bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract PR09: Pharmacologic targeting of Gq reveals new pathways in uveal melanoma
Authors: Onken Michael D. , Makepeace Carol M. , Kaltenbronn Kevin M. , Kanai Stanley M. , Todd Tyson D. , Wang Shiqi , Broekelmann Thomas J. , Rao Prabakar Kumar , Cooper John A. , Blumer Kendall J. 
Published: June 2022

Abstract
Constitutively activating mutations in GNAQ (Gαq) or GNA11 (Gα11) are the oncogenic drivers of uveal (eye) melanoma (UM), occurring in over 90% of tumors. We show that constitutively active Gαq in UM cells can be targeted by the cyclic depsipeptide FR900359 (FR). FR inhibits GDP/GTP exchange allosterically to trap constitutively active Gαq in inactive GDP-bound Gαβγ heterotrimers, and allosteric inhibition of other Gα subunits can be achieved by introduction of an FR binding site. In UM cells driven by constitutively active Gαq, FR inhibits second messenger signaling, arrests proliferation, and reinstates melanocytic differentiation. At higher doses, FR also induces apoptosis. FR has no effect on Gαq/11-wild-type UM cells. FR promotes UM cell differentiation by reactivating polycomb repressive complex 2 (PRC2)-mediated gene silencing, antagonized by a heretofore unrecognized effector system of constitutively active Gαq in UM. Constitutively active Gαq and PRC2 therefore provide important therapeutic targets for UM. Further, the development of FR analogs specific for other Gα subunit subtypes may provide novel therapeutic approaches for diseases driven by constitutively active Gα subunits or multiple G protein-coupled receptors where targeting a single receptor is ineffective.
This abstract is also being presented as Poster A10.
Citation Format: Michael D. Onken, Carol M. Makepeace, Kevin M. Kaltenbronn, Stanley M. Kanai, Tyson D. Todd, Shiqi Wang, Thomas J. Broekelmann, Prabakar Kumar Rao, John A. Cooper, Kendall J. Blumer. Pharmacologic targeting of Gq reveals new pathways in uveal melanoma [abstract]. In: Proceedings of the AACR Special Conference on Melanoma: From Biology to Target; 2019 Jan 15-18; Houston, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(19 Suppl):Abstract nr PR09.
TRAF4 Inhibits Bladder Cancer Progression by Promoting BMP/SMAD Signaling
Authors: Iyengar Prasanna Vasudevan , Marvin Dieuwke Louise , Lama Dilraj , Tan Tuan Zea , Suriyamurthy Sudha , Xie Feng , van Dinther Maarten , Mei Hailiang , Verma Chandra Shekhar , Zhang Long , Ritsma Laila , ten Dijke Peter 
Published: June 2022

Abstract

Patients with bladder cancer often have a poor prognosis due to the highly invasive and metastatic characteristics of bladder cancer cells. Epithelial-to-mesenchymal transition (EMT) has been causally linked to bladder cancer invasion. The E3 ubiquitin ligase, tumor necrosis factor receptor–associated factor 4 (TRAF4) has been implicated as a tumor promoter in a wide range of cancers. In contrast, here we show that low TRAF4 expression is associated with poor overall survival in patients with bladder cancer. We show that the TRAF4 gene is epigenetically silenced and that ERK mediates TRAF4 phosphorylation, resulting in lower TRAF4 protein levels in bladder cancer cells. In addition, we demonstrate that TRAF4 is inversely correlated with an EMT gene signature/protein marker expression. Functionally, by manipulating TRAF4 expression, we show that TRAF4 regulates EMT genes and epithelial and invasive properties in bladder cancer cells. Transcriptomic analysis of dysregulated TRAF4 expression in bladder cancer cell lines revealed that high TRAF4 expression enhances the bone morphogenetic protein (BMP)/SMAD and inhibits the NF-κB signaling pathway. Mechanistically, we show that TRAF4 targets the E3 ubiquitin ligase SMURF1, a negative regulator of BMP/SMAD signaling, for proteasomal degradation in bladder cancer cells. This was corroborated in patient samples where TRAF4 positively correlates with phospho-SMAD1/5, and negatively correlates with phospho-NFκb-p65. Lastly, we show that genetic and pharmacologic inhibition of SMURF1 inhibits the migration of aggressive mesenchymal bladder cancer cells.

