bluuebunny/crossref_metadata_2025 huggingface dataset:
Culture, Status, and Hypocrisy: High-Status People Who Don’t Practice What They Preach Are Viewed as Worse in the United States Than China
Authors: Dong Mengchen , van Prooijen Jan-Willem , Wu Song , van Lange Paul A. M.
Published: February 2021

Status holders across societies often take moral initiatives to navigate group practices toward collective goods; however, little is known about how different societies (e.g., the United States vs. China) evaluate high- (vs. low-) status holders’ transgressions of preached morals. Two preregistered studies (total N = 1,374) examined how status information (occupational rank in Study 1 and social prestige in Study 2) influences moral judgments of norm violations, as a function of word–deed contradiction and cultural independence/interdependence. Both studies revealed that high- (vs. low-) status targets’ word–deed contradictions (vs. noncontradictions) were condemned more harshly in the United States but not China. Mediation analyses suggested that Americans attributed more, but Chinese attributed less, selfish motives to higher status targets’ word–deed contradictions. Cultural in(ter)dependence influences not only whom to confer status as norm enforcers but also whom to (not) blame as norm violators.
Prolonged survival with systemic chemotherapy in an advanced malignant mesothelioma: A case report
Authors: Elghali Mohamed Amine , Bourigua Rym , Belaid Imtinene , Nasri Salsabil , Mestiri Sara , Yaacoub Sara , Makni Amine , Letaief Rached
Published: February 2021

Peritoneal mesotheliomas are very rare tumors. Their prognosis is poor, average survival does not exceed 1 year after peritoneal cytoreduction. Systemic chemotherapy is considered to have no proven value in the management of peritoneal mesotheliomas. Objective responses with systemic chemotherapy are very rare. We report here a case of an advanced peritoneal mesothelioma which achieved an unexpected partial response with chemotherapy, allowing the patient to have a right colectomy. The patient was referred to a specialized center on HIPEC, but taking in account the long awaiting interval, the HIPEC was judged to be inefficient and then the poursuit of 6 cycles of systemic chemotherapy was decided. The patient is still alive without any symptom and with a good performance status at 59 months after diagnosis. Throughout our case, we provide an encouraging evidence of the role of initial systemic chemotherapy in the downstaging of initially unresectable primary malignant mesothelioma and in the improvement of overall survival.
Adapting Nephrology Training Curriculum in the Era of COVID-19
Authors: Cunningham Amanda , Hung Wayne , Levin Adeera , Jamal Abeed
Published: February 2021

Purpose of review:

The COVID-19 pandemic has widespread implications not only for clinical practice but also for academic medicine and postgraduate training. The need to promote physical distancing and flexibility within our department has generated important revisions to the core curriculum for the Adult Nephrology Training Program in Vancouver, Canada.

Sources of information:

We reviewed available educational resources and objectives to develop curricular adaptations informed by staff and trainee feedback.

Methods:

Many facets of the program including clinical rotations, scholarly activities, evaluation, and wellness have been impacted, and thus revised for online delivery where possible. Trainees have personalized a learning plan based on individual goals and supplemented by a list of internet-based resources for independent review. Changes in learning objectives and methods for specific rotations have occurred and are described. Ongoing evaluation will be undertaken.

Key findings:

Curriculum adaptation in the era of COVID-19 is necessary to ensure ongoing high-quality education for future nephrologists. We describe existing changes to formal training in British Columbia (BC), which will be tailored as the pandemic evolves, and anticipate them to have lasting impact on the way we structure training programs in the future. Standardization and harmonization of modified curriculum may be possible across Canada with sharing of these learnings.

Limitations:

Formal evaluation of these changes in terms of knowledge acquisition and examination performance has not yet been undertaken. Next steps will include assessing and documenting the impact of this curricular transformation to further optimize scheduling, educational yield, and trainee wellness.
Reversible Taste Loss in a COVID-19 Patient With Preexisting Chronic Smell Impairment
Authors: Klein Hadar , Karni Noam , Israel Sarah , Gross Menachem , Muszkat Mordechai , Niv Masha Y.
Published: February 2021

Smell loss is important for coronavirus disease-2019 (COVID-19) screening and diagnosis. Particular attention should be paid to individuals with pre-COVID-19 chronic hyposmia or anosmia. We report a case of reversible taste impairment in a COVID-19 patient with chronically impaired sense of smell. This case emphasizes the importance of COVID-19-related taste assessment.
An Unusual Case of Prolymphocytic Leukemia Transformation in a Patient With Chronic Lymphocytic Leukemia
Authors: Bell Stephen , Lattanzio Natalia , Braham Julaine , Campdesuner Victoria , Abdelal Qassem , Vartanov Alexander , Pelayo Miguel
Published: February 2021

B-cell prolymphocytic leukemia (B-PLL) is a rare leukemia characterized by rapidly increasing leukocytosis with splenomegaly and lymphadenopathy. Treatment strategies are largely based on studies of chronic lymphocytic leukemia (CLL). Antibodies against the cell surface protein CD20 are considered to be first-line therapy. A 76-year-old male with known CLL presented 2 weeks after starting chemoimmunotherapy for newly refractory CLL after failing ibrutinib therapy. White blood cell count was elevated at 226.7 × 103/µL. Fluorescent in situ hybridization analysis of a bone marrow specimen showed new development of complex cytogenetics. Flow cytometry revealed B cells appearing slightly dimmer on CD45 and brighter on CD20 compared with typical B-CLL suggestive of less mature lymphocyte forms. The patient was diagnosed with B-PLL and started on obinutuzumab and venetoclax with rapid normalization of white blood cells. This case recapitulates the challenges in diagnosing and treating B-PLL. Ibrutinib resistance is a growing area of study with several proposed mechanisms of acquired resistance. The pathogenesis of B-PLL is not completely understood, although mutations in MYC are presumed to play a role.
A Place of Belonging: Including Individuals With Significant Disabilities in Faith Communities
Authors: Carter Erik W.
Published: February 2021

