bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Effectiveness of a Modified Gui Zhi Fu Ling Wan Formulation (Gynoclear™) for The Treatment of Endometriosis: A Study Protocol for a Placebo Controlled, Double Blind, Randomised Controlled Trial.
Authors: Armour Mike , Al-Dabbas Mahmoud , Ee Carolyn , Smith Caroline , Ussher Jane , Arentz Susan , Lawson Kenny , Abbott Jason 
Published: December 2020

Abstract
Background: Endometriosis is the presence of tissue similar to that of the endometrium outside the uterine cavity and is the most common cause of chronic pelvic pain. Current non-surgical treatments such as non-steroidal anti-inflammatories, oral contraceptive pills, and hormonal treatments have limited effectiveness and the side effect profile is bothersome. This study will evaluate the efficacy of Gynoclear™ by change in endometriosis related pain based on the Endometriosis Pain Daily Diary (EPPD) scores.Methods: This randomised, double-blind, placebo-controlled trial will recruit a minimum of 90 adult participants across Australia who have a laparoscopic visualisation/confirmation of endometriosis in the last five years and have current moderate or greater pelvic pain. Participants will be randomly allocated in a 1:1 ratio to receive either Gynoclear™ (active) or placebo. Gyncolear’s active ingredients are Carthamus tinctorius (Safflower), Cinnamomum cassia (Chinese cinnamon), Poria cocos (Hoelen), Paeonia suffriticosa (Tree peony), Paeonia lactiflora (Peony) and Salvia miltiorrhiza (Red sage). Participants are asked to complete a total of five months’ worth of pain diary entries via the EPDD v3, including one-month screening, three-months treatment period and one-month post-treatment follow up. The primary outcome variable is change in endometriosis related pain based on the EPDD v3 scores. Secondary outcomes include change in health-related quality of life via the Endometriosis Health Profile (EHP-30), SF-12 and EQ5D scores as well as changes in rescue analgesic usage, dyspareunia and fatigue via the EPDD.Discussion: This study will determine the safety and efficacy of Gynoclear™ to reduce the severity and duration of non-cyclical pelvic pain, dysmenorrhea, dyspareunia and other symptoms of endometriosis. Study outcomes will be of interest to health professionals, and members of the public who suffer from endometriosis.Trial registration: Australia and New Zealand Clinical Trials Registry, ACTRN12619000807156 (https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=377571). Registered on 03-Jun-2019.
Comparison of Bone Single-Photon Emission Computed Tomography&nbsp;(SPECT)/CT and Bone Scintigraphy in Assessing Knee Joints
Authors: An Young-Sil , Park Do Young , Min Byoung-Hyun , Yoon Joon-Kee 
Published: December 2020

Abstract
Background: This study attempted to compare the radiopharmaceutical uptake findings of planar bone scintigraphy (BS) and single photon emission computed tomography (SPECT)/computed tomography (CT) performed on knee joints.Methods: We retrospectively included 104 patients who underwent bone SPECT/CT and BS 4 hours after the intravenous administration of technetium-99m-hydroxymethylene diphosphonate (99mTc-HDP) for pain in the knee joint. The uptake degree of each of the knee regions (medial femoral, lateral femoral, medial tibial, lateral tibial, and patellar area) in planar images and SPECT/CT were evaluated by visual (grades 0 to 2) and quantitative analyses (uptake counts for planar image and standardized uptake values [SUVs] for SPECT/CT). Results: The uptake grades assessed visually on the planar images differed significantly from the uptake grades on SPECT/CT images in all areas of the knee (all p < 0.001), and SPECT/CT imaging revealed a larger number of uptake lesions than those noted in planar imaging for each patient (3.3 ± 2.0 versus 2.4 ± 2.3, p < 0.0001). In all regions of the knee, all of the quantitative values, including uptake counts obtained from the planar image as well as the maximum SUV (SUVmax) and mean SUV (SUVmean) obtained from SPECT/CT, showed statistically higher values as their visual grades increased (all p <0.001). However, when analyzed for each area, only the SUVmax showed a significant difference by grade in all knee regions. Quantitative uptake values obtained from planar images were moderately correlated with SUVs of SPECT/CT images (r = 0.58 for SUVmean and r = 0.53 for SUVmax, all p <0.001) in the total knee regions. Looking at each area, there was a significant but low correlation between the uptake counts of the planar images and the SUVs on SPECT/CT in the right lateral tibial region (r = 0.45 for SUVmean, r = 0.31 for SUVmax, all p <0.001).Conclusions: In assessing knee joints, the findings of planar images and SPECT/CT images differ both visually and quantitatively, and more lesions can be found in SPECT/CT than in the planar images.
Goal Attainment and Outcomes of Physiotherapy Participants Funded by an Individualised Government Package’
Authors: Bravo katherine Melissa Alava , McCredie Laura , Scrivener Katharine 
Published: December 2020

