bluuebunny/crossref_metadata_2025 huggingface dataset:
Leucine and Sildenafil Combination Therapy Reduces Body Weight and Metformin Enhances the Effect at Low Dose: A Randomized Controlled Trial
Authors: Rebello Candida J. , Zemel Michael B. , Kolterman Orville , Fleming Gilbert Alexander , Greenway Frank L.
Published: December 2020

Background:

This study evaluated the potential of activating the fuel-sensing enzymes Adenine monophosphate (AMP)-activated protein kinase and the deacetylase sirtuin1, to promote weight loss. We tested the efficacy of a fixed dose combination of the amino acid leucine and 2 well-characterized agents with established safety profiles to modulate energy metabolism and facilitate weight loss.

Study Question:

Will a combination of l-leucine with low-dose metformin and sildenafil produce a novel synergistic interaction that reduces body weight?

Study Design:

We conducted a 24-week randomized controlled trial evaluating the effect on weight loss of leucine 1.1 g and sildenafil 1.0 mg or 4.0 mg, with and without metformin 500 mg (Leu/Sil 1.0, Leu/Sil 4.0, Leu/Met/Sil 1.0, and Leu/Met/Sil 4.0 twice/day). We enrolled 267 participants who were 18–65 years of age without diabetes and with the body mass index (BMI) of 30–45 kg/m2.

Measures and Outcomes:

The primary endpoint was percentage weight change after 24 weeks. Adverse events were evaluated. The primary analysis was performed using the perprotocol population analysis of covariance estimation. Subgroup analyses of patients residing above certain threshold limits at baseline and in populations at increased risk of obesity were assessed post-hoc as exploratory end points.

Results:

Placebo-adjusted mean bodyweight reductions in the Leu/Met/Sil 1.0, Leu/Met/Sil 4.0, and Leu/Sil 4.0 groups were −1.99%, −1.69%, and −1.67% (P = 0.015, 0.035, and 0.036, respectively). The most common adverse events were gastrointestinal-related and occurred in the metformin-treated groups consistent with metformin treatment. In African Americans, Leu/Met/Sil 1.0 produced 5.4% mean weight loss. In participants with BMI <40 kg/m2 treated with Leu/Met/Sil 1.0, the weight loss increased to 2.84%, particularly in participants with baseline insulin ≥12mU/L (3.5%).

Conclusions:

Leu/Met/Sil 1.0 and 4.0 and Leu/Sil 4.0 reduced body weight, but Leu/Met/Sil 1.0 was associated with robust weight loss in African Americans, and individuals with BMI 30–39.9 kg/m2, especially participants with hyperinsulinemia.
Meta-analysis and Systematic Review of the Use of a Prosthetic Mesh for Prevention of Parastomal Hernia
Authors: Prudhomme Michel , Fabbro-Peray Pascale , Rullier Eric , Occean Bob V. , Bertrand Martin M.
Published: December 2020

Objective:

The primary endpoint of this meta-analysis was the PSH rate at 1 year of follow-up with or without the use of a mesh.

Summary of Background Data:

European guidelines currently recommend the use of a mesh at the time of a stoma formation for the prevention of PSH. These recommendations are based on the RCT and meta-analyses published before 2017. More recently 2 large RCT found no benefit in the mesh group. We investigated whether these latest results could change the conclusion of a meta-analysis.

Methods:

We conducted a comprehensive literature search and analyzed RCT investigating the use of a mesh to prevent PSH formation. All studies including end colostomies were included in the qualitative analysis no matter the surgical technique or the type of mesh. All studies with a limited risk of bias and presenting with usable data were used in the quantitative analysis.

Results:

There is a large heterogeneity among the studies, in terms of position of the mesh, surgical technique, and diagnostic method for the PSH.

No statistically significant difference was found on the PSH rate at 1 or 2 years between the mesh and non-mesh groups.

Conclusions:

Based on this meta-analysis including the latest RCT on the prevention of PSH, the use of a mesh should not be recommended.
Serous Cystic Neoplasms of the Pancreas Management in the Real-world
Authors: Marchegiani Giovanni , Caravati Andrea , Andrianello Stefano , Pollini Tommaso , Bernardi Giulia , Biancotto Marco , Malleo Giuseppe , Bassi Claudio , Salvia Roberto
Published: December 2020

Objective:

Our aim is to provide a real-life picture of serous cystic neoplasms (SCNs) management once a presumptive diagnosis is made.

Summary of Background Data:

SCNs of the pancreas are invariably benign entities. While consensus about their management is lacking, surgical resection still plays a role.

Methods:

Presumed SCNs evaluated from 1990 to 2018 were included. Indications for surgery, predictors of resection, rate, and predictors of misdiagnosis in the surgical cohort and time trends of management strategies were the main outcomes.

Results:

A total of 672 presumed SCNs were included. Presence of symptoms (37%) and large size (34.1%) were the most frequent indications for surgery. Symptoms (60.4% vs 19.0%, P < 0.001), size (45 vs 30 mm, P < 0.001), solid components (19.7% vs 6.2%, P < 0.001), thick walls (14.4 vs 5.6%, P = 0.001) and main pancreatic duct dilation (13.4% vs 5.6%, P = 0.004) were associated with upfront resection (n = 134, 19.9%). Upfront resection decreased over time and 15.4% of patients eventually crossed over to surgery. Increase in size (6.9 vs 1.3 mm/yr), development of symptoms (25.3% vs 3.4%, P < 0.001), solid component (6.0% vs 1.4%, P = 0.010) or jaundice (3.6% vs 0.7%, P = 0.028) were associated with crossing over to surgery. Major morbidity and mortality occurred in 17.1% and 1.7% of patients, respectively. Misdiagnosis occurred mostly in case of macrocystic/unilocular lesions of the body-tail.

