bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quality of life and clinical factors in women with endometriosis, the role of Dienogest vs EE/ Dienogest over time: a single-center study.
Authors: Maiorana Antonio , Alfano Pietro , Mercurio Antonella , Marcantonio Salvatore , Minneci Gabriella , Incandela Domenico , Audino Palma 
Published: January 2023

Abstract
Purpose: The aims of this observational study were: to assess the relationship between psychological variables, pain, Duration Untreated Endometriosis (DUE) in a sample of women with Endometriosis; and to assess the effect of Dienogest 2 mg/daily (DNG) and Dienogest/ethinylestradiol 0.03 mg/daily (EE/DNG) on Symptoms, QoL, HRQoL, pain and sexual satisfaction, over time.
Methods: 64 women constituted the study group; (56%) took DNG and (44%) took EE/DNG. VAS, SF-36, EHP-30 and ISS were used to assess endometriosis-associated pelvic pain, QoL, HRQoL and sexual satisfaction, respectively. The study included one follow-up at 18 months.
Results: At T0, a longer period of DUE was related both to worst HRQoL and Physical QoL. At T1, a correlation was found between longer DUE and worst HRQoL. At T0, a negative correlation was found between VAS and PCS and between VAS and EHP-30.
At T1, the same above correlation was found between VAS and PCS/MCS and VAS and EHP-30 scale. There was a correlation between ISS and VAS.
ANOVA showed a reduction in dysmenorrhea, in general pain level and an improvement in emotional wellbeing, relationship with medical profession, and PCS over time, regardless to type of treatment. Moreover, a significant time × treatment group interaction for dysmenorrhea was found.
Conclusion: DUE and pain are important variables related to psychological aspects of women with endometriosis. Treatment with both DNG and EE/DNG may have positive effects on the QoL, HRQoL and symptoms. Moreover, DNG seems to have a greater effect than EE/DNG on dyspareunia reduction over time.
Capecitabine Metronomic Chemotherapy for Metastatic Colorectal Cancer Patients Reaching NED Status: A Protocol for a Prospective, Randomized, Controlled Trial
Authors: Wu Jiaming , Dong Yu , WU Lexia , Meng Jincheng , Zhang Huatang , Li Luzhen , Fang Cantu 
Published: January 2023

Abstract
Background: A increasing number of patients with metastatic colorectal cancer (mCRC) have achieved no evidence of diseases (NED) status after surgery or other treatments. However, the latest guidelines for colorectal cancer do not recommend an appropriate treatment for patients with mCRC who achieve NED status. Capecitabine has the advantages of significant efficacy and minimal adverse reactions. Thus, capecitabine metronomic chemotherapy is a potential effective method for maintenance treatment for mCRC, but no relevant clinical studies have been reported. Therefore, we designed a randomized controlled trial to evaluate the efficacy and safety of capecitabine metronomic chemotherapy as maintenance treatment for mCRC patients who achieve NED.
Methods/design: This study is a prospective, randomized controlled study that evaluates the efficacy and safety of capecitabine metronomic chemotherapy for patients with mCRC who achieve NED status. Sixty eligible participants will be randomly assigned to either a capecitabine metronomic chemotherapy group or a “watch and wait” group at a 1:1 allocation ratio. Eligible patients diagnosed with stage IV mCRC, both the primary tumor and the metastases, are those who have achieved R0 resection (or complete destruction by ablation) and reached NED. Participants who are enrolled in the capecitabine group will receive capecitabine 500 mg/m2 (bid) for 2 years. Meanwhile, those who are assigned to the control group will receive regular imaging examination and follow-up only. All participants will follow up for one year after receiving 2 years of intervention. The primary outcomes will be progression-free survival (PFS) and overall survival (OS) from randomization. Secondary outcomes will include 2-year and 1-year survival, adverse reactions and quality of life scores.
Discussion: As a potentially effective treatment, low-dose capecitabine metronomic chemotherapy has been explored in clinical practice. The results of this trial will provide evidence on the efficacy and safety of capecitabine metronomic chemotherapy for patients with mCRC who have reached NED status.
Trial registration: Chinese Clinical Trial Registry (ChiCTR2100047149, protocol version number F2.0)
Green extraction of phenolics and flavonoids from black mulberry fruit using natural deep eutectic solvents: optimization and surface morphology
Authors: Vo Tan Phat , Pham Thuy Vy , Weina Kasia , Tran Thi Ngoc Huyen , Vo Le Thao Vy , Nguyen Phuc Thanh , Bui Tran Linh Ha , Phan Thuy Han , Nguyen Dinh Quan 
Published: January 2023

