bluuebunny/crossref_metadata_2025_split huggingface dataset:
HDAC inhibitors target IRS4 to enhance anti-androgen receptor (AR) therapy in AR-positive triple negative breast cancer
Authors: He Yang , Ma Yue , Zhu ye , Zhang Yi , Zhao rong , Zhang Di , Xu Danni , zhao peng , Tong sheng 
Published: January 2023

Abstract
Triple negative breast cancer (TNBC) is the most malignant subtype of breast cancer. Androgen receptor (AR)-positive TNBC has been identified as a potential therapeutic target; however, clinical trials have not produced an effective treatment. This study aimed to identify a new treatment regimen to improve the prognosis of AR-positive TNBC. First, we used a combination of an AR inhibitor (enzalutamide, Enz) and selective histone deacetylase inhibitor (chidamide, Chid) to treat AR-positive TNBC cell lines and observed a synergistic effect of the drugs. The combination treatment inhibited cell growth and migration by arresting the cell cycle at the G2/M phase. We used next-generation sequencing to detect changes in gene regulation. The results showed that the PI3K/Akt signalling pathway was significantly inhibited by the combination treatment of Enz and Chid, and gene set enrichment analysis (GSEA) revealed that KRAS signalling was significantly enriched. Analysis of associated genes revealed that insulin receptor substrate 4 (IRS4) plays a critical role in blocking the activation of KRAS signalling. In a mouse xenograft model, combination treatment also inhibited the PI3K/Akt signalling pathway by upregulating the expression of IRS4 and thereby suppressing tumour growth. In conclusion, we found that Enz and Chid combination treatment upregulates IRS4, which results in the blocking of KRAS signalling and suppression of tumour growth. We hypothesize that the expression level of IRS4 can be used as a biomarker for screening patients with AR-positive TNBC using enzalutamide and chidamide combination therapy.
Anti-amphiphysin antibody-associated paraneoplastic brainstem encephalitis with pruritus and dysphagia as the first symptoms: a case report
Authors: Wang Jin , Mi Xiaokun , Ban Feng , Li Ruoyang , Zhao Xuewei , Zhang Yaxi , Zhang Wei , Jia Yaqiong , Zhang Jing , Zhao Jingxia 
Published: January 2023

Abstract
Anti-amphiphysin antibodies are uncommonly detected in paraneoplastic neurologic syndromes (PNS). If this happens, it is likely to present as a stiff-person syndrome (SPS). Here, we report the first case of PNS with pruritus as the first complaint,whose serum examination showed anti-amphiphysin antibodies IG+++, and the lung puncture confirmed small-cell lung cancer (SCLC). During the progression of the disease, the patient developed dysphagia and anxiety. With chemotherapy and paroxetine 20mg/d, his symptoms significantly improved. This case report emphasizes that clinicians should consider diagnoses other than anxiety states or esophageal cancer in a patient with pruritus and dysphagia, such as PNS.
A Prospective Precision Medicine Phase 3 Clinical Trial of Low-dose Ondansetron (a 5-ht3 Antagonist) to Treat Heavy and Very Heavy Drinkers With Alcohol Use Disorder
Authors: Johnson Bankole , Alho Hannu , Addolorato Giovanni , Lesch Otto , Chick Jonathan , Liu Lei , Reich Jack , Schuyler Vinzant , Rodd Zachary 
Published: January 2023