Faith is central to the flourishing of so many children and adults with significant disabilities and their families. For congregations striving to be a place of inclusion and belonging for their entire community, the theological call to welcome people with disabilities can introduce a host of questions: What does it mean to be a community marked by belonging? What strategies and supports should we adopt to include people well? How can others assist us in this essential endeavor? This article presents a framework for reflecting on the practices and commitments of local congregations that contribute to belonging within a community of faith.
Alemtuzumab Versus Anti-Thymocyte Globulin As Conditioning Method for Allogenic Hematopoietic Stem Cell Transplant; A Meta-Analysis
Authors: Poonsombudlert Kittika , Kewcharoen Jakrin , Prueksapraopong Chattip , Nath Limpruttidham
Published: February 2021

Objective: Anti-thymocyte Globulin (ATG) and Alemtuzumab (Ale) are common methods for T cell depletion in the setting of allogenic hematopoietic stem cell transplant. They are both used to promote engraftment and prevent graft-versus-host disease (GVHD). Currently, there's no comparative meta-analysis for safety and efficacy of Ale versus ATG. Therefore, we conducted a meta-analysis to compare the risk of acute graft-versus-host disease (aGVHD), chronic graft-versus-host disease (cGVHD), odd of relapse and overall survival (OS) between Ale and ATG.

Method: We performed a comprehensive literature search in MEDLINE (Pubmed), Cochrane library and EMBASE database from inception to April 2020 for studies that compared the use of Ale and ATG. We conducted a random effect meta-analysis of 11 studies involving a total of 4,239 participants (Ale=1,293, ATG=2,946) and reported the pooled odd ratio (OR) for development of aGVHD, cGVHD, relapse and OS.

Result: We found a significant decreased in odd of aGVHD and cGVHD in the Ale group compared to the ATG group (pooled OR 0.44, 95% CI 0.32-0.61, I2=56.1% and 0.58, 95% CI 0.44-0.77, I2=47.5% respectively) but there were no statistically significant increase in the odd of relapse and OS (pooled OR 1.14, 95% CI 0.81-1.59, I2=64.5% and 1.20, 95% CI 0.83-1.72, I2=76.3% respectively).

Conclusion: There is significantly decreased odd of aGVHD and cGVHD with use of Ale compared to ATG, but there is no statistically significant increased odd of relapse or OS. We concluded that Ale could be the superior method of T cell depletion in terms of decreased aGVHD and cGVHD but there's no significant difference in odd of relapse and OS.

Disclosures

No relevant conflicts of interest to declare.
The Impact of Chromothripsis on the Clinical Outcomes of Acute Myeloid Leukemia (AML): A Meta-Analysis
Authors: Haddad Philip A , Hammoud Dalia , Gallagher Kevin M.
Published: February 2021

Introduction: Chromothripsis is a single genomic catastrophic event that can involve one or several chromosomes resulting in chromosomal fragmentation. Genomic instability leading to loss of chromosomes and complex karyotype is known to be associated with resistance to chemotherapy and poor prognosis in AML. While chromothripsis is associated with aggressive clinical course in various cancers, its impact on AML clinical outcomes has not been consistently conclusive. The purpose of this meta-analysis is to evaluate the pooled effect of chromothripsis on the response rates and overall survival of patients with AML.

Methods: A review of the medical literature was conducted using online databases. Inclusion criteria consisted of AML diagnosis, English language, and studies reporting OS with hazard ratios (HR) or Kaplan-Meier curves that compared AML outcomes with and without chromothripsis. A meta-analysis using an inverse variance method with a random-effects model was conducted.

Results: Two comparative studies with a total of 444 patients were included in this meta-analysis. In the presence of chromothripsis OS was adversely impacted (HR 1.78, 95%CI: 1.05-3.01, p=0.03) with a heterogeneity estimate, I2=40%. Moreover, response rates were significantly lower in AML cases with chromothripsis versus those without (19% vs. 62%, p<0.05).

Conclusions: This meta-analysis confirms the adverse impact of chromothripsis on response rates and OS of patients with AML.

Disclosures

No relevant conflicts of interest to declare.
Incidence of CDI in a Cohort of US Patients with Newly Diagnosed Acute Myeloid Leukemia Receiving Intensive Chemotherapy
Authors: Lurienne Lise , Le Bescop Clément , Buffet Renaud , Bandinelli Pierre-Alain
Published: February 2021

Background: The immunosuppression seen in Acute Myeloid Leukemia (AML) patients due to the intensive chemotherapy and consolidation therapies used to treat them is often associated with prolonged episodes of neutropenia. This immediately triggers the use of broad-spectrum antibiotics leading to a profound disruption of the gut microbiota that can persist for months. This dysbiosis increases the risk of Clostridioides difficile infection (CDI), the most common cause of healthcare associated infectious diarrhea.

Aim: The objective of the present study was to assess the anticipated incidence of CDI in patients newly diagnosed with AML and receiving intensive chemotherapies.