Abstract
Purpose: To determine goal attainment and change in physical outcomes of individuals participating in a community Physiotherapy program funded by a new government funding package, the National Disability Insurance Scheme (NDIS). Additionally, to describe the alignment of NDIS goals with Physiotherapy goals and the impact of the NDIS on access to Physiotherapy.Methods: A consecutive case series was conducted involving 12 participants attending NDIS-funded Physiotherapy at a private clinic in Sydney, Australia. Outcome measures were recorded upon entry to the study and again after 6 months or at discharge, whichever occurred first. The primary outcome was goal attainment measured by the Goal Attainment Scale. Secondary outcomes included the 5-metre walk test, Motor Assessment Scale, World Health Organisation Quality of Life questionnaire and Exercise Self Efficacy Scale.Results: Forty-one percent of goals were fully attained and for 53% performance was equal to baseline, however, this was not reflected in concurrently measured outcomes where small changes occurred. Physiotherapy goals focused on mobility whilst NDIS goals varied. Changes in outcome measures differed between individuals. NDIS funding provided all participants access to more frequent or otherwise inaccessible Physiotherapy.Conclusion: Physiotherapy participants funded by an individualised government package had improved access to Physiotherapy where participants attained individualised goals.
Testing a Breast Cancer Prevention and a Multiple Disease Prevention Weight Loss Programme Among Women Within The UK NHS Breast Screening Programme - A Randomised Feasibility Study
Authors: Harvie Michelle , French David P , Pegington Mary , Cooper Grace , Howell Anthony , McDiarmid Sarah , Lombardelli Cheryl , Donnelly Louise , Ruane Helen , Sellers Katharine , Barrett Emma , Armitage Christopher J. , Evans D Gareth 
Published: December 2020

Abstract
Excess weight and unhealthy behaviours (sedentariness, high alcohol and suboptimal diet) are common among women attending breast screening. These factors increase the risk of breast cancer and other diseases. We tested the feasibility and acceptability of a weight loss/ behaviour change programme framed to reduce breast cancer risk (breast cancer prevention programme, BCPP) compared to one framed to reduce risk of breast cancer, cardiovascular disease (CVD) and diabetes (T2D) (multiple disease prevention programme, MDPP). Methods Women aged 47-73 years with overweight or obesity (n=1356) in the NHS Breast Screening Programme (NHSBSP) were randomized (1:2) to be invited to join a BCPP or a MDPP. The BCPP included personalised information on individual level of breast cancer risk and a web and phone weight loss/behaviour change intervention. The MDPP also included an NHS Health Check (lipids, blood pressure, HbA1c and personalised feedback for risk of CVD [QRISK2] and T2D [QDiabetes and HbA1c]). Uptake, retention, change in weight, and potential harms (anxiety and self-rated health) were assessed, along with the numbers in the MDPP with previously unknown CVD and T2D risk.ResultsThe BCPP and MDPP had comparable rates of uptake; 45/508 (9%) vs. 81/848 (10%) 12-month retention; 33/45 (73%) vs. 53/81 (65%) and numbers (%) losing ≥5% body weight at 12 months; 26/45 (58%) vs. 46/81 (57%) with baseline observation carried forward imputation. Both groups experienced reductions in state anxiety score; BCPP (n=37) -0.7 (-4.6 to 3.2), MDPP (n=60) -3.5 (-6.7 to -0.4) and an increase in the EQ-5D-5L score; BCPP (n=40) 4.1 (0.6 to 7.6), MDPP (n=60) 7.3 (3.6 to 11.1). The MDPP identified 15% of women with a previously unknown 10 year CVD QRISK2 of ≥10% and 56% with 10-year Qdiabetes risk of ≥10%.ConclusionsThe MDPP identified previously unknown CVD and T2D risk factors but does not appear to increase engagement with behaviour change beyond a standard BCPP amongst women attending breast screening. The results suggest a definitive effectiveness trial of the BCPP intervention is warranted, with acceptable uptake and retention, and a clear weight loss signal.Trial Registration ISRCTN91372184, https://doi.org/10.1186/ISRCTN91372184, registered 28 September 2014.
BRD4 PROTAC Degrader ARV-825 Inhibits T-Cell Acute Lymphoblastic Leukemia by Targeting 'Undruggable' Myc-pathway Genes
Authors: Wu Shuiyan , Jiang You , Hong Yi , Chu Xinran , Zhang Zimu , Tao Yanfang , Fan Ziwei , Bai Zhenjiang , Li Xiaolu , Chen Yan-Ling , Li Zhiheng , Ding Xin , Lv Haitao , Du Xiaoli , Lim Su Lin , Zhang Yongping , Huang Saihu , Lu Jun , Pan Jian , Hu Shaoyan 
Published: December 2020

