bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrated transcriptome and proteome analyses identify novel regulatory network of nucleus pulposus cells in intervertebral disc degeneration
Authors: Xu Chen , Luo Shengchang , Wei Leixin , Wu Huiqiao , Gu Wei , Zhou Wenchao , Sun Baifeng , Hu Bo , Zhou Hongyu , Liu Yang , Chen Huajiang , Ye Xiaojian , Yuan Wen
Published: February 2021

Background

Degeneration of intervertebral disc is a major cause of lower back pain and neck pain. Studies have tried to unveil the regulatory network using either transcriptomic or proteomic analysis. However, neither have fully elucidated the exact mechanism of degeneration process. Since post-transcriptional regulation may affect gene expression by modulating the translational process of mRNA to protein product, a combined transcriptomic and proteomic study may provide more insight into the key regulatory network of Intervertebral disc degeneration.

Methods

In order to obtain the proteomic and transcriptomic data, we performed label-free proteome analysis on freshly isolated nucleus pulposus cells and obtained transcriptome profiling data from the Gene Expression Omnibus repository. To identify the key regulatory network of intervertebral disc degeneration in nucleus pulposus cells, we performed bioinformatic analyses and established a protein-RNA interacting network. To validate the candidate genes, we performed in vitro experimentation and immunochemistry labeling to identify their potential function during nucleus pulposus degeneration.

Results

The label-free proteome analysis identified altogether 656 proteins, and 503 of which were differentially expressed between nucleus pulposus cells from degenerated or normal disc cells. Using the existing nucleus pulposus transcriptomic profiling data, we integrated the proteomic and transcriptomic data of nucleus pulposus cells, and established a protein-RNA interacting network to show the combined regulatory network of intervertebral disc degeneration. In the network, we found 9 genes showed significant changes, and 6 of which (CHI3L1, KRT19, COL6A2, DPT, TNFAIP6 and COL11A2) showed concordant changes in both protein and mRNA level. Further functional analysis showed these candidates can significantly affect the degeneration of the nucleus pulposus cell when altering their expression.

Conclusions

This study is the first to use combined analysis of proteomic and transcriptomic profiling data to identify novel regulatory network of nucleus pulposus cells in intervertebral disc degeneration. Our established protein-RNA interacting network demonstrated novel regulatory mechanisms and key genes that may play vital roles in the pathogenesis of intervertebral disc degeneration.
Impact of Haemophilus influenzae type b combination vaccination on asthma symptoms and pneumonia in 5-year-old children in rural Bangladesh: a longitudinal study and comparison with a previous cross-sectional study
Authors: Takeuchi Haruko , Hasan S. M. Tafsir , Zaman Khalequ , Takanashi Sayaka , Hore Samar Kumar , Yeasmin Sultana , Ahmad Shaikh Meshbahuddin , Alam Md Jahangir , Jimba Masamine , Iwata Tsutomu , Khan Md Alfazal
Published: February 2021

Background

Although the prevalence of bronchial asthma has been increasing worldwide since the 1970′s, the prevalence among 5-year-old children was significantly lower in 2016 than in 2001 in rural Bangladesh. We aimed to determine whether the Haemophilus influenzae type b (Hib) combination vaccination (without booster) started in 2009 contributed to this decrease.

Methods

A case–control study was conducted among 1658 randomly selected 5-year-old children from Matlab, Bangladesh. Data on wheezing were collected using the International Study of Asthma and Allergies in Childhood questionnaire. The vaccination data were collected from the records of the Matlab Health and Demographic Surveillance System, while data on pneumonia were obtained from the clinical records of Matlab Hospital. Adjusted odds ratios (aORs) were calculated for the risk for wheezing. The reduction rate was calculated to determine the impact of the vaccination on pneumonia history between the present study and our previous study conducted in 2001 by using the following formula: (percentage of pneumonia cases in 2001 − percentage of pneumonia cases in 2016)/(percentage of pneumonia cases in 2001) times 100 (%).

Results

Hib combination vaccination was a protecting factor against wheezing (aOR: 0.50; p = 0.010), while pneumonia at 1, 2, 3–4 years of age were risk factors for wheezing (aOR: 2.86, 3.19, 2.86; p = 0.046, 0.030, 0.030, respectively). The history of pneumonia was significantly lower in the 2016 study participants than those in 2001 both in the overall cohort and the wheezing group (paired t-test: p = 0.012, p < 0.001, respectively). Whereas the history of pneumonia decreased when the children grew older in the 2001 overall cohort, it peaked at the age of 2 years in 2016 wheezing group. The reduction rate decreased when children grew older in both the overall cohort and the wheezing group, however, it decreased faster in the wheezing group.

Conclusions

Hib combination vaccination was a protective factor against wheezing in 0-year-old children. However, the effects of vaccination might have attenuated at the ages of 1–4 years, because no booster dose was administered. The addition of a booster dose might further decrease the prevalence of asthma and wheezing.
F0F1 ATP synthase regulates extracellular calcium influx in human neutrophils by interacting with Cav2.3 and modulates neutrophil accumulation in the lipopolysaccharide-challenged lung
Authors: Zhu Baoyi , Feng Zhengfu , Guo Yan , Zhang Tian , Mai Ai , Kang Zhanfang , Weijen Ting , Wang Dai , Yin Dazhong , Zhu Dongxing , Gao Jun
Published: February 2021

Background

Neutrophils form the first line of innate host defense against invading microorganisms. We previously showed that F0F1 ATP synthase (F-ATPase), which is widely known as mitochondrial respiratory chain complex V, is expressed in the plasma membrane of human neutrophils and is involved in regulating cell migration. Whether F-ATPase performs cellular functions through other pathways remains unknown.