Methods: A retrospective analysis was conducted using databases of Truven Health Analytics®. Comprehensive hospitalization data of US patients undergoing induction chemotherapy due to AML were analyzed to detect the incidence of CDI during or after the hospitalization with induction chemotherapy. C. difficile infections were detected through the use of the corresponding 008.45 (ICD-9-CM) or A04.7 (ICD-10-CM) codes in the diagnoses reported in the database records.

Findings: Out of the 81,033 patients diagnosed with hematologic diseases between January 2014 and December 2017 found in the dataset, 1,092 patients were included in the study. The incidence of CDI in the 180 days prior to hospitalization was 0.6%. The in-hospital incidence of CDI was 5.4% and increased to 11.9% at 120 days and 16.1% at 1 year after the start of the intensive chemotherapy.

Conclusions: CDI frequently complicates the care of patients with AML during and after the induction chemotherapy and is to be monitored closely in hospital wards managing patients with hematologic diseases.

Disclosures

Lurienne: Da Volterra: Ended employment in the past 24 months. Le Bescop:Da Volterra: Current Employment. Buffet:Da Volterra: Current Employment; Alfa Collaborative Group: Current Employment. Bandinelli:Da Volterra: Current Employment, Current equity holder in private company.
Allogeneic Hematopoietic Stem Cell Transplantation Overcomes the Poor Prognosis in MLL-Rearranged Solid Tumor Therapy Related-Acute Myeloid Leukemia
Authors: Qi Hanzhou , Jin Hua , Liu Qifa
Published: February 2021

BACKGROUND: MLL rearrangement is very common in solid tumor therapy-related acute myeloid leukemia (t-AML). This study investigated the prognosis of MLL t-AML.

METHODS: Patients with solid tumor t-AML and MLL de novo AML were enrolled in this retrospective study. The patients were divided into 3 groups: non-MLL t-AML(n=41), MLL t-AML(n=18) and MLL de novo AML(n=98).

RESULTS: Of the 157 patients enrolled, 150 patients underwent anti-leukemia therapy. The complete remission (CR) rate was 83.3%, 85.5% and 86.2%(P=0.251), respectively, in MLL t-AML, non-MLL t-AML and MLL AML groups. The 3-years overall survival (OS) was 37.5%, 21.5% and 20.4% (P=0.046). The 3-years leukemia-free survival (LFS) was 28.0%, 32.2% and 22.7% (P=0.031), and the incidence of relapse was 30.0%, 50.4% and 53.5% (P=0.382), respectively, in the three groups. Multivariate analysis revealed that MLL t-AML was a risk factor while allo-HSCT a protective factor for relapse, LFS, and OS (P=0.005, P<0.001 and P<0.001) (P<0.001, P<0.001 and P=0.002, respectively). The 3-years OS was 0%, 17.9% and 0%(P=0.038), LFS was 0%, 23.1% and 0%(P=0.017), and relapse was 100%, 53.1% and 74.4% (P=0.001), respectively among three groups in patients undergoing chemotherapy alone, while OS was 64.3%, 52.7% and 40.7% (P=0.713), LFS was 60.0%, 48.8% and 37.0% (P=0.934), and relapse was 25.0%, 47.4% and 47.5% (P=0.872), respectively, among these group in the patients undergoing allo-HSCT. Intriguingly, MLL t-AML was no longer risk factor for relapse and LFS (P=0.882 and P=0.484, respectively), while it became a favorable factor for OS (P=0.011) in the patients undergoing allo-HSCT

CONCLUSIONS: MLL t-AML had poor prognosis compared with non-MLL t-AML and MLL de novo AML,, but allo-HSCT might overcome the poor prognosis of MLL t-AML.

Disclosures

Liu: Nanfang Hospital, Southern Medical University: Research Funding.
Observations of PET Scan Levels of Standard Uptake Values (SUV) in Low Grade Follicular Lymphoma (LGFL) with High Proliferation Index (HPI)
Authors: Aldyab Mahmoud , Shiekhmohammed Mohammed
Published: February 2021

Introduction: Low grade follicular lymphoma (LGFL) with high proliferation index (HPI) behave more like high grade follicular lymphoma (HGFL) and therefore, may require different therapeutic options. Currently they're only identified histologically.

We studied the PET scan observations of this subset of follicular lymphoma (FL) which occupy a clinical grey zone between LGFL and HGFL to determine whether these lymphomas can be distinguished based on PET scan SUV.

Methods: One hundred and twenty-four FL cases at the pathology department at Albany Medical Center between years 2013-2019 were collected. The grade, evaluated based upon the WHO criteria for grading of FL, and KI67 index were recorded. PET scan reports of these cases were reviewed. Cases with no PET scan report, or where the PET scan report did not match the date criteria or site of the biopsy (Bx) were excluded. Of the 87 cases that were included 67 cases were of low grade and 20 cases were of high grade. Among the low grade cases, 23 cases had a high proliferation index (KI67>40%).

53 cases were excisional Bx and 34 Core Bx. The male to female ratio was: 46:40, and the age ranged from 35-92 with a mean of 63.59.

Results: KI67 and SUV means were compared using an independent sample t test and the analysis (table 1) shows that although PET SUV may differentiate HGFL from LGFL, it does not differentiate HGFL from LGFL with HPI when using KI67≥40 % or KI67≥30% as cutoff points.

However, the statistical significance noted in SUV between HGFL and LGFL with HPI when using KI67≥20% as a cut off point, is probably due to the grade of lymphoma, given the loss of significance (p>0.05) when LGFL with KI67≥20% is compared to LGFL with KI67≤20%.

