bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhancing mental health pre-service training with the WHO mhGAP Intervention Guide: experiences learned and the way forward
Authors: Iversen Silje Akselberg , Ogallo Brian , Belfer Myron , Fung Daniel , Hoven Christina W. , Carswell Kenneth , Skokauskas Norbert 
Published: January 2021

AbstractThere is currently a high global demand for mental health professionals, including child and adolescent mental health professionals. In 2020, the World Health Organization (WHO) published “Enhancing mental health pre-service training with the mhGAP-Intervention Guide: experiences and lessons learned” to address the proposition of implementing Mental Health Gap Action Programme Intervention Guide (mhGAP-IG) materials and principles as a component of pre-service training. By integrating the mhGAP-IG within pre-service training, future healthcare providers will acquire theoretical knowledge and early exposure to practical knowledge and will be better prepared for their future work.Examples demonstrate that mhGAP-IG pre-service training can be successfully implemented in diverse settings and in various pre-service training programs. It can be used in small group learning activities and short courses, taught through lectures, used as a clinical tool to teach students (i.e. medical, nursing students) and medical doctors in training. We can enhance pre-service training with the mhGAP-IG and contribute to a learning environment, which nurtures knowledge and skills required to help people with mental health needs.
Identification of the active substances and mechanisms of ginger for the treatment of colon cancer based on network pharmacology and molecular docking
Authors: Zhang Meng-Meng , Wang Dan , Lu Feng , Zhao Rong , Ye Xun , He Lin , Ai Li , Wu Chun-Jie 
Published: January 2021

Abstract
Background and objective
Colon cancer is occurring at an increasing rate and ginger (Zingiber officinale), as a commonly used herbal medicine, has been suggested as a potential agent for colon cancer. This study was aimed to identify the bioactive components and potential mechanisms of ginger for colon cancer prevention by an integrated network pharmacology approach.

Methods
The putative ingredients of ginger and its related targets were discerned from the TCMSP and Swiss target prediction database. After that, the targets interacting with colon cancer were collected using Genecards, OMIM, and Drugbank databases. KEGG pathway and GO enrichment analysis were performed to explore the signaling pathways related to ginger for colon cancer treatments. The PPI and compound-target-disease networks were constructed using Cytoscape 3.8.1. Finally, Discovery studio software was employed to confirm the key genes and active components from ginger.

Results
Six potential active compounds, 285 interacting targets in addition to 1356 disease-related targets were collected, of which 118 intersection targets were obtained. A total of 34 key targets including PIK3CA, SRC, and TP53 were identified through PPI network analysis. These targets were mainly focused on the biological processes of phosphatidylinositol 3-kinase signaling, cellular response to oxidative stress, and cellular response to peptide hormone stimulus. The KEGG enrichment manifested that three signaling pathways were closely related to colon cancer prevention of ginger, cancer, endocrine resistance, and hepatitis B pathways. TP53, HSP90AA1, and JAK2 were viewed as the most important genes, which were validated by molecular docking simulation.

Conclusion
This study demonstrated that ginger produced preventive effects against colon cancer by regulating multi-targets and multi-pathways with multi-components. And, the combined data provide novel insight for ginger compounds developed as new drug for anti-colon cancer.
Pegylated liposomal doxorubicin in patients with epithelial ovarian cancer
Authors: Yuan Zhen , Zhang Ying , Cao Dongyan , Shen Keng , Li Qingshui , Zhang Guonan , Wu Xiaohua , Cui Manhua , Yue Ying , Cheng Wenjun , Wang Li , Qu Pengpeng , Tao Guangshi , Hou Jianqing , Sun Lixin , Meng Yuanguang , Li Guiling , Li Changzhong , Shi Huirong , Chen Yaqing 
Published: January 2021

Abstract
Objective
To evaluate the efficacy and safety of PLD in treating of in patients who experience epithelial ovarian, fallopian tubal, and peritoneal cancer progression within 12 months after the first-line platinum-based therapy.

Methods
This was an open-label, single-arm and multicenter clinical trial. The ORR was the interim primary objective, and the DCR, AEs and QOL were the secondary objectives. The impact of factors on efficacy outcomes, the change trend of CA125 and the artificial platinum-free interval were exploratory endpoints.

