bluuebunny/crossref_metadata_2025_split huggingface dataset:
High-throughput screening identifies modulators of sarcospan that stabilize muscle cells and exhibit activity in the mouse model of Duchenne muscular dystrophy
Authors: Shu Cynthia , Parfenova Liubov , Mokhonova Ekaterina , Collado Judd R. , Damoiseaux Robert , Campagna Jesus , John Varghese , Crosbie Rachelle H. 
Published: September 2020

Abstract
Background
Duchenne muscular dystrophy (DMD) is a degenerative muscle disease caused by mutations in the dystrophin gene. Loss of dystrophin prevents the formation of a critical connection between the muscle cell membrane and the extracellular matrix. Overexpression of sarcospan (SSPN) in the mouse model of DMD restores the membrane connection and reduces disease severity, making SSPN a promising therapeutic target for pharmacological upregulation.

Methods
Using a previously described cell-based promoter reporter assay of SSPN gene expression (hSSPN-EGFP), we conducted high-throughput screening on libraries of over 200,000 curated small molecules to identify SSPN modulators. The hits were validated in both hSSPN-EGFP and hSSPN-luciferase reporter cells. Hit selection was conducted on dystrophin-deficient mouse and human myotubes with assessments of (1) SSPN gene expression using quantitative PCR and (2) SSPN protein expression using immunoblotting and an ELISA. A membrane stability assay using osmotic shock was used to validate the functional effects of treatment followed by cell surface biotinylation to label cell surface proteins. Dystrophin-deficient mdx mice were treated with compound, and muscle was subjected to quantitative PCR to assess SSPN gene expression.

Results
We identified and validated lead compounds that increased SSPN gene and protein expression in dystrophin-deficient mouse and human muscle cells. The lead compound OT-9 increased cell membrane localization of compensatory laminin-binding adhesion complexes and improved membrane stability in DMD myotubes. We demonstrated that the membrane stabilizing benefit is dependent on SSPN. Intramuscular injection of OT-9 in the mouse model of DMD increased SSPN gene expression.

Conclusions
This study identifies a pharmacological approach to treat DMD and sets the path for the development of SSPN-based therapies.
Harnessing the strategy of metagenomics for exploring the intestinal microecology of sable (Martes zibellina), the national first-level protected animal
Authors: Yan Jiakuo , Wu Xiaoyang , Chen Jun , Chen Yao , Zhang Honghai 
Published: September 2020

AbstractSable (Martes zibellina), a member of family Mustelidae, order Carnivora, is primarily distributed in the cold northern zone of Eurasia. The purpose of this study was to explore the intestinal flora of the sable by metagenomic library-based techniques. Libraries were sequenced on an Illumina HiSeq 4000 instrument. The effective sequencing data of each sample was above 6000 M, and the ratio of clean reads to raw reads was over 98%. The total ORF length was approximately 603,031, equivalent to 347.36 Mbp. We investigated gene functions with the KEGG database and identified 7140 KEGG ortholog (KO) groups comprising 129,788 genes across all of the samples. We selected a subset of genes with the highest abundances to construct cluster heat maps. From the results of the KEGG metabolic pathway annotations, we acquired information on gene functions, as represented by the categories of metabolism, environmental information processing, genetic information processing, cellular processes and organismal systems. We then investigated gene function with the CAZy database and identified functional carbohydrate hydrolases corresponding to genes in the intestinal microorganisms of sable. This finding is consistent with the fact that the sable is adapted to cold environments and requires a large amount of energy to maintain its metabolic activity. We also investigated gene functions with the eggNOG database; the main functions of genes included gene duplication, recombination and repair, transport and metabolism of amino acids, and transport and metabolism of carbohydrates. In this study, we attempted to identify the complex structure of the microbial population of sable based on metagenomic sequencing methods, which use whole metagenomic data, and to map the obtained sequences to known genes or pathways in existing databases, such as CAZy, KEGG, and eggNOG. We then explored the genetic composition and functional diversity of the microbial community based on the mapped functional categories.
Effective educational interventions for the promotion of sexual and reproductive health and rights for school-age children in low- and middle-income countries: a systematic review protocol
Authors: Fantaye Arone Wondwossen , Buh Amos Wung , Idriss-Wheeler Dina , Fournier Karine , Yaya Sanni 
Published: September 2020

Abstract
Background
Biological changes underlying the sexual and reproductive maturation of school-age children are linked with various sexual and reproductive health and rights risks. SRHR risks are predictors of poor SRHR outcomes, such as poor knowledge of sexually transmitted diseases and early sexual initiation occurring predominantly among school-age children. The aim of this proposed review, therefore, is to identify educational interventions that have proven to be effective in promoting or supporting the sexual and reproductive health and rights of school-aged children in low- and middle-income countries.