Conclusions:

In the real-life scenario, SCNs still represent an indication for surgery particularly once large and symptomatic. During surveillance, resection occurs mostly in younger individuals for body/tail lesions. Evidence-based consensus on appropriate indications for surgery is urgently needed.
Potentin vitroanti-SARS-CoV-2 activity by gallinamide A and analogues via inhibition of cathepsin L
Authors: Ashhurst Anneliese S. , Tang Arthur H. , Fajtová Pavla , Yoon Michael , Aggarwal Anupriya , Stoye Alexander , Larance Mark , Beretta Laura , Drelich Aleksandra , Skinner Danielle , Li Linfeng , Meek Thomas D. , McKerrow James H. , Hook Vivian , Tseng Chien-Te K. , Turville Stuart , Gerwick William H. , O’Donoghue Anthony J. , Payne Richard J.
Published: December 2020

The emergence of SARS-CoV-2 in late 2019, and the subsequent COVID-19 pandemic, has led to substantial mortality, together with mass global disruption. There is an urgent need for novel antiviral drugs for therapeutic or prophylactic application. Cathepsin L is a key host cysteine protease utilized by coronaviruses for cell entry and is recognized as a promising drug target. The marine natural product, gallinamide A and several synthetic analogues, were identified as potent inhibitors of cathepsin L activity with IC50values in the picomolar range. Lead molecules possessed selectivity over cathepsin B and other related human cathepsin proteases and did not exhibit inhibitory activity against viral proteases Mpro and PLpro. We demonstrate that gallinamide A and two lead analogues potently inhibit SARS-CoV-2 infectionin vitro, with EC50values in the nanomolar range, thus further highlighting the potential of cathepsin L as a COVID-19 antiviral drug target.
A SARS-CoV-2 spike binding DNA aptamer that inhibits pseudovirus infection in vitro by an RBD independent mechanism
Authors: Schmitz Anton , Weber Anna , Bayin Mehtap , Breuers Stefan , Fieberg Volkmar , Famulok Michael , Mayer Günter
Published: December 2020

The receptor binding domain (RBD) of the spike glycoprotein of the coronavirus SARS-CoV-2 (CoV2-S) binds to the human angiotensin converting enzyme 2 (ACE2) representing the initial contact point for leveraging the infection cascade. We used an automated selection process and identified an aptamer that specifically interacts with CoV2-S. The aptamer does not bind to the RBD of CoV2-S and does not block the interaction of CoV2-S with ACE2. Notwithstanding, infection studies revealed potent and specific inhibition of pseudoviral infection by the aptamer. The present study opens up new vistas in developing SARS-CoV2 infection inhibitors, independent of blocking the ACE2 interaction of the virus and harnesses aptamers as potential drug candidates and tools to disentangle hitherto inaccessible infection modalities, which is of particular interest in light of the increasing number of escape mutants that are currently being reported.
Exploring epitope and functional diversity of anti-SARS-CoV2 antibodies using AI-based methods
Authors: Dumet C. , Jullian Y. , Musnier A. , Rivière Ph. , Poirier N. , Watier H. , Bourquard T. , Poupon A.
Published: December 2020

Since the beginning of the COVID19 pandemics, an unprecedented research effort has been conducted to analyze the antibody responses in patients, and many trials based on passive immunotherapy — notably monoclonal antibodies — are ongoing. Twenty-one antibodies have entered clinical trials, 6 having reached phase 2/3, phase 3 or having received emergency authorization. These represent only the tip of the iceberg, since many more antibodies have been discovered and represent opportunities either for diagnosis purposes or as drug candidates. The main problem facing laboratories willing to develop such antibodies is the huge task of analyzing them and choosing the best candidate for exhaustive experimental validation. In this work we show how artificial intelligence-based methods can help in analyzing large sets of antibodies in order to determine in a few hours the best candidates in few hours. The MAbCluster method, which only requires knowledge of the amino acid sequences of the antibodies, allows to group the antibodies having the same epitope, considering only their amino acid sequences and their 3D structures (actual or predicted), and to infer some of their functional properties. We then use MAbTope to predict the epitopes for all antibodies for which they are not already known. This allows an exhaustive comparison of the available epitopes, but also gives a synthetic view of the possible combinations. Finally, we show how these results can be used to predict which antibodies might be affected by the different mutations arising in the circulating strains of the virus, such as the N501Y mutation that has started to spread in Great-Britain.
Shedding Light on Microbial Dark Matter with A Universal Language of Life
Authors: Hoarfrost A , Aptekmann A , Farfañuk G , Bromberg Y
Published: December 2020

