bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mortality and morbidity in scleroderma renal crisis: A systematic literature review
Authors: Kim Hyein , Lefebvre Frédéric , Hoa Sabrina , Hudson Marie 
Published: June 2020

Objectives: The objective of this study was to systematically review the mortality and morbidity associated with scleroderma renal crisis and to determine temporal trends. Methods: We searched MEDLINE, Embase and the Cochrane Database of Systematic Reviews from database inception to 10 February 2020. Bibliographies of selected articles were hand-searched for additional references. Data were extracted using a standardized extraction form. Study quality was assessed using the Newcastle–Ottawa scale. Results were analysed qualitatively. Results: Twenty studies with 14,059 systemic sclerosis subjects, of which 854 had scleroderma renal crisis and 4095 had systemic sclerosis–associated end-stage renal disease, met inclusion criteria. Study quality was generally moderate. Cumulative mortality in the post-angiotensin-converting enzyme inhibitor era was approximately 20% at 6 months, 30%–36% at 1 year, 19%–40% at 3 years and almost 50% at 10 years from scleroderma renal crisis onset. Although the introduction of angiotensin-converting enzyme inhibitors in the early 1970s resulted in a 50% improvement in scleroderma renal crisis mortality, there was no further improvement thereafter. Scleroderma renal crisis mortality rates were proportionally higher than mortality rates associated with other systemic sclerosis organ involvement. The rate of permanent dialysis after scleroderma renal crisis in the post-angiotensin-converting enzyme inhibitor era ranged from 19%–40%. Three to 17% of systemic sclerosis patients underwent renal transplant. Survival was better in patients post-renal transplant (54%–91%) compared to those on dialysis (31%–56%). Graft survival improved over time and appeared similar to that of patients with other types of end-stage renal disease. Conclusion: While there has been considerable improvement in scleroderma renal crisis–related outcomes since the introduction of angiotensin-converting enzyme inhibitors, morbidity and mortality remain high for affected patients without convincing evidence of further improvement in the post-angiotensin-converting enzyme inhibitor era. Novel treatments are required to improve outcomes of scleroderma renal crisis.
Mn porphyrins as a novel treatment targeting sickle cell NOXs to reverse and prevent acute vaso-occlusion in vivo
Authors: Thamilarasan Madhan , Estupinan Rodolfo , Batinic-Haberle Ines , Zennadi Rahima 
Published: June 2020

Abstract
In sickle cell disease (SCD), adhesion of sickle red blood cells (SSRBCs) and activated leukocytes in inflamed venules affects blood rheology, causing vaso-occlusive manifestations and vital reduction in microvascular blood flow. Recently, we found that NADPH oxidases (NOXs) create a vicious feedback loop within SSRBCs. This positive feedback loop mediates SSRBC adhesion to the endothelium. We show for the first time the therapeutic effectiveness of the redox-active manganese (Mn) porphyrins MnTnBuOE-2-PyP5+ (MnBuOE; BMX-001) and MnTE-2-PyP5+ (MnE; BMX-010, AEOL10113) to treat established vaso-occlusion in a humanized sickle mouse model of an acute vaso-occlusive crisis using intravital microscopy. These Mn porphyrins can suppress SSRBC NOX activity. Subcutaneous administration of only 1 dose of MnBuOE or MnE at 0.1 to 2 mg/kg after the inflammatory trigger of vaso-occlusion, or simultaneously, reversed and reduced leukocyte and SSRBC adhesion, diminished leukocyte rolling, restored blood flow, and increased survival rate. Furthermore, MnBuOE and MnE administered to sickle mice subcutaneously at 0.1 to 1 mg/kg for 28 days (except on weekends) did not exacerbate anemia, which seemed to be due to downregulation of both SSRBC reactive oxygen species production and exposure of the eryptotic marker phosphatidylserine. In addition, Mn porphyrins ameliorated leukocytosis, venous blood gases, endothelial activation, and organ oxidative damage. Our data suggest that Mn porphyrins, likely by repressing NOX-mediated adhesive function of SSRBCs and activated leukocytes, could represent a novel, safe therapeutic intervention to treat or prevent the establishment of acute pain crises. These NOX-targeted antioxidants merit further assessment in SCD clinical trials.
Genistein and exercise modulated lipid peroxidation and improved steatohepatitis in ovariectomized rats
Authors: Witayavanitkul Namthip , Werawatganon Duangporn , Chayanupatkul Maneerat , Klaikeaw Naruemon , Sanguanrungsirikul Sompol , Siriviriyakul Prasong 
Published: June 2020

Abstract
Background
The prevalence of nonalcoholic steatohepatitis (NASH) in menopausal women is increasing, but current treatments have not been proven effective. The objective of this study was to investigate the treatment effects of genistein and running exercise in ovariectomized (OVX) rats with NASH.