Abstract
This study deployed ultrasonic-assisted extraction (UAE), combined with natural deep eutectic solvents (NADES), to extract phenolics and flavonoids from the black mulberry fruit, and the antioxidant activity was examined. The extraction yields of NADES-based UAE were assessed based on total phenolic and flavonoid contents (TPC and TFC, respectively). NADES produced from choline chloride-lactic acid at a 1:2 molar ratio had the highest extraction yield. One-factor experiments evaluated the effect of UAE conditions (liquid-to-solid ratio, water content in NADES, temperature, and time) on TPC, TFC, and antioxidant activity. Response surface methodology with the Box-Behnken design model optimized the NADES-based UAE process based on response (TPC, TFC, ABTS, OH, and DPPH). The optimal conditions for the NADES-based UAE process were 70 ml/g of LSR, 38.9% water content in NADES, 67.9°C, and 24.2 min of retention time. The predicted values of the Box-Behnken design were compatible with the experimental results. Moreover, scanning electron microscopy was used to survey the surface of black mulberry fruit with and without sonication. This study proposes an efficient and green method for extracting bioactive compounds from black mulberry fruits.
A multicenter, open-label, multiple-dose Phase Ib/II study evaluating the safety and tolerability of CS3008 (BLU-554) in combination with CS1001 in subjects with locally advanced or metastatic hepatocellular carcinoma (HCC) Research
Authors: Zhou Mingzhen , Zhu Sihui , Xu Chen , Liu Baorui , Shen Jie 
Published: January 2023

Abstract
Objective: The treatment model of targeted therapy combined with immunotherapy has become the treatment modality for hepatocellular carcinoma due to problems such as single drug resistance. This trial was designed to evaluate the safety and tolerability of the fibroblast growth factor receptor 4 inhibitor CS3008 (BLU-554) in combination with the anti-PD-L1 monoclonal antibody CS1001 in patients with locally advanced or metastatic hepatocellular carcinoma (HCC).
patients and methods: This multicenter, open-label, multidose Phase Ib/II trial enrolled patients with locally advanced or metastatic hepatocellular carcinoma (HCC). Patients received CS1001 1200 mg intravenously every three weeks and BLU-554 600 mg orally daily. The primary endpoint was objective response rate (ORR) as assessed according to RECISTv1.1.
Result: A total of 18 patients were screened, of which 8 patients were FGF19 positive. And only four patients ultimately received the combination of treatment CS3008 (BLU-554) and CS1001 after entry row review, with ORR of 50% and DCR of 100%, and only one patient had an immune-related adverse reaction.
Conclusion: Preliminary confirmation that CS3008 (BLU-554) in combination with CS1001 is safe and effective in the treatment of patients with locally advanced or metastatic hepatocellular carcinoma.
Registration number: NCT04194801
Efficacy of a stretching exercise versus transcranial direct current stimulation(tDCS) on task performance, kinematic and electroencephalography (EEG) spectrum in subjects with slump posture: A study protocol
Authors: Abdollahzade zahra , Rasanani Mohammad-Reza Hadian , Kahnmohammadi Roya , Talebian saeed 
Published: January 2023

Abstract
Background

Slumped sitting is a common poor posture which may cause mental fatigue and some disturbances in social activity. The management of slump posture often focuses on some biomechanical recommendations. To date, almost limited studies have explored the non-biomechanical factors such as the central component including mental fatigue of poor posture. Therefore, utilizing the quantitative electroencephalography (QEEG) to find out the changes after a prolonged repetitive task might be considered as a tool for tracking the central part in poor posture individuals. Accordingly, this study was designed to find out the differences of EEG parameters between normal and poor posture individuals; also, in the second step, to explore the effect of stretching exercises and tDCS to monitor the mentioned parameters during a continuous activity of typing in subjects with slump posture.

Methods

A sample of 60 volunteers will participate in this study and they will be assigned to two equal groups of people with normal and slump postures. In the first and last 3 minutes of 60 minutes of continuous typing, these people will be assessed for outcome measures of mental fatigue through QEEG and visual analog fatigue scale, the typing performances (i.e. speed and errors of typing), musculoskeletal discomfort and kinematic behavior of neck. Furthermore, the effects of stretching exercises and transcortical stimulation on the outcome measures in slump posture group will be evaluated.

Discussion

With the assumption of providing individuals' differences in terms of outcome measures in normal and slump posture and also by showing the possible changes of the measures, due to either tDCS as a central modality or stretching exercises as a peripheral modality; we might conclude that first, a central component is critical for evaluation in poor posture and second, may provide evidence to introduce the effective method to overcome mental fatigue and promote work productivity.