Implications:
Our findings identify E3 ubiquitin ligase TRAF4 as a potential therapeutic target or biomarker for bladder cancer progression.
Converting 2D magnetic resource imagining brain tumors to 3D structure using depth map machine learning techniques
Authors: Riyazudeen K. A. Mohamed , Sathik Mohamed 
Published: June 2022

<span>The use <span>of medical imaging technology aids clinicians in recognizing and assessing patient problems, as well as improving treatment procedures. However, while conducting complex procedures such as the excision of brain tumors, the knowledge and biological research gathered from 2D images are insufficient. Converting 2D images to 3D images may assist doctors in determining the size, shape, and sharp area of tumor cells in the brain. The feasibility of translating 2D medical image data to a 3D model is described in this work. A suggested framework for predicting the size, shape, and location of a brain tumor using a minimized genetic machine learning method, and then converting the tumor information into 3D images using a depth map estimation approach after detecting the tumor information. When the tumor is located, the left and right view data are combined to form a 3D magnetic resonance imaging reconstruction. We used mixed reality methods to minimize file size while preserving the greatest quality of the model during a brain surgical operation.</span></span>
Knockout of Sorbin And SH3 Domain Containing 2 (Sorbs2) in Cardiomyocytes Leads to Dilated Cardiomyopathy in Mice
Authors: McLendon Jared M. , Zhang Xiaoming , Matasic Daniel S. , Kumar Mohit , Koval Olha M. , Grumbach Isabella M. , Sadayappan Sakthivel , London Barry , Boudreau Ryan L. 
Published: June 2022

BackgroundSorbin and SH3 domain containing 2 (Sorbs2) protein is a cytoskeletal adaptor with an emerging role in cardiac biology and disease; yet, its potential relevance to adult‐onset cardiomyopathies remains underexplored. Sorbs2 global knockout mice display lethal arrhythmogenic cardiomyopathy; however, the causative mechanisms remain unclear. Herein, we examine Sorbs2 dysregulation in heart failure, characterize novel Sorbs2 cardiomyocyte‐specific knockout mice (Sorbs2‐cKO), and explore associations between Sorbs2 genetic variations and human cardiovascular disease.Methods and ResultsBioinformatic analyses show myocardial Sorbs2 mRNA is consistently upregulated in humans with adult‐onset cardiomyopathies and in heart failure models. We generated Sorbs2‐cKO mice and report that they develop progressive systolic dysfunction and enlarged cardiac chambers, and they die with congestive heart failure at about 1 year old. After 3 months, Sorbs2‐cKO mice begin to show atrial enlargement and P‐wave anomalies, without dysregulation of action potential–associated ion channel and gap junction protein expressions. After 6 months, Sorbs2‐cKO mice exhibit impaired contractility in dobutamine‐treated hearts and skinned myofibers, without dysregulation of contractile protein expressions. From our comprehensive survey of potential mechanisms, we found that within 4 months, Sorbs2‐cKO hearts have defective microtubule polymerization and compensatory upregulation of structural cytoskeletal and adapter proteins, suggesting that this early intracellular structural remodeling is responsible for contractile dysfunction. Finally, we identified genetic variants that associate with decreased Sorbs2 expression and human cardiac phenotypes, including conduction abnormalities, atrial enlargement, and dilated cardiomyopathy, consistent with Sorbs2‐cKO mice phenotypes.ConclusionsOur studies show that Sorbs2 is essential for maintaining structural integrity in cardiomyocytes, likely through strengthening the interactions between microtubules and other cytoskeletal proteins at cross‐link sites.
Safety and Efficacy of SSRIs in Improving Poststroke Recovery: A Systematic Review and Meta‐Analysis
Authors: Kalbouneh Heba M. , Toubasi Ahmad A. , Albustanji Farah H. , Obaid Yazan Y. , Al‐Harasis Layla M. 
Published: June 2022

Background
Several studies investigated the role of selective serotonin reuptake inhibitors (SSRIs) in improving poststroke recovery; thus, we have decided to conduct this systematic review and meta‐analysis to investigate the efficacy and safety of SSRIs in poststroke recovery.