Results
Totally, 115 patients were enrolled in this study and included in the ITT population. Moreover, 101 patients were included in the safety population. The median follow-up time was 4 months (IQR 2–6). In the ITT population, the confirmed ORR was 37.4% (95% CI, 28.4–46.4%), and the DCR was 65.2% (95% CI, 56.4–74.1%). The previous response status to platinum-based chemotherapy and baseline CA125 levels were significantly correlated with the ORR. The ORR was significantly higher in patients with a CA125 decrease after the first cycle than in the patients with a CA125 increase. The most common grade 3 or higher AE was hand-foot syndrome (3 [3.0%] of 101 patients). No statistically significant differences existed between the baseline and the postbaseline questionnaires.

Conclusions
For patients who experience platinum-resistant and platinum-refractory relapse, the use of PLD may be acceptable because of the associated satisfactory efficacy, low frequency of AEs and high patient QOL. Moreover, a low CA125 level at baseline and a reduction in CA125 after the first cycle are predictive factors for satisfactory efficacy.
Human recombinant arginase I [HuArgI (Co)-PEG5000]-induced arginine depletion inhibits ovarian cancer cell adhesion and migration through autophagy-mediated inhibition of RhoA
Authors: El-Mais Nour , Fakhoury Isabelle , Abdellatef Sandra , Abi-Habib Ralph , El-Sibai Mirvat 
Published: January 2021

AbstractOvarian carcinoma is the second most common malignancy of the female reproductive system and the leading cause of death from female reproductive system malignancies. Cancer cells have increased proliferation rate and thus require high amounts of amino acids, including arginine. L-arginine is a non-essential amino acid synthesized from L-citrulline by the Arginosuccinate synthetase (ASS1) enzyme. We have previously shown that the ovarian cancer cells, SKOV3, are auxotrophic to arginine, and that arginine deprivation by treatment with the genetically engineered human arginase I (HuArgI (Co)-PEG5000) triggers the death of SKOV3 cells by autophagy. In this study we examine the effect of HuArgI (Co)-PEG5000 on ovarian cancer cell migration and we dissect the mechanism involved. Wound healing assays, 2D random cell migration assays and cell adhesion analysis indicate that arginine deprivation decreases SKOV3 cell migration and adhesion. This effect was mimicked when autophagy was induced through rapamycin and reversed with the autophagy inhibitor chloroquine when autophagy was inhibited. This proved that arginine deprivation leads to the inhibition of cancer cell migration through autophagy, in addition to cell death. In addition, we were able to establish through pull-down assays and reversal experiments, that arginine deprivation-mediated autophagy inhibits cell migration through a direct inhibition of RhoA, member of the Rho family of GTPases. In conclusion, here we identify, for the first time, an autophagy-mediated inhibition of RhoA that plays an important role in regulating ovarian cancer cells motility and adhesion in response to arginine depletion.
Minimally Invasive Versus open AbdominoThoracic Esophagectomy for esophageal carcinoma (MIVATE) — study protocol for a randomized controlled trial DRKS00016773
Authors: Nickel Felix , Probst Pascal , Studier-Fischer Alexander , Nienhüser Henrik , Pauly Jana , Kowalewski Karl-Friedrich , Weiterer Sebastian , Knebel Philipp , Diener Markus K. , Weigand Markus A. , Büchler Markus W. , Schmidt Thomas , Müller-Stich Beat P. 
Published: January 2021

Abstract
Background
The only curative treatment for most esophageal cancers is radical esophagectomy. Minimally invasive esophagectomy (MIE) aims to reduce postoperative morbidity, but is not yet widely established. Linear stapled anastomosis is a promising technique for MIE because it is quite feasible even without robotic assistance. The aim of the present study is to compare total MIE with linear stapled anastomosis to open esophagectomy (OE) with circular stapled anastomosis with special regard to postoperative morbidity in an expertise-based randomized controlled trial (RCT).