Conclusion: Our findings indicate that LGFL with HPI cannot be reliably identified on PET scan alone. Histology remains the gold standard for identifying low grade follicular lymphoma with high proliferation index.

Disclosures

No relevant conflicts of interest to declare.
In Vivo HSC Gene Therapy with Base Editors Allows for Efficient Reactivation of Fetal Globin in Beta-Yac Mice
Authors: Li Chang , Georgakopoulou Afrodite , Gil Sucheol , Lieber Andre
Published: February 2021

Base editors are capable of installing precise nucleotide mutations at targeted genomic loci and present the advantage of avoiding double-stranded DNA breaks. Here, we aimed to target critical motifs regulating gamma-globin reactivation with base editors delivered via HDAd5/35++ vectors. Through optimized design, we successfully rescued a panel of cytidine and adenine base editors (CBE and ABE) targeting the BCL11A enhancer or recreating naturally occurring Hereditary Persistence of Fetal Hemoglobin (HPFH) mutations in the HBG1/2 promoter. In HUDEP-2 cells, all five tested vectors efficiently installed target base conversion and led to gamma-globin reactivation. We observed significant gamma-globin protein production (~23% over β-globin) by using an ABE vector HDAd-ABE-sgHBG#2 specific to the -113A to G HPFH mutation in HBG1/2 promoter. This vector was therefore chosen for downstream in vivo hematopoietic progenitor/stem cell (HSPC) transduction studies in mice that carry 248kb of the human β-globin locus (β-YAC mice) and thus accurately reflect globin switching. An EF1a-mgmtP140K expression cassette flanked by frt and transposon sites was included in the vector for allowing in vivo selection of transduced cells. After in vivo HSPC transduction with HDAd-ABE-HBG#2 + HDAd-SB and low doses of chemoselection, an average of over 40% HbF-positive cells in peripheral red blood cells was measured. This corresponded to ~21% gamma-globin production over human β-globin. The -113 A to G conversion in total bone marrow cells was on average 20%. Compared to untransduced mice, no alterations in hematological parameters, erythropoiesis and bone marrow cellular composition were observed after treatment, demonstrating a good safety profile of our approach. No detectable editing was found at top-scored potential off-target genomic sites. Bone marrow lineage-negative cells, isolated from primary mice at week 16 after transduction, were capable of reconstituting secondary transplanted mice with stable HbF expression. Importantly, the advantage of base editing over CRISPR/Cas9 was reflected by the markedly lower rates of intergenic 4.9kb deletion and no detectable toxicity in human CD34+ stem cells. Our observations demonstrate that base editors delivered by HDAd5/35++ vectors represent a promising strategy for precise in vivo genome engineering for the treatment of hemoglobinopathies.

Disclosures

Lieber: Ensoma, Inc: Consultancy, Research Funding.
Alternative Consolidation Strategy after High Dose Methotrexate, Rituximab and Temozolamide in Primary CNS Lymphoma - the Henry Ford Experience
Authors: Philip Joyce , Sharma Shivani , Donthireddy Vijayalakshmi
Published: February 2021

Background: Treatment for primary CNS lymphoma involves a methotrexate-based induction therapy followed by consolidation. The optimal consolidation treatment after induction with a high dose Methotrexate (HD-MTX), Rituximab and Temozolomide regimen has not been fully established. The CALGB 50202 regimen using Etoposide and Cytarabine consolidation was associated with significant toxicity. We sought to review the results of alternative consolidation regimens and evaluate the progression free survival and overall survival.

Methods: A retrospective cohort study was conducted to evaluate the efficacy of alternative consolidation regimens such as autologous stem cell transplant and HDMTx alone. Patients diagnosed with primary CNS lymphoma between November 2012 and March 2019 were identified. All patients received the same induction chemotherapy based on the CALGB 50202 protocol. Data was collected for baseline characteristics, progression free survival and overall survival.

Results: 38 patients had a diagnosis of primary CNS lymphoma. 15 patients received treatment as per the CALBG 50202 induction protocol with high dose Methotrexate, Rituximab and Temozolomide. Of the 15 patients, 11 patients (69%) achieved a complete remission (CR) after induction therapy. 7 patients received an autologous stem cell transplant for consolidation, 5 patients received HD-MTX alone for consolidation and one patient was placed on Lenalidomide maintenance. 2 patients did not receive any consolidation therapy due to progressive disease and/or death. At a median follow up of 2.7 years for the entire cohort, median PFS was 31.7+ months and median OS was 32.5+ months. At a median follow up of 2.7 years for patients who were consolidated with an autologous stem cell transplant, median PFS and median OS was 27.2+ and 32.5+ months respectively. At a median follow up of 5.5 years for patients who were consolidated with treatments other than transplant, median PFS and OS was 65.6+ months. There were no deaths attributed to treatment related toxicity. To date, 4 patients of the entire cohort have died, with a median survival time among surviving patients of 3.6 years (range, 0.68-7.05 years). There were no deaths attributed to treatment related toxicity.

Conclusion: Patients with primary CNS lymphoma who received induction therapy as per CALGB 50202 regimen and received alternative consolidation therapies with either autologous stem cell transplant or HD-MTX based consolidation achieved prolonged PFS and OS comparable if not superior to the Etoposide and Cytarabine consolidation. Results of the ongoing CALGB 51101 trial will determine the utility of EA consolidation.

