bluuebunny/crossref_metadata_2025_split huggingface dataset:
Xanthohumol microbiome and signature in adults with Crohn’s disease (the XMaS trial): a protocol for a phase II triple-masked, placebo-controlled clinical trial
Authors: Langley Blake O. , Ryan Jennifer Joan , Phipps John , Buttolph Lita , Bray Brenna , Aslan Joseph E. , Metz Thomas O. , Stevens Jan F. , Bradley Ryan 
Published: October 2022

Abstract
Background
Xanthohumol (XN), a bioactive flavonoid from Humulus lupulus with anti-inflammatory properties, has potential benefits for patients with Crohn’s disease (CD), a type of inflammatory bowel disease. We recently completed and published results of a placebo-controlled phase I clinical trial demonstrating the safety and tolerability of 24 mg XN daily for 8 weeks. The present study aims to evaluate the safety and tolerability of the same dose of XN adults with clinically active CD in a placebo-controlled phase II clinical trial. Additional aims will assess the impact of XN on inflammatory biomarkers, platelet function, CD clinical activity, and stool microbial composition. The metabolism of XN will also be evaluated. This article provides a model protocol for consideration in investigations of XN or other natural products in disease states.

Methods
A triple-masked, randomized, placebo-controlled trial will be conducted in adults with clinically active CD. Participants (n ≤ 32) will be randomized to either 24 mg encapsulated XN per day or placebo and followed for 8 weeks. Throughout the trial, participants will be queried for adverse events. Biomarkers of clinical safety, blood and stool markers of inflammation, platelet function, Crohn’s Disease Activity Index score, stool microbial composition, and XN metabolite profiles in blood, urine, and stool will be assessed every 2 weeks.

Discussion
We describe the protocol for a phase II clinical trial that evaluates the safety and tolerability of XN in adults with active CD, as well as evaluate metabolism and mechanisms that are relevant to CD and other diseases with underlying inflammation and/or gut permeability. The effects of XN on inflammatory biomarkers, platelet function, the microbiota, and multi-omics biomarkers measured in this phase II trial of adults with CD will be compared to the effects of XN in healthy adults in our previous phase I trial. The results of the study will advance the evidence guiding the use of XN in patients with CD.

Trial registration
ClinialTrials.gov NCT04590508. Registered on October 19, 2020
High-dose Intensity-modulated proton therapy versus Standard-dose Intensity-modulated RadIation therapy for esophageal squamous cell carcinoma (HI-SIRI): study protocol for a randomized controlled clinical trial
Authors: Lertbutsayanukul Chawalit , Kitpanit Sarin , Kannarunimit Danita , Chakkabat Chakkapong , Oonsiri Sornjarod , Thephamongkhol Kullathorn , Puataweepong Putipun , Katanyoo Kanyarat , Sukhaboon Jirasak , Tovanabut Chokaew , Chongsathientham Sirikanya , Treeratsapanich Pornravee , Soonthornrak Jirarat , Prayongrat Anussara 
Published: October 2022

Abstract
Background
Chemoradiotherapy is the standard of care for esophageal cancer as a neoadjuvant treatment before surgery, or as a definitive treatment for unresectable disease. Intensity-modulated radiotherapy (IMRT) has been considered the standard radiation technique. However, patients suffer from treatment-related toxicities, and most die from disease progression or recurrence. With emerging technological advancement, proton therapy has theoretical advantages over IMRT because it offers apparent dosimetric benefits to allow dose escalation to the target while better sparing surrounding tissues such as the lungs, heart, liver, and spinal cord. The purpose of this study protocol is to investigate the survival benefit of proton therapy using modern intensity-modulated proton therapy (IMPT) compared to standard IMRT for esophageal cancer.