Methods

Blue native polyacrylamide gel electrophoresis followed by nano-ESI-LC MS/MS identification and bioinformatic analysis were used to identify protein complexes containing F-ATPase. Then, the identified protein complexes containing F-ATPase were verified by immunoblotting, immunofluorescence colocalization, immunoprecipitation, real-time RT-PCR and agarose gel electrophoresis. Immunoblotting, flow cytometry and a LPS-induced mouse lung injury model were used to assess the effects of the F-ATPase-containing protein complex in vitro and in vivo.

Results

We found that the voltage-gated calcium channel (VGCC) α2δ-1 subunit is a binding partner of cell surface F-ATPase in human neutrophils. Further investigation found that the physical connection between the two proteins may exist between the F1 part (α and β subunits) of F-ATPase and the α2 part of VGCC α2δ-1. Real-time RT-PCR and PCR analyses showed that Cav2.3 (R-type) is the primary type of VGCC expressed in human neutrophils. Research on the F-ATPase/Cav2.3 functional complex indicated that it can regulate extracellular Ca2+ influx, thereby modulating ERK1/2 phosphorylation and reactive oxygen species production, which are typical features of neutrophil activation. In addition, the inhibition of F-ATPase can reduce neutrophil accumulation in the lungs of mice that were intratracheally instilled with lipopolysaccharide, suggesting that the inhibition of F-ATPase may prevent neutrophilic inflammation-induced tissue damage.

Conclusions

In this study, we identified a mechanism by which neutrophil activity is modulated, with simultaneous regulation of neutrophil-mediated pulmonary damage. These results show that surface F-ATPase of neutrophils is a potential innate immune therapeutic target.

Graphical abstract
Association of ultra-processed food consumption with cardiovascular mortality in the US population: long-term results from a large prospective multicenter study
Authors: Zhong Guo-Chao , Gu Hai-Tao , Peng Yang , Wang Kang , Wu You-Qi-Le , Hu Tian-Yang , Jing Feng-Chuang , Hao Fa-Bao
Published: February 2021

Background

Ultra-processed foods have now become dominant in the global food system. Whether their consumption is associated with cardiovascular mortality remains controversial. Moreover, data on ultra-processed foods and cardiovascular outcomes are scarce in the US population. We aimed to examine the association of ultra-processed food consumption with cardiovascular mortality in a US population.

Methods

A population-based cohort of 91,891 participants was identified from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Dietary data were collected through a validated 137-item food frequency questionnaire. Ultra-processed foods were defined by the NOVA classification. Cox regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for cardiovascular mortality. Restricted cubic spline regression was used to test nonlinearity. Subgroup analyses were conducted to identify the potential effect modifiers.

Results

After an average follow-up of 13.5 years (1,236,049.2 person-years), 5490 cardiovascular deaths were documented, including 3985 heart disease deaths and 1126 cerebrovascular deaths. In the fully adjusted model, participants in the highest vs. the lowest quintiles of ultra-processed food consumption had higher risks of death from cardiovascular disease (HRquintile 5 vs. 1, 1.50; 95% CI, 1.36–1.64) and heart disease (HRquintile 5 vs. 1, 1.68; 95% CI, 1.50–1.87) but not cerebrovascular disease (HRquintile 5 vs. 1, 0.94; 95% CI, 0.76–1.17). A nonlinear dose–response pattern was observed for overall cardiovascular and heart disease mortality (allPnonlinearity < 0.05), with a threshold effect observed at ultra-processed food consumption of 2.4 servings/day and 2.3 servings/day, respectively; below the thresholds, no significant associations were observed for these two outcomes. Subgroup analyses showed that the increased risks of mortality from ultra-processed foods were significantly higher in women than in men (allPinteraction < 0.05).

Conclusions

High consumption of ultra-processed foods is associated with increased risks of overall cardiovascular and heart disease mortality. These harmful associations may be more pronounced in women. Our findings need to be confirmed in other populations and settings.
Brain lateralization in children with upper-limb reduction deficiency
Authors: Zuniga Jorge M. , Pierce James E. , Copeland Christopher , Cortes-Reyes Claudia , Salazar David , Wang YingYing , Arun K. M. , Huppert Theodore
Published: February 2021

Background

The purpose of the current study was to determine the influence of upper-limb prostheses on brain activity and gross dexterity in children with congenital unilateral upper-limb reduction deficiencies (ULD) compared to typically developing children (TD).

Methods

Five children with ULD (3 boys, 2 girls, 8.76 ± 3.37 years of age) and five age- and sex-matched TD children (3 boys, 2 girls, 8.96 ± 3.23 years of age) performed a gross manual dexterity task (Box and Block Test) while measuring brain activity (functional near-infrared spectroscopy; fNIRS).

Results

There were no significant differences (p = 0.948) in gross dexterity performance between the ULD group with prosthesis (7.23 ± 3.37 blocks per minute) and TD group with the prosthetic simulator (7.63 ± 5.61 blocks per minute). However, there was a significant (p = 0.001) difference in Laterality Index (LI) between the ULD group with prosthesis (LI = − 0.2888 ± 0.0205) and TD group with simulator (LI = 0.0504 ± 0.0296) showing in a significant ipsilateral control for the ULD group. Thus, the major finding of the present investigation was that children with ULD, unlike the control group, showed significant activation in the ipsilateral motor cortex on the non-preferred side using a prosthesis during a gross manual dexterity task.

