bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship of visceral adipose tissue with surrogate insulin resistance and liver markers in individuals with metabolic syndrome chronic complications
Authors: Bullón-Vela Vanessa , Abete Itziar , Tur Josep A. , Konieczna Jadwiga , Romaguera Dora , Pintó Xavier , Corbella Emili , Martínez-González Miguel A. , Sayón-Orea Carmen , Toledo Estefanía , Corella Dolores , Macías-Gonzalez Manuel , Tinahones Francisco J. , Fitó Montserrat , Estruch Ramon , Ros Emilio , Salas-Salvadó Jordi , Daimiel Lidia , Mascaró Catalina M. , Zulet Maria Angeles , Martínez José Alfredo
Published: October 2020

Background:

Visceral adipose tissue (VAT) has a hazardous influence on systemic inflammation, insulin resistance and an adverse metabolic profile, which increases the risk of developing non-alcoholic fatty liver disease (NAFLD) and chronic complications of diabetes. In our study we aimed to evaluate the association of VAT and the triglyceride glucose (TyG) as a proxy of insulin resistance surrogated with metabolic and liver risk factors among subjects diagnosed with metabolic syndrome (MetS).

Methods:

A cross-sectional study was performed including 326 participants with MetS (55–75 years) from the PREDIMED-Plus study. Liver-status markers, VAT and TyG were assessed. Participants were stratified by tertiles according to VAT ( n = 254) and TyG ( n = 326). A receiver operating characteristic curve was used to analyse the efficiency of TyG for VAT.

Results:

Subjects with greater visceral fat depots showed worse lipid profile, higher homeostatic model assessment for insulin resistance (HOMA-IR), TyG, alanine transaminase (ALT), fibroblast growth factor-21 (FGF-21), fatty liver index (FLI) and hepatic steatosis index (HSI) compared with participants in the first tertile. The multi-adjusted linear-regression analyses indicated that individuals in the third tertile of TyG (>9.1−10.7) had a positive association with HOMA-IR [ β = 3.07 (95% confidence interval (CI) 2.28−3.86; p trend < 0.001)], ALT [ β = 7.43 (95% CI 2.23−12.63; p trend = 0.005)], gamma glutamyl transferase (GGT) [ β = 14.12 (95% CI 3.64−24.61; p trend = 0.008)], FGF-21 [ β = 190.69 (95% CI 93.13−288.25; p trend < 0.001)], FLI [ β = 18.65 (95% CI 14.97−22.23; p trend < 0.001)] and HSI [ β = 3.46 (95% CI, 2.23−4.68; p trend < 0.001)] versus participants from the first tertile. Interestingly, the TyG showed the largest area under the receiver operating curve (AUC) for women (AUC = 0.713; 95% CI 0.62−0.79) compared with men (AUC = 0.570; 95% CI 0.48−0.66).

Conclusions:

A disrupted VAT enlargement and impairment of TyG are strongly associated with liver status and cardiometabolic risk factors linked with NAFLD in individuals diagnosed with MetS. Moreover, the TyG could be used as a suitable and reliable marker estimator of VAT.
Assessing the Attitudes, Awareness, and Behavioral Alterations of Patients Awaiting Total Hip Arthroplasty During the COVID-19 Crisis
Authors: Fahy Stephen , Moore Joss , Kelly Michael , Irwin Shane , Kenny Paddy
Published: October 2020

Background:

COVID-19 has placed a huge burden on healthcare systems which has led to widespread cancellation elective surgical care. Ireland is recovering from the first wave of COVID-19 and as such the expeditious return of elective surgical care is important. This is the first study to examine the attitudes of patients to undergoing total joint arthroplasty during the COVID-19 crisis.

Methods:

A prospective qualitative study was undertaken in our institution during the week 13/05/2020-20/05/2020. 65 patients completed a questionnaire assessing attitudes, awareness, and behavioral changes associated with COVID-19, a Charlson Comorbidity Index, modified-Harris Hip Score, and a Short Form-12 score.

Results:

86% of patients felt that they were at little to no risk of COVID-19 infection. The majority of patients were happy to proceed with surgery at the current level of COVID-19 related threat (86%). Patients with higher mHHS were more likely to postpone their operation than those with lower mHHS scores. Our cohort had low patient reported outcome measures in both mHHS and SF-12, indicating the significant burden of hip osteoarthritis on both physical and mental health.

Conclusion:

Patients reported a significant disease-related impairment of physical function and subsequent deterioration in mental health as a result of hip osteoarthritis. Patients with worse hip function, as measured by the mHHS are more willing to proceed with surgery than those with superior hip function. This offers a potential mechanism by which to triage patients once elective surgical pathways reopen in the coming months.
A Terminal Colovesical Fistula in an Anorectal Malformation
Authors: Aihole Jayalaxmi Shripati
Published: October 2020

Anorectal malformations are relatively common anomalies encountered in pediatric surgical practice. They are usually recognized at birth with absent anal canal or failure to pass meconium and hence can lead to life threatening bowel obstruction without surgical intervention. We are reporting a rare case of non-syndromic, sporadic, terminal colovesical fistula associated with high anorectal malformation not associated with congenital pouch colon in a neonate.
Dysfunction of the Microbiota-Gut-Brain Axis in Neurodegenerative Disease: The Promise of Therapeutic Modulation With Prebiotics, Medicinal Herbs, Probiotics, and Synbiotics
Authors: Peterson Christine Tara
Published: October 2020

