Act in order to bring Digital Therapeutics into standard medical care. This is one of the first regulatory pathways to reimbursement for Digital Therapeutics (DTx). The Digital Therapeutic sinCephalea is intended to act as a prophylactic treatment of migraine by reducing the migraine days. For this, sinCephalea determines personalized nutritional recommendations using continuous glucose monitoring (CGM) data and enables the patients to follow a personalized low-glycemic nutrition. Migraine is a headache disorder with the highest socioeconomic burden. Emerging evidence shows that CGM-based personalized nutritional recommendations are of prophylactic use in episodic migraine. However, prospective data are yet missing to demonstrate clinical effectiveness. This study is designed to fill this gap.

Methods
Patients between 18 and 65 years of age with proven migraine and a minimal disease severity of 3 migraine days per month are included. After a 4-week baseline phase as a pre-study, patients are randomized to the DTx intervention or a waiting-list control. The objective of the study is to show differences between the intervention and control groups regarding the change of migraine symptoms and of effects of migraine on daily life.

Discussion
To our knowledge, this is the first systematic clinical trial with a fully digital program to enable patients with migraine to follow a personalized low-glycemic nutrition in order to reduce their number of migraine days and the migraine-induced impact on daily life. Designing a clinical study using a digital intervention includes some obstacles, which are addressed in this study approach.

Trial registration
German Registry of Clinical Studies (Deutsches Register Klinischer Studien) DRKS-ID DRKS00024657. Registered on March 8, 2021.
Effects of alpha-lipoic acid on sperm quality in patients with varicocele-related male infertility: study protocol for a randomized controlled clinical trial
Authors: Zhang Qi-Feng , Wang Sheng , Zhang Han , Liu Qi-Li , Wei Yu , Deng Wei , Wang Chuang , Yang Bo 
Published: December 2022

Abstract
Background
Varicocele is a high incidence and is considered to be the most common and correctable cause of male infertility. Oxidative stress (OS) plays a central role in the pathogenesis of varicocele-related male infertility. In addition to varicocelectomy, antioxidant supplementation seems to be an effective scheme for the treatment of varicocele-related male infertility, but it is still controversial. The purpose of this study is to determine the effects of alpha-lipoic acid (ALA) supplementation on sperm quality in patients with varicocele-related male infertility.

Methods
In this randomized controlled clinical trial, we will randomize 80 patients with varicocele-related male infertility from Guilin People’s Hospital. The non-surgical observation group (n = 20) will receive ALA, the non-surgical control group (n = 20) will receive vitamin E, the surgical observation group (n = 20) will receive ALA after the operation, and the surgical control group (n = 20) will receive vitamin E after the operation. The course of treatment will be 3 months. The results will compare the changes in semen parameters, sex hormones, testicular volume, sperm DNA fragment index (DFI), seminal plasma malondialdehyde (MDA), and total antioxidant capacity (TAC) between the groups at baseline and after 3 months of antioxidant supplementation.

Discussion
Whether it is necessary to use antioxidants in varicocele-related male infertility, how potent antioxidants should be used, postoperative application or non-surgical independent application still needs to be explored. This study attempts to compare the effects of two antioxidants (ALA and vitamin E) on sperm quality in patients with varicocele-related male infertility (surgical or non-surgical) and attempted to answer the above questions.

Trial registration
Chinese Clinical Trial Registry (ChiCTR) ChiCTR2100054958. Registered on 29 December 2021
Effect of remimazolam tosilate versus etomidate on hemodynamics in patients undergoing valve replacement surgery: study protocol for a randomized controlled trial
Authors: Hu Bailong , Zhou Haiyan , Zou Xiaohua , Tan Li , Song Tao , Zellmer Lucas , Li Xingyu 
Published: December 2022

Abstract
Background
Patients with a history of cardiac disease are prone to develop cardiovascular adverse events such as hypotension, hypertension, and tachycardia during anesthesia induction. Therefore, hemodynamic stability is one of the most important concerns for induction of anesthesia in patients undergoing cardiac surgery. Remimazolam tosilate is a new, ultra-short-acting benzodiazepine agent, with the advantages of rapid onset, rapid offset, and minimal cardiorespiratory depression. We aim to compare the effect of remimazolam tosilate and etomidate on hemodynamics during anesthesia induction in patients undergoing valve replacement surgery.