Conclusions

This ipsilateral response may be a compensation strategy in which the existing cortical representations of the non-affected (preferred) side are been used by the affected (non-preferred) side to operate the prosthesis. This study is the first to report altered lateralization in children with ULD while using a prosthesis.

Trial registrationThe clinical trial (ClinicalTrial.gov ID: NCT04110730 and unique protocol ID: IRB # 614-16-FB) was registered on October 1, 2019 (https://clinicaltrials.gov/ct2/show/NCT04110730) and posted on October 1, 2019. The study start date was January 10, 2020. The first participant was enrolled on January 14, 2020, and the trial is scheduled to be completed by August 23, 2023. The trial was updated January 18, 2020 and is currently recruiting
Data analytics and clinical feature ranking of medical records of patients with sepsis
Authors: Chicco Davide , Oneto Luca
Published: February 2021

Background

Sepsis is a life-threatening clinical condition that happens when the patient’s body has an excessive reaction to an infection, and should be treated in one hour. Due to the urgency of sepsis, doctors and physicians often do not have enough time to perform laboratory tests and analyses to help them forecast the consequences of the sepsis episode. In this context, machine learning can provide a fast computational prediction of sepsis severity, patient survival, and sequential organ failure by just analyzing the electronic health records of the patients. Also, machine learning can be employed to understand which features in the medical records are more predictive of sepsis severity, of patient survival, and of sequential organ failure in a fast and non-invasive way.

Dataset and methods

In this study, we analyzed a dataset of electronic health records of 364 patients collected between 2014 and 2016. The medical record of each patient has 29 clinical features, and includes a binary value for survival, a binary value for septic shock, and a numerical value for the sequential organ failure assessment (SOFA) score. We disjointly utilized each of these three factors as an independent target, and employed several machine learning methods to predict it (binary classifiers for survival and septic shock, and regression analysis for the SOFA score). Afterwards, we used a data mining approach to identify the most important dataset features in relation to each of the three targets separately, and compared these results with the results achieved through a standard biostatistics approach.

Results and conclusions

Our results showed that machine learning can be employed efficiently to predict septic shock, SOFA score, and survival of patients diagnoses with sepsis, from their electronic health records data. And regarding clinical feature ranking, our results showed that Random Forests feature selection identified several unexpected symptoms and clinical components as relevant for septic shock, SOFA score, and survival. These discoveries can help doctors and physicians in understanding and predicting septic shock. We made the analyzed dataset and our developed software code publicly available online.
High dispersal capacity of Culicoides obsoletus (Diptera: Ceratopogonidae), vector of bluetongue and Schmallenberg viruses, revealed by landscape genetic analyses
Authors: Mignotte Antoine , Garros Claire , Dellicour Simon , Jacquot Maude , Gilbert Marius , Gardès Laetitia , Balenghien Thomas , Duhayon Maxime , Rakotoarivony Ignace , de Wavrechin Maïa , Huber Karine
Published: February 2021

Background

In the last two decades, recurrent epizootics of bluetongue virus and Schmallenberg virus have been reported in the western Palearctic region. These viruses affect domestic cattle, sheep, goats and wild ruminants and are transmitted by native hematophagous midges of the genus Culicoides (Diptera: Ceratopogonidae). Culicoides dispersal is known to be stratified, i.e. due to a combination of dispersal processes occurring actively at short distances and passively or semi-actively at long distances, allowing individuals to jump hundreds of kilometers.

Methods

Here, we aim to identify the environmental factors that promote or limit gene flow of Culicoides obsoletus, an abundant and widespread vector species in Europe, using an innovative framework integrating spatial, population genetics and statistical approaches. A total of 348 individuals were sampled in 46 sites in France and were genotyped using 13 newly designed microsatellite markers.

Results

We found low genetic differentiation and a weak population structure for C. obsoletus across the country. Using three complementary inter-individual genetic distances, we did not detect any significant isolation by distance, but did detect significant anisotropic isolation by distance on a north-south axis. We employed a multiple regression on distance matrices approach to investigate the correlation between genetic and environmental distances. Among all the environmental factors that were tested, only cattle density seems to have an impact on C. obsoletus gene flow.

Conclusions

The high dispersal capacity of C. obsoletus over land found in the present study calls for a re-evaluation of the impact of Culicoides on virus dispersal, and highlights the urgent need to better integrate molecular, spatial and statistical information to guide vector-borne disease control.

Graphical Abstract
Reliability of the Clinical Frailty Scale in very elderly ICU patients: a prospective European study
Authors:   the VIP2 Study Group, Flaatten Hans , Guidet Bertrand , Andersen Finn H. , Artigas Antonio , Cecconi Maurizio , Boumendil Ariane , Elhadi Muhammed , Fjølner Jesper , Joannidis Michael , Jung Christian , Leaver Susannah , Marsh Brian , Moreno Rui , Oeyen Sandra , Nalapko Yuriy , Schefold Joerg C. , Szczeklik Wojciech , Walther Sten , Watson Ximena , Zafeiridis Tilemachos , de Lange Dylan W.
Published: February 2021

Purpose

Frailty is a valuable predictor for outcome in elderly ICU patients, and has been suggested to be used in various decision-making processes prior to and during an ICU admission. There are many instruments developed to assess frailty, but few of them can be used in emergency situations. In this setting the clinical frailty scale (CFS) is frequently used. The present study is a sub-study within a larger outcome study of elderly ICU patients in Europe (the VIP-2 study) in order to document the reliability of the CFS.