Methods
A systematic review of studies on the strategies promoting the SRHR of school-aged children shall be conducted. Electronic searches will be conducted from January 2000 onwards on the following databases: MEDLINE(R) ALL (Ovid), Embase (Ovid), CINAHL (EBSCOHost), APA PsycInfo (Ovid), ERIC (Ovid), Cochrane Central Register of Controlled Trials (Ovid), Education Source (EBSCOHost), Web of Science (Clarivate Analytics), SciELO Citation Index (Clarivate Analytics), Global Health (Ovid), and Sociological Abstract (Proquest). Studies eligible for inclusion will be randomized control trials (RCTs), non-randomized trials, quasi-experimental studies (e.g., pre-post tests), and observational studies (cross-sectional and cohort studies). Peer-reviewed studies published in English and/or French and involving school-aged children 5–10 years old will be included. The primary outcomes of interest will include knowledge, awareness, or attitudes about SRHR topics. The secondary outcomes of interest will include sexual and reproductive behaviors. Two reviewers will independently screen all citations, abstract data, and full-text articles, and the methodological quality of each study will be appraised using JBI critical appraisal tools. A narrative synthesis of extracted data will be conducted.

Discussion
The systematic review will synthesize the evidence on existing educational interventions targeting SRHR outcomes of school-aged children in low- and middle-income countries. It will identify which interventions have proven to be effective, and which interventions have not proven to be effective in promoting or supporting their SRHR. Review findings will provide a useful reference for policy-makers, program developers, global health leaders, and decision makers who wish to support the SRHR of school-age children.

Systematic review registration
The protocol has been registered at the International Prospective Register of Systematic Reviews (PROSPERO CRD42020173158).
Hermite–Hadamard-type inequalities for the interval-valued approximately h-convex functions via generalized fractional integrals
Authors: Zhao Dafang , Ali Muhammad Aamir , Kashuri Artion , Budak Hüseyin , Sarikaya Mehmet Zeki 
Published: September 2020

AbstractIn this paper, we present a new definition of interval-valued convex functions depending on the given function which is called “interval-valued approximatelyh-convex functions”. We establish some inequalities of Hermite–Hadamard type for a newly defined class of functions by using generalized fractional integrals. Our new inequalities are the extensions of previously obtained results like (D.F. Zhao et al. in J. Inequal. Appl. 2018(1):302, 2018 and H. Budak et al. in Proc. Am. Math. Soc., 2019). We also discussed some special cases from our main results.
Blow-up criterion for the density dependent inviscid Boussinesq equations
Authors: Li Li , Zhou Yanping 
Published: September 2020

AbstractIn this work, we consider the density-dependent incompressible inviscid Boussinesq equations in$\mathbb{R}^{N}\ (N\geq 2)$RN(N≥2). By using the basic energy method, we first give the a priori estimates of smooth solutions and then get a blow-up criterion. This shows that the maximum norm of the gradient velocity field controls the breakdown of smooth solutions of the density-dependent inviscid Boussinesq equations. Our result extends the known blow-up criteria.
Senses of place: architectural design for the multisensory mind
Authors: Spence Charles 
Published: September 2020

AbstractTraditionally, architectural practice has been dominated by the eye/sight. In recent decades, though, architects and designers have increasingly started to consider the other senses, namely sound, touch (including proprioception, kinesthesis, and the vestibular sense), smell, and on rare occasions, even taste in their work. As yet, there has been little recognition of the growing understanding of the multisensory nature of the human mind that has emerged from the field of cognitive neuroscience research. This review therefore provides a summary of the role of the human senses in architectural design practice, both when considered individually and, more importantly, when studied collectively. For it is only by recognizing the fundamentally multisensory nature of perception that one can really hope to explain a number of surprising crossmodal environmental or atmospheric interactions, such as between lighting colour and thermal comfort and between sound and the perceived safety of public space. At the same time, however, the contemporary focus on synaesthetic design needs to be reframed in terms of the crossmodal correspondences and multisensory integration, at least if the most is to be made of multisensory interactions and synergies that have been uncovered in recent years. Looking to the future, the hope is that architectural design practice will increasingly incorporate our growing understanding of the human senses, and how they influence one another. Such a multisensory approach will hopefully lead to the development of buildings and urban spaces that do a better job of promoting our social, cognitive, and emotional development, rather than hindering it, as has too often been the case previously.
A new report on gene expression of three killer toxin genes with antimicrobial activity of two killer toxins in Iraq
Authors: Abu-Mejdad Najwa Mohammed Jameel Ali , Al-Badran Adnan I. , Al-Saadoon Abdullah H. , Minati Mohammed Hussein 
Published: September 2020