Abstract
BackgroundT-cell acute lymphoblastic leukemia (T-ALL) is an aggressive disease with a high risk of induction failure and poor outcomes, with relapse due to drug resistance. Targeting bromodomains and extra-terminal (BET) protein inhibitors are promising anti-cancer agents, and ARV-825, comprising a BET inhibitor conjugated with cereblon, was recently shown to attenuate the growth of multiple tumors in vitro and in vivo. However, the functional and molecular mechanisms of ARV-825 in T-ALL remain unclear. This study aimed to investigate the therapeutic efficacy and potential mechanism of ARV825 in T-ALL.MethodsExpression levels of the BET protein BRD4 were determined in pediatric T-ALL samples and differential gene expression after ARV-825 treatment was explored by RNA-seq and quantitative reverse transcription-polymerase chain reaction. T-ALL cell viability was measured by CCK8 assay after ARV-825 administration. Cell cycle was analyzed by propidium iodide (PI) staining and apoptosis was assessed by Annexin V/PI staining. The functional and molecular pathways involved in ARV-825 treatment of T-ALL were verified by western blot and chromatin immunoprecipitation (ChIP).ResultsBRD4 expression was higher in pediatric T-ALL samples compared with T-cells from healthy donors. High BRD4 expression indicated a poor outcome. ARV-825 suppressed cell proliferation in vitro by arresting the cell cycle and inducing apoptosis, with elevated poly-ADP ribose polymerase and cleaved caspase 3. BRD4, BRD3, and BRD2 were degraded in line with reduced cereblon expression in T-ALL cells. ARV-825 had a lower IC50 in T-ALL cells compared with the BET inhibitors JQ1 and dBET1. ARV-825 perturbed the H3K27Ac-Myc pathway and reduced c-Myc protein levels in T-ALL cells according to RNA-seq and ChIP. Moreover, ARV-825 inhibited cell proliferation by depleting BET and c-Myc proteins in T cell lines and in pediatric T-ALL patients. ConclusionsBRD4 indicates a poor prognosis in T-ALL. The BRD4 degrader ARV-825 can effectively suppress the proliferation and promote apoptosis of T-ALL cells via BET protein depletion and c-Myc inhibition, thus providing a new strategy for the treatment of T-ALL.
Prone Position Ventilation for Pediatric Acute Respiratory Distress Syndrome with Extracorporeal Membrane Oxygenation: A Propensity Score-Matched Retrospective Multicenter Cohort Study
Authors: Zhao Zhe , Lu Guoping , Li Shuanglei , Yang Baowang , Zhang Huiling , Cheng Ye , Zhou Yiping , Cui Yun , Cheng Wenzhe , Wang Jie , Cheng Yibing , Chen Yingfu , Liu Chengjun , Cheng Dongliang , Shi Changsong , Guo Yuxiong , Hu Yan , Hui Yi , Qu Dong , Kong Chengxiang , Jin Ping , Yu Bin , Lu Xiulan , Jin Youpeng , Yan Huiying , Hong Xiaoyang , Zhang Yucai , Feng Zhi-Chun 
Published: December 2020