The majority of microbial genomes have yet to be cultured, and most proteins predicted from microbial genomes or sequenced from the environment cannot be functionally annotated. As a result, current computational approaches to describe microbial systems rely on incomplete reference databases that cannot adequately capture the full functional diversity of the microbial tree of life, limiting our ability to model high-level features of biological sequences. The scientific community needs a means to capture the functionally and evolutionarily relevant features underlying biology, independent of our incomplete reference databases. Such a model can form the basis for transfer learning tasks, enabling downstream applications in environmental microbiology, medicine, and bioengineering. Here we present LookingGlass, a deep learning model capturing a “universal language of life”. LookingGlass encodes contextually-aware, functionally and evolutionarily relevant representations of short DNA reads, distinguishing reads of disparate function, homology, and environmental origin. We demonstrate the ability of LookingGlass to be fine-tuned to perform a range of diverse tasks: to identify novel oxidoreductases, to predict enzyme optimal temperature, and to recognize the reading frames of DNA sequence fragments. LookingGlass is the first contextually-aware, general purpose pre-trained “biological language” representation model for short-read DNA sequences. LookingGlass enables functionally relevant representations of otherwise unknown and unannotated sequences, shedding light on the microbial dark matter that dominates life on Earth.

Availability

The pretrained LookingGlass model and the transfer learning-derived models demonstrated in this paper are available in the LookingGlass release v1.01. The open source fastBio Github repository and python package provides classes and functions for training and fine tuning deep learning models with biological data2. Code for reproducing analyses presented in this paper are available as an open source Github repository3.
Cell-type apoptosis in lung during SARS-CoV-2 infection
Authors: Liu Yakun , Garron Tania M. , Chang Qing , Su Zhengchen , Zhou Changcheng , Gong Eric C. , Zheng Junying , Yin Yw , Ksiazek Thomas , Brasel Trevor , Jin Yang , Boor Paul , Comer Jason E. , Gong Bin
Published: December 2020

The SARS-CoV-2 pandemic has inspired renewed interest in understanding the fundamental pathology of acute respiratory distress syndrome (ARDS) following infection because fatal COVID-19 cases are commonly linked to respiratory failure due to ARDS. The pathologic alteration known as diffuse alveolar damage in endothelial and epithelial cells is a critical feature of acute lung injury in ARDS. However, the pathogenesis of ARDS following SRAS-CoV-2 infection remains largely unknown.

In the present study, we examined apoptosis in post-mortem lung sections from COVID-19 patients and lung tissues from a non-human primate model of SARS-CoV-2 infection, in a cell-type manner, including type 1 and 2 alveolar cells and vascular endothelial cells (ECs), macrophages, and T cells. Multiple-target immunofluorescence (IF) assays and western blotting suggest both intrinsic and extrinsic apoptotic pathways are activated during SARS-CoV-2 infection. Furthermore, we observed that SARS-CoV-2 fails to induce apoptosis in human bronchial epithelial cells (i.e., BEAS2B cells) and primary human umbilical vein endothelial cells (HUVECs), which are refractory to SARS-CoV-2 infection. However, infection of co-cultured Vero cells and HUVECs or Vero cells and BEAS2B cells with SARS-CoV-2 induced apoptosis in both Vero cells and HUVECs/BEAS2B cells, but did not alter the permissiveness of HUVECs or BEAS2B cells to the virus. Post-exposure treatment of the co-culture of Vero cells and HUVECs with an EPAC1-specific activator ameliorated apoptosis in HUVECs. These findings may help to delineate a novel insight into the pathogenesis of ARDS following SARS-CoV-2 infection.
Preclinical drug response metric based on cellular response phenotype provides better pharmacogenomic variables with phenotype relevance
Authors: Kim Sanghyun , Hwang Sohyun
Published: December 2020

Background and Purpose

Assessment of drug response is typically performed by constructing a dose-response curve of viability and summarizing it to a representative value. However, this is limited by its dependency on the assay duration and lack of reflections regarding actual cellular response phenotypes. To resolve these limitations, we considered contribution of each response phenotype upon a drug treatment to the overall growth behavior.

Experimental Approach

The differential equation of phenotype population dynamics was solved analytically without numerical computation. By using the properly figured population dynamics, we explored how the conventional assessment method itself affects the assessment result of drug response, in the context of drug screening. Alternative phenotype metric was compared with the conventional metrics through evaluation of the publicly available drug response data.

Key Results

The conventional assessment showed several limitations in the comparative analysis of drug response: a significant time-dependency, and ambiguities in assessment results based on a dose-response curve. Instead, the alternative phenotype metrics provide time-independent phenotype rates of change, that contain all the information of the drug response at a given dose, and better classification including the mechanism underlying growth inhibition.

Conclusion and Implications

The conventional dose-response curve is useful for a visual presentation of overall drug responses upon a certain molecular feature qualitatively. In contrast, the phenotype metric is better for assessing therapeutic effectiveness, and would improve preclinical pharmacogenomic analysis through its relevance to a response phenotype.

Bullet point summary

What is already known

Drug response is investigated by constructing a dose-response curve in wide range.

Conventional assessment metrics of drug response lack reflections regarding actual cellular response phenotypes.

What this study adds

Limitations of conventional assessments are due to time-dependency of dose-response curve and customary summarization.

Phenotype metric evaluate a single dose-response that is time-independent and phenotype-relevant.

Clinical significance

Phenotype metric would improve pharmacogenomic analysis with better classification and phenotype-relevance of drug response.

