bluuebunny/crossref_metadata_2025 huggingface dataset:
Cardiovascular risk assessment in multiple myeloma patients undergoing carfilzomib therapy: a new risk prediction model for cardiovascular adverse events
Authors: Astarita A , Mingrone G , Airale L , Vallelonga F , Catarinella C , Cesareo M , Leone D , Bruno G , Maffei I , Veglio F , Milan A
Published: February 2021

Funding Acknowledgements

Type of funding sources: None.

Background

Cardiovascular adverse events (CVAEs) are closely related to Carfilzomib (CFZ) therapy in multiple myeloma (MM), but validated management protocols are lacking. Moreover, the incidence, nature and risk factors for each type of CVAEs are incompletely characterized.

Purpose

To assess if the European Myeloma Network Guidelines (EMN) protocol is effective on cardiovascular risk assessment before CFZ starting. A prediction model for estimating the probability of CVAEs was developed and validated. Major and hypertensive-related CVAEs were investigated.

Methods

A perspective study on 116 MM patients scheduled for CFZ therapy was conducted from 2015 to 2020. Before CFZ starting, a baseline evaluation, according to the EMN protocol, was performed; during the follow-up, the incidence of CVAEs was detected. The potential risk factors for CVAEs were identified and a risk score was developed.

Results

The rate of all-grade CVAEs was 44.8% (24.1% CTCAE≥3): 14.7% experienced major CVEAs (41.2% arrhythmias, 23.5% acute ischemic cardiopathy as most represented) and 30.2% hypertensive-related CVAEs. At baseline, five independent predictors for all-CVAEs were identified: office systolic blood pressure (p = 0.003), 24-hours blood pressure variability (p = 0.004), left ventricular mass (p = 0.015), pulse wave velocity (p = 0.002) and global longitudinal strain (p = 0.033). The resulting CVAEs risk score allows to define the low- and high-risk groups, obtaining a sensibility of 94% in predicting CVAEs (AUC 0.76).

Conclusions

The comprehensive evaluation of EMN Guidelines is effective in CVAEs prediction. The use of CVAEs risk score will identify the higher risk patients, targeting appropriate follow-ups and organizing effective risk mitigation strategies.

Instrumental determinants with CVAEs Parameters No CVAEs N = 64 [N (%)] CVAEs N = 52[N (%)] P value LV mass/BSA 85.30 ± 19.72 95.14 ± 21.75 0.013 LV hypertrophy [> = 95 g/m2 F > = 115 g/m2 M] 8 (12.7) 16 (30.8) 0.018 LV dilation 5 (9.3) 4 (8.9) 0.949 LV EF % 63.03 ± 6.56 61.96 ± 7.13 0.414 GLS % -22.37 ± 2.56 -21.3 ± 2.46 0.029 LV Diastolic dysfunction 1 (1.6) 0(0) 0.362 PWV 7.41 ± 1.63 8.55 ± 1.855 0.002 PWV ³ 8.75 m/s 10 (17.5) 24 (54.2) 0.000 SBP Systolic Blood Pressure; ABPM Ambulatory Blood Pressure Monitoring; BPV Blood Pressure Variability; BSA Body Surface Area; SD Standard Deviation; EF Ejection Fraction; GLS Global Longitudinal Strain; LV Left Ventricle; PWV Pulse Wave Velocity Abstract Figure. CVAEs risk score
Machine learning: principles and applications for thoracic surgery
Authors: Ostberg Nicolai P , Zafar Mohammad A , Elefteriades John A
Published: February 2021

OBJECTIVES

Machine learning (ML) has experienced a revolutionary decade with advances across many disciplines. We seek to understand how recent advances in ML are going to specifically influence the practice of surgery in the future with a particular focus on thoracic surgery.

METHODS

Review of relevant literature in both technical and clinical domains.

RESULTS

ML is a revolutionary technology that promises to change the way that surgery is practiced in the near future. Spurred by an advance in computing power and the volume of data produced in healthcare, ML has shown remarkable ability to master tasks that had once been reserved for physicians. Supervised learning, unsupervised learning and reinforcement learning are all important techniques that can be leveraged to improve care. Five key applications of ML to cardiac surgery include diagnostics, surgical skill assessment, postoperative prognostication, augmenting intraoperative performance and accelerating translational research. Some key limitations of ML include lack of interpretability, low quality and volumes of relevant clinical data, ethical limitations and difficulties with clinical implementation.

CONCLUSIONS

In the future, the practice of cardiac surgery will be greatly augmented by ML technologies, ultimately leading to improved surgical performance and better patient outcomes.
Diameter change in completely remodelled proximal descending aorta after acute type I dissection repair: implications for estimating the pre-dissection size
Authors: Jung Joon Chul , Sohn Bongyeon , Chang Hyoung Woo , Lee Jae Hang , Kim Dong Jung , Kim Jun Sung , Lim Cheong , Park Kay-Hyun
Published: February 2021

OBJECTIVES

Pre-dissection diameter of the proximal descending thoracic aorta (p-DTA), if available, would be the reference for determining the size of the stent graft or elephant trunk. Acute type B dissection is known to increase p-DTA diameter by 23% (Rylski factor). This study aimed to investigate the accuracy of estimating post-remodelling diameter of the p-DTA based on the Rylski factor and other post-dissection morphological parameters in acute type I dissection, based on the assumption that the post-remodelling diameter is similar to the pre-dissection diameter.

METHODS

In 60 patients with acute type I dissection showing complete remodelling of the p-DTA false lumen after surgical repair, preoperative and post-remodelling computed tomography scans were reviewed. Parameters, including maximal true lumen diameter (TLDmax) and aortic area-derived diameter divided by the Rylski factor (AoDRylski), were measured at the p-DTA.