Trial registration

Registered on the Iranian Registry of Clinical Trials on 21 September 2022, IRCT Identifier: IRCT20161026030516N2
Prone versus lateral position in acute hypoxemic respiratory failure patients with HFNO therapy: study protocol for a multicentre randomised controlled open-label trial
Authors: Zhou Xixin , Luo Xiaoqing , Chen Guihua , Li Qin , Tong Jin , Deng Wang 
Published: January 2023

Abstract
Background: High flow nasal oxygen (HFNO) therapy is a leading treatment technique for acute hypoxemic respiratory failure (AHRF), but its treatment failure rate remains high. The awake prone position（APP） has been proven to inease oxygenation and reduce the endotracheal intubation rate in patients with COVID-19-induced AHRF. However, because the APP is poorly tolerated in patients, its performance in improving prognoses is controversial. The lateral position has a similar mechanism and effect to the prone position, but it is more tolerable than the prone position. Thus, it is worth exploring whether the lateral position is better for awake patients with acute respiratory failure.
Methods: This is a protocol for a three-arm parallel group multicentre randomised controlled open-label exploratory trial. A total of 220 patients from two teaching hospitals in Chongqing, China, will be randomised to take the semirecumbent position, lateral position, or prone position at a ratio of 1:1:1. Patients are all diagnosed with AHRF secondary to non-COVID-19-related pneumonia or lung infection and receiving HFNO therapy. The primary outcome is 28-day all-cause mortality. The secondary outcomes are the 28-day intubation rate, total position change time, the incidence of adverse events, number of days using HFNO therapy, length of hospital and intensive care unit (ICU) stay, and others. We will conduct subgroup analyses on the arterial partial pressure of oxygen to the fraction of inspiration oxygen（PaO2/FiO2）ratio (>200 mmHg or ≤200 mmHg), time from hospitalisation to implementation (<24 h or ≥24 h), position changing time, and different diagnoses.
Discussion: Thistrial will explore the prognostic effects of the APP with that of the lateral position in awake patients with non-COVID-19 induced AHRF, and compare the differences between them. To provide evidence for clinical decision-making and further research on position management.
Trial registration: This trial was registered in the Chinese Clinical Trial Registry. The registration number is ChiCTR2200055822. Registered on January 20, 2022 ，https://www.chictr.org.cn/showproj.aspx?proj=130563
The electrophysiological signature of dorsal hippocampus-basolateral amygdala circuit in anxiety-like behavior in the intrahippocampal kainic acid mice model of temporal lobe epilepsy: With emphasis on the impact of glycolysis inhibition
Authors: Khatibi Vahid Ahli , Salimi Morteza , Rahdar Mona , Rezaei Mahmoud , Nazari Milad , Dehghan Samaneh , Davoudi Shima , Raoufy Mohammad Reza , Mirnajafi-Zadeh Javad , Javan Mohammad , Hosseinmardi Narges , Behzadi Gila , Janahmadi Mahyar 
Published: January 2023

Abstract
Pharmacoresistant temporal lobe epilepsy affects millions of people around the world with uncontrolled seizures and comorbidities, like anxiety, being the most problematic aspects calling for novel therapeutic procedures. The intrahippocampal kainic acid model of temporal lobe epilepsy is an appropriate rodent model to evaluate the effects of novel interventions, including glycolysis inhibition, on epilepsy-induced alterations. Here, we investigated kainic acid-induced changes in the dorsal hippocampus (dHPC) and basolateral amygdala (BLA) circuit and the efficiency of a glycolysis inhibitor, 2-deoxy D-glucose (2-DG), in resetting such alterations using simultaneous LFP recording and elevated zero-maze test. dHPC theta and gamma powers were lower in epileptic groups, both in the baseline and anxiogenic conditions. BLA theta power was higher in baseline condition while it was lower in anxiogenic condition in epileptic animals and 2-DG could reverse it. dHPC-BLA coherence was altered only in anxiogenic condition and 2-DG could reverse it only in gamma frequency. This coherence was significantly correlated with the time in which the animals exposed themselves to the anxiogenic condition. Further, theta-gamma phase-locking was lower in epileptic groups in the dHPC-BLA circuit and 2-DG could considerably increase it.
Focused ultrasound-mediated brain genome editing
Authors: Leong Kam , Lao Yeh-Hsing , Ji Robin , Zhou Joyce , Snow Kathy , Kwon Nancy , Saville Ethan , He Siyu , Chauhan Shradha , Chi Chun-Wei , Datta Malika , Zhang Hairong , Quek Chai Hoon , Cai Sarah , Li Mingqiang , Gaitan Yaned , Bechtel Lawrence , Wu Shih-Ying , Lutz Cathleen , Tomer Raju , Murray Stephen , Chavez Alejandro , Konofagou Elisa 
Published: January 2023