Improvement in preclinical pharmacology would bring better translation and useful information in clinical studies.
How do ecological and social environments reflect parental roles in birds? A comparative analysis
Authors: Long Xiaoyan , Liu Yang , Liker András , Weissing Franz J. , Komdeur Jan , Székely Tamás
Published: December 2020

Parental roles are highly diverse in animal taxa. Since caring is an important determinant of fitness, understanding the origin and maintenance of various parental care strategies is a key question in evolutionary biology. Here we investigate parental care patterns in birds, which exhibit a remarkable diversity of parental sex roles. By means of phylogenetically informed comparative analyses we investigate whether and how care provisioning is predicted by ecology and social environment. Making use of the most comprehensive dataset including 1101 species that represent 126 avian families, we show that sex differences in parental care are neither related to food type nor to nest type, two key ecological factors. However, we found an effect of the social environment, as males tend to care relatively more in in colonial species than in non-colonial species. Taken together, these results highlight the importance of social effects for evolution of diverse parental sex roles.
Segmentation pathway genes in the Asian citrus psyllid,Diaphorina citri
Authors: Miller Sherry , Shippy Teresa D. , Hosmani Prashant S , Flores-Gonzalez Mirella , Mueller Lukas A , Hunter Wayne B , Brown Susan J , D’elia Tom , Saha Surya
Published: December 2020

Insects have a segmented body plan that is established during embryogenesis when the anterior-posterior (A-P) axis is divided into repeated units by a cascade of gene expression. The cascade is initiated by protein gradients created by translation of maternally provided mRNAs, localized at the anterior and posterior poles of the embryo. Particular combinations of these proteins activate specific gap genes to divide the embryo into distinct regions along the A-P axis. Gap genes then activate pair-rule genes, which are usually expressed in part of every other segment. The pair-rule genes, in turn, activate expression of segment polarity genes in a portion of each segment. The segmentation genes are generally conserved among insects, although there is considerable variation in how they are deployed. We annotated 24 segmentation gene homologs in the Asian citrus psyllid,Diaphorina citri. We identified most of the genes that were expected to be present based on known phylogenetic distribution. Two exceptions wereeagleandinvected, which are present in at least some hemipterans, but were not identified inD. citri. Many of these genes are likely to be essential forD. citridevelopment and thus may be useful targets for pest control methods.
Inferring Toll-Like Receptor induced epitope subunit vaccine candidate against SARS-CoV-2: A Reverse Vaccinology approach
Authors: Nayak Ananya , Gadnayak Ayushman , Sahoo Maheswata , Bhairappanavar Shivarudrappa B , Rout Bidyutprava , Mohanty Jatindra Nath , Das Jayashankar
Published: December 2020

Toll-Like Receptors (TLRs) are a group of Pattern Recognition Receptors (PRRs) which bind to the exogenous pathogen associated molecular patterns (PAMPs) like other PRRs; hence the main function is to sense the harmness and mediate the innate immune response to pathogens. TLRs play an important role in innate immune responses to infection. The host has evolved to use other TLR and PAMP agonists as agents to stimulate a protective inflammatory immune response against infection. Because only a small number of doses are given, TLR agonists appear to have greater potential and fewer safety concerns than other uses as vaccine adjuvants. In the present days, development of peptides targeting immune response can be approved for survival in biological monitoring systems before vaccine exposures. Peptide vaccines are easy to synthesize, more stable and relatively safe. In addition, production of peptides becomes simple, easily reproducible, fast and cost effective. Getting vaccinated against Covid-19, which has become a pandemic in the human population, is the most practical way to control the outbreak. The new coronavirus does not contain a drug or vaccine to prevent it from spreading to humans. To getting a proper vaccine candidate against the novel coronavirus, the present study used the reverse vaccinology approach by using a complete set of SARS-CoV-2 proteins; such as: Spike, Envelope, Nucleocapsid, Membrane, NSPs, and ORFs to extract the antigenic elements that produce B-cell, T-cell and IFN positive epitopes. These epitopes with precise binding to the Toll-Like receptors (1-10) have developed epitope based vaccine candidates. We have prioritized a set of epitopes based on their antigenicity, allergenicity, sequence conservation and projected population coverage world-wide. The selected epitopes were employed for in-silico docking interactions with Toll-Like receptors and molecular dynamic simulation confirmed the stability of the vaccine candidates resulting epitope of spike proteins with both the TLR 7 and 8 shows the best binding affinity. We believe that this ideal epitope vaccine candidate could enhance the immune response of the host and reduce the reinfection risk.
Computational profiling of hiPSC-derived heart organoids reveals chamber defects associated with Ebstein’s anomaly
Authors: Feng Wei , Schriever Hannah , Jiang Shan , Bais Abha , Kostka Dennis , Li Guang
Published: December 2020

Heart organoids have the potential to generate primary heart-like anatomical structures and hold great promise as in vitro models for cardiac disease. However, their properties have not yet been carefully studied, which hinders a wider spread application. Here we report the development of differentiation systems for ventricular and atrial heart organoids, enabling the study of heart disease with chamber defects. We show that our systems generate organoids comprising of major cardiac cell types, and we used single cell RNA sequencing together with sample multiplexing to characterize the cells we generate. To that end, we also developed a machine learning label transfer approach lever-aging cell type, chamber, and laterality annotations available for primary human fetal heart cells. We then used this model to analyze organoid cells from an isogeneic line carrying an Ebstein’s anomaly associated genetic variant, and we successfully recapitulated the disease’s atrialized ventricular defects. In summary, we have established a workflow integrating heart organoids and computational analysis to model heart development in normal and disease states.
TaxOnTree: a tool that generates trees annotated with taxonomic information
Authors: Sakamoto Tetsu , Ortega J. Miguel
Published: December 2020