RESULTS

After complete remodelling, p-DTA diameter decreased by 4.1 mm (P < 0.001). The equivalent to the Rylski factor was 15%. Both TLDmax and AoDRylski frequently showed ≥2 mm discrepancy from post-remodelling aortic diameter (36.7% and 48.3%, respectively, P = 0.30). When 2 parameters coincided within 2 mm, two-third of their estimations were accurate. AoDRylski was more accurate than TLDmax in patients with a large extent of circumferential dissection, and vice versa with less circumferential dissection (P = 0.027).

CONCLUSIONS

Prediction of post-remodelling aortic diameter relying on a single morphologic parameter carries a substantial risk of overestimation and underestimation. Evaluation based on the extent of circumferential dissection together with the 2 parameters may provide a more reliable estimation.
Near-Chromosome-Level Genome Assembly of the Dark Septate Endophyte Laburnicola rhizohalophila: A Model for Investigating Root-Fungus Symbiosis
Authors: He Xinghua , Yuan Zhilin
Published: February 2021

The novel DSE Laburnicola rhizohalophila (Pleosporales, Ascomycota) is frequently found in the halophytic seepweed (Suaeda salsa). In this article, we report a near-chromosome-level hybrid assembly of this fungus using a combination of short-read Illumina data to polish assemblies generated from long-read Nanopore data. The reference genome for L. rhizohalophila was assembled into 26 scaffolds with a total length of 64.0 Mb and a N50 length of 3.15 Mb. Of them, 17 scaffolds approached the length of intact chromosomes, and 5 had telomeres at one end only. A total of 10,891 gene models were predicted. Intriguingly, 27.5 Mb of repeat sequences that accounted for 42.97% of the genome was identified, and long terminal repeat retrotransposons were the most frequent known transposable elements, indicating that transposable element proliferation contributes to its increased genome size. BUSCO analyses using the Fungi_odb10 data set showed that 95.0% of genes were complete. In addition, 292 carbohydrate active enzymes, 33 secondary metabolite clusters, and 84 putative effectors were identified in silico. The resulting high-quality assembly and genome features are not only an important resource for further research on understanding the mechanism of root-fungi symbiotic interactions but will also contribute to comparative analyses of genome biology and evolution within Pleosporalean species.
Extreme diversification driven by parallel events of massive loss of heterozygosity in the hybrid lineage of Candida albicans
Authors: Mixão Verónica , Saus Ester , Boekhout Teun , Gabaldón Toni
Published: February 2021

Candida albicans is the most commonly reported species causing candidiasis. The taxonomic classification of C. albicans and related lineages is controversial, with Candida africana (syn. C. albicans var. africana) and Candida stellatoidea (syn. C. albicans var. stellatoidea) being considered different species or C. albicans varieties depending on the authors. Moreover, recent genomic analyses have suggested a shared hybrid origin of C. albicans and C. africana, but the potential parental lineages remain unidentified. Although the genomes of C. albicans and C. africana have been extensively studied, the genome of C. stellatoidea has not been sequenced so far. In order to get a better understanding of the evolution of the C. albicans clade, and to assess whether C. stellatoidea could represent one of the unknown C. albicans parental lineages, we sequenced C. stellatoidea type strain (CBS 1905). This genome was compared to that of C. albicans and of the closely related lineage C. africana. Our results show that, similarly to C. africana, C. stellatoidea descends from the same hybrid ancestor as other C. albicans strains and that it has undergone a parallel massive loss of heterozygosity.
What Can Serology Tell Us About the Burden of Infertility in Women Caused by Chlamydia?
Authors: Horner Patrick J , Anyalechi Gloria E , Geisler William M
Published: February 2021

Chlamydia  trachomatis (CT) causes pelvic inflammatory disease, which may result in tubal factor infertility (TFI) in women. Serologic assays may be used to determine the proportion of women with and without TFI who have had previous CT infection and to generate estimates of infertility attributable to chlamydia. Unfortunately, most existing CT serologic assays are challenged by low sensitivity and, sometimes, specificity for prior CT infection; however, they are currently the only available tests available to detect prior CT infection. Modeling methods such as finite mixture modeling may be a useful adjunct to quantitative serologic data to obtain better estimates of CT-related infertility. In this article, we review CT serological assays, including the use of antigens preferentially expressed during upper genital tract infection, and suggest future research directions. These methodologic improvements, coupled with creation of new biomarkers for previous CT infection, should improve our understanding of chlamydia’s contribution to female infertility.
Oral Immunotherapy With Human Secretory Immunoglobulin A Improves Survival in the Hamster Model of Clostridioides difficile Infection
Authors: Chiari Estelle F , Weiss William , Simon Michael R , Kiessig Stephan T , Pulse Mark , Brown Stephen C , Gerding Hanne R , Mandago Maurice , Gisch Karina , von Eichel-Streiber Christoph
Published: February 2021

Coadministration of human secretory IgA (sIgA) together with subtherapeutic vancomycin enhanced survival in the Clostridioides difficile infection (CDI) hamster model. Vancomycin (5 or 10 mg/kg × 5 days) plus healthy donor plasma sIgA/monomeric IgA (TID × 21 days) or hyperimmune sIgA/monomeric IgA (BID × 13 days) enhanced survival. Survival was improved compared to vancomycin alone, P = .018 and .039 by log-rank Mantel-Cox, for healthy and hyperimmune sIgA, respectively. Passive immunization with sIgA (recombinant human secretory component plus IgA dimer/polymer from pooled human plasma) can be administered orally and prevents death in a partially treated CDI hamster model.
Settling Interstate Trade Disputes: Lessons from the EFTA Complaints Procedure
Authors: Fahner Johannes Hendrik
Published: February 2021