Methods/design
This superiority RCT compares MIE with linear stapled anastomosis (intervention) to OE with circular stapled anastomosis (control) for Ivor-Lewis esophagectomy. It was initiated in February 2019, and recruitment is expected to last for 3 years. For inclusion, patients must be 18 years of age or more with a resectable primary malignancy in the distal esophagus. Participants with tumor localizations above the azygos vein, metastasis, or infiltration into adjacent tissue will be excluded. In an expertise-based approach, the allocated treatment will only be carried out by the single most experienced surgeon of the surgical center for each respective technique. The sample size was calculated with 20 participants per group for the primary endpoint postoperative morbidity according to comprehensive complication index (CCI) within 30 postoperative days. Secondary endpoints include anastomotic insufficiency, pulmonary complications, other intra- and postoperative outcome parameters such as estimated blood loss, operative time, length of stay, short-term oncologic endpoints, adherence to a standardized fast-track protocol, postoperative pain, and postoperative recovery (QoR-15). Quality of life (SF-36, CAT EORTC QLQ-C30, CAT EORTC QLQ-OES18) and oncological outcomes are evaluated with 60 months follow-up.

Discussion
MIVATE is the first RCT to compare OE with circular stapled anastomosis to total MIE with linear stapled anastomosis exclusively for intrathoracic anastomosis. The expertise-based approach limits bias due to heterogeneity of surgical expertise. The use of a dedicated fast-track protocol in both OE and MIE will shed light on the role of the access strategy alone in this setting. The findings of this study will serve to define which approach has the best perioperative outcome for patients requiring esophagectomy.

Trial registration
German Clinical Trials Register DRKS00016773. Registered on 18 February 2019.
Viral load-guided immunosuppression after lung transplantation (VIGILung)—study protocol for a randomized controlled trial
Authors: Gottlieb Jens , Reuss Alexander , Mayer Konstantin , Weide Karin , Schade-Brittinger Carmen , Hoyer Susanne , Jaksch Peter 
Published: January 2021

Abstract
Background
Immunosuppression including high-dose calcineurin inhibitors (CNI) is essential after lung transplantation. Dosing is usually guided by therapeutic drug monitoring adjusted to target trough levels of CNIs to keep the balance between over-dose causing severe toxicity and increased risk of infections or under-dose with a risk of graft injury. Adaptation of CNI-based immunosuppression by monitoring of torque teno virus (TTV), a latent nonpathogenic DNA virus, measured in the whole blood in addition to conventional therapeutic drug monitoring may reduce the toxicity of immunosuppression with similar efficacy.

Methods/design
An open-label, randomized, controlled, parallel-group, multicenter trial in lung transplant recipients will be conducted to investigate the safety and efficacy of immunosuppression guided by TTV monitoring as an add-on to conventional therapeutic drug monitoring. Adult lung transplant recipients 21 to 42 days after transplantation are eligible to participate. Patients (N = 144) will be randomized 1:1 to the experimental intervention (arm 1: immunosuppression guided by TTV monitoring in addition to conventional therapeutic drug monitoring of tacrolimus trough levels) and control intervention (arm 2: conventional therapeutic drug monitoring). Outcomes will be assessed 12 months after randomization with the change in glomerular filtration rate as the primary endpoint. Secondary endpoints will be additional measurements of renal function, allograft function, incidence of acute rejections, incidence of chronic lung allograft dysfunction, graft loss, and infections.

Discussion
The results of this randomized controlled trial may reduce the toxicity of immunosuppression after lung transplantation while maintaining the efficacy of immunosuppression. Study results are transferable to all other solid organ transplantations.

Trial registration
ClinicalTrials.gov NCT04198506. Registered on 12 December 2019
Prevalence of asymptomatic visceral leishmaniasis in human and dog, Benishangul Gumuz regional state, Western Ethiopia
Authors: Bejano Shibabaw , Shumie Girma , Kumar Ashwani , Asemahagn Eyuel , Damte Demekech , Woldie Sinkinesh , Mulugeta Abate , Manaye Nigus , Genetu Abebe , Gadisa Endalamaw , Mamo Gezahegn 
Published: January 2021

Abstract
Background
The Benishangul-Gumuz region is an important development corridor in Ethiopia. Large-scale projects such as the Great Renaissance Dam, mining and agriculture have entailed huge environmental modifications and settlement pattern changes. There is no detailed epidemiological information on visceral leishmaniasis (VL) in the region.