Recent data suggest gut microbiota dysbiosis as a contributing factor in neurodegenerative diseases, such as Parkinson’s Disease (PD) and Alzheimer’s Disease (AD), and these pathologies may manifest via the microbiota-gut-brain-axis, which comprises bidirectional communication through neuroimmune, neuroendocrine, and direct neural pathways such as the vagus nerve. Preclinical and human clinical trial data reveal exciting potential for novel treatment targets and therapeutic modulation with prebiotics, medicinal herbs, probiotics, and synbiotics in health, aging, and neurodegeneration and are reviewed here. While greater insights and characterization of the microbiota-gut-brain axis have been revealed over the past decade, salient questions related to the pathology, pathogenesis and clinical treatment of the axis in the context of both health and neurodegenerative disease remain and are discussed in this review. Future directions such as additional well-controlled, large scale, longitudinal human clinical trials are urgently needed to further elucidate both mechanism and therapeutic opportunity in health, neurological disease, and disease subpopulations to ensure that the next decade ushers the dawn of targeted therapeutic modulation of the microbiota-gut-brain axis.
Listening to survive: Classical music and conflict in the musico-literary novel
Authors: Harling-Lee Katie
Published: October 2020

This article addresses the possibility that Western classical music might be used as a source of hope for a post-conflict future by considering a literary depiction of music and conflict resolution. As a case study, Steven Galloway’s The Cellist of Sarajevo is identified as a “musico-literary novel,” and established within the framework of Stephen Benson’s “literary music” and Hazel Smith’s methodological development of musico-literary studies through extended interdisciplinarity. The novel features three Sarajevan citizens who hear a cellist play in the rubble-strewn streets, and their music-listening experiences motivate them to work toward a post-conflict future. To consider the potential insights and blind spots surrounding ideas about music’s potential power in this narrative, the soundscape of the novel is identified to establish the significance of sound, music, and active listening in the text; parallels are highlighted between the ending of The Cellist of Sarajevo and Michael Walzer’s Just and Unjust Wars, revealing music as an active moral force; and similarities between Galloway’s novel and Craig Robertson’s “Music and conflict transformation in Bosnia” are illustrated, demonstrating how interdisciplinary analysis of a musico-literary novel can offer a valid contribution to discussions surrounding the use of music to exit violence.
Transcriptional profile of platelets and iPSC-derived megakaryocytes from whole-genome and RNA sequencing
Authors: Kammers Kai , Taub Margaret A. , Rodriguez Benjamin , Yanek Lisa R. , Ruczinski Ingo , Martin Joshua , Kanchan Kanika , Battle Alexis , Cheng Linzhao , Wang Zack Z. , Johnson Andrew D. , Leek Jeffrey T. , Faraday Nauder , Becker Lewis C. , Mathias Rasika A.
Published: October 2020

Genome-wide association studies have identified common variants associated with platelet-related phenotypes, but because these variants are largely intronic or intergenic, their link to platelet biology is unclear. In 290 normal subjects from the GeneSTAR Research Study (110 African Americans [AAs] and 180 European Americans [EAs]), we generated whole-genome sequence data from whole blood and RNA sequence data from extracted nonribosomal RNA from 185 induced pluripotent stem cell-derived megakaryocyte (MK) cell lines (platelet precursor cells) and 290 blood platelet samples from these subjects. Using eigenMT software to select the peak single-nucleotide polymorphism (SNP) for each expressed gene, and meta-analyzing the results of AAs and EAs, we identify (q-value < 0.05) 946 cis-expression quantitative trait loci (eQTLs) in derived MKs and 1830 cis-eQTLs in blood platelets. Among the 57 eQTLs shared between the 2 tissues, the estimated directions of effect are very consistent (98.2% concordance). A high proportion of detected cis-eQTLs (74.9% in MKs and 84.3% in platelets) are unique to MKs and platelets compared with peak-associated SNP-expressed gene pairs of 48 other tissue types that are reported in version V7 of the Genotype-Tissue Expression Project. The locations of our identified eQTLs are significantly enriched for overlap with several annotation tracks highlighting genomic regions with specific functionality in MKs, including MK-specific DNAse hotspots, H3K27-acetylation marks, H3K4-methylation marks, enhancers, and superenhancers. These results offer insights into the regulatory signature of MKs and platelets, with significant overlap in genes expressed, eQTLs detected, and enrichment within known superenhancers relevant to platelet biology.
Diagnostic biomarkers to differentiate sepsis from cytokine release syndrome in critically ill children
Authors: Diorio Caroline , Shaw Pamela A. , Pequignot Edward , Orlenko Alena , Chen Fang , Aplenc Richard , Barrett David M. , Bassiri Hamid , Behrens Edward , DiNofia Amanda M. , Gonzalez Vanessa , Koterba Natalka , Levine Bruce L. , Maude Shannon L. , Meyer Nuala J. , Moore Jason H. , Paessler Michele , Porter David L. , Bush Jenny L. , Siegel Don L. , Davis Megan M. , Zhang Donglan , June Carl H. , Grupp Stephan A. , Melenhorst J. Joseph , Lacey Simon F. , Weiss Scott L. , Teachey David T.
Published: October 2020

