bluuebunny/crossref_metadata_2025 huggingface dataset:
Burden of Cardiovascular Diseases in Nepal from 1990 to 2019: The Global Burden of Disease Study, 2019
Authors: Pandey Achyut Raj , Dhimal Meghnath , Shrestha Niraj , Sharma Dikshya , Maskey Jasmine , Dhungana Raja Ram , Bista Bihungum , Aryal Krishna Kumar
Published: June 2023

Cardiovascular diseases (CVDs) have emerged as the leading cause of deaths worldwide in 2019. Globally, more than three-quarters of the total deaths due to CVDs occur in low- and middle-income countries like Nepal. Although increasing number of studies is available on the prevalence of CVDs, there is limited evidence presenting a complete picture on the burden of CVDs in Nepal. In this context, this study aims to provide comprehensive picture on the burden of CVDs in the country. This study is based on the Global Burden of Disease (GBD) study 2019, which is a multinational collaborative research covering 204 countries and territories across the world. The estimations made from the study are publicly available in the GBD Compare webpage operated by the Institute for Health Metrics and Evaluation (IHME), University of Washington. This article makes use of those data available on the GBD Compare page of IHME website to present the comprehensive picture of the burden of CVDs in Nepal. Overall, in 2019, there were an estimated 1,214,607 cases, 46,501 deaths, and 1,104,474 disability-adjusted life years (DALYs) due to CVDs in Nepal. The age-standardized mortality rates for CVDs witnessed a marginal reduction from 267.60 per 100,000 population in 1990 to 245.38 per 100,000 population in 2019. The proportion of deaths and DALYs attributable to CVDs increased from 9.77% to 24.04% and from 4.82% to 11.89%, respectively, between 1990 and 2019. Even though there are relatively stable rates of age-standardized prevalence, and mortality, the proportion of deaths and DALYs attributed to CVDs have risen sharply between 1990 and 2019. Besides implementing the preventive measures, the health system also needs to prepare itself for the delivery of long-term care of patients with CVDs which could have significant implications on resources and operations.
Incredible Combination of Lifestyle Modification and Herbal Remedies for Polycystic Ovarian Syndrome Management
Authors: Balkrishna Acharya , Rana Maneesha , Mishra Shalini , Srivastava Deepika , Bhardwaj Rohit , Singh Shalini , Rajput Satyendra Kumar , Arya Vedpriya
Published: June 2023

A relatively frequent endocrine‐metabolic illness called polycystic ovarian syndrome (PCOS) is characterized by polycystic ovaries, persistent anovulation, and hyperandrogenism, which cause symptoms such as irregular menstruation, infertility, and hirsutism. PCOS is linked to obesity, insulin resistance, and increased amounts of androgens, or male hormones. The sedentary lifestyle, dietary fluctuations, inactivity, and stress are other contributing variables. According to estimates from India in 2021, around 22.5% of women, or one in five Indian women, suffer from PCOS. Evidence‐based medical care for PCOS places a strong focus on a multidisciplinary approach, as standard pharmacological treatment frequently targets a single symptom, may be contraindicated, has adverse effects, and is ineffective in certain circumstances. However, long‐term treatments have drawbacks and are likely to be ineffective, making complementary and alternative therapies a worthwhile choice. Yoga science is a thorough treatment plan for a healthy body and mind that may eradicate PCOS’s primary causes, stress and obesity. Some common herbal remedies, including Foeniculum vulgare, Tinospora cordifolia, Asparagus racemosus, Ocimum tenuiflorum, Areca catechu, and Lepidium meyenii, have been highly regarded sources that have the benefits of lowering PCOS as well as having hypoglycemic and antiobesity effects. In light of existing literature, women with PCOS experienced symptomatic relief, improvement in hormonal balance, and the quality of life by utilizing yoga practices as well as herbal remedies. In conclusion, combining lifestyle modifications with herbal remedies can be used in the management of PCOS as a holistic approach. Therefore, this review opens a new window for researchers all across the world to validate such findings.
Fulminant Neonatal Liver Failure in MPV 17-Related Mitochondrial DNA Depletion Syndrome
Authors: Abduljalil Razan , Ben Turkia Hadhami , Fakhroo Aysha , Skrypnyk Cristina
Published: June 2023

Mitochondrial depletion syndromes are well established causes of liver failure in infants. Hepatocerebral variant related to MPV17 gene defect is characterized by infantile onset of progressive liver failure, developmental delay, neurological manifestations, lactic acidosis, hypoglycemia, and mtDNA depletion in liver tissue. We report a hepatocerebral variant of mitochondrial DNA depletion syndrome in a neonate who presented with septic shock picture, hypoglycemia, jaundice, hypotonia, and rotatory nystagmus. Family history was significant for consanguinity and a brother who died at the age of 4 months. Investigations showed mild liver function derangement contrasting with severe coagulopathy, hyperlactatemia, and generalized aminoaciduria. The brain MRI was normal. Next generation sequencing (NGS) panel identified a MPV17 gene missense homozygous pathogenic variant. The infant expired at the age of 2 weeks with refractory ascites. This case illustrates a challenging diagnosis causing liver failure and death in neonatal period. Genetic testing of mitochondrial DNA depletion syndromes should be a part of liver failure workup in addition to other treatable disorders presenting with encephalo-hepatopathy in infancy.
Microdrilling Studies PLA/Bronze Composite Samples Printed Using Fused Deposition Model
Authors: Sneha P. , Balamurugan K. , Jyothi Y. , Krishnan Santhosh
Published: June 2023