Methods
This is a two-arm open phase II/III multi-institution randomized controlled trial. Eligible patients will have histologically confirmed squamous cell carcinoma of the thoracic esophagus with no evidence of tracheoesophageal/esophagobronchial fistula or distant metastasis. After stratification according to resectability status (resectable vs. borderline resectable/unresectable), a total of 232 patients will be randomized to receive IMPT or IMRT using a 1:1 allocation ratio. In resectable cases, surgical resection following concurrent chemoradiation will be attempted for the patients who are medically fit at the time of surgery. In those with initially borderline resectable/unresectable disease, definitive concurrent chemoradiation will be performed. The phase II study will assess safety (toxicity and postoperative complications) and feasibility (recruitment rate and chemoradiation dose modification) in 40 patients into each arm. The study will then continue into phase III, further recruit 76 patients into each arm, and compare progression-free survival between IMPT vs IMRT groups. The secondary endpoints will be overall survival, local and distant control, toxicities, health-related quality of life, and cost-utility. This protocol describes a detailed radiotherapy and chemotherapy.

Discussion
This randomized clinical trial will demonstrate the clinical benefit of IMPT in esophageal cancer treatment in terms of survival and toxicity outcomes which will further establish high-level evidence for radiation modality in squamous cell carcinoma of the thoracic esophagus.

Trial registration
TCTR20200310006. Registered 10 March 2020.
Use of a real-time risk-prediction model to identify pediatric patients at risk for thromboembolic events: study protocol for the Children’s Likelihood Of Thrombosis (CLOT) trial
Authors: Walker Shannon C. , French Benjamin , Moore Ryan , Domenico Henry J. , Wanderer Jonathan P. , Balla Sreenivasa , Creech C. Buddy , Byrne Daniel W. , Wheeler Allison P. 
Published: October 2022

Abstract
Background
Pediatric patients have increasing rates of hospital-associated venous thromboembolism (HA-VTE), and while several risk-prediction models have been developed, few are designed to assess all general pediatric patients, and none has been shown to improve patient outcomes when implemented in routine clinical care.

Methods
The Children’s Likelihood Of Thrombosis (CLOT) trial is an ongoing pragmatic randomized trial being conducted starting November 2, 2020, in the inpatient units at Monroe Carell Jr. Children’s Hospital at Vanderbilt in Nashville, TN, USA. All admitted patients who are 21 years of age and younger are automatically enrolled in the trial and randomly assigned to receive either the current standard-of-care anticoagulation practice or the study intervention. Patients randomized to the intervention arm are assigned an HA-VTE risk probability that is calculated from a validated VTE risk-prediction model; the model is updated daily with the most recent clinical information. Patients in the intervention arm with elevated risk (predicted probability of HA-VTE ≥ 0.025) have an additional review of their clinical course by a team of dedicated hematologists, who make recommendations including pharmacologic prophylaxis with anticoagulation, if appropriate. The anticipated enrollment is approximately 15,000 patients. The primary outcome is the occurrence of HA-VTE. Secondary outcomes include initiation of anticoagulation, reasons for not initiating anticoagulation among patients for whom it was recommended, and adverse bleeding events. Subgroup analyses will be conducted among patients with elevated HA-VTE risk.

Discussion
This ongoing pragmatic randomized trial will provide a prospective assessment of a pediatric risk-prediction tool used to identify hospitalized patients at elevated risk of developing HA-VTE.

Trial registration
ClinicalTrials.gov NCT04574895. Registered on September 28, 2020. Date of first patient enrollment: November 2, 2020.
Home-based intensive treatment of chronic radiation-associated dysphagia in head and neck cancer survivors (HIT-CRAD trial)
Authors: Massonet Hanne , Goeleven Ann , Van den Steen Leen , Vergauwen Alice , Baudelet Margot , Van Haesendonck Gilles , Vanderveken Olivier , Bollen Heleen , van der Molen Lisette , Duprez Fréderic , Tomassen Peter , Nuyts Sandra , Van Nuffelen Gwen 
Published: October 2022

Abstract
Background
Chronic radiation-associated dysphagia (C-RAD) is considered to be one of the most severe functional impairments in head and neck cancer survivors treated with radiation (RT) or chemoradiation (CRT). Given the major impact of these late toxicities on patients’ health and quality of life, there is a strong need for evidence-based dysphagia management. Although studies report the benefit of strengthening exercises, transference of changes in muscle strength to changes in swallowing function often remains limited. Therefore, combining isolated strengthening exercises with functional training in patients with C-RAD may lead to greater functional gains.