When the European Free Trade Association (EFTA) was founded 60 years ago, the contracting parties established a dispute settlement procedure that sought to strike a balance between the need to supervise compliance with the EFTA Convention and the need to respect the sovereignty of the member states. The procedure of Article 31 empowered the EFTA Council to hear interstate complaints, establish examining committees, issue recommendations, and authorize retaliation. This article investigates the successes and failures of this mechanism on the basis of historical documents from the EFTA archives. It provides an overview of the complaints that were brought under Article 31 and analyses how the Council exercised its functions in dealing with these cases. The article evaluates why the complaints procedure quickly fell into disuse, finding that it failed to provide a real alternative to ordinary discussions in the Council. The article argues that lessons can be drawn from this understudied chapter of European integration, concluding that systems of dispute settlement in international economic law should avoid fusing diplomatic and judicial elements if this might preclude an independent evaluation of the legal questions raised in the context of a concrete dispute.
Off-pump external pericardial patch repair for post-infarct left ventricular free wall rupture: a case series
Authors: Mohamed S , Mazhar K , Patel A J , Jeeji R , Ridley P , Balacumaraswami L
Published: February 2021

We describe an off-pump surgical approach to this challenging condition supported by our results from a case series, which would add to existing literature in the management of this life-threatening complication. We identified seven patients who underwent surgical intervention for left ventricular (LV) free wall rupture at our institution. They were all diagnosed to have cardiac tamponade secondary to free wall rupture of the LV in the presence of acute myocardial infarction. The surgical technique comprised of utilizing an external pericardial patch which was secured using surgical biological glues (fibrin-based sealants or gelatin hydrogels). The 30-day mortality, 1-year survival and 2-year survival were 57, 42 and 42%, respectively. Advanced age, female gender and use of cardiopulmonary bypass were characteristics that were not significantly associated with survival. We advocate the use of an off-pump external pericardial patch repair strategy as a ‘bridge to recovery’ in this extremely high-risk group of patients.
Sternal mass caused by Mycobacterium tuberculosis in an immunocompetent young adult
Authors: Tordjman Mickael , Pouchelon Clara , Canouï Etienne , Omri Manel , Dion Elisabeth
Published: February 2021

Differential diagnosis of sternal masses in migrant patients should include tuberculosis. Imaging characteristics on computed tomography scan and magnetic resonance imaging are of great interest. Sternal tuberculous abscess exhibits a slightly hyperintense rim on T1-weighted pre-contrast images that can be associated with osteomyelitis of the sternum.
Ultra high-risk PFA ependymoma is characterized by loss of chromosome 6q
Authors: Baroni Lorena V , Sundaresan Lakshmikirupa , Heled Ayala , Coltin Hallie , Pajtler Kristian W , Lin Tong , Merchant Thomas E , McLendon Roger , Faria Claudia , Buntine Molly , White Christine L , Pfister Stefan M , Gilbert Mark R , Armstrong Terri S , Bouffet Eric , Kumar Sachin , Taylor Michael D , Aldape Kenneth D , Ellison David W , Gottardo Nicholas G , Kool Marcel , Korshunov Andrey , Hansford Jordan R , Ramaswamy Vijay
Published: February 2021

Background

Within PF-EPN-A, 1q gain is a marker of poor prognosis, however, it is unclear if within PF-EPN-A additional cytogenetic events exist which can refine risk stratification.

Methods

Five independent non-overlapping cohorts of PF-EPN-A were analyzed applying genome-wide methylation arrays for chromosomal and clinical variables predictive of survival.

Results

Across all cohorts, 663 PF-EPN-A were identified. The most common broad copy number event was 1q gain (18.9%), followed by 6q loss (8.6%), 9p gain (6.5%), and 22q loss (6.8%). Within 1q gain tumors, there was significant enrichment for 6q loss (17.7%), 10q loss (16.9%), and 16q loss (15.3%). The 5-year progression-free survival (PFS) was strikingly worse in those patients with 6q loss, with a 5-year PFS of 50% (95% CI 45%-55%) for balanced tumors, compared with 32% (95% CI 24%-44%) for 1q gain only, 7.3% (95% CI 2.0%-27%) for 6q loss only and 0 for both 1q gain and 6q loss (P = 1.65 × 10−13). After accounting for treatment, 6q loss remained the most significant independent predictor of survival in PF-EPN-A but is not in PF-EPN-B. Distant relapses were more common in 1q gain irrespective of 6q loss. RNA sequencing comparing 6q loss to 6q balanced PF-EPN-A suggests that 6q loss forms a biologically distinct group.

Conclusions

We have identified an ultra high-risk PF-EPN-A ependymoma subgroup, which can be reliably ascertained using cytogenetic markers in routine clinical use. A change in treatment paradigm is urgently needed for this particular subset of PF-EPN-A where novel therapies should be prioritized for upfront therapy.
Baseline Frailty Status Influences Recovery Patterns and Outcomes Following Alignment Correction of Cervical Deformity
Authors: Pierce Katherine E , Passias Peter G , Daniels Alan H , Lafage Renaud , Ahmad Waleed , Naessig Sara , Lafage Virginie , Protopsaltis Themistocles , Eastlack Robert , Hart Robert , Burton Douglas , Bess Shay , Schwab Frank , Shaffrey Christopher , Smith Justin S , Ames Christopher ,   on behalf of the International Spine Study Group (ISSG)
Published: February 2021

BACKGROUND

Frailty severity may be an important determinant for impaired recovery after cervical spine deformity (CD) corrective surgery.