Materials and methods

From the VIP-2 study, 129 ICUs in 20 countries participated in this sub-study. The patients were acute admissions ≥ 80 years of age and frailty was assessed at admission by two independent observers using the CFS. Information was obtained from the patient, if not feasible, from the family/caregivers or from hospital files. The profession of the rater and source of data were recorded along with the score. Interrater variability was calculated using linear weighted kappa analysis.

Results

1923 pairs of assessors were included and background data of patients were similar to the whole cohort (n = 3920). We found a very high inter-rater agreement (weighted kappa 0.86), also in subgroup analyses. The agreement when comparing information from family or hospital records was better than using only direct patient information, and pairs of raters from same profession performed better than from different professions.

Conclusions

Overall, we documented a high reliability using CFS in this setting. This frailty score could be used more frequently in elderly ICU patients in order to create a more holistic and realistic impression of the patient´s condition prior to ICU admission.
Substance use and substance use disorder, in relation to COVID-19: protocol for a scoping review
Authors: Kumar Navin , Janmohamed Kamila , Nyhan Kate , Martins Silvia S. , Cerda Magdalena , Hasin Deborah , Scott Jenny , Pates Richard , Ghandour Lilian , Wazaify Mayyada , Khoshnood Kaveh
Published: February 2021

Background

The COVID-19 pandemic is creating severe issues for healthcare and broad social structures, exposing societal vulnerabilities. Among the populations affected by COVID-19 are people engaged in substance use, such as people who smoke; vape (e-cigarette use); use opioids, cannabis, alcohol, or psychoactive prescription drugs; or have a substance use disorder (SUD). Monitoring substance use and SUD during the pandemic is essential, as people who engage in substance use or present with SUD are at greater risk for COVID-19, and the economic and social changes resulting from the pandemic may aggravate SUD. There have been several reviews focused on COVID-19 in relation to substance use and SUD. Reviews generally did not consider on a large range of substance use variants or SUDs. We plan a scoping review that seeks to fill gaps in our current understanding of substance use and SUD, in the COVID-19 era.

Methods

A scoping review focused on substance use and SUD, in relation to COVID-19, will be conducted. We will search (from January 2020 onwards) Cumulative Index to Nursing and Allied Health Literature, Africa-Wide Information, Web of Science Core Collection, Embase, Global Health, WHO Global Literature on Coronavirus Disease Database, WHO Global Index Medicus, PsycINFO, PubMed, Middle Eastern Central Asian Studies, CINAHL Complete, and Sociological Abstracts. Grey literature will be identified using Disaster Lit, Google Scholar, HSRProj, governmental websites, and clinical trials registries (e.g., ClinicalTrial.gov, World Health Organization, International Clinical Trials Registry Platform and International Standard Randomized Con-trolled Trial Number registry). Study selection will conform to Joanna Briggs Institute Reviewers’ Manual 2015 Methodology for JBI Scoping Reviews. Only English language, original studies investigating substance use and SUD, in relation to COVID-19 in all populations and settings, will be considered for inclusion. Two reviewers will independently screen all citations, full-text articles, and abstract data. A narrative summary of findings will be conducted. Data analysis will involve quantitative (e.g., frequencies) and qualitative (e.g., content and thematic analysis) methods.

Discussion

Original research is urgently needed to mitigate the risks of COVID-19 on substance use and SUD. The planned scoping review will help to address this gap.

Systematic review registration

Open Science Framework (osf/io/tzgm5).
MiR-146a-5p targeting SMAD4 and TRAF6 inhibits adipogenensis through TGF-β and AKT/mTORC1 signal pathways in porcine intramuscular preadipocytes
Authors: Zhang Que , Cai Rui , Tang Guorong , Zhang Wanrong , Pang Weijun
Published: February 2021

Background

Intramuscular fat (IMF) content is a vital parameter for assessing pork quality. Increasing evidence has shown that microRNAs (miRNAs) play an important role in regulating porcine IMF deposition. Here, a novel miRNA implicated in porcine IMF adipogenesis was found, and its effect and regulatory mechanism were further explored with respect to intramuscular preadipocyte proliferation and differentiation.

Results

By porcine adipose tissue miRNA sequencing analysis, we found that miR-146a-5p is a potential regulator of porcine IMF adipogenesis. Further studies showed that miR-146a-5p mimics inhibited porcine intramuscular preadipocyte proliferation and differentiation, while the miR-146a-5p inhibitor promoted cell proliferation and adipogenic differentiation. Mechanistically, miR-146a-5p suppressed cell proliferation by directly targeting SMAD family member 4 (SMAD4) to attenuate TGF-β signaling. Moreover, miR-146a-5p inhibited the differentiation of intramuscular preadipocytes by targeting TNF receptor-associated factor 6 (TRAF6) to weaken the AKT/mTORC1 signaling downstream of theTRAF6pathway.

Conclusions

MiR-146a-5p targetsSMAD4andTRAF6to inhibit porcine intramuscular adipogenesis by attenuating TGF-β and AKT/mTORC1 signaling, respectively. These findings provide a novel miRNA biomarker for regulating intramuscular adipogenesis to promote pork quality.
COVID-19 case fatality risk by age and gender in a high testing setting in Latin America: Chile, March–August 2020
Authors: Undurraga Eduardo A. , Chowell Gerardo , Mizumoto Kenji
Published: February 2021

Background

Early severity estimates of coronavirus disease 2019 (COVID-19) are critically needed to assess the potential impact of the ongoing pandemic in different demographic groups. Here we estimate the real-time delay-adjusted case fatality rate across nine age groups by gender in Chile, the country with the highest testing rate for COVID-19 in Latin America.