Methods
This 3-arm multicenter randomized trial aims to compare the efficacy and possible detraining effects of mere strengthening exercises (group 1) with a combination of strengthening exercises and functional swallowing therapy (group 2) and non-invasive brain stimulation added to that combination (group 3) in 105 patients with C-RAD. Patients will be evaluated before and during therapy and 4 weeks after the last therapy session by means of swallowing-related and strength measures and quality of life questionnaires.

Discussion
Overall, this innovative RCT is expected to provide new insights into the rehabilitation of C-RAD to optimize post-treatment swallowing function.

Trial registration
International Standard Randomized Controlled Trials Number (ISRCTN) registry ID ISRCTN57028065. Registration was accepted on 15 July 2021.
Brief internet-delivered cognitive-behavioural intervention for children and adolescents with symptoms of anxiety and depression during the COVID-19 pandemic: a randomised controlled trial protocol
Authors: Casella Caio Borba , Zuccolo Pedro Fonseca , Sugaya Luisa , de Souza Aline Santana , Otoch Luara , Alarcão Fernanda , Gurgel Wagner , Fatori Daniel , Polanczyk Guilherme V. 
Published: October 2022

Abstract
Background
The COVID-19 pandemic has had major impacts in many different spheres, including mental health. Children and adolescents are especially vulnerable because their central nervous system is still in development and they have fewer coping resources than do adults. Increases in the prevalence of depressive and anxiety symptomatology have been reported worldwide. However, access to mental health care is limited, especially for the paediatric population and in low- and middle-income countries. Therefore, we developed a brief internet-delivered cognitive-behavioural intervention for children and adolescents with symptoms of anxiety and depression. The aim of this proposed study is to test the efficacy of the intervention.

Methods
We will conduct a two-arm, parallel randomised controlled trial involving children and adolescents (8–11 and 12–17 years of age, respectively) with symptoms of anxiety, depression or both, according to the 25-item Revised Child Anxiety and Depression Scale (t-score > 70). A total of 280 participants will be randomised to the intervention group or the active control group, in a 1:1 ratio. Those in the intervention group will receive five weekly sessions of cognitive-behavioural therapy via teleconference. The sessions will focus on stress responses, family communication, diaphragmatic breathing, emotions, anger management, behavioural activation and cognitive restructuring. Participants in both groups will have access to 15 videos covering the same topics. Participant-guardian pairs will be expected to attend the sessions (intervention group), watch the videos (control group) or both (intervention group only). A blinded assessor will collect data on symptoms of anxiety, depression and irritability, at baseline, at the end of the intervention and 30 days thereafter. Adolescents with access to a smartphone will also be invited to participate in an ecological momentary assessment of emotional problems in the week before and the week after the intervention, as well as in passive data collection from existing smartphone sensors throughout the study.

Discussion
Internet-delivered interventions play a major role in increasing access to mental health care. A brief, manualised, internet-delivered intervention might help children and adolescents with anxiety or depressive symptomatology, even outside the context of the COVID-19 pandemic.

Trial registration
ClinicalTrials.gov NCT05139433. Registered prospectively in November 2021. Minor amendments made in July 2022.
Synergistic effects of silybin and curcumin on virulence and carbapenemase genes expression in multidrug resistant Klebsiella oxytoca
Authors: Omer Farah H. , Al-Khafaji Noor S. K. , Al-Alaq Farah Tareq , Al-Dahmoshi Hussein O. M. , Memariani Mojtaba , Saki Morteza 
Published: October 2022

Abstract
Objective
Silybin and curcumin have potential antimicrobial effects. This study aimed to evaluate the synergistic antimicrobial effects of silybin and curcumin on virulence and carbapenemase genes expression among multidrug-resistant (MDR) Klebsiella oxytoca.