Abstract
Background
The K1, K2, and K28 toxins are usually encoded by several cytoplasmically genetic satellite dsRNAs (M1, M2, and M28), which are encapsulated with virus-like particles (VLPs) and reliant on an additional assembly of assistant yeast viruses (L-A) for their reproduction and encapsidation. Ascomycetous yeast species that have these VLPs are especially attractive targets for finding killer toxins like proteins. This is because the organisms are known in producing a large variety of secondary metabolites and extracellular enzymes, which have medical importance as alternative drugs for resistance bacterial strains, particularly multi-resistance drugs (MRD).

Results
For the first time, 31 type strains of yeasts were tested for killer toxin production in Iraq via the measurement of gene expression of three killer toxin genes (M1, M2, and M28) within the mycovirus in yeasts. All the type strains gave an expression for the three killer toxins with variable levels. The highest expression was recorded for the killer toxin genes in Torulaspora delbrueckii followed by Wickerhamomyces anomalus. Determined antibacterial activity of two killer toxins appeared with high inhibition zone against pathogenic strains of bacteria. Cytotoxicity against human blood cells was not found. These results considered the first record of killer toxins isolated from type strains in Iraq.

Conclusion
The two typical strains Torulaspora delbrueckii and Wickerhamomyces anomalus showed the highest level of gene expression for the three killer toxins.
Cause-Specific Mortality Following Initial Chemotherapy in a Population-Based Cohort of Patients With Classical Hodgkin Lymphoma, 2000-2016
Authors: Dores Graça M. , Curtis Rochelle E. , Dalal Nicole H. , Linet Martha S. , Morton Lindsay M. 
Published: September 2020

PURPOSE Mortality for patients with classical Hodgkin lymphoma (cHL) treated during an era characterized in the United States by widespread use of doxorubicin, bleomycin, vinblastine, and dacarbazine and diminishing use of radiotherapy is not well understood. PATIENTS AND METHODS We identified 20,007 individuals diagnosed with stage I/II (early) or III/IV (advanced) cHL between age 20 and 74 years treated with initial chemotherapy in US population-based cancer registries during 2000-2015 (follow-up through 2016). We used standardized mortality ratios (SMRs) to compare cause-specific relative mortality risk following cHL to that expected in the general population and estimated excess absolute risks (EARs; per 10,000 patient-years) to quantify disease-specific death burden. RESULTS We identified 3,380 deaths in the cHL cohort, including 1,321 (39%) not attributed to lymphoma. Overall, noncancer SMRs were increased 2.4-fold (95% CI, 2.2 to 2.6; observed, 559; EAR, 61.6) and 1.6-fold (95% CI, 1.4 to 1.7; observed, 473; EAR, 18.2) for advanced- and early-stage cHL, respectively, compared with the general US population. SMRs and EARs differed substantially by cause of death and cHL stage. Among the highest EARs for noncancer causes of death were those for heart disease (EAR, 15.1; SMR, 2.1), infections (EAR, 10.6; SMR, 3.9), interstitial lung disease (ILD; EAR, 9.7; SMR, 22.1), and adverse events (AEs) related to medications/drugs (EAR, 7.4; SMR, 5.0) after advanced-stage cHL and heart disease (EAR, 6.6; SMR, 1.7), ILD (EAR, 3.7; SMR, 13.1), and infections (EAR, 3.1; SMR, 2.2) after early-stage cHL. Strikingly elevated SMRs for ILD, infections, and AEs were observed < 1 year after cHL. Individuals age 60-74 years with advanced-stage cHL experienced a disproportionate excess of deaths as a result of heart disease, ILD, infections, AEs, and solid tumors. CONCLUSION Despite evolving cHL treatment approaches, patients continue to face increased nonlymphoma mortality risks from multiple, potentially preventable causes. Surveillance, early interventions, and cHL treatment refinements may favorably affect patient longevity, particularly among high-risk subgroups.
Consolidation Radiotherapy Could Be Safely Omitted in Advanced Hodgkin Lymphoma With Large Nodal Mass in Complete Metabolic Response After ABVD: Final Analysis of the Randomized GITIL/FIL HD0607 Trial
Authors: Gallamini Andrea , Rossi Andrea , Patti Caterina , Picardi Marco , Romano Alessandra , Cantonetti Maria , Oppi Sara , Viviani Simonetta , Bolis Silvia , Trentin Livio , Gini Guido , Battistini Roberta , Chauvie Stephane , Sorasio Roberto , Pavoni Chiara , Zanotti Roberta , Cimminiello Michele , Schiavotto Corrado , Viero Piera , Mulé Antonino , Fallanca Federico , Ficola Umberto , Tarella Corrado , Guerra Luca , Rambaldi Alessandro 
Published: September 2020