AbstractThis 6-month, double-blind, randomized, Phase-3 clinical trial in Alcohol Use Disorder (AUD; n = 303) tested ondansetron 0.33 mg/twice daily (AD04) vs placebo in reducing the Percentage of Heavy Drinking Days (PHDD) among a genetic subgroup with variations at the serotonin transporter and 5-HT3A/5-HT-3B receptors who consumed < 10 Standard Drinks/Drinking Day (DDD) (heavy drinkers) or ≥ 10 DDD (very heavy drinkers). At Month 6, the least square (LS) mean change in PHDD from baseline was 8.5% greater in the heavy drinkers AD04 group compared with placebo (LS mean (SD): -46.7% (2.7%), 95%CI: -52.1% to -41.2% vs. -38.1% (2.9%), 95%CI: -43.8% to -32.5%; p = 0.03) with lower effect (LS mean difference: 7.0%, p = 0.07) for Months 5 and 6 combined. At Month 6, for the total AD04 group compared with the placebo group, heavy drinkers had a better quality of life (OR = 3.4, 95% CI: 1.03–11.45, p = 0.04), fewer AUD symptoms (Mild: AD04 group 33% vs. placebo group 39%; Severe: AD04 group 10% vs. placebo group 24%) (p = 0.05), and similar adverse event profiles. No treatment-related effects differentiated AD04 and placebo in very heavy drinkers. This study showed AD04’s promise as a precision medicine treatment for heavy drinkers with a specific genetic profile.
Capacity Building through Comprehensive Implementation Research Training and Mentorship: An approach for translating knowledge into practice
Authors: Asampong Emmanuel , Kamau Edward Mberu , Tabong Philip Teg-Nefaah , Glozah Franklin , Nwameme Adanna , Opoku-Mensah Kwabena , Amankwa Belynda , Dako-Gyeke Phyllis 
Published: January 2023

Abstract

Background:Implementation research (IR) is increasingly gaining popularity as the act of carrying an intention into effect. It is thus an important approach to addressing individual practices, policies, programmes and other technologies to solving public health problems. Low- and middle-income countries (LMICs) continue to experience public health problems which could be addressed using implementation research. These countries however fall behind prioritizing implementation research due to the disorganized approach used to providing knowledge about the value and scope of implementation research. This paper seeks to explain steps taken to resolve this by capacity strengthening activities through a comprehensive implementation research training and mentorship programme.Methods:The roll-out of the comprehensive implementation research training and mentorship was done in phases, including engaging the implementation research community through TDR Global, competency building for programme officers and ethical review board/committee members, and practical guidance to develop an implementation research proposal.Results:The findings identified critical areas of mentors and how mentorship should be structured and the most effective ways of delivering mentorship. These findings were used to develop a mentorship guide in IR.Thementorship guidance is to be used as a check-tool for mentoring participants during trainings as part of the package of resources in implementation research through to developing six implementation research projects. It is also to be used in equipping review board members with knowledge on ethical issues in implementation research.Conclusion:The approach for providing comprehensive implementation research training and mentorship for programme personnel has provided an opportunity for both potential mentors and mentees to make inputs into developing a mentorship guidance for LMICs. This guidance would help address mentorship initiation and implementation challenges in IR.
HYpofractionated, Dose-redistributed RAdiotherapy with protons and photons to combat radiation-induced immunosuppression in head and neck squamous cell carcinoma: study protocol of the phase-I HYDRA trial
Authors: Elbers Joris B.W. , Gunsch Pascal A. , Vulpen Marco van , Debets Reno , Keereweer Stijn , Meerten Esther van , Zindler Jaap , Norden Yvette van , Hoogeman Mischa , Verduijn Gerda M. , Kroesen Michiel , Nout Remi A. 
Published: January 2023