Chimeric antigen receptor (CAR) T-cells directed against CD19 have drastically altered outcomes for children with relapsed and refractory acute lymphoblastic leukemia (r/r ALL). Pediatric patients with r/r ALL treated with CAR-T are at increased risk of both cytokine release syndrome (CRS) and sepsis. We sought to investigate the biologic differences between CRS and sepsis and to develop predictive models which could accurately differentiate CRS from sepsis at the time of critical illness. We identified 23 different cytokines that were significantly different between patients with sepsis and CRS. Using elastic net prediction modeling and tree classification, we identified cytokines that were able to classify subjects as having CRS or sepsis accurately. A markedly elevated interferon γ (IFNγ) or a mildly elevated IFNγ in combination with a low IL1β were associated with CRS. A normal to mildly elevated IFNγ in combination with an elevated IL1β was associated with sepsis. This combination of IFNγ and IL1β was able to categorize subjects as having CRS or sepsis with 97% accuracy. As CAR-T therapies become more common, these data provide important novel information to better manage potential associated toxicities.
Management of heparin-induced thrombocytopenia: systematic reviews and meta-analyses
Authors: Morgan Rebecca L. , Ashoorion Vahid , Cuker Adam , Begum Housne , Ross Stephanie , Martinez Nina , Chong Beng H. , Linkins Lori A. , Warkentin Theodore E. , Wiercioch Wojtek , Nieuwlaat Robby , Schünemann Holger , Santesso Nancy
Published: October 2020

Heparin-induced thrombocytopenia (HIT) is a prothrombotic adverse drug reaction occurring in <0.1% to 7% of patients receiving heparin products depending on the patient population and type of heparin. Management of HIT is highly dependent on a sequence of tests for which clinicians may or may not have the results when care decisions need to be made. We conducted systematic reviews of the effects of management strategies in persons with acute HIT, subacute HIT A or B, and remote HIT. We searched Medline, EMBASE, and the Cochrane Database through July 2019 for previously published systematic reviews and primary studies. Two investigators independently screened and extracted data and assessed the certainty of the evidence using the Grading of Recommendations Assessment, Development and Evaluation approach. We found primarily noncomparative studies and case series assessing effects of treatments, which led to low to very low certainty evidence. There may be little to no difference in the effects between nonheparin parenteral anticoagulants and direct oral anticoagulants in acute HIT. The benefits of therapeutic-intensity may be greater than prophylactic-intensity anticoagulation. Using inferior vena cava filters or platelet transfusion may result in greater harm than not using these approaches. Evidence for management in special situations, such as for patients undergoing cardiovascular interventions or renal replacement therapy, was also low to very low certainty. Additional research to evaluate nonheparin anticoagulants is urgently needed, and the development of novel treatments that reduce thrombosis without increasing hemorrhage should be a priority.
Target screening of plant secondary metabolites in river waters by liquid chromatography coupled to high-resolution mass spectrometry (LC–HRMS)
Authors: Nanusha Mulatu Yohannes , Krauss Martin , Schönsee Carina D. , Günthardt Barbara F. , Bucheli Thomas D. , Brack Werner
Published: October 2020

Background

Substantial efforts have been made to monitor potentially hazardous anthropogenic contaminants in surface waters while for plant secondary metabolites (PSMs) almost no data on occurrence in the water cycle are available. These metabolites enter river waters through various pathways such as leaching, surface run-off and rain sewers or input of litter from vegetation and might add to the biological activity of the chemical mixture. To reduce this data gap, we conducted a LC–HRMS target screening in river waters from two different catchments for 150 plant metabolites which were selected from a larger database considering their expected abundance in the vegetation, their potential mobility, persistence and toxicity in the water cycle and commercial availability of standards.

Results

The screening revealed the presence of 12 out of 150 possibly toxic PSMs including coumarins (bergapten, scopoletin, fraxidin, esculetin and psoralen), a flavonoid (formononetin) and alkaloids (lycorine and narciclasine). The compounds narciclasine and lycorine were detected at concentrations up to 3 µg/L while esculetin and fraxidin occurred at concentrations above 1 µg/L. Nine compounds occurred at concentrations above 0.1 µg/L, the Threshold for Toxicological Concern (TTC) for non-genotoxic and non-endocrine disrupting chemicals in drinking water.

Conclusions

Our study provides an overview of potentially biologically active PSMs in surface waters and recommends their consideration in monitoring and risk assessment of water resources. This is currently hampered by a lack of effect data including toxicity to aquatic organisms, endocrine disruption and genotoxicity and demands for involvement of these compounds in biotesting.
A rank-based marker selection method for high throughput scRNA-seq data
Authors: Vargo Alexander H. S. , Gilbert Anna C.
Published: October 2020

Background

High throughput microfluidic protocols in single cell RNA sequencing (scRNA-seq) collect mRNA counts from up to one million individual cells in a single experiment; this enables high resolution studies of rare cell types and cell development pathways. Determining small sets of genetic markers that can identify specific cell populations is thus one of the major objectives of computational analysis of mRNA counts data. Many tools have been developed for marker selection on single cell data; most of them, however, are based on complex statistical models and handle the multi-class case in an ad-hoc manner.

Results

We introduce RankCorr, a fast method with strong mathematical underpinnings that performs multi-class marker selection in an informed manner. RankCorr proceeds by ranking the mRNA counts data before linearly separating the ranked data using a small number of genes. The step of ranking is intuitively natural for scRNA-seq data and provides a non-parametric method for analyzing count data. In addition, we present several performance measures for evaluating the quality of a set of markers when there is no known ground truth. Using these metrics, we compare the performance of RankCorr to a variety of other marker selection methods on an assortment of experimental and synthetic data sets that range in size from several thousand to one million cells.