Fused deposition models (FDMs) are the latest trends for constructing complicated and instinctive 3D printing. Polylactic acid (PLA) is the most widely used raw material in extrusion-based three-dimensional (3D) printing in many areas since it is biodegradable and environmentally friendly; however, its utilization is limited due to some of its disadvantages such as mechanical weakness and water solubility rate. To increase the mechanical properties of the FDM, nano bronze particles have been added as advanced research. Printing the hole less than a millimetre is complicated, and there is a limited report available in FDM. In this paper, polylactic acid (PLA) with a 14% bronze composite filament is made by hot extruding under the desired FDM conditions. The samples are built with 100% infilled density with 45° orientation to a sample size of 50 × 50 × 10 mm. To examine the printing state and the effect of microdrilling on the printed specimen, two different specimens are printed with and without holes. An industrial drill with specified feed, speed, and cutting width is used to perform the test. The size of the drilled hole is checked by scanning electron microscopy. The quality of the drilled hole and the wear of the tool is investigated and reported. According to the observation, it is noted that the secondary machining operation becomes unavoidable to have a hole of less than a millimetre. Machining, cutting speed, and feed speed influence the delamination zone and the circumference of the hole.
The Prognostic Effect of Immune Cell Infiltration Depends on Molecular Subtype in Endometrioid Ovarian Carcinomas
Authors: Heinze Karolin , Cairns Evan S. , Thornton Shelby , Harris Bronwyn , Milne Katy , Grube Marcel , Meyer Charlotte , Karnezis Anthony N. , Fereday Sian , Garsed Dale W. , Leung Samuel C.Y. , Chiu Derek S. , Moubarak Malak , Harter Philipp , Heitz Florian , McAlpine Jessica N. , DeFazio Anna , Bowtell David D.L. , Goode Ellen L. , Pike Malcolm , Ramus Susan J. , Pearce C. Leigh , Staebler Annette , Köbel Martin , Kommoss Stefan , Talhouk Aline , Nelson Brad H. , Anglesio Michael S.
Published: June 2023

Purpose:

Endometrioid ovarian carcinoma (ENOC) is the second most-common type of ovarian carcinoma, comprising 10%–20% of cases. Recently, the study of ENOC has benefitted from comparisons to endometrial carcinomas including defining ENOC with four prognostic molecular subtypes. Each subtype suggests differential mechanisms of progression, although tumor-initiating events remain elusive. There is evidence that the ovarian microenvironment may be critical to early lesion establishment and progression. However, while immune infiltrates have been well studied in high-grade serous ovarian carcinoma, studies in ENOC are limited.

Experimental Design:

We report on 210 ENOC, with clinical follow-up and molecular subtype annotation. Using multiplex IHC and immunofluorescence, we examine the prevalence of T-cell lineage, B-cell lineage, macrophages, and populations with programmed cell death protein 1 or programmed death-ligand 1 across subtypes of ENOC.

Results:

Immune cell infiltrates in tumor epithelium and stroma showed higher densities in ENOC subtypes with known high mutation burden (POLEmut and MMRd). While molecular subtypes were prognostically significant, immune infiltrates were not (overall survival P > 0.2). Analysis by molecular subtype revealed that immune cell density was prognostically significant in only the no specific molecular profile (NSMP) subtype, where immune infiltrates lacking B cells (TILB minus) had inferior outcome (disease-specific survival: HR, 4.0; 95% confidence interval, 1.1–14.7; P < 0.05). Similar to endometrial carcinomas, molecular subtype stratification was generally superior to immune response in predicting outcomes.

Conclusions:

Subtype stratification is critical for better understanding of ENOC, in particular the distribution and prognostic significance of immune cell infiltrates. The role of B cells in the immune response within NSMP tumors warrants further study.
TABLE 2 from Maternal Embryonic Leucine Zipper Kinase is Associated with Metastasis in Triple-negative Breast Cancer
Authors: Xie Xuemei , Chauhan Gaurav B. , Edupuganti Ramakrishna , Kogawa Takahiro , Park Jihyun , Tacam Moises , Tan Alex W. , Mughees Mohd , Vidhu Fnu , Liu Diane D. , Taliaferro Juliana M. , Pitner Mary Kathryn , Browning Luke S. , Lee Ju-Hyeon , Shen Yu , Wang Jian , Ueno Naoto T. , Krishnamurthy Savitri , Hortobagyi Gabriel N. , Tripathy Debu , Van Laere Steven J. , Bartholomeusz Geoffrey , Dalby Kevin N. , Bartholomeusz Chandra
Published: June 2023

Univariate Cox regression model for OS, PFS, and DMFS among patients with breast cancer (World IBC Consortium dataset; n = 314)
TABLE 1 from Maternal Embryonic Leucine Zipper Kinase is Associated with Metastasis in Triple-negative Breast Cancer
Authors: Xie Xuemei , Chauhan Gaurav B. , Edupuganti Ramakrishna , Kogawa Takahiro , Park Jihyun , Tacam Moises , Tan Alex W. , Mughees Mohd , Vidhu Fnu , Liu Diane D. , Taliaferro Juliana M. , Pitner Mary Kathryn , Browning Luke S. , Lee Ju-Hyeon , Shen Yu , Wang Jian , Ueno Naoto T. , Krishnamurthy Savitri , Hortobagyi Gabriel N. , Tripathy Debu , Van Laere Steven J. , Bartholomeusz Geoffrey , Dalby Kevin N. , Bartholomeusz Chandra
Published: June 2023