Abstract
Background: Radiotherapy (RT) is standard of care for most advanced head and neck squamous cell carcinoma (HNSCC) and results in an unfavorable 5-year overall survival of 40%. Despite strong biological rationale, combining RT with immune checkpoint inhibitors does not result in a survival benefit. Our hypothesis is that the combination of these individually effective treatments fails because of radiation-induced immunosuppression and lymphodepletion. By integrating modern radiobiology and innovative radiotherapy concepts, the patient’s immune system could be maximally retained by: (1) increasing the dose per fraction so that the total-dose and number of fractions can be reduced (HYpofractionation), (2) redistributing the radiation dose towards a higher peak dose within the tumor center and a lowered elective lymphatic field dose (Dose-redistribution), and by (3) using RAdiotherapy with protons instead of photons (HYDRA).
Methods: The primary aim of this multicenter study is to determine the safety of HYDRA proton- and photon radiotherapy by conducting two parallel phase-I trials. Both HYDRA arms are randomized with standard of care for longitudinal immune profiling. There will be a specific focus on actionable immune targets and their temporal patterns that can be tested in future hypofractionated immuno-radiotherapy trials. The HYDRA dose prescriptions (in 20 fractions) are 40 Gy elective dose and 55 Gy simultaneous integrated boost on the clinical target volume with a 59 Gy focal boost on the tumor center. A total of 100 patients (25 per treatment group) will be recruited, the final analysis will be performed one year after the last patient has been included.
Discussion: In the context of HNSCC, hypofractionation has historically only been reserved for small tumors out of fear for late normal tissue toxicity. To date, hypofractionated radiotherapy may also be safe for larger tumors as both the radiation dose and volume can be reduced by the combination of advanced imaging for better target definition, novel accelerated repopulation models and high-precision radiation treatment planning and dose delivery. HYDRA’s expected immune sparing effect may lead to improved outcome by allowing for future effective combination treatment with immunotherapy.
Trial registration: The trial is registered at ClinicalTrials.gov; NCT05364411 (registered on May 6th, 2022).
A randomised AI-supported long-term evaluation of a layer-by-layer macular thickness profile after manual and femtosecond laser cataract surgery
Authors: Schwarzenbacher Luca , Schmidt-Erfurth Ursula , Höftberger Theresa , Schartmueller Daniel , Röggla Veronika , Leydolt Christina , Menapace Rupert , Reiter Gregor 
Published: January 2023

Abstract
Objectives: To evaluate retinal thickening 18-months after low-pulse energy femtosecond laser-assisted (LCS) and manual cataract surgery (MCS) using artificial intelligence (AI)-based automated retinal layer segmentation.
Methods:
Design: Prospective, randomised, intraindividual-controlled study
Setting: Department of Ophthalmology, Medical University of Vienna.
Patient Population: 120 eyes of sixty patients with age-related cataract
Intervention: Bilateral same-day LCS and MCS in a randomised sequence.
Main Outcome Measure: Retinal thickness preoperative, after 1 week, 3 weeks, 6 weeks and 18 months in the central 1mm, 3mm, 6mm. Inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL), total retinal thickness (TRT) and photoreceptor (PR) thickness were segmented from Spectralis optical coherence tomography (OCT) using automated AI retinal layer segmentation.
Results: Fifty-six patients completed the follow-up. LCS compared to MCS did not impact any of the investigated retinal layers at any follow-up visit (p>0.05). For the central 1mm, a significant increase in TRT was seen after 1 week followed by an elevated plateau thereafter. For the 3mm and 6mm, TRT increased only after 3 weeks and 6 weeks and decreased again until 18-months. TRT remained significantly increased compared to preoperative thickness (p<0.001). INL and ONL were the main causative layers for the total TRT increase. PR declined 1 week after surgery but regained preoperative values 18 months after surgery.
Conclusions: Low-energy femtosecond laser pre-treatment did not influence thickness of the retinal layers in any topographic area compared to manual high fluidic phacoemulsification. TRT did not return to preoperative values 18 months after surgery.
Prevalence of Halitosis in Children and Associated Factors: A Systematic Review and Meta-Analysis.
Authors: Buj-Acosta Cindy , García-Sanz Verónica , Bellot-Arcís Carlos , Paredes-Gallardo Vanessa , Tarazona-Álvarez Beatriz , Tortajada-Girbés Miguel , Montiel-Company José María 
Published: January 2023

Abstract
Background: Halitosis is a common and well-studied condition throughout the world. There are several publications on the etiology and prevalence of halitosis in the adult population. However, in children, studies are inconclusive. This study aims to perform a systematic review and meta-analysis to establish the prevalence and factors involved in halitosis in the pediatric population.
Methods: A systematic review was conducted in the databases: Scopus, Cocharne Library, Medline, and Embase, complemented by a manual search. This review was carried out according to PRISMA standards and registered in PROSPERO (CRD42020183948).
Results: Twenty-five studies met the inclusion criteria for conducting the qualitative synthesis. Twelve studies were used for quantitative synthesis and meta-analysis. It was estimated that 36.6% of the children who participated in the studies had halitosis. The presence of oral breathing, coating of the tongue, gingival inflammation and inadequate oral hygiene were the main risk factors for the development of halitosis, with an odds ratio of 8.036 (95% CI: 1-44-9), 3.24 (95% CI 1.38-7.62), 1.577 (95% CI 1.14-2.19) and 3.09 (95% CI 2.36-4.04) respectively.
Conclusions: Given the high prevalence of halitosis in children and the many associated risk factors, a preventive approach is necessary to avoid its the negative social impact.
Vitamin D ameliorates age-induced nonalcoholic fatty liver disease by increasing the mitochondrial contact site and cristae organizing system (MICOS) 60 level.
Authors: Lim Joo Hyun , Kim Gyu Hee , Jeong Hyeon-Ju , Lee Yoo Jeong , Koo Soo Kyung 
Published: January 2023