Methods

We used a publicly available real-time daily series of age-stratified COVID-19 cases and deaths reported by the Ministry of Health in Chile from the beginning of the epidemic in March through August 31, 2020. We used a robust likelihood function and a delay distribution to estimate real-time delay-adjusted case-fatality risk and estimate model parameters using a Monte Carlo Markov Chain in a Bayesian framework.

Results

As of August 31, 2020, our estimates of the time-delay adjusted case fatality rate (CFR) for men and women are 4.16% [95% Credible Interval (CrI): 4.09–4.24%] and 3.26% (95% CrI: 3.19–3.34%), respectively, while the overall estimate is 3.72% (95% CrI: 3.67–3.78%). Seniors aged 80 years and over have an adjusted CFR of 56.82% (95% CrI: 55.25–58.34%) for men and 41.10% (95% CrI: 40.02–42.26%) for women. Results showed a peak in estimated CFR during the June peak of the epidemic. The peak possibly reflects insufficient laboratory capacity, as illustrated by high test positivity rates (33% positive 7-day average nationally in June), which may have resulted in lower reporting rates.

Conclusions

Severity estimates from COVID-19 in Chile suggest that male seniors, especially among those aged ≥ 70 years, are being disproportionately affected by the pandemic, a finding consistent with other regions. The ongoing pandemic is imposing a high death toll in South America, and Chile has one of the highest reported mortality rates globally thus far. These real-time estimates may help inform public health officials' decisions in the region and underscore the need to implement more effective measures to ameliorate fatality.
Pre-clinical characterisation of E2814, a high-affinity antibody targeting the microtubule-binding repeat domain of tau for passive immunotherapy in Alzheimer’s disease
Authors: Roberts Malcolm , Sevastou Ioanna , Imaizumi Yoichi , Mistry Kavita , Talma Sonia , Dey Madhurima , Gartlon Jane , Ochiai Hiroshi , Zhou Zhi , Akasofu Shigeru , Tokuhara Naoki , Ogo Makoto , Aoyama Muneo , Aoyagi Hirofumi , Strand Kate , Sajedi Ezat , Agarwala Kishan Lal , Spidel Jared , Albone Earl , Horie Kanta , Staddon James M. , de Silva Rohan
Published: February 2021

Tau deposition in the brain is a pathological hallmark of many neurodegenerative disorders, including Alzheimer’s disease (AD). During the course of these tauopathies, tau spreads throughout the brain via synaptically-connected pathways. Such propagation of pathology is thought to be mediated by tau species (“seeds”) containing the microtubule binding region (MTBR) composed of either three repeat (3R) or four repeat (4R) isoforms. The tau MTBR also forms the core of the neuropathological filaments identified in AD brain and other tauopathies. Multiple approaches are being taken to limit tau pathology, including immunotherapy with anti-tau antibodies. Given its key structural role within fibrils, specifically targetting the MTBR with a therapeutic antibody to inhibit tau seeding and aggregation may be a promising strategy to provide disease-modifying treatment for AD and other tauopathies. Therefore, a monoclonal antibody generating campaign was initiated with focus on the MTBR. Herein we describe the pre-clinical generation and characterisation of E2814, a humanised, high affinity, IgG1 antibody recognising the tau MTBR. E2814 and its murine precursor, 7G6, as revealed by epitope mapping, are antibodies bi-epitopic for 4R and mono-epitopic for 3R tau isoforms because they bind to sequence motif HVPGG. Functionally, both antibodies inhibited tau aggregation in vitro. They also immunodepleted a variety of MTBR-containing tau protein species. In an in vivo model of tau seeding and transmission, attenuation of deposition of sarkosyl-insoluble tau in brain could also be observed in response to antibody treatment. In AD brain, E2814 bound different types of tau filaments as shown by immunogold labelling and recognised pathological tau structures by immunohistochemical staining. Tau fragments containing HVPGG epitopes were also found to be elevated in AD brain compared to PSP or control. Taken together, the data reported here have led to E2814 being proposed for clinical development.
Molecular analysis of pediatric CNS-PNET revealed nosologic heterogeneity and potent diagnostic markers for CNS neuroblastoma with FOXR2-activation
Authors: Korshunov Andrey , Okonechnikov Konstantin , Schmitt-Hoffner Felix , Ryzhova Marina , Sahm Felix , Stichel Damian , Schrimpf Daniel , Reuss David E. , Sievers Philipp , Suwala Abigail Kora , Kumirova Ella , Zheludkova Olga , Golanov Andrey , Jones David T. W. , Pfister Stefan M. , Kool Marcel , von Deimling Andreas
Published: February 2021

Primitive neuroectodermal tumors of the central nervous system (CNS-PNETs) are highly malignant neoplasms posing diagnostic challenge due to a lack of defining molecular markers. CNS neuroblastoma with forkhead box R2 (FOXR2) activation (CNS_NBL) emerged as a distinct pediatric brain tumor entity from a pool previously diagnosed as primitive neuroectodermal tumors of the central nervous system (CNS-PNETs). Current standard of identifying CNS_NBL relies on molecular analysis. We set out to establish immunohistochemical markers allowing safely distinguishing CNS_NBL from morphological mimics. To this aim we analyzed a series of 84 brain tumors institutionally diagnosed as CNS-PNET. As expected, epigenetic analysis revealed different methylation groups corresponding to the (1) CNS-NBL (24%), (2) glioblastoma IDH wild-type subclass H3.3 G34 (26%), (3) glioblastoma IDH wild-type subclass MYCN (21%) and (4) ependymoma with RELA_C11orf95 fusion (29%) entities. Transcriptome analysis of this series revealed a set of differentially expressed genes distinguishing CNS_NBL from its mimics. Based on RNA-sequencing data we established SOX10 and ANKRD55 expression as genes discriminating CNS_NBL from other tumors exhibiting CNS-PNET. Immunohistochemical detection of combined expression of SOX10 and ANKRD55 clearly identifies CNS_NBL discriminating them to other hemispheric CNS neoplasms harboring “PNET-like” microscopic appearance. Owing the rarity of CNS_NBL, a confirmation of the elaborated diagnostic IHC algorithm will be necessary in prospective patient series.
Rapid water parcel transport across the Kuroshio Extension in the lower thermocline from dissolved oxygen measurements by Seaglider
Authors: Hosoda Shigeki , Inoue Ryuichiro , Nonaka Masami , Sasaki Hideharu , Sasai Yoshikazu , Hirano Mizue
Published: February 2021