Methods
Thirty-six female Sprague-Dawley rats were divided into 6 groups, control; OVX with standard diet; OVX with high fat and high fructose (HFHF) diet for 4 weeks; OVX with HFHF and genistein treatment (16 mg/kg BW/day) for 5 weeks (OVX + HFHF+GEN); OVX with HFHF and moderate intensity exercise for 5 weeks (OVX + HFHF+EX); OVX with HFHF and combined treatments (OVX + HFHF+GEN + EX). Serum interleukin-6 (IL-6) levels, hepatic free fatty acid (FFA), hepatic glutathione (GSH), and hepatic malondialdehyde (MDA) levels were measured. Liver histology was examined to determine NASH severity.

Results
OVX + HFHF group had the highest levels of hepatic FFA compared with OVX and control groups (5.92 ± 0.84 vs. 0.37 ± 0.01 vs. 0.42 ± 0.04 nmol/mg protein, respectively, p < 0.01). Serum IL-6 levels were significantly elevated in both OVX and OVX + HFHF groups as compared with controls (112.13 ± 6.50 vs. 121.47 ± 3.96 vs. 86.13 ± 2.40 pg/mL, respectively, p < 0.01). In OVX + HFHF group, hepatic MDA levels were higher, while GSH levels were lower than in OVX and control groups (MDA; 0.98 ± 0.04 vs. 0.82 ± 0.02 vs. 0.78 ± 0.03 nmol/mg protein, and GSH; 46.01 ± 0.91 vs. 55.21 ± 1.40 vs. 57.94 ± 0.32, respectively; p < 0.01 for both). Comparing with OVX + HFHF group, rats that received genistein, exercise and combined treatments demonstrated an improvement in liver histopathology, decreased levels of hepatic FFA (1.44 ± 0.21 vs. 0.45 ± 0.04 vs. 0.49 ± 0.05 nmol/mg protein, respectively, p < 0.01), serum IL-6 (82.80 ± 2.07 vs. 83.47 ± 2.81 vs. 94.13 ± 1.61 pg/mL, respectively, p < 0.01), and hepatic MDA (0.80 ± 0.03 vs. 0.76 ± 0.02 vs. 0.76 ± 0.03 nmol/mg protein, respectively, p < 0.01).

Conclusions
Genistein and moderate intensity exercise were effective in reducing the severity of NASH in OVX rats through the reduction in liver inflammation, oxidative stress and liver fat contents.
Depressive symptoms and use of health services among older adults in Israel
Authors: Bentur Netta , Heymann Anthony David 
Published: June 2020

AbstractObjectivesDepressive symptoms are often undetected, particularly among older adults. The purpose of this study is to provide information on the prevalence, characteristics, and patterns of depressive symptoms among older adults residing in the community in Israel, and their health-care utilization.MethodsA cross-sectional survey was conducted among a random sample of 2502 members of one HMO in Israel, aged 65+. They were interviewed by telephone with the GDS-15 scale, which serves as the gold standard for depressive symptoms. Data from the computerized medical records of the HMO were added to the interview file, including the diagnosis of depression, purchase of antidepressant medication and use of services.ResultsThe average age of respondents was 73; 54% were women. They tended to be older, living alone, suffering from falls and from sleep disorders, and to have poor subjective health status. 24% scored 6+ on the GDS scale. A significant association was found between a GDS score of 6+ and increased hospitalizations, visits to the emergency room and/or to family physicians and specialists.ConclusionWe found a high prevalence of depression. Its negative effects on the individual and increased costs to the health system, supports the screening and treatment of the disease in the older population. This problem should be a national priority, with screening and treatment becoming part of the national quality of care indicators which would then be implemented by the HMOs as part of an integrated disease management program for the elderly.
Mitochondria as a target for neuroprotection: role of methylene blue and photobiomodulation
Authors: Yang Luodan , Youngblood Hannah , Wu Chongyun , Zhang Quanguang 
Published: June 2020