Methods/design
The trial is a prospective, randomized, double-blinded, controlled, single-center trial to compare the effect of remimazolam tosilate and etomidate on hemodynamics in patients undergoing valve replacement surgery. One hundred seventeen patients undergoing selective valve replacement surgery between January 1, 2022, and December 31, 2023, will be enrolled and randomly allocated into one of three groups: low-dose remimazolam group (Group LR), high-dose remimazolam group (Group HR), or etomidate group (Group E). The primary outcome is hemodynamic fluctuations during anesthesia induction (the difference between mean arterial pressure [MAP] to baseline, ▴MAP; and the difference between maximum or minimum heart rate [HR] and baseline, ▴HR). Secondary outcomes include the incidence of adverse cardiovascular events (hypotension, severe bradycardia, hypertension, tachycardia, and arrhythmia), the cumulative doses of vasoactive drugs used per patient, incidence and degree of injection pain and myoclonus, blood glucose values, and vital signs at different time points.

Discussion
This research will determine the effectiveness and safety of remimazolam tosilate induction on hemodynamics in patients undergoing valve replacement surgery.

Trial registration
www.chictr.org.cn identifier ChiCTR2100052535. Registered on 17th Dec 2021, http://www.chictr.org.cn/).
Voltammetric approach for pharmaceutical samples analysis; simultaneous quantitative determination of resorcinol and hydroquinone
Authors: Nabatian Ebrahim , Mousavi Mahdi , Pournamdari Mostafa , Yoosefian Mehdi , Ahmadzadeh Saeid 
Published: December 2022

AbstractA simple and precise analytical approach developed for single and simultaneous determination of resorcinol (RC) and hydroquinone (HQ) in pharmaceutical samples using carbon paste electrode (CPE) modified with 1-Ethyl-3-methylimidazolium tetrafluoroborate as ionic liquid and ZnFe2O4 nanoparticle. A significant enhancement in the peak current and sensitivity of the proposed sensor observed by using modifiers in the composition of working electrode compared to bare CPE which is in accordance with the results obtained from electrochemical impedance spectroscopy investigations. Electrochemical investigations revealed a well-defined irreversible oxidation peak for RC over a wide concentration range from 3.0 µM to 500 µM in 0.1 M phosphate buffer solution (pH 6.0) with the linear regression equations of Ip (µA) = 0.0276 CRC (µM) + 0.5508 (R2 = 0.997). The limit of detection and quantification for RC analysis were found to be 1.46 µM and 4.88 µM, respectively. However, the obtained SW voltammograms for simultaneous determination of RC and HQ exhibited a desirable peak separation of about 360 mV potential difference and a satisfactory linear response over the range of 50–700 µM and 5-350 µM with the favorable correlation coefficient of 0.991 and 0.995, respectively. The diffusion coefficient (D) of RC and the electron transfer coefficient (α) at the surface of ZnFe2O4/NPs/IL/CPE estimated to be 2.83 × 10− 4 cm s− 1 and 0.76. The proposed sensor as a promising and low-cost method successfully applied for determination of RC in commercial pharmaceutical formulations such as the resorcinol cream of 2% O/W emulsion available on the market with the recovery of 98.47 ± 0.04.
Preparation of hydroxyethyl cellulose/ mangiferin edible films and their antimicrobial properties
Authors: Tohamy Hebat-Allah S. , El-Sakhawy Mohamed , El-Masry Hossam M. , Saleh Ibrahim A. , AbdelMohsen Mona M. 
Published: December 2022

AbstractIn this study, we have used hydroxyethyl cellulose (HEC) to prepare antimicrobial films for multipurpose applications. Using HEC gives mangiferin powder (M) mechanical properties, while mangiferin powder gives HEC antimicrobial activities. Various concentrations of M (2.5, 5 and 10% wt/vol) were added to HEC to enhance the antimicrobial ability of HEC/M films. The results showed that 10% (wt/vol) was the optimum concentration to accomplish the antimicrobial activity. Various analyses were performed to study the prepared films’ physical, chemical, mechanical, and antimicrobial properties.
Characterization of two 1,3-β-glucan-modifying enzymes from Penicillium sumatraense reveals new insights into 1,3-β-glucan metabolism of fungal saprotrophs
Authors: Scafati Valentina , Troilo Francesca , Ponziani Sara , Giovannoni Moira , Scortica Anna , Pontiggia Daniela , Angelucci Francesco , Di Matteo Adele , Mattei Benedetta , Benedetti Manuel 
Published: December 2022

Abstract
Background
1,3-β-glucan is a polysaccharide widely distributed in the cell wall of several phylogenetically distant organisms, such as bacteria, fungi, plants and microalgae. The presence of highly active 1,3-β-glucanases in fungi evokes the biological question on how these organisms can efficiently metabolize exogenous sources of 1,3-β-glucan without incurring in autolysis.