Small water parcels, which are characterized by a low salinity and high dissolved oxygen (DO) are observed by Seaglider in the main thermocline (26.0–27.0 σθ) south of the Kuroshio Extension (KE), have horizontal and vertical scales of a few tens of kilometers and a few tens of meters, respectively. Water mass analyses revealed larger negative salinity anomalies (<− 0.05) and positive DO anomalies (> 15 μmol kg−1) than those of the surrounding water. The characteristics are similar to those of water mass with low salinity and high DO in the subpolar Northwestern Pacific Ocean. Additionally, higher DO anomaly water parcels appear in the upper layer (< 26.7 σθ) while low salinity parcels appear in the lower layer (> 26.7 σθ). Oxygen consumption rates from the apparent oxygen utility suggest that the small water parcels consume less oxygen than the surrounding water, implying that they migrate in a shorter time across the KE after subduction and their characteristics may reflect the sea surface temperature, salinity, and DO in the subduction region. Similar small water parcels represented by high-resolution numerical simulations indicate that they pass through the KE in 1 month. The simulations support the oxygen consumption rate from the Seaglider observations. The existence of a fast process for water mass migration via meso- and submesoscale subduction processes across the KE affects the amount, subduction, and exchange process of water mass. Our study indicates that a small water mass contributes to the exchange process across the KE rapidly, which had not been identified in previous studies. Consequently, detailed observations using multiple Seagliders should capture detailed spatial and temporal variability of the water mass exchange process.
Jejunal limb obstruction by a tumor thrombus from pancreatic metastasis of renal cell carcinoma: a case report
Authors: Sakamoto Shinya , Matsumura Masaru , Tani Keigo , Nemoto Satoshi , Tsuchida Kazuhito , Koga Fumitaka , Seyama Yasuji
Published: February 2021

Background

Renal cell carcinoma (RCC) is a primary tumor with the highest frequency of pancreatic metastasis. Although surgical resection can improve the prognosis of some patients with pancreatic metastasis of RCC (PM-RCC), the role of palliative surgery remains unclear. Herein, we described a case of jejunal limb occlusion caused by a tumor thrombus arising from a PM-RCC which was treated by surgical resection.

Case presentation

A 75-year-old, male patient with metastatic RCC was admitted to our hospital with new-onset dysphagia and weight loss. Twenty years earlier he underwent a right nephrectomy with an adrenalectomy for the first surgical resection of RCC, and 12 years ago he underwent a left partial nephrectomy for metachronous primary RCC. Nine years later, multiple pancreatic metastases were detected. After discontinuing interferon therapy, he was followed up at his request without anticancer treatment. Multiple, pulmonary metastases developed 3 years ago, and resection of a brain metastasis was performed 6 months ago. He had also undergone a total gastrectomy with Roux-en Y reconstruction and splenectomy for gastric cancer 23 years ago. Computed tomography revealed a metastatic lesion in the pancreatic tail extending into the jejunal limb, which was obstructed by a tumor thrombus. Jejunal limb resection was performed concomitantly with a distal pancreatectomy as palliative surgery. The jejunal limb remnant was approximately 30 cm long and was re-anastomosed to the esophagus using a circular stapler. Blood perfusion at the anastomotic site was confirmed by indocyanine green fluorescence imaging. He was discharged on postoperative day 24 and was followed in the outpatient clinic. He achieved sufficient oral intake at 8 months postoperatively.

Conclusions

PM-RCC can invade the gastrointestinal tract and cause tumor thrombus formation resulting in bowel occlusion requiring surgical intervention.
Intermittent fasting: is there a role in the treatment of diabetes? A review of the literature and guide for primary care physicians
Authors: Albosta Michael , Bakke Jesse
Published: February 2021

Background

Type 2 Diabetes is a metabolic disorder characterized by hyperglycemia that causes numerous complications with significant long-term morbidity and mortality. The disorder is primarily due to insulin resistance particularly in liver, skeletal muscle, and adipose tissue. In this review, we detail the hormonal mechanisms leading to the development of diabetes and discuss whether intermittent fasting should be considered as an alternative, non-medicinal treatment option for patients with this disorder.

Methods

We searched PubMed, Ovid MEDLINE, and Google Scholar databases for review articles, clinical trials, and case series related to type 2 diabetes, insulin resistance, and intermittent fasting. Articles were carefully reviewed and included based on relevance to our topic. We excluded abstracts and any non-English articles.

Results

The majority of the available research demonstrates that intermittent fasting is effective at reducing body weight, decreasing fasting glucose, decreasing fasting insulin, reducing insulin resistance, decreasing levels of leptin, and increasing levels of adiponectin. Some studies found that patients were able to reverse their need for insulin therapy during therapeutic intermittent fasting protocols with supervision by their physician.