PURPOSE To investigate the role of consolidation radiotherapy (cRT) in advanced-stage Hodgkin lymphoma (HL) presenting at baseline with a large nodal mass (LNM) in complete metabolic response after doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy. PATIENTS AND METHODS Advanced-stage (IIB-IVB) HL patients, enrolled in the HD 0607 trial (Clinicaltrial.gov identifier NCT00795613 ), with both a negative PET after two (PET-2) and six (PET-6) ABVD cycles, who presented at baseline with an LNM, defined as a nodal mass with the largest diameter ≥ 5 cm, were prospectively randomly assigned to receive cRT over the LNM or no further treatment (NFT). RESULTS Among 296 randomly assigned patients, the largest diameter of LNM at baseline was 5-7 cm in 101 (34%; subgroup A) and 8-10 cm in 96 (32%; subgroup B), whereas classic bulky (diameter > 10 cm) was detected in 99 (33%; subgroup C). Two hundred eighty patients (88%) showed a postchemotherapy RM. The median dose of cRT was 30.6 Gy (range, 24-36 Gy). After a median follow-up of 5.9 years (range, 0.5-10 years), the 6-year progression-free survival rate of patients who underwent cRT or NFT was, respectively, 91% (95% CI, 84% to 99%) and 95% (95% CI, 89% to 100%; P = .62) in subgroup A; 98% (95% CI, 93% to 100%) and 90% (95% CI, 80% to 100%; P = .24) in subgroup B; 89% (95% CI, 81% to 98%) and 86% (95% CI, 77% to 96%; P = .53) in subgroup C (classic bulky). CONCLUSION cRT could be safely omitted in patients with HL presenting with an LNM and a negative PET-2 and PET-6 scan, irrespective from the LNM size detected at baseline.
Longer Follow-Up Confirms Recurrence-Free Survival Benefit of Adjuvant Pembrolizumab in High-Risk Stage III Melanoma: Updated Results From the EORTC 1325-MG/KEYNOTE-054 Trial
Authors: Eggermont Alexander M. M. , Blank Christian U. , Mandala Mario , Long Georgina V. , Atkinson Victoria G. , Dalle Stéphane , Haydon Andrew M. , Meshcheryakov Andrey , Khattak Adnan , Carlino Matteo S. , Sandhu Shahneen , Larkin James , Puig Susana , Ascierto Paolo A. , Rutkowski Piotr , Schadendorf Dirk , Koornstra Rutger , Hernandez-Aya Leonel , Di Giacomo Anna Maria , van den Eertwegh Alfonsus J. M. , Grob Jean-Jacques , Gutzmer Ralf , Jamal Rahima , Lorigan Paul C. , van Akkooi Alexander C. J. , Krepler Clemens , Ibrahim Nageatte , Marreaud Sandrine , Kicinski Michal , Suciu Stefan , Robert Caroline 
Published: September 2020

PURPOSE We conducted the phase III double-blind European Organisation for Research and Treatment of Cancer (EORTC) 1325/KEYNOTE-054 trial to evaluate pembrolizumab versus placebo in patients with resected high-risk stage III melanoma. On the basis of 351 recurrence-free survival (RFS) events at a 1.25-year median follow-up, pembrolizumab prolonged RFS (hazard ratio [HR], 0.57; P < .0001) compared with placebo. This led to the approval of pembrolizumab adjuvant treatment by the European Medicines Agency and US Food and Drug Administration. Here, we report an updated RFS analysis at the 3.05-year median follow-up. PATIENTS AND METHODS A total of 1,019 patients with complete lymph node dissection of American Joint Committee on Cancer Staging Manual (seventh edition; AJCC-7), stage IIIA (at least one lymph node metastasis > 1 mm), IIIB, or IIIC (without in-transit metastasis) cutaneous melanoma were randomly assigned to receive pembrolizumab at a flat dose of 200 mg (n = 514) or placebo (n = 505) every 3 weeks for 1 year or until disease recurrence or unacceptable toxicity. The two coprimary end points were RFS in the overall population and in those with programmed death-ligand 1 (PD-L1)–positive tumors. RESULTS Pembrolizumab (190 RFS events) compared with placebo (283 RFS events) resulted in prolonged RFS in the overall population (3-year RFS rate, 63.7% v 44.1% for pembrolizumab v placebo, respectively; HR, 0.56; 95% CI, 0.47 to 0.68) and in the PD-L1–positive tumor subgroup (HR, 0.57; 99% CI, 0.43 to 0.74). The impact of pembrolizumab on RFS was similar in subgroups, in particular according to AJCC-7 and AJCC-8 staging, and BRAF mutation status (HR, 0.51 [99% CI, 0.36 to 0.73] v 0.66 [99% CI, 0.46 to 0.95] for V600E/K v wild type). CONCLUSION In resected high-risk stage III melanoma, pembrolizumab adjuvant therapy provided a sustained and clinically meaningful improvement in RFS at 3-year median follow-up. This improvement was consistent across subgroups.
Retrograde Autologous Priming in Cardiac Surgery: Results From a Systematic Review and Meta-analysis
Authors: Hensley Nadia B. , Gyi Richard , Zorrilla-Vaca Andres , Choi Chun W. , Lawton Jennifer S. , Brown Charles H. , Frank Steve M. , Grant Michael C. , Cho Brian C. 
Published: September 2020