Abstract
Gene editing in the mammalian brain has been challenging because of the restricted transport imposed by the blood-brain barrier (BBB). Current approaches rely on local injection to bypass the BBB. However, such administration is highly invasive and not amenable to treating certain delicate regions of the brain. We demonstrate a safe and effective gene editing technique by using focused ultrasound (FUS) to transiently open the BBB for the transport of intravenously delivered CRISPR/Cas9 machinery to the brain.
Monitoring for micronutrient deficiency after bariatric surgery - what is the risk?
Authors: Lewis Carrie-Anne , Osland Emma , de Jersey Susan , Hopkins George , Seymour Matthew , Webb Lindsey , Chatfield Mark , Hickman Ingrid 
Published: January 2023

Abstract
Background: Bariatric surgery may increase the risk of micronutrient deficiencies; however, confounders including preoperative deficiency, supplementation and inflammation are rarely considered.
Objective: To examine the impact of bariatric surgeries, supplementation and inflammation on micronutrient deficiency.
Setting: Two public hospitals, Australia.
Methods: Participants were recruited to an observational study monitoring biochemical micronutrient outcomes, supplementation dose, inflammation and glycemic control, pre-operatively and at 1-3, 6 and 12 months after gastric bypass (GB; Roux-en-Y Gastric Bypass and Single Anastomosis Gastric Bypass; N=66) or sleeve gastrectomy (SG; N=144). Participant retention at 12 months was 81%.
Results: Pre-operative micronutrient deficiency was common, for vitamin D (29-30%), iron (13-22%) and selenium (39% GB cohort). Supplement intake increased after surgery; however, dose was <50% of target for most nutrients. After SG, folate was vulnerable to deficiency at 6-months (OR 13 [95% CI 2, 84]; p=0.007), with folic acid supplementation being independently associated with reduced risk. Within 1-3 months of GB, three nutrients had higher deficiency rates compared to pre-operative levels; vitamin B1 (21% vs. 6%, p<0.01), vitamin A (21% vs. 3%, p<0.01) and selenium (59% vs. 39%, p<0.05). Vitamin B1 deficiency was independently associated with surgery and inflammation, selenium deficiency with improved glycemic control after surgery and inflammation, whilst vitamin A deficiency was associated with inflammation only.
Conclusion: In the setting of prophylactic post-surgical micronutrient prescription, few nutrients are at risk of de novo deficiency. Although micronutrient supplementation and monitoring remains important, rationalising high frequency biochemical testing protocols in the first year after surgery may be warranted.
WONDER-01: immediate necrosectomy vs. drainage-oriented step-up approach after endoscopic ultrasound-guided drainage of walled-off necrosis—study protocol for a multicentre randomised controlled trial
Authors: Sato Tatsuya , Saito Tomotaka , Takenaka Mamoru , Iwashita Takuji , Shiomi Hideyuki , Fujisawa Toshio , Hayashi Nobuhiko , Iwata Keisuke , Maruta Akinori , Mukai Tsuyoshi , Masuda Atsuhiro , Matsubara Saburo , Hamada Tsuyoshi , Inoue Tadahisa , Ohyama Hiroshi , Kuwatani Masaki , Kamada Hideki , Hashimoto Shinichi , Shiratori Toshiyasu , Yamada Reiko , Kogure Hirofumi , Ogura Takeshi , Nakahara Kazunari , Doi Shinpei , Chinen Kenji , Isayama Hiroyuki , Yasuda Ichiro , Nakai Yousuke 
Published: January 2023