Conclusion

Current evidence suggests that intermittent fasting is an effective non-medicinal treatment option for type 2 diabetes. More research is needed to delineate the effects of intermittent fasting from weight loss. Physicians should consider educating themselves regarding the benefits of intermittent fasting. Diabetic patients should consult their physician prior to beginning an intermittent fasting regimen in order to allow for appropriate oversight and titration of the patients medication regimen during periods of fasting.
Plasma proteome profiling of cardiotoxicity in patients with diffuse large B-cell lymphoma
Authors: Mörth Charlott , Sabaa Amal Abu , Freyhult Eva , Christersson Christina , Hashemi Jamileh , Hashemi Nashmil , Kamali-Moghaddam Masood , Molin Daniel , Höglund Martin , Eriksson Anna , Enblad Gunilla
Published: February 2021

Background

Cardiovascular toxicity is a notorious complication of doxorubicin (DXR) therapy for diffuse large B-cell lymphoma (DLBCL). Although surveillance of well-known biological markers for cardiovascular disease (CVD) as NTproBNP and Troponins may be helpful, there are no established markers to monitor for evolving CVD during treatment. New possibilities have arisen with the emergence of newer techniques allowing for analysis of plasma proteins that can be associated with cardiovascular disease. Proximity Extension Assay is one of them.

Objectives

We aimed to illustrate the incidence of CVD in DLBCL patients treated with DXR and to establish whether there are plasma proteins associated with pre-existing or emerging CVD.

Methods

In 95 patients, 182 different proteins from OLINK panels, NTproBNP, Troponin I and CRP were assessed prior to, during and after treatment. For comparison, samples from controls were analyzed.

Results

In the DLBCL cohort, 33.3% had pre-treatment CVD compared to 5.0% in the controls and 23.2% developed new CVD. Of the 32.6% who died during follow up, CVD was the cause in 4 patients. Spondin-1 (SPON-1) correlated to pre-treatment CVD (1.22 fold change, 95% CI 1.10–1.35, p = 0.00025, q = 0.045). Interleukin-1 receptor type 1 (IL-1RT1) was associated to emerging CVD (1.24 fold change, 95% CI 1.10–1.39, p = 0.00044, q = 0.082).

Conclusion

We observed a higher prevalence of CVD in DLBCL patients compared to controls prior to DXR therapy. Two proteins, SPON-1 and IL-1RT1, were related to pre-existing and emerging CVD in DXR treated patients. If confirmed in larger cohorts, IL-1RT1 may emerge as a reliable biomarker for unfolding CVD in DLBCL.
Correction to: Isolation and identification of Bacillus thuringiensis strains native of the Eastern Province of Saudi Arabia
Authors: Hassan Amina A. , Youssef Mohamed A. , Elashtokhy M. M. A. , Ismail I. M. , Aldayel Munirah , Afkar Eman
Published: February 2021

An amendment to this paper has been published and can be accessed via the original article.
Creation of an ex-vivo bovine kidney flow model for testing embolic agents: work in progress
Authors: Garza Luis , Bitar Ryan , O’Donnell Barrett , Parker Matthew , Ortiz Carlos , Hyman Charles , Walker John , Song Ho-Young , Lopera Jorge
Published: February 2021

Objectives

To develop an ex- vivo perfusion flow model using a bovine kidney for future testing of embolic agents in an inexpensive and easy way.

Methods

Six bovine adult kidneys were used for this study. Kidneys were cannulated and perfused via a roller pump. Three embolic agents, coils, Gelfoam, and a glue mixture of Histoacryl + Lipiodol, were deployed by targeting three secondary segmental arteries per kidney via a 5Fr catheter under fluoroscopic guidance. Cannulation time, success rate of segmental artery selection and embolic agent deployment, total operational time, and fluoroscopy dose were recorded.

Results

Average kidney weight was 0.752 +/− 0.094 kg. All six bovine kidneys were successfully cannulated in 21.6 min +/− 3.0 min. Deployment of coils and glue was achieved in every case (12/12); however, Gelfoam injection was not successful in one instance (5/6, 83%). Coil deployment demonstrated no embolic effect while Gelfoam and glue injections demonstrated decreased distal contrast filling post-embolization. Mean dose area product was 12.9 ± 1.8 Gy·cm2, fluoroscopy time was 10 ± 4 min and operational time was 27 ± 8 min.

Conclusions

We describe the creation of an ex vivo bovine kidney flow model for the preclinical evaluation of different embolic materials. The flow model can be modified to provide extensive bench testing and it is a promising tool for hands -on training in basic and advanced embolization techniques .
ABO groups can play a role in susceptibility and severity of COVID-19
Authors: Samra S. , Habeb M. , Nafae R.
Published: February 2021

Background

A few people infected by the coronavirus become seriously ill, while others show little to no signs of the symptoms, or are asymptomatic. Recent researches are pointing to the fact that the ABO blood group might play an important role in a person’s susceptibility and severity of COVID-19 infection. Aim of the study: try to understand the relationship between ABO groups and COVID-19 (susceptibility and severity).

Results

A total of (507) patients were included in this study. The study population was divided based on the ABO blood group into types A+, A−, B+, AB, O+, and O−. Blood group A was associated with high susceptibility of infection: group A, 381 (75.1%); and less common in group O, 97 (19.2%), group B, 18 (3.5%), and group AB, 11 (2.2%). The severity of COVID-19 infection was common in non-blood group O where (20 (7.1%), 4 (26.7%), 2 (11%), and 1 (9%) in type A+, A−, B+, and AB, respectively), while in type O 3.1%. And mechanically ventilated patients were 22 (5.9%), 2 (13.4%), 2 (11.1%), and 1 (1%). Mortality was high in blood groups A and B, 16 (4.37%) and 1 (5.5%), respectively, while in blood group O, it was 1%.