Conclusions

According to the metrics introduced in this work, RankCorr is consistently one of most optimal marker selection methods on scRNA-seq data. Most methods show similar overall performance, however; thus, the speed of the algorithm is the most important consideration for large data sets (and comparing the markers selected by several methods can be fruitful). RankCorr is fast enough to easily handle the largest data sets and, as such, it is a useful tool to add into computational pipelines when dealing with high throughput scRNA-seq data. RankCorr software is available for download at https://github.com/ahsv/RankCorrwith extensive documentation.
A new esophageal gland transcriptome reveals signatures of large scale de novo effector birth in the root lesion nematode Pratylenchus penetrans
Authors: Vieira Paulo , Shao Jonathan , Vijayapalani Paramasivan , Maier Thomas R. , Pellegrin Clement , Eves-van den Akker Sebastian , Baum Thomas J. , Nemchinov Lev G.
Published: October 2020

Background

The root lesion nematode Pratylenchus penetrans is a migratory plant-parasitic nematode responsible for economically important losses in a wide number of crops. Despite the importance of P. penetrans, the molecular mechanisms employed by this nematode to promote virulence remain largely unknown.

Results

Here we generated a new and comprehensive esophageal glands-specific transcriptome library for P. penetrans. In-depth analysis of this transcriptome enabled a robust identification of a catalogue of 30 new candidate effector genes, which were experimentally validated in the esophageal glands by in situ hybridization. We further validated the expression of a multifaceted network of candidate effectors during the interaction with different plants. To advance our understanding of the “effectorome” of P. penetrans, we adopted a phylogenetic approach and compared the expanded effector repertoire of P. penetrans to the genome/transcriptome of other nematode species with similar or contrasting parasitism strategies. Our data allowed us to infer plausible evolutionary histories that shaped the effector repertoire of P. penetrans, as well as other close and distant plant-parasitic nematodes. Two remarkable trends were apparent: 1) large scale effector birth in the Pratylenchidae in general and P. penetrans in particular, and 2) large scale effector death in sedentary (endo) plant-parasitic nematodes.

Conclusions

Our study doubles the number of validated Pratylenchus penetrans effectors reported in the literature. The dramatic effector gene gain in P. penetrans could be related to the remarkable ability of this nematode to parasitize a large number of plants. Our data provide valuable insights into nematode parasitism and contribute towards basic understating of the adaptation of P. penetrans and other root lesion nematodes to specific host plants.
Identification, expression, and artificial selection of silkworm epigenetic modification enzymes
Authors: Gao Rui , Li Chun-Lin , Tong Xiao-Ling , Han Min-Jin , Lu Kun-Peng , Liang Shu-Bo , Hu Hai , Luan Yue , Zhang Bi-Li , Liu Yan-Yu , Dai Fang-Yin
Published: October 2020

Background

Understanding the genetic basis of phenotype variations during domestication and breeding is of great interest. Epigenetics and epigenetic modification enzymes (EMEs) may play a role in phenotypic variations; however, no comprehensive study has been performed to date. Domesticated silkworm(Bombyx mori)may be utilized as a model in determining how EMEs influence domestication traits.

Results

We identified 44EMEsin the genome of silkworm (Bombyx mori) using homology searching. Phylogenetic analysis showed that genes in a subfamily among different animals were well clustered, and the expression pattern ofEMEsis constant amongBombyx mori,Drosophila melanogaster, andMus musculus. These are most highly expressed in brain, early embryo, and internal genitalia. By gene-related selective sweeping, we identified fiveBmEMEsunder artificial selection during the domestication and breeding of silkworm. Among these selected genes,BmSuv4–20 and BmDNMT2harbor selective mutations in their upstream regions that alter transcription factor-binding sites. Furthermore, these two genes are expressed higher in the testis and ovary of domesticated silkworm compared to wild silkworms, and correlations between their expression pattern and meiosis of the sperm and ova were observed.

Conclusions

The domestication of silkworm has induced artificial selection on epigenetic modification markers that may have led to phenotypic changes during domestication. We present a novel perspective to understand the genetic basis underlying animal domestication and breeding.
Drought-hardening improves drought tolerance in Nicotiana tabacum at physiological, biochemical, and molecular levels
Authors: Khan Rayyan , Ma Xinghua , Shah Shahen , Wu Xiaoying , Shaheen Aaqib , Xiao Lixia , Wu Yuanhua , Wang Shusheng
Published: October 2020

Background

Drought stress is the most harmful one among other abiotic stresses with negative impacts on crop growth and development. Drought-hardening is a feasible and widely used method in tobacco seedlings cultivation. It has gained extensive interests due to its role in improving drought tolerance. This research aimed to investigate the role of drought-hardening and to unravel the multiple mechanisms underlying tobacco drought tolerance and adaptation.