Abstract
Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease. Despite intensive research, considerable NAFLD development remains to be revealed. In this study, we examined the effects of vitamin D on age-induced NAFLD, especially in connection with mitochondrial abnormalities.
We observed effective prevention of liver steatosis in 22-month-old C57BL/6 mice fed a vitamin D3-supplemented (20,000 IU/kg) diet, in contrast to mice fed a control (1,000 IU/kg) diet. We evaluated whether vitamin D3 supplementation enhanced mitochondrial functions and found that the mitochondrial contact site and cristae organizing system (MICOS) 60 (Mic60) level was reduced and was specifically restored by vitamin D3 supplementation in the aged mice. In addition, depletion of Immt, the human gene encoding the Mic60 protein, induced changes in gene expression that led to fat accumulation in HepG2 human hepatocellular carcinoma cells, which is effectively prevented by vitamin D3 supplementation. In contrast, silencing of Lonp1, the main matrix protease involved in mitochondrial quality control system and also expressed at a reduced level in aged mice, did not induce triglyceride (TG) accumulation in HepG2 cells. Moreover, VDR-RXR increased Mic60 levels by directly binding to the Immt 5' promoter region spanning from position − 3157 to -2323. Our study demonstrates, for the first time, that a reduction in Mic60 level due to aging may be one of the underlying mechanisms to development aging-associated NAFLD. In addition, vitamin D3 could positively regulate Mic60 expression, which may be one of the important molecular mechanisms that vitamin D could ameliorate age induced NAFLD.
Community-Based Distributed Flight Cluster Malicious Node Detection Based on Neural Network
Authors: Zhao Runhui , Wen Hong , Liu Qiang , Chen Zhiwei , Lin Haojie 
Published: January 2023

Abstract
A flight cluster refers to a group of unmanned aerial vehicles (UAVs) that can work together to perform complex tasks through specific organizational and control protocols. The flight state of each node of a flight cluster under distributed control depends on its flight state and neighbors. When a node in a flight cluster is attacked, it becomes a malicious node, which can use the distributed control protocol to launch a variety of attacks that cause the flight cluster to crash. To overcome such fatal weakness, we propose a peer-to-peer network model for the flight cluster networks based on the flight cluster characteristics that include the cluster control relationship topology network and the cluster communication link topology network. A malicious node detection scheme for flight clusters based on community partitioning is presented, which fully considers the flight cluster control topology and communication topology. Then, a novel malicious node detection model for the flight cluster based on neural network is given. Finally, the experiment is performed under the virtual cluster simulation environment. The results show that the scheme is low complexity, feasible, and effective in improving the operational efficiency of the detection model.
Antibiotic cocktail followed by Clostridium butyricum (CBM588) supplementation improves colonic anastomotic healing in mice
Authors: Chen Chun-Hsien , Chen Jenn-Wei , Lai Chao-Han , Chen Chien-Chin , Lin Wei-Chen , Chen Po-Chuan , Tsai Chih-Ming 
Published: January 2023