Materials and methods
A cross-sectional study was carried out to assess the epidemiology and risk factors associated with Leishmania infection. A leishmanin skin test (LST) was done for 1342 participants, and for 253 of them rK39 and DAT were carried out. Thirty-six dogs owned by households with LST-positive member(s) were rK39 and DAT tested. A pretested questionnaire was used to capture individual and household characteristics.

Results
Of the 89.2% (1197/1342) who availed themselves of the LST reading, 6.0% were positive. The rk39 and DAT positivity among the 253 tested were 3.2% and 5.9%, respectively. In dogs, positivity rates by rK39 and DAT were 13.9% and 5.6%, respectively. Of the household and individual risk factors, presence of a dog in the household (P = 0.005), male sex (0.003), residence woreda (0.000) and occupation (0.023) showed a strong positive association with LST positivity. Individuals who lived in households that had dogs were 2.6 times more likely to be LST positive (AOR = 2.6; 95% CI = 1.54, 4.40). Being female decreased the probability of being LST positive by 0.38 times (AOR = 0.38; 95% CI = 0.20, 0.72). People living in Guba and Kurmuk had 4.7 (AOR = 4.74, 95% CI 1.83, 12.31) and 5.9 (AOR = 5.85, 95% CI 2.27, 15.09) times more risk of being infected.

Conclusions
We demonstrated the presence of active VL transmission in the areas. Thus, we underline the need to establish the responsible vector(s) and reservoir(s) for comprehensive early containment plans to prevent potentially harmful public health and economic consequences.

Graphical Abstract
The leishmanicidal effect of Lucilia sericata larval saliva and hemolymph on in vitro Leishmania tropica
Authors: Rahimi Sara , khamesipour Ali , Akhavan Amir Ahmad , Rafinejad Javad , Ahmadkhaniha Reza , Bakhtiyari Mahmood , Veysi Arshad , Akbarzadeh Kamran 
Published: January 2021

Abstract
Background
Leishmaniasis is a major parasitic disease worldwide, except in Australia and Antarctica, and it poses a significant public health problem. Due to the absence of safe and effective vaccines and drugs, researchers have begun an extensive search for new drugs. The aim of the current study was to investigate the in vitro leishmanicidal activity of larval saliva and hemolymph of Lucilia sericata on Leishmania tropica.

Methods
The effects of different concentrations of larval products on promastigotes and intracellular amastigotes of L. tropica were investigated using the mouse cell line J774A.1 and peritoneal macrophages as host cells. The 3-(4.5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and direct observation and counting method were used to assess the inhibitory effects and cell cytotoxicity of the larval products. The effects of larval products on the amastigote form of L. tropica were quantitatively estimated by calculating the rate of macrophage infection, number of amastigotes per infected macrophage cell, parasite load and survival index.

Results
The 50% cytotoxicity concentration (CC50) value of both larval saliva and hemolymph was 750 µg/ml, and the 50% inhibitory concentration (IC50) values were 134 µg/ml and 60 µg/ml for larval saliva and larval hemolymph, respectively. The IC50 for Glucantime, used a positive control, was (11.65 µg/ml). Statistically significant differences in viability percentages of promastigotes were observed for different doses of both larval saliva and hemolymph when compared with the negative control (p ≤ 0.0001). Microscopic evaluation of the amastigote forms revealed that treatment with 150 µg/ml larval hemolymph and 450 µg/ml larval saliva significantly decreased the rate of macrophage infection and the number of amastigotes per infected macrophage cell.

Conclusion
Larval saliva and hemolymph of L. sericata have acceptable leishmanicidal properties against L. tropica.