Phylogenetic analysis is a widely used approach for analyzing and illustrating gene/protein/species evolution and is being benefited by the increasing number of species with their DNA/genome sequenced. Generating a phylogenetic tree with sequences from hundreds of species can be considered a routine task. However, tree visualization has been challenged to organize and bring by accessible means relevant information, e.g. taxonomy, about the sampled genes/proteins. Here we present TaxOnTree, a computational tool that incorporates and allows a quick accession of the taxonomic information of samples in a phylogenetic tree. TaxOnTree takes as input a single phylogenetic tree in Newick format containing gene/protein identifiers from NCBI or Uniprot databases in their leaves but TaxOnTree also allows users to have as input a protein identifier, a single protein in FASTA, a list of protein accessions, or a(n) (un)aligned multi-FASTA file. Non-tree inputs are submitted to a phylogenetic reconstruction pipeline implemented into TaxOnTree. The tree provided by the user or generated by the pipeline is converted to Nexus format and then automatically annotated with the taxonomic information of each sample comprising the tree. The taxonomic information is retrieved by web requests from NCBI or Uniprot servers or from a local MySQL database and annotated as tags in the tree nodes. The final tree archive is in Nexus format and should be opened with FigTree software which allows visual inspection, by branch coloring or tip/node labeling, of the taxonomic information incorporated in the tree. TaxOnTree provides prompt inspection of the taxonomic distribution of orthologs and paralogs. It can be used for manual curation of taxonomic/phylogenetic scenarios and coupled to any tool that links homologous sequences to a seed sequence. TaxOnTree provides computational support to help users to inspect phylogenetic trees with a taxonomic view, even without being taxonomy experts. TaxOnTree is available athttp://bioinfo.icb.ufmg.br/taxontree.
Bottom‐up effect of eradications: The unintended consequences for top‐order predators when eradicating invasive prey
Authors: Travers Toby , Lea Mary‐Anne , Alderman Rachael , Terauds Aleks , Shaw Justine
Published: December 2020

The eradication of invasive species from islands yields significant conservation returns. However, novel challenges continue to arise as projects expand in their scope, complexity and scale. Prey‐loss and secondary poisoning were historically considered to have limited impact on native top‐order predators when planning eradications, but this has rarely been tested quantitatively.

We used a 10‐year timeseries of Brown Skua Stercorarius antarcticus lonnbergi breeding surveys and isotopic dietary analysis on Macquarie Island to investigate how prey‐loss and secondary poisoning deaths resulting from the eradication of an abundant invasive prey species, European rabbits Oryctolagus cuniculus, affected a top‐order predator.

Skua nest density declined from 7.14 nests/km2 (95% CI: 6.01–8.27) in the presence of rabbits (pre‐eradication) to 3.73 nests/km2 (95% CI: 2.96–4.51) in the first 3 years after the eradication of rabbits, before showing signs of recovery in the 4 years thereafter. However, breeding success dropped from 1.01 chicks/nest (95% CI: 0.76–1.26) to as low as 0.38 chicks/nest (95% CI: 0.23–0.53) with little evidence of recovery.

Secondary poisoning affected a greater number of skuas than anticipated prior to the eradication, including skuas nesting in areas where rabbits were not typically hunted as prey. We highlight that invasive prey often replace native prey in the diet of native predators rather than provide an additional source of food, and rapid eradication of non‐native prey can have long‐term impacts for predators, particularly when recovery of native prey is slow.

Synthesis and applications. Monitoring programmes that complement large‐scale eradication projects and address (a) trophic‐driven declines in predator populations and (b) population‐level impacts of secondary poisoning are integral to ensuring bottom‐up effects of eradications are anticipated and adequately quantified. If prey deficits caused by eradication of invasive prey are expected to be severe but short‐lived, supplementary feeding programmes may buffer against increased predation pressure on native prey and reduced breeding success of native predators. Alternatively, if the rapid recovery of native prey is not expected to occur naturally, breeding programmes and translocation of native prey prior to assist recovery of native predators should be considered to support ecosystem restoration.
From Socialist Subject to Capitalist Object: Industry Enclave Life Past and Present in Wuhan
Authors: Phelps Nicholas A. , Miao Julie T. , Li Zhigang , Lin Sainan
Published: December 2020

There is no better place to explore the relationship of industry enclaves to urban life than China, where traditionaldanweis(work units) have coexisted with new foreign direct investment enclaves. Here we draw on original interviews with workers at Wuhan Iron and Steel Company (WISCO) and Foxconn in the city of Wuhan to examine industry enclaves old and new in terms of their spatial arrangement, work, institutions, and social life and identity. The article is one of the first to integrate urban and economic geographical perspectives on the subject of enclaves. It provides evidence of similarities and contrasts in the spatial arrangement of work, institutions, life and identity centred on industry enclaves old and new. These contrasts reflect wider relations between the state and the market and between social subject and commodified labour in China. In conclusion, we identify several research directions concerning the scale, diversity and reach of urban enclavism in China and beyond.
Social Representations of Sociopolitical Groups on r/The_Donald and Emergent Conflict Narratives: A Qualitative Content Analysis
Authors: McLamore Quinnehtukqut , Uluğ Özden Melis
Published: December 2020