Conclusion

The incidence, severity, and mortality of COVID-19 were common in non-blood group O. While blood group O was protected against COVID-19.
Application of time series prediction techniques for coastal bridge engineering
Authors: Yu Enbo , Wei Huan , Han Yan , Hu Peng , Xu Guoji
Published: February 2021

In this study, three machine learning techniques, the XGBoost (Extreme Gradient Boosting), LSTM (Long Short-Term Memory Networks), and ARIMA (Autoregressive Integrated Moving Average Model), are utilized to deal with the time series prediction tasks for coastal bridge engineering. The performance of these techniques is comparatively demonstrated in three typical cases, the wave-load-on-deck under regular waves, structural displacement under combined wind and wave loads, and wave height variation along with typhoon/hurricane approaching. To enhance the prediction accuracy, a typical data preprocessing method is adopted and an improved prediction framework for the LSTM model after the rolling forecast prediction is proposed. The obtained results show that: (a) When making a prediction on data featured with periodic regularity, both the XGBoost and ARIMA models perform well, and the XGBoost model can make predictions multi-step ahead, (b) The ARIMA model can predict just one step ahead based on aperiodic dataset with limited amplitude more accurately, while the XGBoost and LSTM models can predict multi-step ahead with appropriate data preprocessing, and (c) All the three models can predict the data tendency with model updating over time, but the prediction accuracy of the LSTM model is more favorable. The successful application of these three machine learning techniques can provide guidance to resolve engineering problems with time-history prediction requirements.
How Patients and Providers Weigh the Risks and Benefits of Long-Term Opioid Therapy for Cancer Pain
Authors: Giannitrapani Karleen F. , Fereydooni Soraya , Silveira Maria J. , Azarfar Azin , Glassman Peter A. , Midboe Amanda , Zenoni Maria , Becker William C. , Lorenz Karl A.
Published: February 2021

PURPOSE:

To understand how patients and providers weigh the risks and benefits of long-term opioid therapy (LTOT) for cancer pain.

METHODS:

Researchers used VA approved audio-recording devices to record interviews. ATLAS t.i., a qualitative analysis software, was used for analysis of transcribed interview data. Participants included 20 Veteran patients and 20 interdisciplinary providers from primary care– and oncology-based practice settings. We conducted semistructured interviews and analyzed transcripts used thematic qualitative methods. Interviews explored factors that affect decision making about appropriateness of LTOT for cancer related pain. We saturated themes for providers and patients separately.

RESULTS:

Factors affecting patient decision-making included influence from various information sources, persuasion from trusted providers, and sometimes deferral of the decision to their provider. Relative prioritization of pain management as the focal patient concern varied with some patients describing comparatively more fear of chemotherapy than opioid analgesics, comparatively more knowledge of opioids in relation to other drugs;patients expressed a preference to spend the limited time they have with their oncologist discussing cancer treatment rather than opioid use. Factors affecting provider decision making included prognosis, patient goals, patient characteristics, and provider experience and biases. Providers differed in how they weigh the relative importance of alleviating pain or avoiding opioids in the face of treating patients with cancer and histories of substance abuse.

CONCLUSION:

Divergent perspectives on factors need to be considered when weighing risks and benefits. Policies and interventions should be designed to reduce variation in practice to promote equal access to adequate pain management. Improved shared decision-making initiatives will take advantage of patient decision-making factors and priorities.
18F-FDG-PET/CT Evaluation of Indeterminate Adrenal Masses in Noncancer Patients
Authors: He Xin , Caoili Elaine M , Avram Anca M , Miller Barbra S , Else Tobias
Published: February 2021

Context

Adrenal tumors in noncancer patients are common.

Objective

Evaluate performance of 18F-fluorodeoxyglucose positron emission tomography computed tomography (18F-FDG-PET/CT) in distinguishing between benign and malignant adrenal tumors.

Design

Retrospective chart review 2010-2019.

Setting

Academic institution.

Patients

One hundred and seventeen noncancer patients, defined as having no history of cancer or with cancer in remission for ≥5 years, completed 18F-FDG-PET/CT to evaluate adrenal masses, with pathologic diagnoses or imaging follow-up (≥12 months).

Intervention

18F-FDG-PET/CT of 117 indeterminate adrenal masses.

Main Outcome Measures

Receiver operator characteristic curve of the ratios of adrenal lesion standardized uptake value (SUV)max to liver SUVmean and of adrenal lesion SUVmax to aortic arch blood pool SUVmean were constructed.

Results

Seventy benign and 47 malignant masses (35 adrenocortical carcinomas [ACCs], 12 adrenal metastases) were identified. Malignant masses had higher median liver SUV and blood pool SUV ratios than benign masses (6.2 and 7.4 vs 1.4 and 2.0, P < .001). Median liver and blood pool SUV ratios of ACC (6.1 and 7.3, respectively) and metastases (6.7 and 7.7, respectively) were higher than those of than adenomas (1.4 and 2.2, P < .05 for all comparisons). Optimal liver SUV ratio to discern between benign and malignant masses was 2.5, yielding 85% sensitivity, 90% specificity, and 7 false negative results (including 3 ACCs). Optimal blood pool SUV ratio was 3.4, yielding 83% sensitivity, 90% specificity, and 8 false negative results (including 4 ACCs).

Conclusion

When used in conjunction with other clinical assessments, 18F-FDG-PET/CT can be a valuable tool in evaluating adrenal masses in noncancer patients.