bluuebunny/crossref_metadata_2025 huggingface dataset:
Favipiravir In Adults with Moderate to Severe COVID-19: A Phase 3 Multicentre, Randomized, Double-Blinded, Placebo-Controlled Trial
Authors: Shenoy Srinivas , Munjal Sagar , Youha Sarah Al , Alghounaim Mohammad , Almazeedi Sulaiman , Alshamali Yousef , Kaszynski Richard H , Al-Sabah Salman ,   Kuwait Clinical Trial Group
Published: November 2021

Aim

To assess the efficacy and safety of favipiravir in adults with moderate to severe coronavirus disease 2019 (COVID-19).

Methods

In this randomized, double-blind, multicenter, phase 3 trial, adults (21-80 years) with real-time reverse transcriptase polymerase chain reaction (rRT-PCR) confirmed SARS-CoV-2 infection and presenting with moderate to severe COVID-19 and requiring hospitalization were randomized 1:1 to oral favipiravir (day 1: 1800 mg BID and days 2-10: 800 mg BID) (FPV) plus standard supportive care (SoC) versus placebo plus SoC (placebo). The primary endpoint was time to resolution of hypoxia.

Results

In total, 353 patients were randomized to receive either FPV or placebo (175 and 178 in the FPV and placebo groups, respectively). Overall, 76% of the patients (240/315, 78% in FPV vs. 75% in placebo group) reached resolution of hypoxia on or before day 28. The median time to resolution of hypoxia was 7 days in the FPV group and 8 days in the placebo group. Treatment effect was not significant [Hazard ratio (HR) (95% CI): 0.991 (0.767, 1.280) (p=0.94)].

Patients in the lower NEWS-2 clinical risk subgroup were more likely to achieve shorter time to resolution of hypoxia with the median time to resolution of hypoxia of 6 days in FPV and 7 days in placebo group [HR (95% CI): 1.21 (0.847, 1.731) (p=0.29)]; shorter time to hospital discharge with a median time to discharge of 8 and 10 days in the FPV and placebo group, respectively [HR (95% CI): 1.47 (1.081, 1.997) (p=0.014)]; and shorter time to improvement by 1-point improvement over baseline in WHO 10-point clinical status score with the median time to improvement by 1-point from baseline of 6 and 7 days in the FPV and placebo group, respectively [HR (95% CI): 1.16 (0.830, 1.624) (p=0.38)] than higher NEWS-2 clinical risk subgroup.

Treatment emergent adverse event (TEAEs) were experienced by 62/334 (19%) patients [35/168 (21%) patients in FPV and 27/166 (16%) in placebo group]. Hyperuricaemia/increased blood uric acid was reported in 9 (3%)/2 (1%) patients [8 (5%)/1(1%) patients in FPV and 1 (1%)/1(1%) in placebo group], which were of mild intensity and transient. Overall, 36 serious adverse events (SAEs) were reported, 20 in FPV and 16 in placebo group.

Conclusion

The trial did not find favipiravir to be effective in moderate to severe, hospitalized COVID-19 patients; favourable clinical trends were observed in patients with lower NEWS-2 risk when early administration of favipiravir could be achieved.
Third dose vaccine With BNT162b2 and its response on Long COVID after Breakthrough infections
Authors: Hoque Ashraful , Rahman Md Marufur , Imam Hossain , Nahar Nurun , Hasan Chowdhury Forhad Uddin
Published: November 2021

Background

Breakthrough events are not rare after emerging of Delta variant. On the other hand, long COVID is an unsolved issue where sufferers suffer a lot. Some study has shown that COVID-19 vaccine has improved some clinical and libratory parameters in long COVID. But what will be the possible measures against long COVID after the breakthrough event is still a burning question.

Method

We have observed the third dose by BNT162b2 in a small group(n=20) who were diagnosed as long COVID after breakthrough infections, in Sheikh Hasina National Institute of Burn & Plastic Surgery Institute, Dhaka, Bangladesh. CRP(C-reactive protein) and Anti S1 RBD IgG responses were measured.