Social media has been integral for the organization and success of right‐wing populist movements in the United States and Europe. Within online communities, discussions take place in which ideologies are formulated, iterated upon, and disseminated. One particular forum, hosted on the popular website reddit.com, r/The_Donald, has received media attention for its political influence. Despite the influence of online spaces in populist, far‐right movements, relatively little attention has been paid to qualitative content of discussions that take place within such spaces, including r/The_Donald. Guided by a social representations approach, we analyzed how discussions on r/The_Donald represent sociopolitical groups. We focused on discussions of political affiliations, race relations, immigration, and culture. From a dataset of 8,198 posts, we selected 1,292 segments from 883 unique Reddit usernames and analyzed them using qualitative content analysis. The results showed that the majority of posts discussed liberals, race relations, and conspiracy theories, and in these posts, liberals and liberal ideas were delegitimized and mocked through their representations. These posts represented conservatives through antinomic contrast and comparison to liberals and liberal policies. The meanings of those representations in intergroup relations are discussed.
Oral management with mouthguards during the mixed dentition period: A case report
Authors: Otsugu Masatoshi , Suehiro Yuto , Hanaoka Issei , Okawa Rena , Nakano Kazuhiko
Published: December 2020

Custom‐made mouthguards are widely used by athletes during training and sporting events for the prevention of oral injuries. However, even though the prevalence of dental injuries in children in the primary or mixed dentition stages is high, few reports have focused on mouthguard use for such cases due to the difficulties associated with adapting them as teeth are lost and replaced. This report presents a case of a Japanese boy in the mixed dentition stage with a custom‐made mouthguard. For fabrication, self‐curing acrylic resin was used to fill portions of a working model to keep space for the later eruption of permanent teeth. However, adjustment was necessary when gingival swelling occurred in association with maxillary canine eruption, after which refabrication was necessary. Regular management of a custom‐made mouthguard by the attending dentist is important for children in the mixed dentition period, especially during maxillary canine eruption, which causes drastic dentition changes. In the present case, custom‐made mouthguards were fully effective based on the prediction of changes in the dentition and with regular dental management.
Effect of combining straw‐derived materials and wood ash on alkaline soil carbon content and the microbial community
Authors: Zhao Huili , Tian Xiaohong , Jiang Yuhan , Zhao Ying , Si Bingcheng
Published: December 2020

The return of organic materials to cultivated fields to improve soil quality and to sequester carbon are widely studied, but the effects of combining different types of organic material on soil microbial diversity and community structure are poorly understood, particularly in alkaline soils. An incubation experiment was performed to study the effects of incorporating two straw‐derived materials (fresh straw and semi‐decomposed straw) alone or in combination with wood ash. The organic carbon content of soil treated with straw‐derived materials was significantly higher than that of soil with no straw and wood addition, but there was no significant difference between the fresh straw and semi‐decomposed straw treatments. Microbial diversity was decreased by the addition of straw on day 7; however, the combination of fresh/semi‐decomposed straw with wood ash increased bacterial diversity on day 118, and the combination of semi‐decomposed straw with wood ash increased fungal diversity. Fresh straw combined with wood ash significantly increased the abundance of Ascomycota by 15.5% relative to that of soil treated with semi‐decomposed straw, and semi‐decomposed straw combined with wood ash increased the abundance of Basidiomycota by 40.5% relative to that of soil treated with fresh straw. Amendment with straw‐derived materials and wood ash shaped the bacterial community in alkaline soil by changing the soil organic carbon, dissolved organic carbon and pH, and the characteristics of straw‐derived materials and wood ash shaped the fungal community. Straw‐return modes that employ semi‐decomposed straw and wood ash addition can maintain organic carbon levels and improve the soil micro‐environment.

Highlights

Combining straw‐derived materials and wood ash affects alkaline soil carbon content and the microbial community.

The effects of fresh and semi‐decomposed wheat straw on soil microorganisms and soil carbon content are reported for the first time.

The combination of semi‐decomposed wheat straw and wood ash enhanced soil fungal diversity and Basidiomycota abundance.

Semi‐decomposed wheat straw and wood ash can maintain organic carbon levels and improve the soil micro‐environment.
Osteochondral fragmentation of the cervical articular process joints; prevalence in horses undergoing CT for investigation of cervical dysfunction
Authors: Tucker Rachel , Hall Yvonne S. , Hughes Thomas K. , Parker Russell A.
Published: December 2020

Background

Computed tomography (CT) imaging of the cervical spine of mature horses under general anaesthesia is becoming increasingly accessible. Osteochondral fragmentation (OF) of the cervical articular process joints (APJs) has been identified on CT imaging; the prevalence, clinical features and significance of this finding are currently unknown.

Objectives

To describe the prevalence and clinical features of a population of horses with CT evidence of OF within the cervical APJs.

Study design

Retrospective, descriptive case series.

Methods

The study population consisted of all horses undergoing CT imaging of the entire cervical spine between April 2016 and December 2019 at Liphook Equine Hospital for investigation of clinical signs localised to this region. CT scans were examined for evidence of OF within the APJs and additional case features were recorded.