Disclosures

No relevant conflicts of interest to declare.
Long non-coding RNA CIR inhibits chondrogenic differentiation of mesenchymal stem cells by epigenetically suppressing ATOH8 via methyltransferase EZH2
Authors: Liu Feng , Song De-Ye , Huang Jun , Yang Hong-Qi , You Di , Ni Jiang-Dong
Published: February 2021

Background

Osteoarthritis (OA) is the most common articular disorder, leading to joint malfunction and disability. Although the incidence of OA is increasing globally, the treatment of OA is very limited. LncRNA CIR has been implicated in OA through unclear mechanisms. Here, we investigated the role of lncRNA CIR in chondrogenic differentiation.

Methods

Human umbilical-cord-derived mesenchymal stem cells (hUC-MSCs) were obtained from human umbilical cords. Flow cytometry was used to analyze the surface markers of hUC-MSCs. Various culture conditions and corresponding staining assays were employed to assess the differentiation abilities of hUC-MSC. qRT-PCR, western blot, and immunostaining were used to measure expression levels of related genes and proteins such as lncRNA CIR, ATOH8, EZH2, and H3K27me3. RNA immunoprecipitation assay, biotin pull-down, and chromatin immunoprecipitaion assay were performed to analyze the interactions of lncRNA CIR, EZH2, H3K27me3 and ATOH8 promoter.

Results

hUC-MSCs exhibited MSCs features and could differentiate into chondrocytes under specific conditions. LncRNA CIR was downregulated while ATOH8 was upregulated during the chondrogenic differentiation of hUC-MSCs. Knockdown lncRNA CIR or overexpression of ATOH8 promoted chondrogenic differentiation. Further, lncRNA CIR bound to EZH2 and repressed ATOH8 expression via EZH2-mediated H3K27me3, which promotes the methylation of ATOH8. Inhibition of ATOH8 reversed the effects of knockdown lncRNA CIR on chondrogenic differentiation.

Conclusion

LncRNA CIR suppresses chondrogenic differentiation of hUC-MSCs. Mechanistically, lncRNA CIR could inhibit ATOH8 expression that functions to promote chondrogenic differentiation through EZH2-mediated epigenetic modifications.
Plant Co-expression Annotation Resource: a web server for identifying targets for genetically modified crop breeding pipelines
Authors: José Andrade Viana Marcos , Zerlotini Adhemar , de Alvarenga Mudadu Mauricio
Published: February 2021

The development of genetically modified crops (GM) includes the discovery of candidate genes through bioinformatics analysis using genomics data, gene expression, and others. Proteins of unknown function (PUFs) are interesting targets for GM crops breeding pipelines for the novelty associated with such targets and also to avoid copyright protection. One method of inferring the putative function of PUFs is by relating them to factors of interest such as abiotic stresses using orthology and co-expression networks, in a guilt-by-association manner. In this regard, we have downloaded, analyzed, and processed genomics data of 53 angiosperms, totaling 1,862,010 genes and 2,332,974 RNA. Diamond and InterproScan were used to discover 72,266 PUFs for all organisms. RNA-seq datasets related to abiotic stresses were downloaded from NCBI/GEO. The RNA-seq data was used as input to the LSTrAP software to construct co-expression networks. LSTrAP also created clusters of transcripts with correlated expression, whose members are more probably related to the molecular mechanisms associated with abiotic stresses in the plants. Orthologous groups were created (OrhtoMCL) using all 2,332,974 proteins in order to associate PUFs to abiotic stress-related clusters of co-expression and therefore infer their function in a guilt-by-association manner. A freely available web resource named “Plant Co-expression Annotation Resource” (https://www.machado.cnptia.embrapa.br/plantannot), Plantannot, was created to provide indexed queries to search for PUF putatively associated with abiotic stresses. The web interface also allows browsing, querying, and retrieving of public genomics data from 53 plants. We hope Plantannot to be useful for researchers trying to obtain novel GM crops resistant to climate change hazards.
Investigating the relevance of major signaling pathways in cancer survival using a biologically meaningful deep learning model
Authors: Feng Jiarui , Zhang Heming , Li Fuhai
Published: February 2021

Background

Survival analysis is an important part of cancer studies. In addition to the existing Cox proportional hazards model, deep learning models have recently been proposed in survival prediction, which directly integrates multi-omics data of a large number of genes using the fully connected dense deep neural network layers, which are hard to interpret. On the other hand, cancer signaling pathways are important and interpretable concepts that define the signaling cascades regulating cancer development and drug resistance. Thus, it is important to investigate potential associations between patient survival and individual signaling pathways, which can help domain experts to understand deep learning models making specific predictions.

Results

In this exploratory study, we proposed to investigate the relevance and influence of a set of core cancer signaling pathways in the survival analysis of cancer patients. Specifically, we built a simplified and partially biologically meaningful deep neural network, DeepSigSurvNet, for survival prediction. In the model, the gene expression and copy number data of 1967 genes from 46 major signaling pathways were integrated in the model. We applied the model to four types of cancer and investigated the influence of the 46 signaling pathways in the cancers. Interestingly, the interpretable analysis identified the distinct patterns of these signaling pathways, which are helpful in understanding the relevance of signaling pathways in terms of their application to the prediction of cancer patients’ survival time. These highly relevant signaling pathways, when combined with other essential signaling pathways inhibitors, can be novel targets for drug and drug combination prediction to improve cancer patients’ survival time.