Abstract
Background: With the increasing popularity of endoscopic ultrasound (EUS)-guided transmural interventions, walled-off necrosis (WON)of the pancreas is increasingly managed via non-surgical endoscopic interventions. However, there has been an ongoing debate over the appropriate treatment strategy following the initial EUS-guided drainage. Endoscopic necrosectomy (EN) directly removes intracavity necrotic tissue, potentially facilitating early resolution of the WON, but may associate with a high rate of adverse events. Given the increasing safety of EN, this trial aims to assess the superiority of immediate EN over the step-up approach in terms of time required for WON resolution.
Methods: The WONDER-01 trial is a multicentre, open-label, superiority, randomised controlled trial, which will enrol WON patients aged ≥ 18 years requiring EUS-guided treatment in 23 centres in Japan. This trial plans to enrol 70 patients who will be randomised at a 1:1 ratio to receive either the immediate EN or drainage-oriented step-up approach (35 patients per arm). In the immediate EN group, EN will be initiated during (or within 72 hours of) the EUS-guided drainage session. In the step-up approach group, drainage-based step-up treatment with on-demand EN will be considered after 72-96 hours observation. The primary endpoint is time to clinical success, which is defined as a decrease in a WON size to ≤ 3 cm and an improvement of inflammatory markers (i.e., body temperature, white blood cell count, and C-reactive protein). Secondary endpoints include technical success, adverse events including mortality, and recurrence of the WON.
Discussion: The WONDER-01 trial will investigate the efficacy and safety of immediate EN compared to the step-up approach for WON patients receiving EUS-guided treatment. The findings will help us to establish new treatment standards for patients with symptomatic WON.
Trial registration: ClinicalTrials.gov NCT05451901, registered on 11 July 2022. UMIN000048310, registered on 7 July 2022. jRCT1032220055, registered on 1 May 2022.
The research status, potential hazards and toxicological mechanisms of fluoroquinolone antibiotics in the environment
Authors: Du Jia , Liu Qinghua , Fu Li , Pan Ying , Yao Meng , Xu Shaodan , Li Huanxuan , Wang Chunhui , Tang Junhong 
Published: January 2023

Abstract
Fluoroquinolone antibioticsare widely used in pharmaceuticals and personal care products due to their disease treatment, growth promotion, and prophylaxis, which lead to increasing biological exposure to fluoroquinolones in the global environment. This paper recapitulates the occurrence, fate, and ecotoxicity of fluoroquinolone antibiotics in various environmental media. The toxicity effect and mechanism are also reviewed based on in vitro and in vivo experiments, referring to many organisms, such as microorganisms, cells, higher plants, land and aquatic animals. The combined toxicity effect and coexisting characteristics of fluoroquinolone antibiotics absorbed with other chemicals to organisms in various environmental matrices are also summarized. The current knowledge gaps, further research interests and toxicity mechanisms of fluoroquinolone antibiotics in the environment have been discussed in this research.
APOEε4 potentiates Aβ effects on longitudinal tangle accumulation via tau phosphorylation
Authors: Ferrari-Souza João Pedro , Bellaver Bruna , Ferreira Pâmela , Benedet Andrea , Povala Guilherme , Lussier Firoza , Leffa Douglas , Therriault Joseph , Tissot Cécile , Soares Carolina , Wang Yi-Ting , Chamoun Mira , Servaes Stijn , Macedo Arthur , Vermeiren Marie , Bezgin Gleb , Kang Min Su , Stevenson Jenna , Rahmouni Nesrine , Pallen Vanessa , Poltronetti Nina , Cohen Ann , Lopez Oscar , Klunk William , Soucy Jean-Paul , Gauthier Serge , Souza Diogo , Triana-Baltzer Gallen , Saad Ziad , Kolb Hartmuth , Karikari Thomas , Villemagne Victor , Tudorascu Dana , Ashton Nicholas , Zetterberg Henrik , Blennow Kaj , Zimmer Eduardo , Rosa-Neto Pedro , Pascoal Tharick 
Published: January 2023

Abstract
The mechanisms by which the apolipoprotein E ε4 (APOEε4) allele influences Alzheimer’s disease (AD) pathophysiological progression are poorly understood. Here, we tested the association of APOEε4 carriership and amyloid-β (Aβ) burden with longitudinal tau pathology progression. We studied 104 individuals across the aging and AD spectrum who underwent clinical assessments, APOE genotyping, magnetic resonance imaging, positron emission tomography (PET) for Aβ ([18F]AZD4694) and tau ([18F]MK-6240) at baseline, as well as a follow-up tau-PET scan (mean follow-up, 2.4 years). We further assessed longitudinal changes in tau phosphorylation (plasma phosphorylated tau at threonine 217 [p-tau217+]), brain atrophy (gray matter density), and clinical function (clinical dementia rating scale sum of boxes). We found that APOEε4 carriership potentiates Aβ effects on longitudinal tau tangle accumulation over two years. The APOEε4-potentiated Aβ effects on tangles were mediated by longitudinal plasma p-tau217+ increase. This longitudinal tau accumulation as measured by PET was accompanied by brain atrophy and clinical decline. Our results support a model in which the APOEε4 allele plays a key role in Aβ downstream effects on the aggregation of phosphorylated tau in the form of neurofibrillary tangles in the living human brain.