Results
A total of 70 MDR K. oxytoca (carrying blaIMP and blaOXA-48-like genes) were included. The antibiotic susceptibility and biofilm production of isolates were determined. The silybin and curcumin at concentrations 10–500 mg/mL alone and in combination were exposed to bacterial isolates in Mueller Hinton broth medium for 24 h. The expression of blaIMP, blaOXA-48-like, mrkA, pilQ, matB and fimA genes was evaluated using quantitative real-time polymerase chain reaction (qRT-PCR).
The mean minimum inhibitory concentration (MIC) of curcumin and silybin were 250 mg/mL and 500 mg/mL, respectively. The anti-virulent effect of 100 mg/mL of silybin and curcumin was shown by significant reduction in the expression of fimA (2.1-fold, P < 0.0001) and mrkA (2.1 fold, P < 0.0001) genes. Moreover, these compounds significantly decreased the expression of blaIMP1 (3.2-fold, P < 0.0001) gene. Notably, there was no significant effect on pilQ, matB and blaOXA-48-like genes. The results showed that silybin and curcumin can be candidate as natural way for control the MDR virulent strains of K. oxytoca.
Diagnostic reliability of serum active B12 (holo-transcobalamin) in true evaluation of vitamin B12 deficiency: Relevance in current perspective
Authors: Dastidar Rinini , Sikder Kunal 
Published: October 2022

Abstract
Objective
Measurement of total vitamin B12 (vit B12) concentration raised concerns over early detection of vit B12 deficiency due to its clinical unreliability. In this present article we aimed to assess the efficacy of holo-transcobolamin (active vit B12) for true evaluation of vit B12 deficiency.

Methods
This retrospective study included 100 participants referred for vit B12 assay. Serum total vit B12, active vit B12 and homocysteine were estimated.

Results
Our study showed 59% of the total participants with vit B12 deficiency (185 ± 64.62 pg/ml) and 18% with hyper-cobalaminemia (1666.9 ± 367.13 pg/ml) based on their total vit B12 concentrations. A comparative study on total vit B12 and active vit B12 was done which reflected a striking disparity in results. Active vit B12 reported 28.8% patients with vit B12 deficiency (19.8 ± 17.48 pg/ml) and only 16.6% patients with hyper-cobalaminemia (224.14 ± 10 pg/ml). Active vit B12 appeared to be more sensitive (82.35% vs 65%) and specific (46.6% vs. 43.8%) diagnostic marker compared to total vit B12. Pearson Correlation study indicated a strong positive correlation (r = 0.695 at p < 0.01) hence justified use of the two methods.

Conclusion
We claim that active vit B12 is a much more reliable biomarker than total vit B12 for early diagnosis of vit B12 deficiency.
Advances in sex disparities for cancer immunotherapy: unveiling the dilemma of Yin and Yang
Authors: Ma Junfu , Yao Yanxin , Tian Ye , Chen Kexin , Liu Ben 
Published: October 2022

AbstractA wide sex disparity has been demonstrated in cancer incidence, tumor aggressiveness, prognosis, and treatment response of different types of cancer. The sex specificity of cancer appears to be a relevant issue in managing the disease, and studies investigating the role of sex and gender are becoming extremely urgent. Immunotherapy plays a leading role in cancer treatment, offering a new perspective on advanced malignancies. Gender has not been considered in standard cancer treatment, suggesting increasing the recognition of sex differences in cancer research and clinical management. This paper provides an overview of sex and gender disparities in cancer immunotherapy efficacy, anti-cancer immune response, predictive biomarkers, and so on. We focus on the molecular differences between male and female patients across a broad range of cancer types to arouse the attention and practice of clinicians and researchers in a sex perspective of new cancer treatment strategies.
Assessing real-world effectiveness of therapies: what is the impact of incretin-based treatments on hospital use for patients with type 2 diabetes?
Authors: Bussiere Clémence , Chauvin Pauline , Josselin Jean-Michel , Sevilla-Dedieu Christine 
Published: October 2022

Abstract
Background
Managing type 2 diabetes represents a major public health concern due to its important and increasing prevalence. Our study investigates the impact of taking incretin-based medication on the risk of being hospitalized and the length of hospital stay for individuals with type 2 diabetes.

Method
We use claim panel data from 2011 to 2015 and provide difference-in-differences (DID) estimations combined with matching techniques to better ensure the treatment and control groups’ comparability. Our propensity score selects individuals according to their probability of taking an incretin-based treatment in 2013 (N = 2,116). The treatment group includes individuals benefiting from incretin-based treatments from 2013 to 2015 and is compared to individuals not benefiting from such a treatment but having a similar probability of taking it.

Results
After controlling for health-related and socio-economic variables, we show that benefiting from an incretin-based treatment does not significantly impact the probability of being hospitalized but does significantly decrease the annual number of days spent in the hospital by a factor rate of 0.621 compared with the length of hospital stays for patients not benefiting from such a treatment.