OBJECTIVE

To evaluate postop clinical recovery among CD patients between frailty states undergoing primary procedures.

METHODS

Patients >18 yr old undergoing surgery for CD with health-related quality of life (HRQL) data at baseline, 3-mo, and 1-yr postoperative were identified. Patients were stratified by the modified CD frailty index scale from 0 to 1 (no frailty [NF] <0.3, mild/severe fraily [F] >0.3). Patients in NF and F groups were propensity score matched for TS-CL (T1 slope [TS] minus angle between the C2 inferior end plate and the C7 inferior end plate [CL]) to control for baseline deformity. Area under the curve was calculated for follow-up time intervals determining overall normalized, time-adjusted HRQL outcomes; Integrated Health State (IHS) was compared between NF and F groups.

RESULTS

A total of 106 CD patients were included (61.7 yr, 66% F, 27.7 kg/m2)—by frailty group: 52.8% NF, 47.2% F. After propensity score matching for TS-CL (mean: 38.1°), 38 patients remained in each of the NF and F groups. IHS-adjusted HRQL outcomes from baseline to 1 yr showed a significant difference in Euro-Qol 5 Dimension scores (NF: 1.02, F: 1.07, P = .016). No significant differences were found in the IHS Neck Disability Index (NDI) and modified Japanese Orthopedic Association between frailty groups (P > .05). F patients had more postop major complications (31.3%) compared to the NF (8.9%), P = .004, though DJK occurrence and reoperation between the groups was not significant.

CONCLUSION

While all groups exhibited improved postop disability and pain scores, frail patients experienced greater amount of improvement in overall health state compared to baseline disability. This signifies that with frailty severity, patients have more room for improvement postop compared to baseline quality of life.
Specific decorations of 17-hydroxygeranyllinalool diterpene glycosides solve the autotoxicity problem of chemical defense inNicotiana attenuata
Authors: Heiling Sven , Llorca Lucas Cortes , Li Jiancai , Gase Klaus , Schmidt Axel , Schäfer Martin , Schneider Bernd , Halitschke Rayko , Gaquerel Emmanuel , Baldwin Ian Thomas
Published: February 2021

The native diploid tobacco Nicotiana attenuata produces abundant, potent anti-herbivore defense metabolites known as 17-hydroxygeranyllinalool diterpene glycosides (HGL-DTGs) whose glycosylation and malonylation biosynthetic steps are regulated by jasmonate signaling. To characterize the biosynthetic pathway of HGL-DTGs, we conducted a genome-wide analysis of uridine diphosphate glycosyltransferases (UGTs) and identified 107 family-1 UGT members. The transcript levels of three UGTs were highly correlated with the transcript levels two key HGL-DTG biosynthetic genes: geranylgeranyl diphosphate synthase (NaGGPPS) and geranyllinalool synthase (NaGLS). NaGLS’s role in HGL-DTG biosynthesis was confirmed by virus-induced gene silencing. Silencing the Uridine diphosphate (UDP)-rhamnosyltransferase gene UGT91T1 demonstrated its role in the rhamnosylation of HGL-DTGs. In vitro enzyme assays revealed that UGT74P3 and UGT74P4 use UDP-glucose for the glucosylation of 17-hydroxygeranyllinalool (17-HGL) to lyciumoside I. Plants with stable silencing of UGT74P3 and UGT74P5 were severely developmentally deformed, pointing to a phytotoxic effect of the aglycone. The application of synthetic 17-HGL and silencing of the UGTs in HGL-DTG-free plants confirmed this phytotoxic effect. Feeding assays with tobacco hornworm (Manduca sexta) larvae revealed the defensive functions of the glucosylation and rhamnosylation steps in HGL-DTG biosynthesis. Glucosylation of 17-HGL is therefore a critical step that contributes to the resulting metabolites’ defensive function and solves the autotoxicity problem of this potent chemical defense.
Social Work Research on Immigrants: A Content Analysis of Leading Journals from 2007 to 2016
Authors: Diaz-Strong Daysi Ximena , Roth Benjamin J. , Velazquillo Angelica , Zuch Michael
Published: February 2021

International migration has emerged as one of the most controversial phenomena of the 21st century. The complexity and implications of global migrations require that social work practitioners and researchers have access to data-informed research and critical analyses. However, the content of recent social work research on international migration has not been adequately examined to assess whether and to what extent this substantive area is being addressed. This article explores how social work research published in five leading social work journals—Health & Social Work, Research on Social Work Practice, Social Service Review, Social Work, and Social Work Research—is advancing our understanding of international migration and where it may be lacking. Focusing on articles published between 2007 and 2016, the authors analyzed content addressing immigrants and refugees. The content analysis indicates that social work research is making a strong contribution in the area of mental health but is not adequately addressing critical dimensions of stratification, including race, ethnicity, and legal status. Authors also find ambiguity in how “immigrant” is defined and in the generation(s) addressed. Authors argue that maximizing social work’s contributions requires offering more nuanced definitions of the immigrant populations addressed and paying greater analytical attention to dimensions of inequality.
Ammonium application mitigates the effects of elevated carbon dioxide on the carbon/nitrogen balance ofPhoebe bourneiseedlings
Authors: Wang Xiao , Wei Xiaoli , Wu Gaoyin , Chen Shengqun
Published: February 2021