Result

All 20 participants in the study received both dosage of “ChAdOx1-nCoV-19” in between February 2021 to April 2021 and had breakthrough infection in the same or following month which led to long COVID syndrome. They all received a third dose of “BNT162b2”. A before and after 3rddose (14 days after) CRP from participants serum was measured. A Wilcoxon matched paired signed rank test revealed significant (P value <0.05) reduction of inflammatory marker (CRP) after receiving the 3rdvaccine dose. Pre and post 3rddose quantitative anti S1-RBD IgG response was measured and compared that revealed significant boosting effect that clearly correlates with the CRP response.

Conclusion

Coverage of vaccines all over the world is still not expected level to control this pandemic. WHO has not recommended the use of a third/booster dose of COVID vaccines. Though our results show some sort of hope for the long COVID in breakthrough events after getting the third dose more study is needed to conclude this issue.
No Evidence that Ongoing HIV-Specific Immune Responses Contribute to Persistent Inflammation and Immune Activation in Persons on Long-Term ART
Authors: Ward Adam R. , Thomas Allison S. , Stevenson Eva M. , Huang Szu-Han , Keating Sheila M. , Gandhi Rajesh T. , McMahon Deborah K. , Bosch Ronald J. , Macatangay Bernard J. , Cyktor Joshua C. , Eron Joseph J. , Mellors John W. , Jones R. Brad ,   for the ACTG A5321 Team
Published: November 2021

Background

People with HIV (PWH) have persistently elevated levels of inflammation and immune activation despite suppressive antiretroviral therapy (ART), with specific biomarkers showing associations with non-AIDS-defining morbidities and mortality. We investigated the potential role of the HIV-specific adaptive immune response, which also persists under ART, in driving levels of these clinically relevant biomarkers.

Methods

HIV-specific T-cell responses and antibody concentrations were measured at study entry in the ACTG A5321 cohort, following a median of 7 years of suppressive ART. HIV persistence measures including cell-associated (CA)-DNA, CA-RNA, and plasma HIV RNA (single-copy assay) were also assessed. Plasma inflammatory biomarkers and T-cell activation and cycling were measured at a pre-ART time point and at study entry.

Results

Neither the magnitudes of HIV-specific T-cell responses nor HIV antibody levels were correlated with levels of the inflammatory or immune activation biomarkers, including hs-CRP, IL-6, neopterin, sCD14, sCD163, %CD38+HLA-DR+ CD8+ and CD4+ cells, and %Ki67+ CD8+ and CD4+ cells – including after adjustment for pre-ART biomarker level. Magnitudes of T-cell responses to HIV-Pol were correlated with TNF-α levels, but this was confounded by several factors. Plasma HIV RNA levels were correlated with CD8+ T-cell activation (r = 0.25, p = 0.027), but other HIV persistence parameters were not associated with these biomarkers. In mediation analysis, relationships between HIV persistence parameters and inflammatory biomarkers were not influenced by either HIV-specific T-cell responses or antibody levels.

Conclusions

Adaptive HIV-specific immune responses do not appear to contribute to the elevated inflammatory and immune activation profile associated with morbidity and mortality under long-term ART.

HIV-specific T-cell and antibody responses persist over years of suppressive ART, but there is no evidence that these ongoing immune responses contribute to elevated levels of inflammation and immune activation in people living with HIV on long-term ART.
Predicting Relative Protein Abundance via Sequence-Based Information
Authors: Parkes Gregory M. , Ewing Robert M. , Niranjan Mahesan
Published: November 2021

Understanding the complex interactions between transcriptome and proteome is essential in uncovering cellular mechanisms both in health and disease contexts. The limited correlations between corresponding transcript and protein abundance suggest that regulatory processes tightly govern information flow surrounding transcription and translation, and beyond. In this study we adopt an approach which expands the feature scope that models the human proteome: we develop machine learning models that incorporate sequence-derived features (SDFs), sometimes in conjunction with corresponding mRNA levels. We develop a large resource of sequence-derived features which cover a significant proportion of the H. sapiens proteome, demonstrate which of these features are significant in prediction on multiple cell lines, and suggest insights into which biological processes can be explained using these features. We reveal that (a) SDFs are significantly better at protein abundance prediction across multiple cell lines both in steady-state and dynamic contexts, (b) that SDFs can cover the domain of translation with relative efficiency but struggle with cell-line specific pathways and (c) provide a resource which can be plugged into many subsequent protein-centric analyses.
A full-length infectious cDNA clone of a dsRNA totivirus-like virus
Authors: Wang Han , Okamoto Kenta
Published: November 2021