Conclusion
These findings highlight the potential implications for our health care system in case of widespread use of these drugs among patients with severe diabetes.
Bacterial communities in co-cultured fish intestines and rice field soil irrigated with aquaculture wastewater
Authors: Guan Weibing , Li Kui , Li Kejun 
Published: October 2022

AbstractIn some regions, integrated rice-fish farms have been developed to balance the needs of aquaculture wastewater discharge and rice field irrigation. In this type of aqua-agriculture system, soil is irrigated with aquaculture wastewater, and intestinal bacteria in cultured fish species likely impact soil bacteria through irrigation. However, little is known about the relationship between soil bacteria and intestinal bacteria in some carp species commonly co-cultured in some Asian regions. Therefore, we co-cultured five carp species in aquaculture ponds and used the aquaculture wastewater to irrigate rice fields for over 5 years, and then compared carp intestinal bacterial communities with rice field soil bacterial communities. The results from analysis of similarity and SourceTracker analysis showed that a low similarity (R = 0.7908, P = 0.001) and contribution (an average of 9.9% of bacterial genera) of intestinal bacteria to soil bacterial communities although 77.5% of soil bacterial genera were shared by intestinal bacteria. Our results also indicated that intestinal bacteria in the numerically dominant fish species in the co-culture system do not necessarily impact soil bacteria more significantly than those of less abundant carp species, and that intestinal bacterial communities in one single fish species may impact certain soil bacterial phyla more significantly than others. Our results provide a better understanding of the impact of aquaculture wastewater on rice fields and will be helpful for the development of this type of aqua-agriculture system.
Single-carrier transmission scheme for extracting characteristic parameters of 32-Point 6PolSK-QPSK
Authors: Li Yupeng , Zhang Yichao , Li Lei , Zhang Mingzhu , Wu Du , Li Qianqian , Ding Xiaoming , Wang Xiaocheng 
Published: October 2022

AbstractSix polarization-shift keying quadrature phase shift keying (6PolSK-QPSK) signal modulation format is formed by different representations of QPSK. A variety of satisfactory single-carrier transmission schemes have been implemented in 24-Point 6PolSK-QPSK. As an extension of 24-Point 6PolSK-QPSK, it has been confirmed that 32-Point 6PolSK-QPSK has higher spectral efficiency (SE). Based on the method of extracting 24-Point 6PolSK-QPSK feature parameters, a 32-Point 6PolSK-QPSK signal transmission scheme is proposed and verified in 100 km single-mode fiber (SMF) with an aggregate transmission rate of 108-Gbps. Simulation results show that the original data could be recovered effectively with the proposed scheme, and the system bit error ratio (BER) could meet the requirement of the forward error correction (FEC) threshold of 3.8e − 3.
AUC optimization for deep learning-based voice activity detection
Authors: Zhang Xiao-Lei , Xu Menglong 
Published: October 2022

AbstractVoice activity detection (VAD) based on deep neural networks (DNN) have demonstrated good performance in adverse acoustic environments. Current DNN-based VAD optimizes a surrogate function, e.g., minimum cross-entropy or minimum squared error, at a given decision threshold. However, VAD usually works on-the-fly with a dynamic decision threshold, and the receiver operating characteristic (ROC) curve is a global evaluation metric for VAD at all possible decision thresholds. In this paper, we propose to maximize the area under the ROC curve (MaxAUC) by DNN, which can maximize the performance of VAD in terms of the entire ROC curve. However, the objective of the AUC maximization is nondifferentiable. To overcome this difficulty, we relax the nondifferentiable loss function to two differentiable approximation functions—sigmoid loss and hinge loss. To study the effectiveness of the proposed MaxAUC-DNN VAD, we take either a standard feedforward neural network or a bidirectional long short-term memory network as the DNN model with either the state-of-the-art multi-resolution cochleagram or short-term Fourier transform as the acoustic feature. We conducted noise-independent training to all comparison methods. Experimental results show that taking AUC as the optimization objective results in higher performance than the common objectives of the minimum squared error and minimum cross-entropy. The experimental conclusion is consistent across different DNN structures, acoustic features, noise scenarios, training sets, and languages.