Conclusion

The proposed DeepSigSurvNet model can facilitate the understanding of the implications of signaling pathways on cancer patients’ survival by integrating multi-omics data and clinical factors.
Melatonin confers heavy metal-induced tolerance by alleviating oxidative stress and reducing the heavy metal accumulation in Exophiala pisciphila, a dark septate endophyte (DSE)
Authors: Yu Yang , Teng Zhaowei , Mou Zongmin , Lv Yan , Li Tao , Chen Suiyun , Zhao Dake , Zhao Zhiwei
Published: February 2021

Background

Melatonin (MT), ubiquitous in almost all organisms, functions as a free radical scavenger. Despite several reports on its role as an antioxidant in animals, plants, and some microorganisms, extensive studies in filamentous fungi are limited. Based upon the role of melatonin as an antioxidant, we investigated its role in heavy metal-induced stress tolerance in Exophiala pisciphila, a dark septate endophyte (DSE), by studying the underlying mechanisms in alleviating oxidative stress and reducing heavy metal accumulation.

Results

A significant decrease in malondialdehyde (MDA) and oxygen free radical (OFR) in E. pisciphila was recorded under Cd, Zn, and Pb stresses as compared to the control. Pretreatment of E. pisciphila with 200.0 μM exogenous melatonin significantly increased the activity of superoxide dismutase (SOD) under Zn and Pb stresses. Pretreatment with 200.0 μM melatonin also lowered Cd, Zn, and Pb concentrations significantly. Melatonin production was enhanced by Cd, Cu, and Zn after 2 d, and melatonin biosynthetic enzyme genes, E. pisciphila tryptophan decarboxylase (EpTDC1) and serotonin N-acetyltransferase (EpSNAT1), were transcriptionally upregulated. The overexpression of EpTDC1 and N-acetylserotonin O-methyltransferase (EpASMT1) in Escherichia coli and Arabidopsis thaliana enhanced its heavy metal-induced stress tolerance. The overexpression of EpTDC1 and EpASMT1 reduced the Cd accumulation in the whole A. thaliana plants, especially in the roots.

Conclusions

Melatonin conferred heavy metal-induced stress tolerance by alleviating oxidative stress, activating antioxidant enzyme SOD, and reducing heavy metal accumulation in E. pisciphila. Melatonin biosynthetic enzyme genes of E. pisciphila also played key roles in limiting excessive heavy metal accumulation in A. thaliana. These findings can be extended to understand the role of melatonin in other DSEs associated with economically important plants and help develop new strategies in sustainable agriculture practice where plants can grow in soils contaminated with heavy metals.
Intergenerational caring: a systematic literature review on young and young adult caregivers of older people
Authors: D’Amen Barbara , Socci Marco , Santini Sara
Published: February 2021

Background

The theme of young family caregivers of older relatives is still partially uncovered, although the phenomenon is increasing worldwide. This Systematic Literature Review discusses methodological and content issues of ten articles covering this topic, in order to contribute to increase the knowledge and provide suggestions for designing effective support services for adolescent young caregivers. To this purpose, the findings of this review are framed within the caregiving stress appraisal model (renamed CSA model) elaborated by Yates’ and collegues, in order to highlight differences between young caregivers and the older ones.

Methods

Multiple databases including PubMed, Web of Science, Scopus, ProQuest - Psychology Database, CINAHL Complete - EBSCOHost were used to carry out a systematic review of the literature. Additional references were retrieved from experts contacted and research knowledge. The selected articles underwent both methodological appraisal and contents analysis: for every article an appraisal score was calculated and themes and sub-themes were identified.

Results

Out of the ten included studies three were mixed methods, six qualitative and one quantitative. Nine reached a high quality methodological score and one medium. Four main themes emerged from the content analysis: aspects of the caregiving relationship; effects of caregiving; coping strategies; recommendations for services, policy and research.

Conclusions

Selected studies explored practical features of the relationship between young caregivers and older family members (tasks performed, motivations, coping strategies) and highlighted both positive and negative outcomes on young people’s everyday life condition and future development. Nevertheless, these evidences were often limited to small samples that did not allow to make generalizations. More studies are needed including large samples in order to deepen the different aspects of caregiving and design tailored support services.
Infection pattern, case fatality rate and spread of Lassa virus in Nigeria
Authors: Yaro Clement Ameh , Kogi Ezekiel , Opara Kenneth Nnamdi , Batiha Gaber El-Saber , Baty Roua S. , Albrakati Ashraf , Altalbawy Farag M. A. , Etuh Innocent Utenwojo , Oni James Paul
Published: February 2021

Background

Lassa fever (LF) is a zoonotic infectious disease of public concern in Nigeria. The infection dynamics of the disease is not well elucidated in Nigeria. This study was carried out to describe the pattern of infection, case fatality rate and spread of lassa virus (LASV) from 2017 to 2020.

Methods

Weekly epidemiological data on LF from December, 2016 to September, 2020 were obtained from Nigeria Centre for Disease Control. The number of confirmed cases and deaths were computed according to months and states. Descriptive statistics was performed and case fatality rate was calculated. Distribution and spread maps of LF over the four years period was performed on ArcMap 10.7.

Results

A total of 2787 confirmed cases and 516 deaths were reported in Nigeria from December, 2016 to September, 2020. Increase in number of cases and deaths were observed with 298, 528, 796 and 1165 confirmed cases and 79, 125, 158 and 158 deaths in 2017, 2018, 2019 and 2020 respectively. Over 60% of the cases were reported in two states, Edo and Ondo states. The LF cases spread from 19 states in 2017 to 32 states and Federal Capital Territory (FCT) in 2020. Ondo state (25.39%) had the highest of deaths rate from LF over the four years. Case fatality rate (CFR) of LF was highest in 2017 (26.5%) with CFR of 23.7, 19.6 and 13.4% in 2018, 2019 and 2020 respectively. The peak of infection was in the month of February for the four years. Infections increases at the onset of dry season in November and decline till April when the wet season sets-in.