Totivirus-like viruses are icosahedral non-enveloped double-stranded (ds)RNA viruses belonging to a group recently discovered and provisionally assigned in the Totiviridae family. Unlike fungal and protozoan Totiviridae viruses, these totivirus-like viruses infect a diverse spectrum of metazoan hosts and currently have enormous impacts on fisheries and agriculture. We developed the first totivirus-like virus Omono River virus (OmRV) infectious full-length DNA clone and produce the infectious particles using an RNA-transcript-based method. Unlike the parent wild-type particles from nature, the reverse-genetically-generated OmRV particles had an indistinguishable cytopathic effect, infectivity, and morphology. The established system is one of the few systems that have been reported for generating a non-segmented dsRNA virus DNA clone.
Accelerating in-silico saturation mutagenesis using compressed sensing
Authors: Schreiber Jacob , Nair Surag , Balsubramani Akshay , Kundaje Anshul
Published: November 2021

In-silico saturation mutagenesis (ISM) is a popular approach in computational genomics for calculating feature attributions on biological sequences that proceeds by systematically perturbing each position in a sequence and recording the difference in model output. However, this method can be slow because systematically perturbing each position requires performing a number of forward passes proportional to the length of the sequence being examined. In this work, we propose a modification of ISM that leverages the principles of compressed sensing to require only a constant number of forward passes, regardless of sequence length, when applied to models that contain operations with a limited receptive field, such as convolutions. Our method, named Yuzu, can reduce the time that ISM spends in convolution operations by several orders of magnitude and, consequently, Yuzu can speed up ISM on several commonly used architectures in genomics by over an order of magnitude. Notably, we found that Yuzu provides speedups that increase with the complexity of the convolution operation and the length of the sequence being analyzed, suggesting that Yuzu provides large benefits in realistic settings. We have made this tool available at https://github.com/kundajelab/yuzu.
Sexual Dimorphic Metabolic and Cognitive Responses of C57BL/6 Mice to Fisetin or Dasatinib and Quercetin Cocktail Oral Treatment
Authors: Fang Yimin , Medina David , Stockwell Robert , McFadden Sam , Quinn Kathleen , Peck Mackenzie R. , Bartke Andrzej , Hascup Kevin N. , Hascup Erin R.
Published: November 2021

Senolytic treatment in aged mice clears senescent cell burden leading to functional improvements. However, less is known regarding the effects of these compounds when administered prior to significant senescent cell accumulation. From 4-13 months of age, C57BL/6 male and female mice received monthly oral dosing of either 100 mg/kg Fisetin or a 5 mg/kg Dasatinib (D) plus 50 mg/kg Quercetin (Q) cocktail. During treatment, several aspects of healthy aging were assayed including glucose metabolism using an insulin and glucose tolerance test, cognitive performance using Morris water maze and novel object recognition, and energy metabolism using indirect calorimetry. Afterwards, mice were euthanized for plasma and tissue specific markers of senescence-associated secretory phenotype (SASP) and white adipose tissue accumulation (WAT). Sexually dimorphic treatment effects were observed. Fisetin treated male mice had reduced SASP, enhanced glucose and energy metabolism, improved cognitive performance, and increased mRNA expression of adiponectin receptor 1 and glucose transporter 4. D+Q treatment had minimal effects in male C57BL/6 mice, but was detrimental to females causing increased SASP expression along with accumulation of WAT depots. Reduced energy metabolism and cognitive performance were also noted. Fisetin treatment had no effect in female C57BL/6 mice potentially due to a slower rate of biological aging. In summary, the senolytic treatment in young adulthood, has beneficial, negligible, or detrimental effects in C57BL/6 mice dependent upon sex and treatment. These observations should serve as a note of caution in this rapidly evolving and expanding field of investigation.