Clinicopathologic characteristics of patients in the World IBC Consortium dataset whose data were used for our analysis (n = 314)
Supplementary Figure S4 from Maternal Embryonic Leucine Zipper Kinase is Associated with Metastasis in Triple-negative Breast Cancer
Authors: Xie Xuemei , Chauhan Gaurav B. , Edupuganti Ramakrishna , Kogawa Takahiro , Park Jihyun , Tacam Moises , Tan Alex W. , Mughees Mohd , Vidhu Fnu , Liu Diane D. , Taliaferro Juliana M. , Pitner Mary Kathryn , Browning Luke S. , Lee Ju-Hyeon , Shen Yu , Wang Jian , Ueno Naoto T. , Krishnamurthy Savitri , Hortobagyi Gabriel N. , Tripathy Debu , Van Laere Steven J. , Bartholomeusz Geoffrey , Dalby Kevin N. , Bartholomeusz Chandra
Published: June 2023

Supplementary Figure S4. Graphical representation of the physical protein-protein interaction network involved in modulating MELK activity in MDA-MB-231 cells.
Supplementary Figure S2 from Maternal Embryonic Leucine Zipper Kinase is Associated with Metastasis in Triple-negative Breast Cancer
Authors: Xie Xuemei , Chauhan Gaurav B. , Edupuganti Ramakrishna , Kogawa Takahiro , Park Jihyun , Tacam Moises , Tan Alex W. , Mughees Mohd , Vidhu Fnu , Liu Diane D. , Taliaferro Juliana M. , Pitner Mary Kathryn , Browning Luke S. , Lee Ju-Hyeon , Bertucci François , Shen Yu , Wang Jian , Ueno Naoto T. , Krishnamurthy Savitri , Hortobagyi Gabriel N. , Tripathy Debu , Van Laere Steven J. , Bartholomeusz Geoffrey , Dalby Kevin N. , Bartholomeusz Chandra
Published: June 2023

Supplementary Figure S2. Volcano plots show differences in gene expression in parental and Cas9-p15 control or MELK knockout (KO) MDA-MB-231 cells.
FIGURE 3 from Targeting Fatty Acid Reprogramming Suppresses CARM1-expressing Ovarian Cancer
Authors: Lombardi Simona , Goldman Aaron R. , Tang Hsin-Yao , Kossenkov Andrew V. , Liu Heng , Zhou Wei , Herlyn Meenhard , Lin Jianhuang , Zhang Rugang
Published: June 2023

CARM1 promotes MUFA synthesis. A, Volcano plot illustrating the changes of metabolite levels in wildtype or CARM1 KO A1847 cells detected by LC/MS. Red dots and green dots indicate metabolites significantly upregulated or downregulated in wildtype compared with knockout cells, respectively. Free oleic acid, palmitoleic acid, palmitic acid, and stearic acid were highlighted in blue. P value was calculated using a two-tailed Student t test. B, The level of free oleic acid (18:1), palmitoleic acid (16:1), stearic acid (18:0), and palmitic acid (16:0) as shown in A. C, Changes in total FA profiling for control treated vehicle or SCD1 inhibitor 5 μmol/L CAY10566 for 48 hours, or CARM1 KO A1847 cells. D, The ratio between total oleic acid (18:1) and stearic acid (18:0) in different lipid species determined by lipid profiling in wildtype and CARM1 KO A1847 cells. PC: Phosphatidylcholine; PE: phosphatidylethanolamine; PI: Phosphatidylinositol; PS: Phosphatidylserine; PG: Phosphatidylglycerol; LPC: Lysophosphatidylcholine; PA: Phosphatidic acid; LPE: lysophosphatidylethanolamine; LPS: Lysophosphastidylserine; LPI: Lysophosphatidylinositol; LPA: Lysophosphatidic acid; DG: Diglyceride; ChE: cholesterol ester; and TG:Triglyceride. P value was calculated using a two-tailed Student t test. Data represent mean ± SEM, n = 3 biologically independent experiments unless otherwise stated.
FIGURE 3 from Maternal Embryonic Leucine Zipper Kinase is Associated with Metastasis in Triple-negative Breast Cancer
Authors: Xie Xuemei , Chauhan Gaurav B. , Edupuganti Ramakrishna , Kogawa Takahiro , Park Jihyun , Tacam Moises , Tan Alex W. , Mughees Mohd , Vidhu Fnu , Liu Diane D. , Taliaferro Juliana M. , Pitner Mary Kathryn , Browning Luke S. , Lee Ju-Hyeon , Bertucci François , Shen Yu , Wang Jian , Ueno Naoto T. , Krishnamurthy Savitri , Hortobagyi Gabriel N. , Tripathy Debu , Van Laere Steven J. , Bartholomeusz Geoffrey , Dalby Kevin N. , Bartholomeusz Chandra
Published: June 2023

Inhibitory effect of MELK-In-17 on anchorage-independent growth, motility, CSC properties, and EMT transition in TNBC cells. A–D, MELK-In-17 inhibited anchorage-independent growth (A), suppressed migration and invasion (B), reduced mammosphere formation (C), and reduced CD44+/CD24− and ALDH1+ CSC subpopulations (D) in TNBC cells. In A, the anchorage-independent growth was determined using a soft-agar assay at week 3 following treatment. In B, cells were pretreated with MELK-In-17 for 2 hours and then assayed for migration and invasion in the presence of MELK-In-17. In C, cells were seeded for mammosphere formation and the next day treated with MELK-In-17. In D, cells were treated with MELK-In-17 for 48 hours and then subjected to flow cytometry analysis. E, Western blot analysis of the effects of treatment with MELK-In-17 on the expression of EMT markers. α-Tubulin was used as a loading control. Band intensity of proteins is normalized to that of α-Tubulin. In A–C, data are presented as mean ± SD. *, P < 0.05; **, P < 0.01; ***, P < 0.001; ****, P < 0.0001.
FIGURE 2 from Maternal Embryonic Leucine Zipper Kinase is Associated with Metastasis in Triple-negative Breast Cancer
Authors: Xie Xuemei , Chauhan Gaurav B. , Edupuganti Ramakrishna , Kogawa Takahiro , Park Jihyun , Tacam Moises , Tan Alex W. , Mughees Mohd , Vidhu Fnu , Liu Diane D. , Taliaferro Juliana M. , Pitner Mary Kathryn , Browning Luke S. , Lee Ju-Hyeon , Bertucci François , Shen Yu , Wang Jian , Ueno Naoto T. , Krishnamurthy Savitri , Hortobagyi Gabriel N. , Tripathy Debu , Van Laere Steven J. , Bartholomeusz Geoffrey , Dalby Kevin N. , Bartholomeusz Chandra
Published: June 2023