Abstract
Background: Extracorporeal membrane oxygen (ECMO) has used for rescuing severe pediatric acute respiratory distress syndrome (PARDS) for half a century. Prone position ventilation (PPV) has been suggested according to the surviving sepsis campaign (SSC) guideline in children in 2020. We aimed to compare the outcomes and effect of PARDS patients with ECMO+PPV and ECMO only.Design: Retrospective Multicenter pair-matched StudySetting: In the present study, propensity score matching was conducted and the outcomes of severe PARDS patients were analyzed. The effect of PPV was compared as well. The efficiency of PPV included PaO2, Oxygen Index (OI), PaO2/FiO2, compliance of respiratory system and resistance of airway. The primary outcome was hospital mortality. Secondary outcomes included ECMO running time, PICU time, hospital days and mechanical ventilation time of survivors. Patients: 137 PARDS patients with criteria of ECMO from 11 hospitals in 5 years.Interventions: No interventions.Measurements and Main Results: Among 137 patients, 93 patients received ECMO+PPV at the same time and 44 patients didn’t. After matching, we got 34 pairs. For the survivors receiving ECMO+PPV, the PaO2, OI and PaO2/FiO2 increased significantly during the PPV period (P<0.01) and sustained for 4 hours at least. However, the hospital mortality of both groups showed no significant difference (50.0 vs. 55.9%, P=0.808). Conclusions: By far, there has been no ECMO+PPV efficiency study in PARDS patients. This study found that PPV was associated with improved oxygen state during ECMO. However, PPV was not associated with survival rate with PARDS patients on ECMO. Clinical Trial Registration: This study was registered at http://www.chictr.org.cn/index.aspx (chiCTR.gov; Identifier: ChiCTR1800019555). Registered 18 November 2018. Name of the registry: Extracorporeal membrane oxygenation in critical ill children with severe acute respiratory distress syndrome - A multicenter study.Take Home Message:1. Our study investigated prone position ventilation (PPV) could improve the oxygen state during ECMO for patients with severe PARDS.2. The results indicated PPV had no influence on the mortality of PARDS with ECMO.
Downregulation of Metallothionein-2 Contributes to Oxaliplatin-induced Neuropathic Pain
Authors: Huang Xuelin , Deng Jie , Xu Ting , Xin Wenjun , Zhang Yuehong , Ruan Xiangcai 
Published: December 2020

Abstract
Background
We previously reported a correlation between small doses of oxaliplatin penetrating onto the spinal cord and acute pain after chemotherapy. Here we propose that MT2 within the spinal dorsal horns participates the development of oxaliplatin-induced neuropathic pain and may be a pharmacological target for the prevention and treatment of chemotherapy-induced peripheral neuropathy (CIPN).
Methods
The rat model of CIPN was established by a 5 consecutive injection of oxaliplatin (0.4 mg/ 100 g/ day). Genetic restoration or inhibition of neuron-specific metallothionein-2 was implemented 21 days before oxaliplatin treatment. Mechanical allodynia and locomotor activity were assayed. Cell-specific expression of metallothionein-2, the mRNA levels of pro-inflammatory cytokines, nuclear translocation of NF-κB, the protein levels of expression of IκB-α, and interaction between IκB-α and P65 were evaluated in the spinal dorsal horns. Also, in vitro interaction of sequentially deleted IκB-α promoter with metallothionein-2 was used to assess the signal transduction mechanism.
Results
We found that oxaliplatin induced downregulation of metallothionein-2 in rat spinal cord neurons. By contrast, genetic restoration of metallothionein-2 in the spinal dorsal horn neuron blocked and reversed neuropathic pain in oxaliplatin-treated rats of both sexes, whereas genetic inhibition of metallothionein-2 triggered neuropathic pain in normal rats. No locomotor impairment was observed after the genetic alterations of metallothionein-2. At the molecular level, metallothionein-2 modulated oxaliplatin-induced neuroinflammation, activation of NF-κB, and transcriptional expression of IκB-α promoter, and these processes could be blocked by genetic restoration of metallothionein-2 in the spinal dorsal horn neurons.
Conclusions
Metallothionein-2 is a potential target for the prevention and treatment of CIPN. A reduction of NF-κB activation and inflammatory responses by enhancing the transcription of IκB-α promoter is proposed in the mechanism.
Developing an interprofessional transition course to improve team-based HIV care for Sub-Saharan Africa
Authors: Kiguli-Malwadde Elsie , Budak Jehan Z , Chilemba Evelyn , Semitala Fred , Von Zinkernagel Deborah , Mosepele Mosepele , Conradie Hoffie , Khanyola J , Haruruvizhe Clara , Martin Shayanne , Kazembe Abigail , De Villiers M , Reid Michael J A 
Published: December 2020