AbstractMitochondrial dysfunction plays a central role in the formation of neuroinflammation and oxidative stress, which are important factors contributing to the development of brain disease. Ample evidence suggests mitochondria are a promising target for neuroprotection. Recently, methods targeting mitochondria have been considered as potential approaches for treatment of brain disease through the inhibition of inflammation and oxidative injury. This review will discuss two widely studied approaches for the improvement of brain mitochondrial respiration, methylene blue (MB) and photobiomodulation (PBM). MB is a widely studied drug with potential beneficial effects in animal models of brain disease, as well as limited human studies. Similarly, PBM is a non-invasive treatment that promotes energy production and reduces both oxidative stress and inflammation, and has garnered increasing attention in recent years. MB and PBM have similar beneficial effects on mitochondrial function, oxidative damage, inflammation, and subsequent behavioral symptoms. However, the mechanisms underlying the energy enhancing, antioxidant, and anti-inflammatory effects of MB and PBM differ. This review will focus on mitochondrial dysfunction in several different brain diseases and the pathological improvements following MB and PBM treatment.
Freshwater viral metagenome reveals novel and functional phage-borne antibiotic resistance genes
Authors: Moon Kira , Jeon Jeong Ho , Kang Ilnam , Park Kwang Seung , Lee Kihyun , Cha Chang-Jun , Lee Sang Hee , Cho Jang-Cheon 
Published: June 2020

Abstract
Background
Antibiotic resistance developed by bacteria is a significant threat to global health. Antibiotic resistance genes (ARGs) spread across different bacterial populations through multiple dissemination routes, including horizontal gene transfer mediated by bacteriophages. ARGs carried by bacteriophages are considered especially threatening due to their prolonged persistence in the environment, fast replication rates, and ability to infect diverse bacterial hosts. Several studies employing qPCR and viral metagenomics have shown that viral fraction and viral sequence reads in clinical and environmental samples carry many ARGs. However, only a few ARGs have been found in viral contigs assembled from metagenome reads, with most of these genes lacking effective antibiotic resistance phenotypes. Owing to the wide application of viral metagenomics, nevertheless, different classes of ARGs are being continuously found in viral metagenomes acquired from diverse environments. As such, the presence and functionality of ARGs encoded by bacteriophages remain up for debate.

Results
We evaluated ARGs excavated from viral contigs recovered from urban surface water viral metagenome data. In virome reads and contigs, diverse ARGs, including polymyxin resistance genes, multidrug efflux proteins, and β-lactamases, were identified. In particular, when a lenient threshold of e value of ≤ 1 × e−5 and query coverage of ≥ 60% were employed in the Resfams database, the novel β-lactamases blaHRV-1 and blaHRVM-1 were found. These genes had unique sequences, forming distinct clades of class A and subclass B3 β-lactamases, respectively. Minimum inhibitory concentration analyses for E. coli strains harboring blaHRV-1 and blaHRVM-1 and catalytic kinetics of purified HRV-1 and HRVM-1 showed reduced susceptibility to penicillin, narrow- and extended-spectrum cephalosporins, and carbapenems. These genes were also found in bacterial metagenomes, indicating that they were harbored by actively infecting phages.

Conclusion
Our results showed that viruses in the environment carry as-yet-unreported functional ARGs, albeit in small quantities. We thereby suggest that environmental bacteriophages could be reservoirs of widely variable, unknown ARGs that could be disseminated via virus-host interactions.
Hypertension prevalence and its trend in Bangladesh: evidence from a systematic review and meta-analysis
Authors: Chowdhury Mohammad Ziaul Islam , Rahman Meshbahur , Akter Tanjila , Akhter Tania , Ahmed Arifa , Shovon Minhajul Arifin , Farhana Zaki , Chowdhury Nashit , Turin Tanvir C. 
Published: June 2020

Abstract
Background
Hypertension, itself being a major chronic condition, is one of the most significant risk factors for premature cardiovascular diseases and mortality. Hypertension is responsible for 13% of global deaths and three-quarters of the world’s hypertensive population reside in low- and middle-income countries. Bangladesh is one of those countries that experiencing an epidemiological transition from communicable to non-communicable diseases, a nutritional transition from a traditional diet to process and fast food, and an increase in a sedentary lifestyle, resulting in increased hypertension prevalence. We carried out a systematic review and meta-analysis to identify existing research on hypertension prevalence in Bangladesh, summarize findings and assess its temporal change.