Abstract
Background
Microbiota manipulation through preoperative probiotic administration with Clostridium butyricum (CBM588) has shown promising results in reducing surgical site infections, but the resulting changes in gut microbiota are unclear. This study, using 16S ribosomal RNA metagenomic analysis, aimed to observe microbiome changes after CBM588 administration before murine colonic anastomosis.
Materials and methods
Eighteen C57BL/6 mice were divided into three groups. All mice, including group A as the control group, received oral neomycin and metronidazole before surgery. Group B received six consecutive days of CBM588 before surgery. Group C received kanamycin, gentamycin, colistin, metronidazole, and vancomycin, followed by six consecutive days of CBM588 before surgery.
Results
Compared with groups A and B, group C had significantly lower adhesion scores (p < 0.001), better postoperative performance (p < 0.05) and anastomotic healing scores (p < 0.001), and lower anastomotic necrosis areas (p < 0.05). Metagenomic analysis revealed that group C was enriched with the order Clostridiales, family Clostridiaceae, and genus Clostridium, with low bacterial diversity and composition.
Conclusions
Using a murine colonic anastomosis model, a preoperative antibiotic cocktail followed by CBM588 supplementation effectively decreased bacterial diversity and increased the percentage of Clostridiaceae. Associated outcomes included lower intra-abdominal adhesion scores, better postoperative performance and anastomotic healing scores, and lower anastomotic necrosis areas.
Observing the Proliferation of Salmonella spp. in Karnaphuli River: Catastrophic for the Riverbank Dwellers.
Authors: Alam Md. Wahidul , khandakar Md. Jahin , Jahan Most. Israt , Rahman MD. Mosfiqur , Aktar Fowzia , Rahman Mohammad Mostafizur , Mehjabin Saif 
Published: January 2023

Abstract
The quality of Karnaphuli river water has an important role in human infection and disease sheltered near Karnaphuli river along with the people of Chittagong. The present study was conducted to systematically examine the prevalence of indicator and pathogenic microorganism Salmonella spp. in water and sediment samples along with their relation with some physiochemical parameters like pH, salinity, DO, temperature, etc. during the post-monsoon time in September. A total of 6 water samples from 6 different stations were taken and samples were examined by the pour plate culture method along with chemical and biological tests for detection of Salmonella spp. This study showed that all water and sediment samples were positive for Salmonella species. There were significant differences between Station no. 2, referred to as Firingee Bazar, and the 6th station, known as Soltgola. The present research shows that pollution indicator like DO and the amount of cell of bacteria prevails in the unhygienic and polluted situation of the river which is a clear picture of uncontrolled hazardous activity.
Multi-source uncertainty propagation and sensitivity analysis of turbine blades with underplatform dampers
Authors: Yang Guang , She Houxin , Xu Bensheng , Zang Chaoping , Li Chaofeng 
Published: January 2023

Abstract

Underplatform dampers (UPDs) can suppress blade vibration through interface friction dissipation. At present, most of the existing UPD analysis models ignore the uncertainties induced by multi-source factors such as manufacturing, excitation, and wear, resulting in insufficient accuracy of dynamic prediction and optimization of UPDs. Therefore, this paper will deeply consider the uncertain factors such as machining tolerances, assembly tolerances, working load environment, and contact surface wear encountered in the actual manufacturing and working process, and carry out the multi-source uncertainty dynamics research of the UPDs. To solve the "dimension disaster" caused by multi-source uncertainty analysis, an adaptive algorithm based on the non-embedded polynomial chaotic expansion (PCE) is proposed. The algorithm selects the integral accuracy of the best chaotic polynomial by generalizing error convergence criteria and then constructs a surrogate model. This algorithm is in agreement with the calculated results based on Monte Carlo simulation (MCS). Through the quantitative characterization of the above uncertain factors, the efficient prediction of the uncertainty zone of the UPDs dynamic response is realized, the influence law of multi-source uncertainty factors on the vibration attenuation characteristics of UPDs is obtained, and sensitivity analysis of all parameters is carried out, which provides data support for the robust optimization design of UPDs. The simulation results show that the adaptive algorithm based on the uncertainty of multi-source parameters can predict the dynamic response of UPDs structure with high precision and high efficiency, and the uncertainty factors have a significant influence on the nonlinear dynamic characteristics of UPDs, In this case, phenomena such as "resonance band" and "frequency shift" will appear, and the uncertainty of multiple source parameters can cause large fluctuations in the dynamic response of UPDs, especially at the formant of the amplitude response. In addition, compared with other nonlinear regions, the Sobol exponents of uncertain parameters near the formant change significantly.