Results

A total of 55 horses underwent CT imaging during the study period. OF was identified in 13 horses, giving a CT prevalence of 24% in the study population. OF occurred in a range of ages, breeds and uses of equine, presenting with varied clinical signs. It was identified at every level of the neck. Additional cervical pathology was identified in 11/13 OF cases.

Main limitations

Retrospective analysis of a clinical caseload with a lack of clinically normal controls orpost mortemconfirmation of imaging findings. Low case numbers.

Conclusions

OF within the cervical APJs is recognised on CT imaging in horses with cervical dysfunction. Fragments are commonly identified in combination with additional cervical pathology. Further investigation is required to confirm their clinical significance and develop potential treatment options where necessary.
Dilatation of lymphatic vessels increases liver stiffness on transient elastography irrespective of fibrosis
Authors: Hirooka Masashi , Koizumi Yohei , Tanaka Takaaki , Sunago Kotarou , Nakamura Yoshiko , Yukimoto Atsushi , Watanabe Takao , Yoshida Osamu , Tokumoto Yoshio , Abe Masanori , Hiasa Yoichi
Published: December 2020

Aim

Liver stiffness measured using transient elastography (TE) is affected by tissue viscosity. The role of intrahepatic lymphatic fluid in liver stiffness is unclear. The present study aimed to investigate the effects of lymphatic vessel dilatation on liver stiffness.

Methods

Patients with chronic liver disease (n = 116) were enrolled from June 2018 to March 2020. All specimens were acquired by laparoscopic liver biopsy. Biopsy samples were stained with D2‐40 for lymphatic vessel quantification based on a five‐point scale for each specimen. Independent associations of liver stiffness measured by TE, strain elasticity (liver fibrosis index), and controlled attenuation parameter with fibrosis, lymphatic vessels, alanine aminotransferase, bilirubin, and steatosis were evaluated.

Results

Fibrosis, splenic stiffness measurement, and splenic volume were significantly correlated with the area of lymphatic vessels. Fibrosis, lymphatic vessels, and alanine aminotransferase were independent factors significantly associated with liver stiffness measurement (LSM; standardized coefficient [β] = 0.375, P < 0.001; β = 0.342, P < 0.001; and β = 0.359, P < 0.001, respectively). Fibrosis was the only independent factor significantly associated with liver fibrosis index (β = 0.360, P < 0.001), whereas the fat deposit area was the only independent factor significantly associated with controlled attenuation parameter (β = 0.455, P < 0.001). The areas under the receiver operating characteristic curves for diagnosing controlled ascites based on LSM, liver fibrosis index, splenic stiffness measurement, collagen proportionate area, and area of lymphatic vessels were 0.94, 0.66, 0.76, 0.64, and 0.79, respectively.

Conclusions

Lymphatic vessel dilatation can affect liver stiffness measured using TE. Liver stiffness measurement is a predictive factor for ascites.
The role of CD8 T cells in controlling HIV beyond the antigen‐specific face
Authors: Zhang C , Hu W , Jin JH , Zhou MJ , Song JW , Deng JN , Huang L , Wang SY , Wang FS
Published: December 2020

Objectives

Understanding the determinants of HIV immune control is important for seeking viable HIV prevention, treatment and curative strategies. The antigen‐specific roles of CD8 T cells in controlling primary HIV infection have been well documented, but their abilities to control the latent HIV reservoir is less well studied.

Methods

The scientific literature on this issue was searched on PubMed.

Results

Recent reports have demonstrated that CD8 T cells are also involved in the control of viral replication in HIV‐infected individuals receiving antiretroviral therapy (ART). However, based on accumulating evidence, the antiviral role of CD8 T cells in ART patients may not be achieved via an antigen‐specific manner as HIV‐specific CD8 T cells can sense, but not effectively eliminate, cells harbouring intact provirus without first being activated. Our recent study indicated that virtual memory CD8 T cells, a semi‐differentiated component of CD8 T cells, may be involved in the mechanism restraining the HIV DNA reservoir in ART patients.

Conclusions

In this review, we summarize recent findings on the role of CD8 T cells in controlling HIV, highlighting differences between conventional antigen‐specific and innate‐like CD8 T cells. A better understanding of the roles of CD8 T cells during HIV infection should benefit the informed design of immune‐based treatment strategies.
The histone deacetylase inhibitor chidamide induces intermittent viraemia in HIV‐infected patients on suppressive antiretroviral therapy
Authors: Li JH , Ma J , Kang W , Wang CF , Bai F , Zhao K , Yao N , Liu Q , Dang BL , Wang BW , Wei QQ , Kang WZ , Sun YT
Published: December 2020

Objectives

To evaluate the safety and efficacy of chidamide to reverse HIV‐1 latency in vivo and to compare the effects of four clinically tested histone deacetylase (HDAC) inhibitors on non‐histone proteins in vitro.

Methods

Participants received chidamide orally at 10 mg twice weekly for 4 weeks while maintaining baseline antiretroviral therapy. The primary outcome was plasma viral rebound during chidamide dosing and the secondary outcomes were safety, pharmacokinetic and pharmacodynamic profiles, changes in cell‐associated HIV‐1 RNA and HIV‐1 DNA, and immune parameters. Western blotting was used to compare the in vitro effects of the four HDAC inhibitors on HSP90, NF‐κB and AP‐1.