Effect of MELK knockdown or overexpression on proliferation, motility, EMT, and CSC properties in TNBC cells. Effect of MELK knockdown or KO (A) or overexpression (B) on proliferation and anchorage-independent growth of TNBC cells. HCC70 and BT-549 cells (A, bottom left) were treated with two different siMELK sequences for 48 hours. MELK expression was then determined using Western blot analysis (top), and cell viability was determined using trypan blue exclusion assay (bottom left). In MELK KO MDA-MB-231 cells (A, bottom right), anchorage-independent growth was determined using soft-agar assay at week 3 following incubation. β-Actin was used as a loading control for Western blot analysis. SUM149 and SUM159 cells (B) were transfected with plasmids encoding WT MELK gene or KD MELK gene and cultured for 48 hours. MELK expression was then determined using Western blot analysis (top), and cell growth was determined using anchorage-independent growth assay (bottom). β-Actin was used as a loading control for Western blot analysis. Effect of MELK knockdown (C) or overexpression (D) on migration and invasion of TNBC cells. Cells were transfected with two different siMELK sequences for 72 hours or plasmids encoding WT MELK gene or KD MELK gene for 48 hours and then assayed for migration and invasion. E, Effect of MELK knockdown on expression of EMT epithelial and mesenchymal markers in TNBC cells. Cells were treated with two different siMELK sequences for 48 hours, and then MELK expression was determined using Western blot analysis. α-Tubulin was used as a loading control. Effect of knockdown or KO (F) or overexpression (G) of MELK on mammosphere formation in TNBC cells. Cells were transfected with two different siMELK sequences or plasmids encoding WT MELK gene or KD MELK gene and 48 hours later were seeded for mammosphere formation. MELK KO clones were cultured for 7 days and then analyzed for mammosphere formation. H, Effect of MELK knockdown on CD44+/CD24− and ALDH1+ subpopulations in TNBC cells. Cells were treated with two different siMELK sequences and 48 hours later subjected to flow cytometry analysis. In A and F, P15 indicates Cas9-p15 control cells; C3, MELK KO C3 clones; and C28, MELK KO C28 clones. In A–D, G, and F, data are presented as mean ± standard deviation. *, P < 0.05; **, P < 0.01; ***, P < 0.001; ****, P < 0.0001.
FIGURE 1 from Maternal Embryonic Leucine Zipper Kinase is Associated with Metastasis in Triple-negative Breast Cancer
Authors: Xie Xuemei , Chauhan Gaurav B. , Edupuganti Ramakrishna , Kogawa Takahiro , Park Jihyun , Tacam Moises , Tan Alex W. , Mughees Mohd , Vidhu Fnu , Liu Diane D. , Taliaferro Juliana M. , Pitner Mary Kathryn , Browning Luke S. , Lee Ju-Hyeon , Shen Yu , Wang Jian , Ueno Naoto T. , Krishnamurthy Savitri , Hortobagyi Gabriel N. , Tripathy Debu , Van Laere Steven J. , Bartholomeusz Geoffrey , Dalby Kevin N. , Bartholomeusz Chandra
Published: June 2023

Clinical relevance of MELK in breast cancer and expression of MELK in breast cancer cell lines. A,MELK mRNA levels in HR−HER2+, HR+HER2−, HR+HER2+, and TNBC tumors in the World Consortium IBC dataset, analyzed by multiple comparison using a general linear model. Data are presented as mean ± SD. – represents median, X represents mean. B, IHC images (200× magnification) showing MELK protein expression in normal epithelial tissue and luminal, HER2+, and TNBC breast tumors. Correlation between MELK mRNA levels (<7 or ≥7) and OS, PFS, and DMFS in patients in the overall cohort (C) and among those with TNBC (D), determined by the Kaplan–Meier method. MELK mRNA levels (E) and protein levels (F) in TNBC and non-TNBC cells. Inset, correlation between MELK mRNA and protein levels in TNBC cell lines. In F, α-tubulin was used as a loading control. MELK mRNA levels were determined using quantitative reverse transcriptase PCR.
Data from Targeting Fatty Acid Reprogramming Suppresses CARM1-expressing Ovarian Cancer
Authors: Lombardi Simona , Goldman Aaron R. , Tang Hsin-Yao , Kossenkov Andrew V. , Liu Heng , Zhou Wei , Herlyn Meenhard , Lin Jianhuang , Zhang Rugang
Published: June 2023