The study of plant responses to increases in atmospheric carbon dioxide (CO2) concentration is crucial to understand and to predict the effect of future global climate change on plant adaptation and evolution. Increasing amount of nitrogen (N) can promote the positive effect of CO2, while how N forms would modify the degree of CO2 effect is rarely studied. The aim of this study was to determine whether the amount and form of nitrogen (N) could mitigate the effects of elevated CO2 (eCO2) on enzyme activities related to carbon (C) and N metabolism, the C/N ratio, and growth of Phoebe bournei (Hemsl.) Y.C. Yang. One-year-old P. bournei seedlings were grown in an open-top air chamber under either an ambient CO2 (aCO2) (350 ± 70 μmol•mol−1) or an eCO2 (700 ± 10 μmol•mol−1) concentration and cultivated in soil treated with either moderate (0.8 g per seedling) or high applications (1.2 g per seedling) of nitrate or ammonium. In seedlings treated with a moderate level of nitrate, the activities of key enzymes involved in C and N metabolism (i.e., Rubisco, Rubisco activase and glutamine synthetase) were lower under eCO2 than under aCO2. By contrast, key enzyme activities (except GS) in seedlings treated with high nitrate or ammonium were not significantly different between aCO2 and eCO2 or higher under eCO2 than under aCO2. The C/N ratio of seedlings treated with moderate or high nitrate under eCO2was significantly changed compared with the seedlings grown under aCO2, whereas the C/N ratio of seedlings treated with ammonium was not significantly different between aCO2 and eCO2. Therefore, under eCO2, application of ammonium can be beneficial C and N metabolism and mitigate effects on the C/N ratio.
Proteobacteria Contain Diverse flg22 Epitopes That Elicit Varying Immune Responses in Arabidopsis thaliana
Authors: Cheng Janis H. T. , Bredow Melissa , Monaghan Jacqueline , diCenzo George C.
Published: February 2021

Bacterial flagellin protein is a potent microbe-associated molecular pattern. Immune responses are triggered by a 22-amino-acid epitope derived from flagellin, known as flg22, upon detection by the pattern recognition receptor FLAGELLIN-SENSING2 (FLS2) in multiple plant species. However, increasing evidence suggests that flg22 epitopes of several bacterial species are not universally immunogenic to plants. We investigated whether flg22 immunogenicity systematically differs between classes of the phylum Proteobacteria, using a dataset of 2,470 flg22 sequences. To predict which species encode highly immunogenic flg22 epitopes, we queried a custom motif (11[ST]xx[DN][DN]xAGxxI21) in the flg22 sequences, followed by sequence conservation analysis and protein structural modeling. These data led us to hypothesize that most flg22 epitopes of the γ- and β-Proteobacteria are highly immunogenic, whereas most flg22 epitopes of the α-, δ-, and ε-Proteobacteria are weakly to moderately immunogenic. To test this hypothesis, we generated synthetic peptides representative of the flg22 epitopes of each proteobacterial class, and we monitored their ability to elicit an immune response in Arabidopsis thaliana. The flg22 peptides of γ- and β-Proteobacteria triggered strong oxidative bursts, whereas peptides from the ε-, δ-, and α-Proteobacteria triggered moderate, weak, or no response, respectively. These data suggest flg22 immunogenicity is not highly conserved across the phylum Proteobacteria. We postulate that sequence divergence of each taxonomic class was present prior to the evolution of FLS2, and that the ligand specificity of A. thaliana FLS2 was driven by the flg22 epitopes of the γ- and β-Proteobacteria, a monophyletic group containing many common phytopathogens.

[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY 4.0 International license .
Genome-Wide Association Studies for Fusarium Head Blight Resistance and Its Trade-Off With Grain Yield in Soft Red Winter Wheat
Authors: Gaire Rupesh , Brown-Guedira Gina , Dong Yanhong , Ohm Herbert , Mohammadi Mohsen
Published: February 2021

Identification of quantitative trait loci for Fusarium head blight (FHB) resistance from different sources and pyramiding them into cultivars could provide effective protection against FHB. The objective of this study was to characterize a soft red winter wheat (SRWW) breeding population that has been subjected to intense germplasm introduction and alien introgression for FHB resistance in the past. The population was evaluated under misted FHB nurseries inoculated with Fusarium graminearum-infested corn spawn for two years. Phenotypic data included disease incidence (INC), disease severity (SEV), Fusarium damaged kernels (FDK), FHB index (FHBdx), and deoxynivalenol concentration (DON). Genome-wide association studies using 13,784 SNP markers identified 25 genomic regions at -logP ≥ 4.0 that were associated with five FHB-related traits. Of these 25, the marker trait associations that explained more than 5% phenotypic variation were localized on chromosomes 1A, 2B, 3B, 5A, 7A, 7B, and 7D, and from diverse sources including adapted SRWW lines such as Truman and Bess, and unadapted common wheat lines such as Ning7840 and Fundulea 201R. Furthermore, individuals with favorable alleles at the four loci Fhb1, Qfhb.nc-2B.1 (Q2B.1), Q7D.1, and Q7D.2 showed better FDK and DON scores (but not INC, SEV, and FHBdx) compared with other allelic combinations. Our data also showed while pyramiding multiple loci provides protection against FHB disease, it has a significant trade-off with grain yield.
Bendamustine in association with rituximab for first-line treatment of diffuse large B-cell lymphoma in frail patients ineligible for R-CHOP/R-CHOP-like treatments
Authors: Castelli Roberto , Gidaro Antonio , Deliliers Giorgio L. , Bergamaschini Luigi
Published: February 2021