Background:
Retrograde autologous priming (RAP) before cardiopulmonary bypass (CPB) may minimize allogeneic red cell transfusion. We conducted a systematic review of the literature to examine the impact of RAP on perioperative allogeneic red cell transfusions in cardiac surgical patients.

METHODS:
This study involved a systematic review and meta-analysis of randomized controlled trials (RCTs) and observational studies evaluating the use of RAP in cardiac surgery involving CPB. The primary outcome was intraoperative allogeneic red cell transfusion. Secondary outcomes included whole hospital allogeneic transfusions and adverse events such as acute kidney injury (AKI) and stroke.

RESULTS:
A total of 11 RCTs (n = 1337 patients) were included, comparing RAP patients (n = 674) to control (n = 663). In addition, 10 observational studies (n = 2327) were included, comparing RAP patients (n = 1257) to control (n = 1070). Overall, RAP was associated with a significantly reduced incidence of intraoperative red cell transfusion (n = 18 studies; odds ratio [OR] = 0.34; 95% confidence interval [CI], 0.22–0.55, P < .001) compared to controls. This effect was seen among RCTs (n = 10 studies; OR = 0.19; 95% CI, 0.08–0.45, P < .001) and observational studies (n = 8 studies; OR = 0.66; 95% CI, 0.50–0.87, P = .004) in isolation. RAP was also associated with a significantly reduced incidence of whole hospital red cell transfusion (n = 5 studies; OR = 0.28; 95% CI, 0.19–0.41, P < .001). Among the studies that reported AKI and stroke outcomes, there was no statistically significant increased odds of AKI or stroke in either RAP or control patients.

CONCLUSIONS:
Based on the pooled results of the available literature, RAP is associated with a significant reduction in intraoperative and whole hospital allogeneic red cell transfusion. Use of RAP may prevent hemodilution of cardiac surgical patients and thus, lessen transfusions. Additional high-quality prospective studies are necessary to determine the ideal priming volume necessary to confer the greatest benefit without incurring organ injury.
Characterization of buccal cell DNA after exposure to azo compounds: a cross-sectional study
Authors: Handajani Juni , Tabtila Urfa , Rully Auliawati Nadia , Rohman Abdul 
Published: September 2020

Background: Azo compounds, containing naphthol and diazonium salts, are synthetic dyes widely used in the batik industry. Azo compounds are considered toxic when they are exposed to human tissue. The purpose of this study was to analyze buccal cell DNA exposed to azo compounds in batik workers. Methods: A cross-sectional study involving 20 male subjects divided into two groups (n=10 group), namely azo-exposed and non-exposed (control group). Inclusion criteria were batik workers of the colouring division who have been exposed to azo for at least 5 years. Buccal cells were taken using cytobrush then DNA were isolated from buccal cell. DNA isolation was done by buccal DNA kit, while the purity and concentration of the DNA was determined using spectrophotometer and electrophoresis. Results: The azo-exposed group revealed higher purity DNA than those in the control group. The purity of the DNA in the azo-exposed group and control group was 0.61±0.93 and 0.21±0.09, respectively, while the concentration of DNA was of 59.02 and 19.35 ng/UL, respectively. The ratio at 260/280 nm was 1.84-1.94 (azo-exposed) and 1.85-1.92 (control). Principal component analysis using the first principle component (PC1) and second principle component (PC2) could successfully classify subjects in the control and azo-exposed groups. Conclusion: Characteristics of DNA could be used as an indication of exposure to azo compounds in workers of batik industries.