Methods and Results
In this meta‐analysis we searched the following databases: PubMed, Cochrane, Scopus, and Google Scholar. The studies were included if they were placebo‐controlled trials in design and reported SSRIs’ effects on poststroke depression, anxiety, disability, dependence, motor abilities, and cognitive functions. The quality of the included studies was assessed using the revised Cochrane risk‐of‐bias tool for randomized trials. The search yielded 44 articles that included 16 164 patients, and about half of the participants were treated with SSRIs. Our results showed that SSRIs had a significant effect on preventing depression (weighted mean difference [WMD], −7.05 [95% CI, −11.78 to −2.31]), treating depression according to the Hamilton Rating Scale for Depression score (WMD, −1.45 [95% CI, −2.77 to −0.14]), anxiety (relative risk, 0.23 [95% CI, 0.09–0.61]), dependence (WMD, 8.86 [95% CI, 1.23–16.48]), motor abilities according to National Institutes of Health Stroke Scale score (WMD, −0.79 [95% CI, −1.42 to −0.15]), and cognitive functions (WMD, 1.00 [95% CI, 0.12–1.89]). On the other hand, no significant effect of SSRIs on disability was observed. Additionally, we found that treating with SSRIs increased the risk of seizures (relative risk, 1.44 [95% CI, 1.13–1.83]), whereas there was no difference in the incidence of gastrointestinal symptoms or bleeding between SSRIs and a placebo.

Conclusions
Our study showed that SSRIs are effective in preventing and treating depression, and improving anxiety, motor function, cognitive function, and dependence in patients after stroke. These benefits were only reproducible with the citalopram subanalysis but not fluoxetine. Further well‐conducted placebo‐controlled trials are needed to investigate the safety and efficacy of citalopram among patients after stroke.

Registration

URL:
www.crd.york.ac.uk/prospero/
; Unique identifier: CRD42021285766.
Water Vapor Transport by an Equivalent-Barotropic Cyclonic Anomaly Corresponding to Extreme Austral Late Summer Precipitation in Southeast Australia during 2021
Authors: Zhang Yue , Zhou Wen , Ling Jian , Qi Lixin 
Published: June 2022

Abstract
Southeast Australia (SEA) experienced a wet February as well as an extremely wet March accompanied by devastating floods during 2021. Regional water vapor balance analysis at different levels indicates the leading role of water vapor inflow through zonal boundaries during February, and the dominant contribution of water vapor input through meridional boundaries during March, providing adequate anomalous moisture for abnormal precipitation. The horizontal distribution of vertically integrated water vapor flux is characterized as an anomalous cyclonic circulation pattern around the Tasman Sea and SEA, responsible for the intensified water vapor transport along northwesterlies from the tropical Indian Ocean and along anomalous onshore easterlies from the Tasman Sea during both months. Partition of the contributions of dynamic and thermodynamic processes to the anomalous atmospheric water vapor flux reveals the dominant role of the anomalous wind field, but the anomalous variation in the moisture field also plays a part in the water vapor convergence for SEA. The presence of upper and lower large-scale atmospheric circulations ascertains that cyclonic water vapor flux is attributed to a dominant equivalent-barotropic cyclone system over SEA. The plausible joint impacts of internal forcing from the positive southern annular mode (SAM) oscillation, and external forcing from La Niña, are further confirmed by composite analysis; a La Niña–induced low pressure system dominates the lower level over the Australian continent, and the SAM-caused anomalous cyclonic disturbance propagating from higher latitudes governs the higher level above southern Australia, leading to the important equivalent-barotropic cyclonic circulation just above the region of interest.
Minimal clinically important difference of the Berg Balance Scale and comfortable walking speed in patients with acute stroke: A multicenter, prospective, longitudinal study
Authors: Hayashi Shota , Miyata Kazuhiro , Takeda Ren , Iizuka Takamitsu , Igarashi Tatsuya , Usuda Shigeru 
Published: June 2022