Graphical Abstract
Global histone protein surface accessibility in yeast indicates a uniformly loosely packed genome with canonical nucleosomes
Authors: Marr Luke T. , Ocampo Josefina , Clark David J. , Hayes Jeffrey J. 
Published: January 2021

AbstractBackgroundThe vast majority of methods available to characterize genome-wide chromatin structure exploit differences in DNA accessibility to nucleases or chemical crosslinking. We developed a novel method to gauge genome-wide accessibility of histone protein surfaces within nucleosomes by assessing reactivity of engineered cysteine residues with a thiol-specific reagent, biotin-maleimide (BM).ResultsYeast nuclei were obtained from cells expressing the histone mutant H2B S116C, in which a cysteine resides near the center of the external flat protein surface of the nucleosome. BM modification revealed that nucleosomes are generally equivalently accessible throughout theS. cerevisiaegenome, including heterochromatic regions, suggesting limited, higher-order chromatin structures in which this surface is obstructed by tight nucleosome packing. However, we find that nucleosomes within 500 bp of transcription start sites exhibit the greatest range of accessibility, which correlates with the density of chromatin remodelers. Interestingly, accessibility is not well correlated with RNA polymerase density and thus the level of gene expression. We also investigated the accessibility of cysteine mutations designed to detect exposure of histone surfaces internal to the nucleosome thought to be accessible in actively transcribed genes: H3 102, is at the H2A–H2B dimer/H3–H4 tetramer interface, and H3 A110C, resides at the H3–H3 interface. However, in contrast to the external surface site, we find that neither of these internal sites were found to be appreciably exposed.ConclusionsOverall, our finding that nucleosomes surfaces withinS. cerevisiaechromatin are equivalently accessible genome-wide is consistent with a globally uncompacted chromatin structure lacking substantial higher-order organization. However, we find modest differences in accessibility that correlate with chromatin remodelers but not transcription, suggesting chromatin poised for transcription is more accessible than actively transcribed or intergenic regions. In contrast, we find that two internal sites remain inaccessible, suggesting that such non-canonical nucleosome species generated during transcription are rapidly and efficiently converted to canonical nucleosome structure and thus not widely present in native chromatin.
Risk of opportunistic infections in patients with rheumatoid arthritis initiating abatacept: cumulative clinical trial data
Authors: Simon Teresa A. , Dong Lixian , Winthrop Kevin L. 
Published: January 2021

Abstract
Background
To evaluate incidence of opportunistic infections (OIs) in patients with rheumatoid arthritis (RA) treated with abatacept in clinical trials.

Methods
This pooled analysis of 16 randomized, double-blind/open-label trials, with ≥ 1 abatacept (intravenous or subcutaneous) arm, and with/without placebo control covered cumulative (controlled short-term and open-label long-term) abatacept exposure periods. OIs were analyzed separately in controlled (abatacept and placebo individually) and cumulative periods. OIs were identified using a prespecified list; events were independently adjudicated. Unadjusted incidence rates (IRs; per 100 patient-years) with 95% confidence intervals (CIs) were calculated.

Results
In cumulative periods, 7044 patients received abatacept, with a mean (standard deviation) duration of exposure of 36.9 (26.2) months (21,274 patient-years of exposure). IRs (95% CIs) of OIs were 0.17 (0.05–0.43) for abatacept and 0.56 (0.22–1.15) for placebo during the controlled periods and 0.21 (0.15–0.28) for abatacept during the cumulative periods. There was 1 case of tuberculosis in both the abatacept (IR [95% CI] 0.04 [0.00–0.24]) and placebo (IR [95% CI] 0.08 [0.00–0.44]) groups during the controlled periods; 13 verified tuberculosis cases (IR [95% CI] 0.06 [0.03–0.10]) were reported in the cumulative period. Herpes zoster was reported numerically more often with abatacept (IR 1.9 [1.4–2.5]), versus placebo (1.7 [1.1–2.6]) in the controlled periods; within the cumulative period, herpes zoster IR (95% CI) was 1.53 (1.36–1.71) for abatacept-treated patients.

Conclusion
In controlled periods of the clinical trials, abatacept-treated patients had similarly low rates of OIs compared with placebo-treated patients. Overall, OI rates were similar among abatacept-treated patients in the controlled and cumulative periods and consistent with the ranges reported in the literature.