Results

Seven aviraemic participants completed eight oral doses of chidamide, and only grade 1 adverse events were observed. Cyclic increases in histone acetylation were also detected. All participants showed robust and repeated plasma viral rebound (peak viraemia 147–3850 copies/mL), as well as increased cell‐associated HIV‐1 RNA, during chidamide treatment. Furthermore, we identified an enhanced HIV‐1‐specific cellular immune response and a modest 37.7% (95% CI: 12.7–62.8%, P = 0.028) reduction in cell‐associated HIV‐1 DNA. Compared with the other three HDAC inhibitors, chidamide had minimal cytotoxicity in vitro at clinically relevant concentrations and showed mechanistically superior effects on non‐histone proteins, including HSP90, NF‐κB and AP‐1.

Conclusions

Chidamide safely and vigorously disrupts HIV‐1 latency in vivo, which makes it a promising latency‐reversing agent.
The study of joint order batching and picker routing problem with food and nonfood category constraint in online‐to‐offline grocery store
Authors: Zhang Jun , Zhang Yanfang , Zhang Xueyan
Published: December 2020

Order picking is the process of retrieving products from the storage locations to meet customer orders, which accounts for more than 55% of the total warehouse cost. The joint order batching and picker routing problem (JOBPRP) is an effective way to improve picking efficiency. Although many warehouses face the physical constraints of products that have impact on the picking sequence, such as weight, size, shape, and fragility, JOBPRP with such physical constraints has not been widely studied in the literature. This paper is inspired by a practical case observed in an online‐to‐offline grocery store in China, where food products should not be carried under nonfood products in the picking container to maintain food safety, called category constraint. Therefore, JOBPRP with category constraint is studied. The JOBPRP optimization models with and without category constraint are formulated to minimize the total processing time, and the modified seed algorithms, with new seed addition rules and modified near‐optimal routing methods are proposed to solve the models. The performance of the proposed algorithms is evaluated in different seed addition rules, routing methods, sort time scenarios, and storage assignment strategies (SASs) in a case study. We found that considering category constraint in JOBPRP can reduce the total processing time, and the modified seed algorithms perform better than the traditional first‐come‐first‐serve benchmark algorithms and the seed algorithms with traditional seed addition rules and S‐shape routing method. The SASs where nonfood and food products are separately in fewer number of zones are recommended.
India Hypertension Control Initiative—Hypertension treatment and blood pressure control in a cohort in 24 sentinel site clinics
Authors: Kaur Prabhdeep , Kunwar Abhishek , Sharma Meenakshi , Mitra Jhilam , Das Chinmoyee , Swasticharan Leimapokpam , Chakma Tapas , Dipak Bangar Sampada , Venkatasamy Vettrichelvan , Dharamsoth Raviteja , Purohit Saurabh , Tayade Sadhana , Singh Gurinder B , Bitragunta Sailaja , Durgad Kiran , Das Bidisha , Dar Sunil , Bharadwaj Rupali , Joshi Chakshu , Bharadwaj Vishwajit , Khedkar Suhas , Chenji Sravan , Reddy Sravan K , Sreedhar Chintala , Parasuraman Ganeshkumar , Kasiviswanathan Savitha , Viswanathan Vidhya , Uike Pankaj , Gaigaware Pooja , Yadav Suniti , Dhaliwal RS , Ramakrishnan Sivasubramanian , Tullu Fikru T , Bhargava Balram
Published: December 2020

The India Hypertension Control Initiative (IHCI) is a multi‐partner initiative, implementing and scaling up a public health hypertension control program across India. A cohort of 21,895 adult hypertension patients in 24 IHCI sentinel site facilities in four Indian states (Punjab, Madhya Pradesh, Maharashtra, and Telangana), registered from January 2018 until June 2019 were assessed at baseline and then followed up for blood pressure (BP) control and antihypertensive medication use. Among all registrations, 11 274 (51%) of the patients returned for a follow‐up visit between July 2019 and September 2019. Among patients returning for follow‐up, 26.3% had BP controlled at registration, and 59.8% had BP controlled at follow‐up (p < .001). The absolute improvement in BP control was more than two times greater in primary care (48.1 percentage point increase) than secondary care facilities (22.9 percentage point increase). Most IHCI patients received prescriptions according to state‐specific treatment protocols. This study demonstrates that a scalable public health hypertension control program can yield substantial BP control improvements, especially in primary care settings. However, high loss to follow‐up limits population health impact; future efforts should focus on improving systems to increase the likelihood that patients will return to the clinic for routine hypertension care.
How families matter for health inequality during the COVID‐19 pandemic
Authors: Thomeer Mieke Beth , Yahirun Jenjira , Colón‐López Alejandra
Published: December 2020

We theorize that the social conditions surrounding the coronavirus disease 2019 (COVID‐19) pandemic have the potential to increase the importance of families for health and widen existing inequalities. We suggest three primary tenets important for understanding families and health during COVID‐19. First, risks of specific COVID‐19 outcomes and other health problems are unevenly distributed across families. Second, how families impact health during the COVID‐19 pandemic is conditional on public policies, organizational decisions, and concurrent events. Third, many health inequalities driven by racism, sexism, classism, and other oppressive societal forces are amplified during COVID‐19, but the extent to which this is occurring is shaped by families and by the public policies, organizational decisions, and concurrent events that also impact families and health. As health disparities continue to emerge from this pandemic, we call on researchers and policymakers to pay attention to the multiple ways that families matter.