Results

This study was designed in which various drought-hardening treatments (CK (no drought-hardening), T1 (drought-hardening for 24 h), T2 (drought-hardening for 48 h), and T3 (drought-hardening for 72 h)) were applied to two tobacco varieties namely HongHuaDaJinYuan (H) and Yun Yan-100 (Y). The findings presented a complete framework of drought-hardening effect at physiological, biochemical, and gene expression levels of the two tobacco varieties under drought stress. The results showed that T2 and T3 significantly reduced the growth of the two varieties under drought stress. Similarly, among the various drought-hardening treatments, T3 improved both the enzymatic (POD, CAT, APX) and non-enzymatic (AsA) defense systems along with the elevated levels of proline and soluble sugar to mitigate the negative effects of oxidative damage and bringing osmoregulation in tobacco plants. Finally, the various drought-hardening treatments (T1, T2, and T3) showed differential regulation of genes expressed in the two varieties, while, particularly T3 drought-hardening treatment-induced drought tolerance via the expression of various stress-responsive genes by triggering the biosynthesis pathways of proline (P5CS1), polyamines (ADC2), ABA-dependent (SnRK2, AREB1), and independent pathways (DREB2B), and antioxidant defense-related genes (CAT, APX1, GR2) in response to drought stress.

Conclusions

Drought-hardening made significant contributions to drought tolerance and adaptation in two tobacco variety seedlings by reducing its growth and, on the other hand, by activating various defense mechanisms at biochemical and molecular levels. The findings of the study pointed out that drought-hardening is a fruitful strategy for conferring drought tolerance and adaptations in tobacco. It will be served as a useful method in the future to understand the drought tolerance and adaptation mechanisms of other plant species.

Graphical abstract

Drought-hardening improved drought tolerance and adaptation of the two tobacco varieties. T1 indicates drought-hardening for 24 h, T2 indicates drought-hardening for 48 h, T3 indicates drought-hardening for 72 h
Metabolomics analysis reveals Embden Meyerhof Parnas pathway activation and flavonoids accumulation during dormancy transition in tree peony
Authors: Zhang Tao , Yuan Yanchao , Zhan Yu , Cao Xinzhe , Liu Chunying , Zhang Yuxi , Gai Shupeng
Published: October 2020

Background

Bud dormancy is a sophisticated strategy which plants evolve to survive in tough environments. Endodormancy is a key obstacle for anti-season culture of tree peony, and sufficient chilling exposure is an effective method to promote dormancy release in perennial plants including tree peony. However, the mechanism of dormancy release is still poorly understood, and there are few systematic studies on the metabolomics during chilling induced dormancy transition.

Results

The tree peony buds were treated with artificial chilling, and the metabolmics analysis was employed at five time points after 0–4 °C treatment for 0, 7, 14, 21 and 28 d, respectively. A total of 535 metabolites were obtained and devided into 11 groups including flavonoids, amino acid and its derivatives, lipids, organic acids and its derivates, nucleotide and its derivates, alkaloids, hydroxycinnamoyl derivatives, carbohydrates and alcohols, phytohormones, coumarins and vitamins. Totally, 118 differential metabolites (VIP ≥ 1,P < 0.05) during chilling treatment process were detected, and their KEGG pathways involved in several metabolic pathways related to dormancy. Sucrose was the most abundant carbohydrate in peony bud. Starch was degradation and Embden Meyerhof Parnas (EMP) activity were increased during the dormancy release process, according to the variations of sugar contents, related enzyme activities and key genes expression. Flavonoids synthesis and accumulation were also promoted by prolonged chilling. Moreover, the variations of phytohormones (salicylic acid, jasmonic acid, abscisic acid, and indole-3-acetic acid) indicated they played different roles in dormancy transition.

Conclusion

Our study suggested that starch degradation, EMP activation, and flavonoids accumulation were crucial and associated with bud dormancy transition in tree peony.
Changes in abscisic acid metabolism in relation to the maturation of grapevine (Vitis vinifera L., cv. Mencía) somatic embryos
Authors: Acanda Yosvanis , Martínez Óscar , Prado María Jesús , González María Victoria , Rey Manuel
Published: October 2020

Background

Somatic embryogenesis in grapevines is a complex process that depends on many physiological and genetic factors. One of its main limitations is the process of precocious germination of the somatic embryos in differentiation medium. This process lowers plant conversion rates from the somatic embryos, and it is probably caused by a low endogenous abscisic acid (ABA) content.

Results

Precocious germination of the somatic embryos was successfully avoided by culturing grapevine cv. Mencía embryogenic aggregates over a semipermeable membrane extended on top of the differentiation medium. The weekly analysis of the endogenous ABA and ABA-glucosyl ester (ABA-GE) contents in the aggregates showed their rapid accumulation. The expression profiles of 9-cis-epoxycarotenoid dioxygenase (VvNCED1), 8′-hydroxylase (VvHyd2), UDP-glucosyltransferase (VvUGT) and β-glucosidase (VvBG2) genes in grapevine revealed that the occurrence of a first accumulation peak of endogenous ABA in the second week of culture over the semipermeable membrane was mainly dependent on the expression of the VvNCED1 gene. A second increase in the endogenous ABA content was observed in the fourth week of culture. At this point in the culture, our results suggest that of those genes involved in ABA accumulation, one (VvNCED1) was repressed, while another (VvBG2) was activated. Similarly, of those genes related to a reduction in ABA levels, one (VvUGT) was repressed while another (VvHyd2) was activated. The relative expression level of the VvNCED1 gene in embryogenic aggregates cultured under the same conditions and treated with exogenous ABA revealed the significant downregulation of this gene.