R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) has been considered the standard of care for diffuse large B cell lymphoma (DLBCL) patients, including in the elderlies, and represent the current standard treatment. Ineligibility for R-CHOP-like treatments seems to be associated with shorter survival. Recent studies have shown that bendamustine and rituximab is linked, in elderly patients affected by DLBCL. Here we report our experience with BR in 40 elderly frail patients affected by DLBCL ineligibles for R-CHOP. The OOR was 77.5%, with 22 complete responses and 9 partial responses statistical analysis showed no significant difference in overall survival (OS) between patients aged 80 years and older and patients younger than 80 years (6·4 vs. 10·2 months, respectively, P = 0·43). Complete responders were more likely patients with good performance status, (ECOG 0-1) 13 patients (60%), 9 patients (40%) were ECOG 2; of the 9 patients who achieved partial response, 7 patients had ECOG 0-1 and 2 patients had ECOG 2. Four patients had stable disease. Progression-free survival (PFS) median PFS was 13.5 months. These preliminary results showed that bendamustine and rituximab has been associated with high response rates, acceptable toxicity in frail DLBCL patients and high rate of OSS. In older patients with advanced IPI scores, no significant difference in OS were observed between patients aged 80 years and older and patients younger than 80 years. We conclude that bendamustine and rituximab seems to be a reasonable alternative for frail DLBCL patients.
The paradoxical pharmacological mechanisms of lenalidomide and bortezomib in the treatment of multiple myeloma
Authors: Wang Busong , Duan Jingjing , Zhou Liang
Published: February 2021

The combination of bortezomib (Velcade, PS-341) and lenalidomide (Revlimid) for the treatment of multiple myeloma was proved by USA Food and Drug Administration in 2006. Lenalidomide prevents the proliferation of multiple myeloma cells through binding to cereblon and promoting the ubiquitinational degradation of IKZF1 (Ikaros)/IKZF3 (Aiolos). However, the proteasome inhibitor bortezomib would inhibit the ubiquitinational degradation of IKZF1/IKZF3. How bortezomib could not block the antiproliferative effect of lenalidomide on multiple myeloma cells, which is the paradoxical pharmacological mechanisms in multiple myeloma. In this review, we summarized recent advances in molecular mechanisms underlying the combination of bortezomib and lenalidomide for the treatment multiple myeloma, discussed the paradoxical pharmacological mechanisms of lenalidomide and bortezomib in the treatment of multiple myeloma.
Tuberculosis cases in a prison in the extreme south of Brazil
Authors: Venske Bierhals Dienefer , Busatto Caroline , Silveira Maria da Penha da Rosa , da Matta Talaier Edilon , Silva Ana Bárbara Scholante , Reis Ana Julia , von Groll Andrea , da Silva Pedro Eduardo Almeida , Ramis Ivy Bastos
Published: February 2021

Introduction. Tuberculosis (TB) control is a challenge, especially in vulnerable populations, such as prisoners.

Hypothesis. In prison houses, the transmission of micro-organisms that cause infectious diseases can occur due to the susceptibility and immune compromise of prisoners, and due to the precarious physical conditions of the prison houses. However, strategies such as monitoring by health professionals, can mitigate the transmission of these micro-organisms, as well as, reduce the number of coinfections and antimicrobials resistance.

Aim. This study attempted to analyse the dynamics of transmission and the antimicrobial resistance profile of

Mycobacterium tuberculosis

strains obtained from prisoners and to characterize the epidemiological, clinical and laboratory profiles of prisoners diagnosed with TB.

Methodology. A cross-sectional and retrospective study was conducted with sputum samples collected from 228 distinct prisoners who were treated at the Health Unit located in the Regional Penitentiary of Rio Grande, Rio Grande do Sul, Brazil. The antimicrobial resistance profile of the strains was evaluated using the Resazurin Microtiter Assay and the transmission dynamics was investigated using 15-loci MIRU-VNTR.

Results. Thirty-five patients (15.4 %) were diagnosed with TB, and when a TB/HIV coinfection was assessed, 8.6 % (3/35) of the patients were positive. In addition, all patients with results available for HBV, HCV, syphilis and diabetes mellitus were negative. Based on the genotypic profile, 55.9 % of the clinical isolates were grouped into five groups. One isolate with mono-resistance to isoniazid and two with mono-resistance to streptomycin were found.

Conclusion. The presence of a Health Unit may have influenced the low numbers of TB/HIV, TB/HBV, TB/HCV, TB/syphilis coinfections and TB cases resistant to antimicrobials. Recent

M. tuberculosis

transmission can be inferred based on the high percentage of formatting of clusters. This situation stresses the need to improve active and passive detection, the screening of individuals for TB upon entrance into prison for early detection, and the implementation of prophylactic measures to reduce

M. tuberculosis

transmission.
Activin A correlates with the worst outcomes in COVID-19 patients, and can be induced by cytokines via the IKK/NF-kappa B pathway
Authors: McAleavy Megan , Zhang Qian , Xu Jianing , Pan Li , Wakai Matthew , Ehmann Peter J. , Wipperman Matthew F. , Shavlakadze Tea , Hamon Sara C. , Boyapati Anita , Morton Lori G. , Kyratsous Christos A. , Glass David J.
Published: February 2021

A fraction of COVID-19 patients develop the most severe form, characterized by Acute Respiratory Disease Syndrome (ARDS). The molecular mechanisms causing COVID-19-induced ARDS have yet to be defined, though many studies have documented an increase in cytokines known as a “cytokine storm.” Here, we demonstrate that cytokines that activate the NF-kappaB pathway can induce Activin A and its downstream marker, FLRG. In hospitalized COVID-19 patients elevated Activin A/FLRG at baseline were predictive of the most severe longitudinal outcomes of COVID-19, including the need for mechanical ventilation, lack of clinical improvement and all-cause mortality. Patients with Activin A/FLRG above the sample median were 2.6/2.9 times more likely to die, relative to patients with levels below the sample median, respectively. The study indicates high levels of Activin A and FLRG put patients at risk of ARDS, and blockade of Activin A may be beneficial in treating COVID-19 patients experiencing ARDS.
Impact on Mental Health of students due to restriction caused by COVID-19 pandemic: Cross-sectional study
Authors: Chaudhary Amar Prashad , Sonar Narayan Sah , TR Jamuna , Banerjee Moumita , Yadav Shailesh
Published: February 2021

Background

The aim of the study was to investigate fear, depression and anxiety symptoms among students of India due to COVID-19 pandemic and its restriction.