Abstract
BackgroundWith funding from the United States Health Resources Service Administration (HRSA), a consortium of health professional training institutions from Africa developed HIV-specific, interprofessional, team-based educational resources to better support trainees during the transition period between pre-service training and professional practice.MethodsTen faculty members representing nine medical and nursing schools in sub-Saharan Africa (SSA) developed a training package of modules focused on core clinical, public health, interprofessional education (IPE), and quality improvement (QI) domains related to HIV service delivery. Curriculum development was informed by a rapid needs assessment of existing tools and future needs for HIV education across 27 SSA health professions training institutions. A total of 17 modules were developed, targeted at newly qualified health care professionals to be taught in a series of two-day workshops meant to complement existing institution specific HIV-curricula. ResultsBetween April and July 2019, a comprehensive case-based HIV training package was developed to support trainees in transition from pre-service training to independent professional practice. Each module, addressing different elements of interprofessional practice, was intended to be delivered in an interprofessional format. Thus far, 70 health professions training institutions in 14 countries have implemented the program; 547 educators facilitated STRIPE workshops, with a total of 5,027 learners trained between September 2019 and September 2020.ConclusionsTo our knowledge this is the first IPE HIV-specific curriculum explicitly focused on enhancing the quality of training provided to graduating health care professionals working in SSA. The collaborative, cross-institutional, interprofessional approach to curriculum development provides a benchmark for how best-practice approaches to education can be disseminated in SSA.
Social gradient in health-related quality of life among urban middle-age residents in Limassol, Cyprus: Research article
Authors: Ellina Panagiota , Middleton Nicos , Lambrinou Ekaterini , Kouta Christiana 
Published: December 2020

Abstract
Background: Social inequalities in health threaten social cohesion and their investigation is an important research field. Monitoring the health of the population is necessary to identify health needs, design programs focused in people’s needs and to evaluate the effectiveness of health policies.Methods: A cross-sectional survey using primary data was applied. The study investigated the size and the extent of social inequalities in quality of life and health behaviours in Limassol, Cyprus. Data collection was done door-to-door in the form of survey interviews. The sample consisted of 450 residents aged 45-64 across 45 randomly selected neighbourhoods, that met the selection criteria. The tools used were: Demographic questionnaire, SF 36 Questionnaire, IPAQ- International Physical Activity Questionnaire short form.Results: The social gradient appears in all social indicators. Physical dimension of health has a strong relationship between health-related quality of life with the education index. Specifically, the range is 12 points for males and 14 points for females (p for interaction= 0.16). Profession systematically appears to have a stronger relationship with men than with women, and is present in both physical and mental dimensions. The range is 13 points for men and 10 points for women (p for interaction= 0.31).Conclusions: It seems that young highly educated males, employed full time, earning high income and engaging in mild physical activity, have significantly higher level of health-related life quality, compared to other middle age adult groups, living in Limassol. This finding is in agreement with other studies that show correlations between gender and the patterns of risk factors.
Metabolic acclimation supports higher aluminium-induced secretion of citrate and malate in an aluminium-tolerant hybrid clone of Eucalyptus
Authors: Li Wannian , Finnegan Patrick M. , Dai Qin , Guo Dongqiang , Yang Mei 
Published: December 2020

Abstract
Background: Eucalyptus is the main plantation wood species, mostly grown in aluminized acid soils. To understand the response of Eucalyptus clones to aluminum (Al) toxicity, the Al-tolerant Eucalyptus grandis × E. urophylla clone GL-9 (designated “G9”) and the Al-sensitive E. urophylla clone GL-4 (designated “W4”) were employed to investigate the production and secretion of citrate and malate by roots.Results: Eucalyptus seedlings in hydroponics were exposed to the presence or absence of 4.4 mM Al at pH 4.0 for 24 hours. The protein synthesis inhibitor cycloheximide (CHM) and anion channel blocker phenylglyoxal (PG) were applied to explore possible pathways involved in organic acid secretion. The secretion of malate and citrate was earlier and greater in G9 than in W4, corresponding to less Al accumulation in G9. The concentration of Al in G9 roots peaked after 1h and decreased afterwards, corresponding with a rapid induction of malate secretion. A time-lag of about 6h in citrate efflux in G9 was followed by robust secretion to support continuous Al-detoxification. Malate secretion alone may alleviate Al toxicity because the peaks of Al accumulation and malate secretion were simultaneous in W4, which did not secrete appreciable citrate. Enhanced activities of citrate synthase (CS) and phosphoenolpyruvate carboxylase (PEPC), and reduced activities of isocitrate dehydrogenase (IDH), aconitase (ACO) and malic enzyme (ME) were closely associated with the greater secretion of citrate in G9. PG effectively inhibited citrate and malate secretion in both Eucalyptus clones. CHM also inhibited malate and citrate secretion in G9, and citrate secretion in W4, but notably did not affect malate secretion in W4. Conclusions: G9 immediately secrete malate from roots, which had an initial effect on Al-detoxification, followed by time-delayed citrate secretion. Pre-existing anion channel protein first contributed to malate secretion, while synthesis of carrier protein appeared to be needed for citrate excretion. The changes of organic acid concentrations in response to Al can be achieved by enhanced CS and PEPC activities, but was supported by changes in the activities of other enzymes involved in organic acid metabolism. The above information may help to further explore genes related to Al-tolerance in Eucalyptus.