Methods
We searched MEDLINE, EMBASE and PubMed and relevant references to identify studies on the prevalence of hypertension in Bangladesh. We used Random-effects meta-analysis to pool the prevalence estimates and performed subgroup analyses. We assessed heterogeneity, a trend in prevalence of hypertension and publication bias in selected studies.

Results
Our search initially identified 735 articles and after removing duplicates, reviewing titles and abstracts, and screening full texts, 53 studies were finally selected. The studies comprised 305,432 subjects and reported overall, gender-specific, geographical location specific and criteria specific prevalence of hypertension. We identified the range of hypertension prevalence is from 1.10% to 75.0% and the overall weighted pooled prevalence of hypertension is 20.0%. An extremely high heterogeneity (I2 = 99.53%; Cochran Q-statistic p < 0.001) was observed in the prevalence of hypertension. Consequently, we performed subgroup analysis based on gender, age group and geographical location of the study participants, the cut-off level used to define hypertension, and the types of hypertension reported and presented our findings accordingly. An overall increasing trend of hypertension prevalence is also observed.

Conclusions
The prevalence of hypertension is high and rising in Bangladesh. Strategies targeting prevention are required to mitigate a further increase in the prevalence and reduce the morbidity and mortality associated with it.
Morphological and molecular characterization of Setaria equina in donkeys
Authors: Abdel Rahman Mona Mohammed I. 
Published: June 2020

Abstract
Background
Adult worms of Setaria equina mainly found in the peritoneal cavity of equine. They were nonpathogenic but might induce varied degrees of peritonitis and might migrate to the eye, brain, lung, and scrotum causing lacrimation, blindness, paraplegia, locomotor, and neurological disturbances. Identification by light microscopy is insufficient to differentiate Setaria species, and so scanning electron microscopy (SEM) is required to observe their ultrastructures. The study was performed on 80 donkeys from May 2018 to January 2019 for the detection of microfilaria in blood and the adult worms in the peritoneal cavity. The blood samples were either stained with Giemsa stain or examined by modified Knott’s technique for the detection of microfilariae. Adult worms were morphologically characterized based on light microscope and scanning electron microscopy (SEM). PCR was performed targeting the 12S rRNA gene followed by sequencing and phylogenetic analysis.

Results
The current study recorded 21.6% and 16.2% prevalence rates for adult worms and microfilariae, respectively. By using SEM, this study was able to clarify the detailed structure of amphids, predeirids, vulva, arrangement, and number of male caudal papillae. PCR amplified products for 12S rRNA gene (408 bp) for adult worm and microfilaria. Sequence and phylogenetic analysis revealed that S. equina isolated in the current study from donkeys in Egypt (accession no., MH345965) shared 100% identity with isolates from horse and man in Italy and Iran, respectively and clustered in the same clade with S. digitata, S. tundra and S. labiatopapillosa.

Conclusions
Identification with light microscopy lacked the ability to characterize different Setaria species, and so using scanning electron microscopy is considered a good choice to distinguish the ultrastructures. In addition, performing the phylogenetic analysis was necessary to detect relationships between different filarial worms, which could not detect by the morphological characterization of adult worms.
Safety and Efficacy of Pembrolizumab With Chemoradiotherapy in Locally Advanced Head and Neck Squamous Cell Carcinoma: A Phase IB Study
Authors: Powell Steven F. , Gold Kathryn A. , Gitau Mark M. , Sumey Christopher J. , Lohr Michele M. , McGraw Steven C. , Nowak Ryan K. , Jensen Ashley W. , Blanchard Miran J. , Fischer Christopher D. , Bykowski Julie , Ellison Christie A. , Black Lora J. , Thompson Paul A. , Callejas-Valera Juan L. , Lee John H. , Cohen Ezra E. W. , Spanos William C. 
Published: June 2020