Objective To determine the minimal clinically important difference between the Berg Balance Scale and comfortable walking speed in acute-phase stroke patients. Design Multicenter, prospective, longitudinal study. Setting Inpatient acute stroke rehabilitation. Subjects Seventy-five patients with acute stroke, mean (SD) age 71.7 (12.2) years. Intervention Inpatients with acute stroke were assessed with the Berg Balance Scale and comfortable walking speed before and after rehabilitation. Physiotherapy was conducted to improve balance and gait over a 2-week period: an average of 40 min/day on weekdays and 20 min/day on weekends and holidays. Main measures The patients’ Berg Balance Scale, comfortable walking speed, Global Rating of Change scale (patient-rated and physiotherapist-rated), and motor score of the Functional Independence Measure were obtained. Minimal clinically important differences were estimated using both anchor- (receiver operating characteristic curves and change difference) and distribution-based approaches (minimal detectable change and 0.5× the change score [SD]). Results The baseline scores were 31.2 (18.9) for the Berg Balance Scale and 0.79 (0.35) m/s for comfortable walking speed. The minimal clinically important difference in the Berg Balance Scale was 6.5–12.5 points by the anchor-based approach and 2.3–4.9 points by the distribution-based approach. The minimal clinically important difference in comfortable walking speed was 0.18–0.25 m/s by the anchor-based and 0.13–0.15 m/s by the distribution-based approach. Conclusions A change of 6.5–12.5 points in the Berg Balance Scale and 0.18–0.25 m/s in the comfortable walking speed is required in these measurements’ anchor-based minimal clinically important differences to be beyond measurement error, and to be perceptible by both patients and clinicians.
Medical laboratory staff satisfaction and their perspective on the role of health institutions to combat COVID-19 pandemic
Authors: Basnet Buddha Bahadur , Satyal Deepa , Pandit Roshan , Maharjan Anjila , Karki Rashmi , Mishra Shyam Kumar , GC Srijana , Basnet Til Bahadur 
Published: June 2022

Objective To assess the facilities and challenges encountered in the clinical laboratories, satisfaction of the medical laboratory staff (MLS) toward their profession and their views on the role of related health institutions during the first wave of the Coronavirus Disease 2019 (COVID-19) pandemic in Nepal. Methods A web-based cross-sectional study was conducted among registered MLS in Nepal. Data were collected using a structured self-reported questionnaire on the Google Docs platform. Results A total of 301 respondents were enrolled in the study; of which 180 were male and 121 were female. Of the 301 respondents, a lack of infrastructure was reported by 241 (80.1%), a lack of skill development training by 204 (67.8%), limited availability of diagnostics kits by 151 (50.2%), overburdened by the workload by 142 (47.2%) and difficulty in sample management by 129 (42.9%). A total of 244 of 301 respondents (81.1%) believed that stakeholder institutions should collaborate with the government during the pandemic. The level of satisfaction during the pandemic (130 of 301; 43.19%) was found to have decreased compared with before the pandemic (203 of 301; 67.4%). Conclusion MLS were not fully satisfied with the available resources during the pandemic.
Ex Vivo Versus In Vivo Liposuction Hemolysis Index in High-Definition Liposuction and Body Contouring
Authors: Mowlavi Arian , Sin Zachary , Young Stephanie , Sahami Chelsea , Sharma Varun 
Published: June 2022

Background: Ex vivo liposuction is a novel technique wherein tissues that are preoperatively planned for excision can be liposuctioned in a sterile manner after removal from the patient. Excised tissues are routinely obtained during a tummy tuck or variant, lateral thigh tuck, buttock tuck, brachioplasty, upper body tuck, and medial thigh tuck. These tucking procedures are performed when moderate to severe skin redundancy is present in patients undergoing body contouring. Traditionally, these tissues were first liposuctioned prior to being excised, termed in vivo liposuction. However, we have developed ex vivo liposuction protocols wherein the tissues are liposuctioned after they have been excised off the patient. Routine processing of harvested fat focuses on minimizing blood products in the aspirate prior to injection. This is because blood products are felt to contain pro-inflammatory products that negatively affect fat graft take. We hypothesized that fat collected by ex vivo technique provides a less bloody harvest than fat collected by in vivo technique. Materials and Methods: We quantitated blood concentrate of ex vivo versus in vivo fat aspirate by comparing the hemolysis index in 14 consecutive patients undergoing high-definition liposuction and body contouring. Results: Comparison of hemolysis index demonstrated significant reduction in blood concentrate in ex vivo versus in vivo fat aspirate. In vivo hemolysis index demonstrated a larger median than ex vivo hemolysis index. These results confirm our clinical observation that fat harvested by ex vivo liposuction is cleaner and less blood-tinged than fat harvested by in vivo liposuction. Conclusion: No patients experienced complications related to fat graft infection nor fat emboli. Ex vivo liposuction has proven a safe and less blood-tinged technique for harvesting fat in patients who require excisional procedures.
Family involvement in nursing homes: an interpretative synthesis of literature
Authors: Hovenga Nina , Landeweer Elleke , Zuidema Sytse , Leget Carlo 
Published: June 2022