Conclusions

Our results demonstrated the involvement of ABA metabolism in the control of the maturation of grapevine somatic embryos cultured over a semipermeable membrane and two important control points for their endogenous ABA levels. Thus, subtle differences in the expression of the antagonistic genes that control ABA synthesis and degradation could be responsible for the final level of ABA during the maturation of grapevine somatic embryos in vitro. In addition, the treatment of somatic embryos with exogenous ABA suggested the feedback-based control of the expression of the VvNCED1 gene by ABA during the maturation of grapevine somatic embryos.
Impact of statin intake on malignant hyperthermia: an in vitro and in vivo swine study
Authors: Gonzalez Asensio , Iles Tinen L. , Iaizzo Paul A. , Bandschapp Oliver
Published: October 2020

Background

Statin intake is associated with muscular side effects, among which the unmasking of latent myopathies and of malignant hyperthermia (MH) susceptibility have been reported. These findings, together with experimental data in small animals, prompt speculation that statin therapy may compromise the performance of skeletal muscle during diagnostic in vitro contracture tests (IVCT). In addition, statins might reduce triggering thresholds in susceptible individuals (MHS), or exacerbate MH progression. We sought to obtain empirical data to address these questions.

Methods

We compared the responses of 3 different muscles from untreated or simvastatin treated MHS and non-susceptible (MHN) pigs. MHS animals were also invasively monitored for signs of impending MH during sevoflurane anesthesia.

Results

Muscles from statin treated MHS pigs responded with enhanced in vitro contractures to halothane, while responses to caffeine were unaltered by the treatment. Neither agent elicited contractures in muscles from statin treated MHN pigs. In vivo, end- tide pCO2, hemodynamic evolution, plasma pH, potassium and lactate concentrations consistently pointed to mild acceleration of MH development in statin-treated pigs, whereas masseter spasm and rigor faded compared to untreated MHS animals.

Conclusions

The diagnostic sensitivity and specificity of the IVCT remains unchanged by a short-term simvastatin treatment in MHS swine. Evidence of modest enhancement in cardiovascular and metabolic signs of MH, as well as masked pathognomonic muscle rigor observed under simvastatin therapy suggest a potentially misleading influence on the clinical presentation of MH. The findings deserve further study to include other statins and therapeutic regimes.
Validation of myocardial infarction diagnosis in patients with congenital heart disease in Sweden
Authors: Fedchenko Maria , Mandalenakis Zacharias , Hultsberg-Olsson Görel , Dellborg Helena , Eriksson Peter , Dellborg Mikael
Published: October 2020

Background

The population of adults with congenital heart disease (CHD) is growing, and increasingly more patients with CHD reach older ages. Patients with CHD are at an increased risk of myocardial infarction (MI) with increased age. Diagnosing MI in patients with CHD can be challenging in clinical practice owing to a high prevalence of aberrant electrocardiograms, ventricular hypertrophy, and heart failure, among other factors. The National Swedish Patient Register (NPR) is widely used in epidemiological studies; however, MI diagnoses specifically in patients with CHD have never been validated in the NPR.

Methods

We contacted hospitals and medical archive services to request medical records for 249 patients, born during 1970–2012, with both CHD and MI diagnoses and who were randomly selected from the NPR by the Swedish National Board of Health and Welfare. Follow-up was until 2015. We performed a medical chart review to validate the MI diagnoses; we also validated CHD diagnoses to ensure that only patients with confirmed CHD diagnoses were included in the MI validation process.

Results

We received medical records for 96.4% (n = 238/249) of patients for validation of CHD diagnoses. In total, 74.8% (n = 178/238) had a confirmed CHD diagnosis; of these, 70.2% (n = 167) had a fully correct CHD diagnosis in the NPR; a further 4.6% (n = 11) had a CHD diagnosis, but it was misclassified. MI diagnoses were validated in 167 (93.8%) patients with confirmed CHD. Of the patients with confirmed CHD, 88.0% (n = 147/167) had correct MI diagnoses. Patients with non-complex CHD diagnoses had more correct MI diagnoses than patients with complex CHD (91.0%, n = 131 compared with 69.6%, n = 16). The main cause for incorrect MI diagnoses was typographical error, contributing to 50.0% of the incorrect diagnoses.

Conclusions

The validity of MI diagnoses in patients with confirmed CHD in the NPR is high, with nearly 9 of 10 MI diagnoses being correct (88.0%). MI in patients with CHD can safely be studied using the NPR.
Predictive approaches to heterogeneous treatment effects: a scoping review
Authors: Rekkas Alexandros , Paulus Jessica K. , Raman Gowri , Wong John B. , Steyerberg Ewout W. , Rijnbeek Peter R. , Kent David M. , van Klaveren David
Published: October 2020

Background

Recent evidence suggests that there is often substantial variation in the benefits and harms across a trial population. We aimed to identify regression modeling approaches that assess heterogeneity of treatment effect within a randomized clinical trial.

Methods

We performed a literature review using a broad search strategy, complemented by suggestions of a technical expert panel.

Results

The approaches are classified into 3 categories: 1) Risk-based methods (11 papers) use only prognostic factors to define patient subgroups, relying on the mathematical dependency of the absolute risk difference on baseline risk; 2) Treatment effect modeling methods (9 papers) use both prognostic factors and treatment effect modifiers to explore characteristics that interact with the effects of therapy on a relative scale. These methods couple data-driven subgroup identification with approaches to prevent overfitting, such as penalization or use of separate data sets for subgroup identification and effect estimation. 3) Optimal treatment regime methods (12 papers) focus primarily on treatment effect modifiers to classify the trial population into those who benefit from treatment and those who do not. Finally, we also identified papers which describe model evaluation methods (4 papers).