Results
To elucidate the molecular mechanisms at the basis of 1,3-β-glucan metabolism in fungal saprotrophs, the putative exo-1,3-β-glucanase G9376 and a truncated form of the putative glucan endo-1,3-β-glucosidase (ΔG7048) from Penicillium sumatraense AQ67100 were heterologously expressed in Pichia pastoris and characterized both in terms of activity and structure. G9376 efficiently converted laminarin and 1,3-β-glucan oligomers into glucose by acting as an exo-glycosidase, whereas G7048 displayed a 1,3-β-transglucanase/branching activity toward 1,3-β-glucan oligomers with a degree of polymerization higher than 5, making these oligomers more recalcitrant to the hydrolysis acted by exo-1,3-β-glucanase G9376. The X-ray crystallographic structure of the catalytic domain of G7048, solved at 1.9 Å of resolution, consists of a (β/α)8 TIM-barrel fold characteristic of all the GH17 family members. The catalytic site is in a V-shaped cleft containing the two conserved catalytic glutamic residues. Molecular features compatible with the activity of G7048 as 1,3-β-transglucanase are discussed.

Conclusions
The antagonizing activity between ΔG7048 and G9376 indicates how opportunistic fungi belonging to Penicillium genus can feed on substrates similar for composition and structure to their own cell wall without incurring in a self-deleterious autohydrolysis.
Effects of different drugs and hormone treatment on Toxoplasma gondii glutathione S-transferase 2
Authors: Li Shuang , Ying Zhu , Xue Yangfei , Sun Zhepeng , Liu Jing , Liu Qun 
Published: December 2022

Abstract
Background
Glutathione S-transferase (GST) in eukaryotic organisms has multiple functions such as detoxifying endogenous/exogenous harmful substances to protect cells from oxidative damage, participating in sterol synthesis and metabolism, and regulating signaling pathways. Our previous work identified an important GST protein in Toxoplasma that contributes to vesicle trafficking called TgGST2, the deletion of which significantly reduces the virulence of the parasite. Meanwhile, we considered that TgGST2 may also play a role in other pathways of parasite life activities.

Methods
The tertiary structures of TgGST2 as well as estradiol (E2) and progesterone (P4) were predicted by trRosetta and Autodock Vina software, the binding sites were analyzed by PyMol's GetBox Plugin, and the binding capacity was evaluated using Discovery Studio plots software. We examined the influence of E2 and P4 on TgGST2 via glutathione S-transferase enzyme activity and indirect immunofluorescence assay (IFA) and through the localization observation of TgGST2 to evaluate its response ability in different drugs.

Results
TgGST2 could bind to exogenous E2 and P4, and that enzymatic activity was inhibited by the hormones in a concentration-dependent manner. Upon P4 treatment, the localization of TgGST2 changed from Golgi and vesicles to hollow circles, leading to abnormal localization of the molecular transporter Sortilin (VPS10) and microneme proteins (M2AP and MIC2), which ultimately affect the parasite life activities, but E2 had no significant effect. Moreover, diverse types of drugs had divergent effects on TgGST2, among which treatment with antifungal agents (voriconazole and clarithromycin), anticarcinogens (KU-60019, WYE-132 and SH5-07) and coccidiostats (dinitolmide and diclazuril) made the localization of TgGST2 appear in different forms, including dots, circles and rod shaped.

Conclusions
Our study shows that TgGST2 plays a role in sterol treatment and can be affected by P4, which leads to deficient parasite motility. TgGST2 exerts divergent effects in response to the different properties of the drugs themselves. Its responsiveness to diverse drugs implies a viable target for the development of drugs directed against Toxoplasma and related pathogenic parasites.

Graphical Abstract