Background Family involvement in nursing homes is generally recognized as highly valuable for residents, staff and family members. However, family involvement continues to be challenging in practice. Aim To contribute to the dialogue about family involvement and develop strategies to improve family involvement in the nursing home. Methods This interpretative synthesis consists of a thematic analysis and care ethical interpretation of issues regarding family involvement from the perspective of families in nursing homes reported in literature. Findings This study reveals the complexities of family involvement in the nursing home by drawing attention to the moral dimension of the issues experienced by families, as seen through the theoretical lens of Baier’s care ethical concept of trust as a theoretical lens. The synthesis of literature resulted in a thematic categorization of issues reported by families, namely, family–staff relationship, psychosocial factors and organizational circumstances. The care ethical interpretation of the synthesis of literature showed that the concept of trust resonates with all reported issues. Trust evolves over time. Early issues are mostly related to getting to know each other. Secondly, families want to experience that staff are competent and of good will. Difficult feelings families may have, such as guilt or loneliness, and dealing with the deterioration of the loved one puts families in a vulnerable position. This power imbalance between family and staff impedes a trusting relationship. Issues related to organizational circumstances, such as understaffing, also undermine families' trust in staff and the nursing home. Discussion and conclusion Baier’s theoretical concept of trust provides a deeper insight into the moral dimension of family involvement from the perspective of families in the nursing home. To improve family involvement in practice, we propose to aim future interventions at reinforcing trust in the relationship between family and staff as well as in the organizational context in which these care relationships occur.
Review of Calcipotriene and Betamethasone Dipropionate Cream in the Treatment of Psoriasis
Authors: Taylor Alexandra , Singh Rohan , Feldman Steven R. 
Published: June 2022

Objective To review the pharmacokinetics, efficacy, and safety of recently approved calcipotriene and betamethasone dipropionate (C-BD) cream. Data sources A literature review was conducted using MEDLINE (PubMed) and ClinicalTrials.gov from 2002 to mid-May 2022. Study selection and data extraction Articles in English discussing the use of C-BD cream in the treatment of psoriasis were included. Data synthesis In 2 phase I trials, there was no phototoxic or photoallergic skin reaction at irradiated C-BD cream sites at baseline, 24 hours, 48 hours, and 72 hours postirradiation. In 2 phase III trials, after 8 weeks of treatment, more subjects treated with C-BD cream achieved Physician’s Global Assessment treatment success (37.4%), compared to C-BD topical suspension (TS) (22.8%, P < 0.0001) and vehicle (3.7%, P < 0.0001). More subjects had greater mean percentage decline in Modified Psoriasis Area Severity Index (Trial 1: 52.9% and Trial 2: 64.6%), when compared to C-BD TS (Trial 1: 51.3%, P < 0.0001 and Trial 2: 56.4%, P < 0.0001) and vehicle (Trial 1: 22.9%, P < 0.0001 and Trial 2: 20.0%, P < 0.0001). Relevance to patient care and clinical practice Psoriasis has a multifactorial pathogenesis and topical treatments are considered first line. Poor adherence is a major hurdle in management; the combination of 2 separate first-line drugs may address this by decreasing the complexity of treatment regimens. A cream formulation can be preferred, and C-BD is now Food and Drug Administration (FDA) approved as one. Conclusions Newly FDA-approved C-BD cream with novel polyaphron dispersion (PAD) technology provides a safe efficacious combination therapy for mild-to-moderate psoriasis which may be preferred by some patients.
Tamoxifen induced maculopathy presenting like macular telangiectasia type 2 in a patient with breast cancer
Authors: Ansari Astaneh Mohammad Reza , Shokoohi Rad Saeed , Ghavami Shahri Seyed Hossein , Heidarzadeh Hamid Reza 
Published: June 2022

Introduction Drug-induced crystalline maculopathy has been reported secondary to tamoxifen use for breast cancer treatment. It could be misdiagnosed as macular telangiectasia type 2 (MacTel type 2). Case Report A 56-year-old woman with a history of diabetes mellitus and breast cancer was referred to our clinic with painless, bilateral, gradual onset of central vision loss for several months. The fundus examination showed the macular pigmentary change in both eyes and a few refractile crystalline deposits in the parafoveal area in the left eye. However, the rest of the retina was normal in both eyes. Management and Outcome With the diagnosis of tamoxifen-induced maculopathy, the drug was discontinued and supplementary treatment was started. Discussion In this report, patient medical and drug history was an important and powerful measure. Due to the side effects of long-term use of tamoxifen, we need further studies on the need for retinal screening in these patients.