Conclusion

There is an annual increase in the number of LASV infection across the states in Nigeria. There is need to heighten control strategies through the use of integrated approach, ranging from vector control, health education and early diagnosis.
Prognostic role of preoperative D-dimer, fibrinogen and platelet levels in patients with oral squamous cell carcinoma
Authors: Liang Yu-jie , Mei Xue-ying , Zeng Bin , Zhang Si-en , Yang Le , Lao Xiao-mei , Liao Gui-qing
Published: February 2021

Background

The relationship between cancer and coagulation has been intensively studied in recent years; however, the effects of coagulation factors on oral squamous cell carcinoma (OSCC) have rarely been reported. This study aimed to investigate the relationship between preoperative D-dimer (DD), fibrinogen (FIB), platelets (PLT) and OSCC, as well as the prognostic value of DD, FIB and PLT in OSCC.

Methods

We retrospectively investigated a total of 202 patients with OSCC treated at Guanghua Hospital of Stomatology, Sun Yat-sen University. Baseline demographic and clinicopathological information as well as both preoperative and postoperative DD, FIB and PLT results were collected from each patient, and patients with primary OSCC were followed up for disease progression, death or the end of the study. The correlations between preoperative DD, FIB, PLT and other clinical features, as well as the therapeutic effect and PFS were analysed statistically, and postoperative DD and surgical parameters were also analysed.

Results

Preoperative DD was significantly correlated with T stage, N stage, clinical stage and relapse of OSCC (P = 0.000, 0.001, 0.000 and 0.000, respectively). Univariate Cox regression analyses showed that high preoperative DD predicted poor prognosis in patients with OSCC (HR = 2.1, P = 0.033), while FIB and PLT showed no prognostic values. Postoperative DD was significantly correlated with preoperative DD and surgical type but not the duration of surgery (P = 0.005, 0.001 and 0.244, respectively).

Conclusion

In this study, we suggested that high preoperative DD level may serve as an indicator for synchronous neck dissection in patients with T1, 2 OSCC, and the elevated DD level might be the marker of disease progression in patient follow up.
A cross-sectional survey of knowledge, attitude and practice (KAP) towards COVID-19 pandemic among the Syrian residents
Authors: Al ahdab Sanaa
Published: February 2021

Background

Effective COVID-19 pandemic management requires adequate understanding of factors that influence behavioral changes. This study aims to assess knowledge, attitudes and practices towards COVID-19 among Syrians in a post-conflict context.

Method

A cross sectional web-based survey was conducted on the Syrian residents of 16 years and above. It contains questions on knowledge, attitudes and practices (KAP) with respect to COVID-19. Participants’ demographic characteristics are recorded and analyzed. The study is conducted during the global outbreak of COVID-19.

Results

A total of 706 participants (female, 444; male, 262) were enrolled. This study included 405 participants aged between 16 and 29, 204 aged between 30 and 49, and 97 aged above 60 years. There were 642 who have a university degree and 61 who have high school degree. Among the participants 253 were students, 316 were employed, 75 work as freelancers, and 62 were unemployed. Results showed that overall knowledge score towards the disease was about 60% (mean score 3.54 ± 1.20; range 0–6). Knowledge scores significantly differed across age groups (P < 0.05), education levels (P = 0.001), and occupations (P < 0.05). Attitude and practice scores were 2.45 ± 0.81 (range 0–4), 5.90 ± 1.52 (range 0–8), respectively. Attitude scores were significantly different between males and females (P < 0.05), whereas practice scores varied significantly across gender (P < 0.05), age groups (P = 0.01), education levels (P = 0.015), occupations (P < 0.05), and according to knowledge score (P = 0.000). Results from multiple linear regression indicated that lower knowledge scores were significantly associated with lower education level (P < 0.05), whereas poor preventive practices were common among male, young and unemployed participants with significance levels of P < 0.01, P = .000, P < 0.01, respectively.

Conclusion

The findings of this study suggest that the Syrian residents demonstrate modest knowledge, attitudes and practices towards COVID-19 at the time of its global outbreak. Efforts should be directed towards raising the awareness of the disease to improve their practices in the current COVID-19 pandemic, as well as for future epidemics.
A scoring system derived from electronic health records to identify patients at high risk for noninvasive ventilation failure
Authors: Stefan Mihaela S. , Priya Aruna , Pekow Penelope S. , Steingrub Jay S. , Hill Nicholas S. , Lagu Tara , Raghunathan Karthik , Bhat Anusha G. , Lindenauer Peter K.
Published: February 2021

Objective

To develop and validate a clinical risk prediction score for noninvasive ventilation (NIV) failure defined as intubation after a trial of NIV in non-surgical patients.

Design

Retrospective cohort study of a multihospital electronic health record database.

Patients

Non-surgical adult patients receiving NIV as the first method of ventilation within two days of hospitalization.

Measurement

Primary outcome was intubation after a trial of NIV. We used a non-random split of the cohort based on year of admission for model development and validation. We included subjects admitted in years 2010–2014 to develop a risk prediction model and built a parsimonious risk scoring model using multivariable logistic regression. We validated the model in the cohort of subjects hospitalized in 2015 and 2016.