The arginine methyltransferase CARM1 exhibits high expression levels in several human cancers, with the trend also observed in ovarian cancer. However, therapeutic approaches targeting tumors that overexpress CARM1 have not been explored. Cancer cells exploit metabolic reprogramming such as fatty acids for their survival. Here we report that CARM1 promotes monounsaturated fatty acid synthesis and fatty acid reprogramming represents a metabolic vulnerability for CARM1-expressing ovarian cancer. CARM1 promotes the expression of genes encoding rate-limiting enzymes of de novo fatty acid metabolism such as acetyl-CoA carboxylase 1 (ACC1) and fatty acid synthase (FASN). In addition, CARM1 upregulates stearoyl-CoA desaturase 1 (SCD1) that produces monounsaturated fatty acid by desaturation. Thus, CARM1 enhances de novo fatty acids synthesis which was subsequently utilized for synthesis of monounsaturated fatty acids. Consequently, inhibition of SCD1 suppresses the growth of ovarian cancer cells in a CARM1 status–dependent manner, which was rescued by the addition of monounsaturated fatty acids. Consistently, CARM1-expressing cells were more tolerant to the addition of saturated fatty acids. Indeed, SCD1 inhibition demonstrated efficacy against ovarian cancer in both orthotopic xenograft and syngeneic mouse models in a CARM1-dependent manner. In summary, our data show that CARM1 reprograms fatty acid metabolism and targeting SCD1 through pharmacological inhibition can serve as a potent therapeutic approach for CARM1-expressing ovarian cancers.
Significance:
CARM1 reprograms fatty acid metabolism transcriptionally to support ovarian cancer growth by producing monounsaturated fatty acids, supporting SCD1 inhibition as a rational strategy for treating CARM1-expressing ovarian cancer.
Hysterectomy Using Vaginal Natural Orifice Transluminal Endoscopic Surgery Compared with Classic Laparoscopic Hysterectomy: A New Advantageous Approach? A Systematic Review on Surgical Outcomes
Authors: Chaccour Christian , Giannini Andrea , Golia D'Augè Tullio , Ayed Amal , Allahqoli Leila , Alkatout Ibrahim , Laganà Antonio Simone , Chiantera Vito , D'Oria Ottavia , Sleiman Zaki
Published: June 2023

Introduction: Minimally invasive surgery aims to reduce surgical trauma and post-operative morbidity. Natural orifice transluminal endoscopic surgery is a safe and valid surgical option for hysterectomy. The present systematic review aims to compare hysterectomy by transvaginal natural orifice transluminal endoscopic surgery (vNOTES) with laparoscopic hysterectomy in terms of efficacy, surgical outcomes, complications, and cost. Materials and Methods: This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. It includes randomized controlled trials, controlled clinical trials, prospective or retrospective cohorts, case-control studies, and previous systematic reviews. Inclusion criteria are as follows: female patients undergoing hysterectomy for benign pathologies by vNOTES or laparoscopic hysterectomy. The assessed outcomes were the following: conversion rate, mean uterus weight (g), operative time (mins), hospital stay (days), peri-operative complications, post-operative complications, peri-operative blood loss (mL), blood transfusion needs, post-operative day 1 hemoglobin (Hb) change (g/dL), post-operative pain level (VAS), and cost (USD) in both techniques. Results: Seven studies were included. vNOTES hysterectomy was not inferior to laparoscopic hysterectomy regarding surgical outcomes, with a shorter operative time, shorter recovery time, less post-operative pain, and fewer post-operative complications. There was no significant difference in the rate of peri-operative complications and no differences in peri-operative blood loss, post-operative day 1 Hb change, and transfusions. Nevertheless, vNOTES hysterectomy was shown to be more expensive than its laparoscopic counterpart. Conclusions: While the feasibility and safety of the vNOTES hysterectomy were already established, this review also underlines the noninferiority of this technique when compared to laparoscopic hysterectomy in terms of surgical outcomes. In addition, vNOTES hysterectomy was associated with faster operating time, shorter hospital stay, and better post-operative pain scores compared with laparoscopic hysterectomy.
Deferred Versus Performed Revascularization for Left Main Coronary Disease With Hemodynamic Significance
Authors: Warisawa Takayuki , Cook Christopher M. , Ahmad Yousif , Howard James P. , Seligman Henry , Rajkumar Christopher , Toya Takumi , Doi Shunichi , Nakajima Akihiro , Nakayama Masafumi , Vera-Urquiza Rafael , Yuasa Sonoka , Sato Takao , Kikuta Yuetsu , Kawase Yoshiaki , Nishina Hidetaka , Al-Lamee Rasha , Sen Sayan , Lerman Amir , Matsuo Hitoshi , Akashi Yoshihiro J. , Escaned Javier , Davies Justin E.
Published: June 2023

Background:

The majority of randomized controlled trials of revascularization decision-making excludes left main coronary artery disease (LMD). Therefore, contemporary clinical outcomes of patients with stable coronary artery disease and LMD with proven ischemia remain poorly understood. The aim of this study was to assess the long-term clinical outcomes of physiologically significant LMD according to the treatment strategies of revascularization versus revascularization deferral.

Methods:

In this international multicenter registry of stable LMD interrogated with the instantaneous wave-free ratio, patients with physiologically significant ischemia (instantaneous wave-free ratio ≤0.89) were analyzed according to the coronary revascularization (n=151) versus revascularization deferral (n=74). Propensity score matching was performed to adjust for baseline clinical characteristics. The primary end point was a composite of death, nonfatal myocardial infarction, and ischemia-driven target lesion revascularization of left main stem. The secondary end points were as follows: cardiac death or spontaneous LMD-related myocardial infarction; and ischemia-driven target lesion revascularization of left main stem.

Results:

At a median follow-up period of 2.8 years, the primary end point occurred in 11 patients (14.9%) in the revascularized group and 21 patients (28.4%) in the deferred group (hazard ratio, 0.42 [95% CI, 0.20–0.89];
P
=0.023). For the secondary end points, cardiac death or LMD-related myocardial infarction occurred significantly less frequently in the revascularized group (0.0% versus 8.1%;
P
=0.004). The rate of ischemia-driven target lesion revascularization of left main stem was also significantly lower in the revascularized group (5.4% versus 17.6%; hazard ratio, 0.20 [95% CI, 0.056–0.70];
P
=0.012).