Method

The cross-sectional web-based research was conducted between mid-November and mid-December 2020 with the objective of understanding the psychological and behavioral consequences of the COVID-19 pandemic effect on students due to the constraint of forced control. The questionnaire included a) socio-demographic questions and b) psychometric scales evaluating the psychological and behavioral impact caused by COVID-19 pandemic and restrictions.

Results

Total number of 324 students participated in this study in which 44.4% were male and 55.6% were female. Fear of COVID-19 scale showed 68.8% of students had high fear, 24.4% had moderate to severe depression and 51.5% had moderate to severe anxiety. The correlation of fear of COVID-19 scale (FCV-19s) with Generalized Anxiety scale (GAD-7) and brief patient health questionnaire scale (PHQ-9) was found to be 0.492 and 0.474 respectively.

Conclusion

This research concludes that there is a very strong fear of COVID-19 among students, along with anxiety and depression symptoms. This study also concludes that the fear of the COVID-19 scale has strong positive correlation with the anxiety (GAD-7) and depression (PHQ-9) scales.
Influence of sex on disease severity in children with COVID-19 and Multisystem Inflammatory Syndrome in Latin America
Authors: Brizuela Martin , Lenzi Jacopo , Ulloa-Gutiérrez Rolando , Yassef Antúnez-Montes Omar , Aida Jorge Alberto Rios , del Aguila Olguita , Arteaga-Menchaca Erick , Campos Francisco , Uribe Fadia , Buitrago Andrea Parra , Londoño Lina Maria Betancur , Gómez-Vargas Jessica , Yock-Corrales Adriana , Buonsenso Danilo
Published: February 2021

Data from adult studies how that COVID-19 is more severe in men than women. However, no data are available for the pediatric population. For this reason, we performed this study aiming to understand if sex influenced disease severity and outcomes in a large cohort of latin-american children with COVID-19 and Multisystem Inflammatory Syndrome (MIS-C). We found that a higher percentage of male children developed MIS-C (8.9% vs 5% in females) and died (1.2% and 0.4% in females), although on multivariate adjusted analyses the only statistically significant difference was found in need of hospitalization, with females less frequently admitted compared with boys (25.6% vs 35.4%). This data are preliminary and need further independent studies to better assess the role of sex.
L18F substrain of SARS-CoV-2 VOC-202012/01 is rapidly spreading in England
Authors: Grabowski Frederic , Kochańczyk Marek , Lipniacki Tomasz
Published: February 2021

The Variant of Concern (VOC)-202012/01 (also known as B.1.1.7) is a rapidly growing lineage of SARS-CoV-2. In January 2021, VOC-202012/01 constituted about 80% of SARS-CoV-2 genomes sequenced in England and was present in 27 out of 29 countries that reported at least 50 viral genomes. As this strain will likely spread globally towards fixation, it is important to monitor its molecular evolution. Based on GISAID data we systematically estimated growth rates of mutations acquired by the VOC lineage to find that L18F substitution in viral spike protein has initiated a substrain characterized by replicative advantage of 1.70 [95% CI: 1.56–1.96] in relation to the remaining VOC-202012/01 substrains. The L18F mutation is of significance because when recently analyzed in the context of the South African strain 501Y.V2 it has been found to compromise binding of neutralizing antibodies. We additionally indicate three mutations that were acquired by VOC-202012/01 in the receptor binding motif of spike, specifically E484K, F490S, and S494P, that may also give rise to escape mutants. Such mutants may hinder efficiency of existing vaccines and expand in response to the increasing after-infection or vaccine-induced seroprevalence.
Galectin-3 as a potential prognostic biomarker of severe COVID-19 in SARS-CoV-2 infected patients
Authors: Cervantes-Alvarez Eduardo , Rosa Nathaly Limon-de la , Salgado-de la Mora Moisés , Valdez-Sandoval Paola , Palacios-Jiménez Mildred , Rodriguez-Alvarez Fátima , Vera-Maldonado Brenda I. , Aguirre-Aguilar Eduardo , Escobar-Valderrama Juan Manuel , Alanis-Mendizabal Jorge , Méndez-Guerrero Osvely , Tejeda-Dominguez Farid , Torres-Ruíz Jiram , Gómez-Martín Diana , Colborn Kathryn L , Kershenobich David , Huang Christene A , Navarro-Alvarez Nalu
Published: February 2021

BACKGROUND

Prognostic biomarkers are needed to identify patients at high-risk for severe COVID-19. Galectin-3 is known to drive neutrophil infiltration and release of pro-inflammatory cytokines contributing to airway inflammation.

METHODS

In this prospective cohort, we assessed galectin-3 levels in 156 hospitalized patients with confirmed COVID-19. COVID-19 patients were diagnosed as eithercritical(>50% lung damage) ormoderate(<50% of lung damage) based on computerized tomography. Patients who required invasive mechanical ventilation (IMV) and/or died during hospitalization were categorized as having asevere outcome, and anon-severe outcomeif they were discharged and none of the former occurred.