Conclusions

Three classes of approaches were identified to assess heterogeneity of treatment effect. Methodological research, including both simulations and empirical evaluations, is required to compare the available methods in different settings and to derive well-informed guidance for their application in RCT analysis.
Determining factors in the retention of physicians in rural and underdeveloped areas: a systematic review
Authors: Mohammadiaghdam Nasrin , Doshmangir Leila , Babaie Javad , Khabiri Roghayeh , Ponnet Koen
Published: October 2020

Background

Imbalance in distribution of Health Care Workers (HCWs) in a country is a global challenge. Almost all of the rural and underdeveloped areas are struggling with the shortage of HCWs, especially physicians. Therefore, this study aimed to identify factors governing the retention of physicians in rural and underdeveloped areas.

Methods

International databases including Scopus, PubMed, Web of Science, Proquest, and Embase were searched using Mesh terms in order to find peer-reviewed journal articles addressing physicians’ retention factors in rural and underdeveloped areas. The records were screened, and any duplicate results were removed. The quality of the studies was assessed according to the Critical Appraisal Skills Program developed for different types of studies. Then, through content analysis, the related factors were identified from finally selected papers, coded, and categorized.

Results

The initial search resulted in 2312 relevant articles. On the basis of specific selection criteria, 35 full-text articles were finally reviewed.. The major affecting factors in physicians’ retention in rural and underdeveloped regions were classified into the following six categories: 1) financial; 2) career and professional; 3) working conditions; 4) personal; 5) cultural; and 6) living conditions factors.

Conclusion

There is a complex interplay of factors governing physicians’ retention in rural and underdeveloped areas. If health organizations are concerned with physicians’ retention in deprived areas, they should take into account these main factors. Moreover, they should develop policies and strategies to attract and retain physicians in rural and underdeveloped areas.
Effect of poor glycemic control in cognitive performance in the elderly with type 2 diabetes mellitus: The Mexican Health and Aging Study
Authors: Mimenza-Alvarado Alberto J. , Jiménez-Castillo Gilberto A. , Yeverino-Castro Sara G. , Barragán-Berlanga Abel J. , Pérez-Zepeda Mario U. , Ávila-Funes J. Alberto , Aguilar-Navarro Sara G.
Published: October 2020

Background

Cognitive impairment is twice more frequent in elderly with type 2 diabetes mellitus (DM). This study was conducted to determine the association between glycemic control and cognitive performance among community-dwelling elderly persons in Mexico.

Methods

Cross-sectional study conducted in individuals aged 60 years or elderly participating in the 2012 Mexican Health and Aging Study. Type 2 DM participants were classified in 3 groups according to their glycated hemoglobin levels (HbA1c): < 7% (intensive control), 7–7.9% (standard control) or ≥ 8% (poor control), and cognitive performance: low (CCCE ≤44 points), intermediate (44.1–59.52 points), or high (≥59.53 points). Multinomial logistic regression models were constructed to determine this association.

Results

Two hundred sixteen community-dwelling adults aged 60 and older with type 2 diabetes were selected. Subjects in the low cognitive performance group were older (69.7 ± 6.6 vs 65.86 ± 5.18 years, p < .001) and had a lower educational level (2.5 ± 2.6 vs 7.44 ± 4.15 years, p < .000) when compared to the high cognitive performance participants. HbA1c ≥ 8% was associated with having low (Odds Ratio (OR) 3.17, 95% CI 1.17–8.60, p = .024), and intermediate (OR 3.23, 95% CI 1.27–8.20, p = .014) cognitive performance; this trend was not found for HbA1c 7.0–7.9% group.

The multinomial regression analysis showed that the presence of HbA1c ≥ 8% (poor glycemic control) was associated with low (OR 3.17, 95% CI = 1.17–8.60, p = .024), and intermediate (OR 3.23, 95% CI = 1.27–8.20, p = .014) cognitive performance. After adjusting for confounding variables.

Conclusions

Glycemic control with a HbA1c ≥ 8% was associated with worse cognitive performance.
Risk factors for recurrent tuberculosis after successful treatment in a high burden setting: a cohort study
Authors: Cudahy Patrick George Tobias , Wilson Douglas , Cohen Ted
Published: October 2020

Background

People successfully completing treatment for tuberculosis remain at elevated risk for recurrent disease, either from relapse or reinfection. Identifying risk factors for recurrent tuberculosis may help target post-tuberculosis screening and care.

Methods

We enrolled 500 patients with smear-positive pulmonary tuberculosis in South Africa and collected baseline data on demographics, clinical presentation and sputum mycobacterial cultures for 24-loci mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) typing. We used routinely-collected administrative data to identify recurrent episodes of tuberculosis occurring over a median of six years after successful treatment completion.

Results

Of 500 patients initially enrolled, 333 (79%) successfully completed treatment for tuberculosis. During the follow-up period 35 patients with successful treatment (11%) experienced a bacteriologically confirmed tuberculosis recurrence. In our Cox proportional hazards model, a 3+ AFB sputum smear grade was significantly associated with recurrent tuberculosis with a hazard ratio of 3.33 (95% CI 1.44–7.7). The presence of polyclonal M. tuberculosis infection at baseline had a hazard ratio for recurrence of 1.96 (95% CI 0.86–4.48).