Conclusions:

In patients who underwent revascularization for stable coronary artery disease and physiologically significant LMD determined by instantaneous wave-free ratio, the long-term clinical outcomes were significantly improved as compared with those in whom revascularization was deferred.
Reperfusion Delays and Outcomes Among Patients With ST-Segment–Elevation Myocardial Infarction With and Without Cardiogenic Shock
Authors: Kochan Andrew , Lee Terry , Moghaddam Nima , Milley Grace , Singer Joel , Cairns John A. , Wong Graham C. , Jentzer Jacob C. , van Diepen Sean , Alviar Carlos , Fordyce Christopher B.
Published: June 2023

Background:

Mortality remains high in patients with ST-segment–elevation myocardial infarction (STEMI) complicated by cardiogenic shock (CS), and early reperfusion has been shown to improve outcomes. We analyzed the association between first medical contact (FMC)-to-percutaneous coronary angiography time with mortality and major adverse cardiovascular events among patients with STEMI with and without CS.

Methods:

We performed a retrospective analysis of the Vancouver Coastal Health Authority STEMI registry, including all patients with STEMI who received primary percutaneous coronary angiography between January 1, 2010, and December 31, 2020, and stratified them by presence or absence of CS at hospital arrival. The primary outcome was in-hospital mortality, the secondary outcome was in-hospital major adverse cardiovascular events, defined as a composite of the first occurrence of mortality, cardiac arrest, heart failure, intracerebral hemorrhage, cerebrovascular accident, or reinfarction. Mixed effects logistic regression with restricted cubic splines was used to estimate the relationships between FMC-to-device time and the outcomes in the CS and non-CS groups.

Results:

2929 patients were included, 9.4% (n=275) had CS. Median FMC-to-device time was 113.5 (interquartile range, 93.0–145.0) and 103.0 (interquartile range, 85.0–130.0) minutes for patients with CS and without CS, respectively. More patients with CS had FMC-to-device times above guideline recommendations (76.6% versus 54.1%,
P
<0.001). Between 60 and 90 minutes, for each 10-minute increase in FMC-to-device time, absolute mortality for patients with CS increased by 4% to 7%, whereas for patients without CS, it increased by <0.5%.

Conclusions:

Among patients with STEMI undergoing primary percutaneous coronary angiography, reperfusion delays among patients with CS are associated with significantly worse outcomes. Strategies to reduce FMC-to-device times for patients with STEMI presenting with CS are required.
‘Abstract Labour and Socialism’: An Introduction
Authors: Salour Sam
Published: June 2023

The article aims to introduce the works of eminent Iranian Marxist theoretician, Kamal Khosravi, to Western readers. Over the past few decades, Khosravi has written extensively on Marx, Marxism, and Marxist methodology. Through translations and his own writings, he has worked tirelessly to introduce Iranian readers to the rich debates on Marxist methodology and value theory that have developed in the West since the 1960s. More recently, as the lead editor of the Iranian journal Critique, his writings are having an influence on the ongoing social movements as they are being disseminated and discussed amongst activists and labour leaders. In this article, we situate his writings within the developments of Iranian and Western Marxism.
Review of Trigona (Nostotrigona) Engel, 2021 from Brazil with description of three new species (Hymenoptera: Apidae: Meliponini)
Authors: RIBEIRO CRISTIANO FEITOSA , NOGUEIRA DAVID SILVA , OLIVEIRA FAVÍZIA FREITAS DE , OLIVEIRA MARCIO LUIZ DE
Published: June 2023

Trigona Jurine, 1807 (Hymenoptera: Apidae: Meliponini) is a Neotropical genus of stingless bees that is most diverse in the Amazon biome. The subgenus T. (Nostotrigona) was recently described and contains the taxa of the T. recursa species-group. In the present study, three new species of this subgenus are described: T. daianeae sp. nov., T. juvenili sp. nov., and T. mandaloriana sp. nov., including new records of T. permodica Almeida, 1992 for Brazil. A distribution map for T. (Nostotrigona) species are also provided.
The Role of ATG4A Clinical Implication and Potential Function in Breast Cancer
Authors: Lv Peng , Lai Lin , Zhang Zhenzhu , He Xiaoyu , Zhang Yukun , He Du , Shi Fengqin
Published: June 2023

We studied the clinical implication and potential function of ATG4A in breast cancer by using publicly accessible patient data. The mRNA and protein levels of ATG4A were up-regulated in breast cancer tissues compared with normal breast tissues. ATG4A is a potential marker for prognosis,
diagnosis and therapeutic target for breast cancer. Autophagy is a conservative catabolic process for cell homeostasis. The mechanism of autophagy in tumors is very complicated, since it can either promote or inhibit the occurrence and development of tumor according to different tumor stages
and types. The purpose of this study was to investigate the clinical significance of an autophagy-related gene ATG4A in breast cancer. Transcriptional expression profiles of ATG4A between breast cancer tissues and normal tissues were retrieved from the Cancer Genome Atlas (TCGA). The ATG4A
protein level was assessed by the Human Protein Atlas. The co-expression genes with ATG4A expression were analyzed using the LinkedOmics database. Protein–protein interaction (PPI) networks were constructed by the STRING. Paired t-test and Mann-Whitney U-test were used
to determine the differences between breast cancer tissues and adjacent normal tissues. Kaplan–Meier curves and log rank tests were conducted for survival analysis. The expression of ATG4A in breast cancer tissues was significantly upregulated than those in adjacent normal tissues. Increased
ATG4A mRNA expression was positively associated with lymph node metastases (P <0.05), ER positive (P <0.001), PR positive (P <0.001), HER-2 positive (P <0.05) and over 60 years of age (P <0.005). Compared with breast cancer patients with LumA,
LumB and HER-2 positive subtypes, the expression of ATG4A mRNA in breast cancer patients with Basal was significantly lower (P <0.001). Kaplan–Meier survival analysis showed that the OS (P <0.001), DSS (P = 0.017) and PFI (P = 0.020) of breast cancer
patients with high ATG4A mRNA expression were significantly shorter than those with low ATG4A mRNA expression. GO and KEGG analysis showed that Endocytosis might be a signal pathway involved in the occurrence and development of breast cancer by ATG4A. Furthermore, we found that RPL4, RPL11,
RPL14, RPL29 and RPS9 may be the potential interacting genes of ATG4A in breast cancer by PPI analysis. ATG4A may be a potential diagnostic, prognostic biomarker and therapeutic target gene for breast cancer at the mRNA and protein levels.
Gun Culture 2.0: The Evolution and Contours of Defensive Gun Ownership in America
Authors: Yamane David
Published: June 2023