RESULTS

Elevated serum galectin-3 was significantly higher in critical patients compared to moderate ones (35.91 ± 19.37 ng/mL vs. 25 ± 14.85 ng/mL, p<0.0001). Patients who progressed to asevere outcomeincluding IMV and/or in-hospital death, presented higher galectin-3 levels (41.17 ng/mL [IQR 29.71 – 52.25] vs. 23.76 ng/mL [IQR 15.78 – 33.97] compared to those of a non-severe outcome, p<0.0001). Galectin-3 discriminated well between those with severe and non-severe outcome, with an AUC of 0.75 (95% CI 0.67 – 0.84, p<0.0001) and was found to be an independent predictor of severe outcome regardless of the percentage of lung involvement. Additionally, the combination of galectin-3, CRP and albumin, significantly improved its individual predicting ability with an AUC 0.84 (95% CI 0.77 – 0.91, p<0.0001).

CONCLUSION

Circulating galectin-3 levels can be used to predict severe outcomes in COVID-19 patients, including the requirement of mechanical ventilation and/or death, regardless of the initial severity of the disease.
Development of a Community Orientation Program (COP) as a Community-Based Medical Education method for undergraduate medical students: An experience from India
Authors: Narapureddy Bayapa Reddy , Kahn Shakeer Patan , Deepthi C Sravana , Chaudhuri Sirshendu , John KR , Chandrasekar Chittooru , Babu Surendra , Nagoor Khadervali , Jeeragyal Devika , Jawahar Basha K. , Nell Theo
Published: February 2021

Background

Intraregional cultural and linguistic differences are common in the Low- and Middle-income countries. They must focus on innovative teaching for the undergraduate (UG) medical students to make them sensitive to the social and contextual determinants of health to achieve the health for all goal. The early introduction of community-based medical education could be a game changing strategy.

Objectives

To describe the methods, evaluation, implication, and challenges of a Community Orientation Programme (COP) adopted for the Indian Medical Graduates (IMG). Methods: The COP was arranged for the first-year UG students, including the community and the local administration. The program was divided into phases like-initial preparation, theoretical sessions, field visits, group activities, data analysis, and dissemination of the findings. In this learner-centric, supervised educational program, the key aim was to focus on developing students’ communication skills, observation power and enhancing their motivation for learning new things through collaborative learning. A mixture of adult learning theories like behaviorism, cognitivism, constructivism, sociocultural theory, critical theory, and humanism included keeping the students’ needs, cultural differences, and varying motivational levels. A structured feedback mechanism from the students was developed to identify the gaps.

Conclusion

The COP has provided a holistic learning framework for the students based on several complementary learning theories in the Indian context. It has touched upon most of the national- and institutional-level objectives envisioned by the regulatory body for the IMGs. All stakeholders should promote such programs and solve the challenges collectively.
Multivariate spatio-temporal analysis of the global COVID-19 pandemic
Authors: Xiang Wen , Swallow Ben
Published: February 2021

The COVID-19 pandemic has caused significant mortality and disruption on a global scale not seen in living memory. Understanding the spatial and temporal vectors of transmission as well as similarities in the trajectories of recorded cases and deaths across countries can aid in understanding the benefit or otherwise of varying interventions and control strategies on virus transmission. It can also highlight emerging globa trends as they occur. Data on number of cases and deaths across the globe have been made available through a variety of databases and provide a wide range of opportunities for the application of multivariate statistical methods to extract information on similarity or difference from them. Here we conduct spatial and temporal multivariate statistical analyses of global COVID-19 cases and deaths for the period spanning January to August 2020, using a variety of distance based multivariate methods to cluster countries according to similar temporal trends in cases and deaths resulting from COVID-19. We also use novel air passenger data as a proxy for movement between countries. The air passenger movement can act as an important vector of transmission and thus scaling covariance matrices before conducting dimension reduction techniques can account for known structures in the data and help highlight important residual spatial and/or temporal trends that may then be attributable to the success of interventions or other cultural differences. Global temporal structure is found to be of significantly more importance than local spatial structure in terms of global dynamics. Our results highlight a significant global change in case and mortality daynamics from early-August, consistent in timing with the emergence of new strains with highger levels of transmission. We propose the methodology offers great potential in real-time analysis of complex, noisy spatio-temporal data and the extraction of emerging changes in pandemic dynamics that can support policy and decision makers.
Two forms of sexual dimorphism in gene expression inDrosophila melanogaster: their coincidence and evolutionary genetics
Authors: Singh Amardeep , Agrawal Aneil F.
Published: February 2021

Phenotypic sexual dimorphism can be mediated by sex differences in gene expression. We examine two forms of sexual dimorphism in gene expression inDrosophila melanogaster: (i) sex-biased gene expression (SBGE) in which the sexes differ in the amount a gene is expressed and (ii) sexual dimorphism in isoform usage, i.e., sex-specific splicing (SSS). In whole body (but not head) expression, we find a negative association between SBGE and SSS, possibly suggesting these are alternate routes to resolving sexual antagonistic selection. Next, we evaluate whether expression dimorphism contributes to the heterogeneity among genes inrmf, the intersexual genetic correlation in body expression that constrains the extent to which a gene’s expression can evolve independently between the sexes. We find lowerrmfvalues for genes with than without SSS. We find higherrmfvalues for male- than female-biased genes (except genes with extreme male-bias), even though male-biased genes are known to have greater evolutionary divergence in expression. Finally, we examine population genetic patterns in relation to SBGE and SSS because genes with expression dimorphism have likely experienced a history of sex differences in selection. SSS is associated with reduced values of Tajima’sDand elevatedDirection of Selection(DoS) values, suggestive of higher rates of adaptive evolution. ThoughDoSis highly elevated for genes with extreme male bias,DoSotherwise tends to decline from female-biased to unbiased to male-biased genes. Collectively, the results indicate that SBGE and SSS are differentially distributed across the genome and are associated with different forms of selection.