Conclusion

Our results indicate that AFB smear grade is independently associated with tuberculosis recurrence after successful treatment for an initial episode while the association between polyclonal M. tuberculosis infection and increased risk of recurrence appears possible.
Evaluation of the performance of an in-house duplex PCR assay targeting the IS6110 and rpoB genes for tuberculosis diagnosis in Cameroon
Authors: Meriki Henry Dilonga , Wung Ndze Henry , Tufon Kukwah Anthony , Tony Nyeke James , Ane-Anyangwe Irene , Cho-Ngwa Fidelis
Published: October 2020

Background

Tuberculosis (TB) remains a major public health concern in many low-income countries accounting for approximately two-thirds of deaths in people living with human immunodeficiency virus (HIV) infection. With prompt, accurate and appropriate treatment, almost all TB disease can be cured. The present study was to evaluate the diagnostic performance of an in-house duplex PCR (D-PCR) usingIS1610andrpoBspecific primers in sputum samples from TB suspected patients.

Methods

A hospital-based cross-sectional study was conducted at the Limbe and Buea Regional Hospitals of the South West Region of Cameroon from June 2016 to April 2017. Sputum samples, decontaminated with hypertonic saline/sodium hydroxide solution were centrifuged and pellets processed for smear microscopy, culture and DNA extraction. Suspected inhibition was resolved by serial dilution of genomic DNA. Results were compared to culture as gold standard as well as a Composite Reference Standard (CRS).

Results

A total of 129 participants aged between 5 to 82 years were enrolled in to the study. The median age of the participants was 37 years (interquartile range, IQR: 27–50 years), with 54.3% being male. Forty-seven samples (36.4%) were positive by direct sputum microscopy, 49 (38%) by microscopy after concentration, 51 (39.5%) by culture and 62 (40.1%) by D-PCR. PCR inhibition was resolved in 85.7% (18/21) of the samples that had inhibition. The overall sensitivity, specificity, positive and negative predictive values, positive and negative likelihood ratios and area under the curve AUC) of the D-PCR was 93.5, 94, 94, 94%, 15.6, 0.005 and 89.0% respectively using CRS as reference. The sensitivities of D-PCR observed among different sample categories were 95.7, 87.5 and 87.5% for smear-and culture-positives, smear-negative/culture-positive, and clinically diagnosed cases respectively.

Conclusion

IS1610andrpoBduplex PCR using relatively cheap decontamination and DNA extraction methods in addition to simple serial dilutions to resolve PCR inhibition shows high sensitivity in the diagnosis of paucibacillary tuberculosis.
Cardiovascular outcomes following percutaneous coronary intervention with drug-eluting balloons in chronic kidney disease: a retrospective analysis
Authors: Jonas Michael , Kagan Maayan , Sella Gal , Haberman Dan , Chernin Gil
Published: October 2020

Background

Chronic kidney disease (CKD) is associated with poorer outcomes following percutaneous coronary intervention (PCI) with drug-eluting stents. Drug-eluting balloons are used for in-stent restenosis and selected cases of de-novo coronary lesions. Little is known regarding the outcomes of individuals with CKD who undergo PCI with drug-eluting balloons. The goal of this study was to assess outcomes of PCI with drug-eluting balloons in individuals with CKD.

Methods

In a retrospective analysis, outcomes of PCI with drug-eluting balloons were compared between 101 patients with CKD and 261 without CKD. CKD was defined as estimated glomerular filtration rate < 60 ml/min/1.73m2. We compared demographics, procedure data and clinical outcomes in the first and second years following the procedure.

Results

Rates of major adverse cardiac events (MACE) and myocardial infarction were higher in patients with than without CKD: 23.8% vs. 13.8%,P < 0.005 and 15.9% vs. 3.8%,P < 0.001, respectively. Rates of target lesion revascularization were similar, 14.9 and 11.5%, respectively,P = 0.4. Shorter duration of dual anti-platelet therapy was observed among patients with than without CKD (10.0 + 3.4 vs. 10.9 + 3.7 months,P < 0.05). First-year hemorrhage episodes were similar in the two groups (0.08 ± 0.4 and 0.03 ± 0.2, respectively,P = 0.2). In a multivariate regression analysis, CKD was associated with increased risks of first year MACE (OR 2.1; 95% confidence interval 1.0-4.3,P < 0.001).

Conclusions

PCI with drug-eluting balloons was associated with increased cardiovascular morbidity and mortality in patients with than without CKD. However, rates of target lesion revascularization were similar in the two groups. Shorter duration of dual anti-platelet therapy was observed in the CKD group.
Exercise as a therapeutic option for acute kidney injury: mechanisms and considerations for the design of future clinical studies
Authors: Asad Anam , Burton James O. , March Daniel S.
Published: October 2020

Acute kidney injury (AKI) is a known risk factor for chronic kidney disease (CKD) and end stage kidney disease (ESKD). The progression from AKI to CKD, despite being well recognised, is not completely understood, although sustained inflammation and fibrosis are implicated. A therapeutic intervention targeting the post AKI stage could reduce the progression to CKD, which has high levels of associated morbidity and mortality. Exercise has known anti-inflammatory effects with animal AKI models demonstrating its use as a therapeutic agent in abrogating renal injury. This suggests the use of an exercise rehabilitation programme in AKI patients following discharge could attenuate renal damage and improve long term patient outcomes. In this review article we outline considerations for future clinical studies of exercise in the AKI population.