I trace the evolution of gun culture in the U.S., starting with the prehistorical normality and significance of projectile weaponry among Homo sapiens, then turning to the largely practical use of firearms as tools in the Colonial, Revolutionary, and Early Republic eras (ca. 1607–1850). I highlight the emergence of Gun Culture 1.0, which centered on sport hunting, recreation, and collecting and was the core of American gun culture from approximately 1850 to 2010. I then show the roots of Gun Culture 2.0, which began in the 1960s and 1970s and centered on self-defense. I use various indicators to document that, by 2010, armed self-defense had become the core of American gun culture. In the penultimate section of the article, I use the great gun-buying spree of 2020+ to show the diversity that exists within Gun Culture 2.0, a theme that carries over to the conclusion, where I consider possible future directions of gun culture.
Mass Shootings in the United States: Prevalence, Policy, and a Way Forward
Authors: Schildkraut Jaclyn , Geller Lisa B.
Published: June 2023

Mass shootings in the U.S. elicit strong reactions and often are followed by demands for preventive or ameliorative policy action. Often, however, little change is made to policy, and the cycle of tragedy and passionate discourse is left to start anew. We assess the efficacy of a range of specific policies that may help to prevent mass shootings or mitigate their harms: we review empirical evidence on their effectiveness and consider arguments that both proponents and opponents of these policies bring to bear on the public discourse. We conclude that extant evidence and policy ideas that are on the table now can, in fact, point to a productive way forward: we argue for a proactive, layered approach to policy implementation that minimizes risks and impacts and capitalizes on effective interventions that enjoy broad public support.
Effectiveness of Firearm Restriction, Background Checks, and Licensing Laws in Reducing Gun Violence
Authors: Zeoli April M. , Mccourt Alexander D. , Paruk Jennifer K.
Published: June 2023

We present the rationale behind four types of laws that restrict access to firearms for those who are deemed to be a high risk for future gun violence and two types of laws that implement firearm purchase prohibitions. We also present evidence on the effectiveness of these laws. Broadly, these are laws that restrict access for domestic violence abusers, individuals convicted of misdemeanor violence, and individuals at high risk of violence against themselves or others. We briefly discuss relinquishment of firearms by those who are newly restricted, but we focus mainly on how purchase restrictions are implemented by the federal government and across states. Extant research shows that well-implemented firearm policy that is based on evidence-based risk factors can be effective in reducing firearm injury.
Understanding Risk and Implementing Data-Driven Solutions for Firearm Suicide
Authors: Anestis Michael D. , Bond Allison E. , Bandel Shelby L.
Published: June 2023

Each year, firearms account for half of all the suicide deaths in the U.S. Research has shown that, worldwide, the most effective way to prevent suicide is so-called means safety: making the tools and methods of suicide less accessible and less lethal. In the U.S., research has shown, time and again, that access to firearms increases the risk for suicide death, particularly when firearms are not stored safely. Means safety, therefore, could be a powerful tool in reducing suicide deaths in America, where firearms are highly lethal, widely available, and frequently used within a specific geographic area. For this nation to sustainably lower its suicide rate, the issue of access to firearms is pivotal. We argue for a public health approach to suicide prevention: one that would improve data linkage; promote the effective upstream use of interventions like lethal means counseling and safe firearm storage messaging; and deploy more systematic efforts to identify and understand subcommunities of firearm owners, including those who obtained their firearms illegally.
Research on the Effects of Hospital-Based Violence Intervention Programs: Observations and Recommendations
Authors: Webster Daniel W. , Richardson Joseph , Meyerson Nicholas , Vil Christopher , Topazian Rachel
Published: June 2023

We conducted a review of studies on the effects of hospital-based violence intervention programs (HVIPs) on subsequent involvement in violence as a victim or perpetrator that included a nontreated control group. We identified seven randomized controlled trials (RCTs) and six observational studies. Most HVIPs evaluated relied principally on credible messengers to engage potential participants and intensive case management to provide social services. Evidence of linkage of HVIPs to community violence intervention programs was lacking. RCTs of the most robust HVIPs showed some evidence of protective effects, but overall evidence of reduced risks for violence was mixed. RCTs were underpowered, and all but one were vulnerable to selection bias. Stronger interventions and research methods are needed to advance our understanding of the potential for HVIPs to reduce risks for future violence.
Gun Violence and Gun Policy in the United States: Understanding American Exceptionalism
Authors: Raissian Kerri M. , Necci dineen Jennifer , Crifasi Cassandra
Published: June 2023