PURPOSE Pembrolizumab is a humanized monoclonal antibody that blocks interaction between programmed death receptor-1 (PD-1) and its ligands (PD-L1, PD-L2). Although pembrolizumab is approved for recurrent/metastatic head and neck squamous cell carcinoma (HNSCC), its role in the management of locally advanced (LA) disease is not defined. We report a phase IB study evaluating the safety and efficacy of adding pembrolizumab to cisplatin-based chemoradiotherapy in patients with LA HNSCC. PATIENTS AND METHODS Eligible patients included those with oral cavity (excluding lip), oropharyngeal, hypopharyngeal, or laryngeal stage III to IVB HNSCC (according to American Joint Committee on Cancer, 7th edition, staging system) eligible for cisplatin-based, standard-dose (70 Gy) chemoradiotherapy. Pembrolizumab was administered concurrently with and after chemoradiotherapy with weekly cisplatin. Safety was the primary end point and was determined by incidence of chemoradiotherapy adverse events (AEs) and immune-related AEs (irAEs). Efficacy was defined as complete response (CR) rate on end-of-treatment (EOT) imaging or with pathologic confirmation at 100 days postradiotherapy completion. Key secondary end points included overall (OS) and progression-free survival (PFS). RESULTS The study accrued 59 patients (human papillomavirus [HPV] positive, n = 34; HPV negative, n = 25) from November 2015 to October 2018. Five patients (8.8%) required discontinuation of pembrolizumab because of irAEs, all of which occurred during concurrent chemoradiotherapy; 98.3% of patients completed the full planned treatment dose (70 Gy) of radiotherapy without any delays ≥ 5 days; 88.1% of patients completed the goal cisplatin dose of ≥ 200 mg/m2. EOT CR rates were 85.3% and 78.3% for those with HPV-positive and -negative HNSCC, respectively. CONCLUSION Pembrolizumab in combination with weekly cisplatin-based chemoradiotherapy is safe and does not impair delivery of curative radiotherapy or chemotherapy in HNSCC. Early efficacy data support further investigation of this approach.
Role of HLA-DP Expression in Graft-Versus-Host Disease After Unrelated Donor Transplantation
Authors: Petersdorf Effie W. , Bengtsson Mats , De Santis Dianne , Dubois Valerie , Fleischhauer Katharina , Gooley Ted , Horowitz Mary , Madrigal J. Alejandro , Malkki Mari , McKallor Caroline , Morishima Yasuo , Oudshoorn Machteld , Spellman Stephen R. , Villard Jean , Stevenson Phil , Carrington Mary ,   on behalf of the,   International Histocompatibility Working Group in Hematopoietic-Cell Transplantation
Published: June 2020

PURPOSE The main aim of this study was to evaluate the significance of HLA-DPB1 expression in acute graft-versus-host disease (GVHD) after hematopoietic cell transplantation (HCT) from HLA-A, -B, -C, -DRB1, -DQB1–matched and –mismatched unrelated donors. PATIENTS AND METHODS Between January 1, 2017, and January 10, 2019, we assessed 19,136 patients who received HCT from an HLA-A, -B, -C, -DRB1, -DQB1–matched or –mismatched unrelated donor performed in Australia, the European Union, Japan, North America, and the United Kingdom between 1988 and 2016. Among transplant recipients with one HLA-DPB1 mismatch, the patient’s mismatched HLA-DPB1 allotype was defined as low or high expression. Multivariable regression models were used to assess risks of GVHD associated with high expression relative to low expression HLA-DPB1 mismatches. The effect of increasing numbers of HLA-DPB1 mismatches on clinical outcome was assessed in HLA-mismatched transplant recipients. RESULTS In HLA-A, -B, -C, -DRB1,-DQB1–matched transplant recipients, donor mismatching against one high-expression patient HLA-DPB1 increased moderate (odds ratio [OR], 1.36; P = .001) and severe acute GVHD (OR, 1.32; P = .0016) relative to low-expression patient mismatches, regardless of the expression level of the donor’s mismatched HLA-DPB1. Among transplant recipients with one HLA-A, -B, -C, -DRB1, or -DQB1 mismatch, the odds of acute GVHD increased with increasing numbers of HLA-DPB1 mismatches (OR, 1.23 for one; OR, 1.40 for two mismatches relative to zero mismatches for moderate GVHD; OR, 1.19 for one; OR, 1.40 for two mismatches relative to zero for severe GVHD), but not with the level of expression of the patient’s mismatched HLA-DPB1 allotype. CONCLUSION The level of expression of patient HLA-DPB1 mismatches informs the risk of GVHD after HLA-A, -B, -C, -DRB1, -DQB1–matched unrelated HCT, and the total number of HLA-DPB1 mismatches informs the risk of GVHD after HLA-mismatched unrelated HCT. Prospective consideration of HLA-DPB1 may help to lower GVHD risks after transplantation.