Main results

Of all the 47,749 patients started on NIV, 11.7% were intubated. Compared with NIV success, those who were intubated had worse mortality (25.2% vs. 8.9%). Strongest independent predictors for intubation were organ failure, principal diagnosis group (substance abuse/psychosis, neurological conditions, pneumonia, and sepsis), use of invasive ventilation in the prior year, low body mass index, and tachypnea. The c-statistic was 0.81, 0.80 and 0.81 respectively, in the derivation, validation and full cohorts. We constructed three risk categories of the scoring system built on the full cohort; the median and interquartile range of risk of intubation was: 2.3% [1.9%–2.8%] for low risk group; 9.3% [6.3%–13.5%] for intermediate risk category; and 35.7% [31.0%–45.8%] for high risk category.

Conclusions

In patients started on NIV, we found that in addition to factors known to be associated with intubation, neurological, substance abuse, or psychiatric diagnoses were highly predictive for intubation. The prognostic score that we have developed may provide quantitative guidance for decision-making in patients who are started on NIV.
Stratified care integrated with eHealth versus usual primary care physiotherapy in patients with neck and/or shoulder complaints: protocol for a cluster randomized controlled trial
Authors: van Tilburg Mark L. , Kloek Corelien J. J. , Pisters Martijn F. , Staal J. Bart , van Dongen Johanna M. , de Weerd Marjolein , Ostelo Raymond W. J. G. , Foster Nadine E. , Veenhof Cindy
Published: February 2021

Background

Neck and shoulder complaints are common in primary care physiotherapy. These patients experience pain and disability, resulting in high societal costs due to, for example, healthcare use and work absence. Content and intensity of physiotherapy care can be matched to a patient’s risk of persistent disabling pain. Mode of care delivery can be matched to the patient’s suitability for blended care (integrating eHealth with physiotherapy sessions). It is hypothesized that combining these two approaches to stratified care (referred to from this point as Stratified Blended Approach) will improve the effectiveness and cost-effectiveness of physiotherapy for patients with neck and/or shoulder complaints compared to usual physiotherapy.

Methods

This paper presents the protocol of a multicenter, pragmatic, two-arm, parallel-group, cluster randomized controlled trial. A total of 92 physiotherapists will be recruited from Dutch primary care physiotherapy practices. Physiotherapy practices will be randomized to the Stratified Blended Approach arm or usual physiotherapy arm by a computer-generated random sequence table using SPSS (1:1 allocation). Number of physiotherapists (1 or > 1) will be used as a stratification variable. A total of 238 adults consulting with neck and/or shoulder complaints will be recruited to the trial by the physiotherapy practices. In the Stratified Blended Approach arm, physiotherapists will match I) the content and intensity of physiotherapy care to the patient’s risk of persistent disabling pain, categorized as low, medium or high (using the Keele STarT MSK Tool) and II) the mode of care delivery to the patient’s suitability and willingness to receive blended care. The control arm will receive physiotherapy as usual. Neither physiotherapists nor patients in the control arm will be informed about the Stratified Blended Approach arm. The primary outcome is region-specific pain and disability (combined score of Shoulder Pain and Disability Index & Neck Pain and Disability Scale) over 9 months. Effectiveness will be compared using linear mixed models. An economic evaluation will be performed from the societal and healthcare perspective.

Discussion

The trial will be the first to provide evidence on the effectiveness and cost-effectiveness of the Stratified Blended Approach compared with usual physiotherapy in patients with neck and/or shoulder complaints.

Trial registration

Netherlands Trial Register:NL8249. Officially registered since 27 December 2019. Date of first enrollment: 30 September 2020. Study status: ongoing, data collection.
Evidence to support a drain-free strategy in kidney transplantation using a retrospective comparison of 500 consecutively transplanted cases at a single center
Authors: Farag Ahmed , Gaynor Jeffrey J. , Serena Giuseppe , Ciancio Gaetano
Published: February 2021

Introduction

Routine placement of surgical drains at the time of kidney transplant has been debated in terms of its prognostic value.

Objectives

To determine whether the placement of a surgical drain affects the incidence rate of developing wound complications and other clinical outcomes, particularly after controlling for other prognostic factors.

Methods

Retrospective analysis of 500 consecutive renal transplant cases who did not (Drain-free, DF) vs. did (Drain, D) receive a drain at the time of transplant was performed. The primary outcome was the development of any wound complication (superficial or deep) during the first 12 months post-transplant. Secondary outcomes included the development of superficial wound complications, deep wound complications, DGF, and graft loss during the first 12 months post-transplant.

Results

388 and 112 recipients had DF/D, respectively. DF-recipients were significantly more likely to be younger, not have pre-transplant diabetes, receive a living donor kidney, receive a kidney-alone transplant, have a shorter duration of dialysis, shorter mean cold-ischemia-time, and greater pre-transplant use of anticoagulants/antiplatelets. Wound complications were 4.6% (18/388) vs. 5.4% (6/112) in DF vs. D groups, respectively (P = 0.75). Superficial wound complications were observed in 0.8% (3/388) vs. 0.0% (0/112) in DF vs. D groups, respectively (P = 0.35). Deep wound complications were observed in 4.1% (16/388) vs. 5.4% ((6/112) in DF vs. D groups, respectively (P = 0.57). Higher recipient body mass index and ≥ 1 year of pre-transplant dialysis were associated in multivariable analysis with an increased incidence of wound complications. Once the prognostic influence of these 2 factors were controlled, there was still no notable effect of drain use (yes/no). The lack of prognostic effect of drain use was similarly observed for the other clinical outcomes.

Conclusions

In a relatively large cohort of renal transplant recipients, routine surgical drain use appears to offer no distinct prognostic advantage.