America has both the highest gun death rate (12 per 100,000 persons) and the highest gun circulation rate (about 121 firearms in circulation for every 100 persons) of any developed country. Taken together, these statistics might lead one to assume that high gun death rates in America are all but a certain outcome. However, gun death rates vary substantially across America suggesting that a range of solutions to reduce gun death and injury exist. This transdisciplinary volume contains a novel collection of articles that overview the evolution of American gun policy, presents evidence on the efficacy of both policy and non-policy interventions, and provides insight on where we go from here given American culture, norms, and legal structures.
Transnational comparison of the impact of COVID-19 on medicolegal death investigations and the administration of justice: Early stages of the pandemic
Authors: Lam Vienna C , King Steff , Fabian Sheryl C , Anderson Gail S
Published: June 2023

COVID-19 has had an unprecedented impact on arguably every sector of our criminal justice system. To assess the impact that this global health crisis has had on our medicolegal investigations and administration of justice during the early stages of the pandemic, this research aims to give voice to the lived experiences of medicolegal death investigators (coroners, medical examiners and pathologists). This research involved in-depth interviews and follow-ups with experienced personnel from Canada (3), Italy (1), the United Kingdom (1) and the United States (4). Results suggest that despite facing similar challenges, each individual office has had to develop their own strategies to overcome obstacles during the early stages of the pandemic. These results help identify overlapping areas for constructive policy and procedural changes, including recommendations for workflow adaptations, strategic partnerships and other approaches to best prepare for subsequent health crises.
Political uncertainty and high-quality economic development: Evidence from China
Authors: Li Xing , Zhao Chunkai , Chen Boou , Liu Zimin
Published: June 2023

We manually collated data on the turnover of party secretaries and mayors in 285 Chinese cities from 2003 to 2016 and calculated the quality of city economic development represented by environmental total factor productivity growth. We find that the political uncertainty caused by official turnover could significantly promote the improvement of the quality of economic development, and this positive can explained by the progress of production technology and government intervention. Moreover, the political uncertainty caused by the turnover of more educated officials, those with local hukou, promoted officials, and experienced officials could better promote high-quality economic development.
Cowpea isoflavones enhance the osteoblast differentiation and antioxidant capacity in synergy with vitamin D and β-carotene: A mechanistic in vitro study
Authors: Venna Naresh Kumar , Lalhruaitluanga Hauhnar , Challa Suresh
Published: June 2023

Background: Osteoporosis (OS) is a pathological condition that makes bones susceptible to fractures by affecting the balance between bone formation and resorption. Recent literature uncovered the possible potential of bioactive compounds with antioxidant mechanisms to counter the issue. Cowpea (CP) isoflavones based on our previous study, vitamin D and natural antioxidant β-carotene for its pleotropic protective effects were assessed alone and in combination. Aim: The study aims to assess the antioxidant and osteoblast differentiation abilities of cowpea isoflavones alone and in combination of vitamin D (VD) and β-carotene (BC) in the human osteosarcoma cell line Saos2. Methods: Saos2 cells were maintained in cell culture conditions and concentrations of CP extract (genistein  +  daidzein), BC and VD required to increase cell proliferation were estimated using MTT assay. Upon treating cells with the EC50 concentrations, lysates were prepared and levels of alkaline phosphatase (ALP) and osteocalcin were evaluated using ELISA. Oxidative stress parameters and osteoblast differentiation markers were evaluated. Results: CP extract (genistein  +  daidzein), BC and VD concentrations which enhanced the cell proliferation rate were determined and elevated levels of ALP and osteocalcin upon treatment was observed. Anti-oxidant stress parameters studied showed an increase in cells upon treatment compared to control. Significant alterations in levels of protein involved in osteoblast differentiation are observed upon treatment. Conclusion: Cowpea isoflavones has shown a significant activity against OS by elevating antioxidant parameters and inducing osteoblast differentiation in the present study.
Contemporary Ecumenical Missiology and the Renewal of Christian Theology
Authors: Ross Kenneth R.
Published: June 2023

There is a symbiotic relationship between mission and theology – they need each other. Just as the conception and practice of Christian mission have been renewed and refreshed through theological creativity, this article explores how Christian theology might be enriched by insights from contemporary ecumenical missiology. It makes particular reference to the World Council of Churches 2012 mission affirmation Together Towards Life: Mission and Evangelism in Changing Landscapes and the Arusha Call to Discipleship issued by the 2018 WCC World Mission Conference held at Arusha, Tanzania. Drawing on these seminal texts, the article considers what it means to do theology with life itself at stake, the question of agency in theology, and the role of spirituality, discipleship and transformation in the construction of theology. It concludes by turning to the question of education and formation, proposing that in today's context, theologians need to be formed as “organic intellectuals.”
Distant but close: Locational, relational and temporal proximity in cloud computing adoption
Authors: Polyviou Ariana , Venters Will , Pouloudi Nancy
Published: June 2023

We show that proximity is significant during cloud computing’s adoption. This is counter to the prevailing assumptions of cloud adoption as being more impersonal and distant, with less interaction between provider and purchaser than on-premise technologies. We do this through an interpretive study of cloud computing adopters across Europe. We develop a conceptual framework of cloud proximity which draws attention to its locational, relational and temporal proximal dimensions. Our proximal analysis leads us to identify three aspects of cloud adoption where proximity plays a key role: mercantile aspect (e.g., cloud sales support), counsel aspect (e.g., access to internal and external expertise) and organi-technical aspect (e.g., the understanding of cloud technology and services alongside their organizational adoption context). By challenging assumptions of distant and remote adoption, we contribute to the cloud computing adoption research and raise questions for IT adoption in general.