Graphical Abstract

Male and female C57BL/6 mice were treated with once monthly oral doses of either Dasatinib (D) + Quercetin (Q) or Fisetin from 4-13 months of age. Females treated with D+Q had increased adiposity and SASP markers (red spheres) along with decreased metabolism (blue flame) and cognitive performance. Males treated with Fisetin had reduced SASP markers (blue spheres) as well as improved metabolism (red flame) and cognition. No effects were observed in females treated with Fisetin or males treated with D+Q.
The molecular evolution of spermatogenesis across mammals
Authors: Murat Florent , Mbengue Noe , Winge Sofia Boeg , Trefzer Timo , Leushkin Evgeny , Sepp Mari , Cardoso-Moreira Margarida , Schmidt Julia , Schneider Celine , Mößinger Katharina , Brüning Thoomke , Lamanna Francesco , Belles Meritxell Riera , Conrad Christian , Kondova Ivanela , Bontrop Ronald , Behr Rüdiger , Khaitovich Philipp , Pääbo Svante , Marques-Bonet Tomas , Grützner Frank , Almstrup Kristian , Schierup Mikkel Heide , Kaessmann Henrik
Published: November 2021

The testis is a key male reproductive organ that produces gametes through the process of spermatogenesis. Testis morphologies and spermatogenesis evolve rapidly in mammals, presumably due to the evolutionary pressure on males to be reproductively successful1,2. The rapid evolution of the testis was shown to be reflected at the molecular level based on bulk-tissue work3-8, but the molecular evolution of individual spermatogenic cell types across mammalian lineages remains largely uncharacterized. Here we report evolutionary analyses of single-nucleus transcriptome data for testes from eleven species that cover the three major mammalian lineages (eutherians, marsupials, egg-laying monotremes) and birds (the evolutionary outgroup), and include seven key primates. Our analyses reveal that the rapid evolution of the testis is driven by accelerated fixation rates of gene expression changes, amino acid altering substitutions, and newly emerged genes in late spermatogenic stages – likely facilitated by reduced pleiotropic constraints, haploid selection, and a transcriptionally permissive chromatin environment. We identify temporal expression changes of individual genes across species, which may have contributed to the emergence of species-specific phenotypes, but also conserved expression programs underlying ancestral spermatogenic processes. Sex chromosome analyses show that genes predominantly expressed in spermatogonia (i.e., germ cells fueling spermatogenesis) and Sertoli cells (i.e., somatic supporting cells) independently accumulated on X chromosomes across mammals during evolution, presumably due to male-beneficial selective forces. Further work uncovered that the process of meiotic sex chromosome inactivation (MSCI) also occurs in monotremes and hence is common to the different mammalian sex chromosome systems, contrary to previous inferences9. Thus, the general mechanism of meiotic silencing of unsynapsed chromatin (MSUC), which underlies MSCI, represents an ancestral mammalian feature. Together, our study illuminates the cellular and molecular evolution of mammalian spermatogenesis and associated selective forces, and provides a resource for investigating the biology of the testis across mammals.
A revised view on the evolution of glutamine synthetase isoenzymes in plants
Authors: Valderrama-Martín José Miguel , Ortigosa Francisco , Ávila Concepción , Cánovas Francisco M. , Hirel Bertrand , Cantón Francisco R. , Cañas Rafael A.
Published: November 2021

Glutamine synthetase (GS) is a key enzyme responsible for the incorporation of inorganic nitrogen in the form of ammonium into the amino acid glutamine. The genes encoding GS are among the oldest existing genes in living organisms. In plants, two groups of functional GS enzymes are found: eubacterial GSIIb (GLN2) and eukaryotic GSIIe (GLN1/GS). Phylogenetic analyses have shown that the GLN2 group originated from bacteria following horizontal gene transfer. Only GLN1/GS genes are found in vascular plants, which suggests that they are involved in the final adaptation of plants to terrestrial life. The present phylogenetic study reclassifies the different GS of seed plants into three clusters: GS1a, GS1b and GS2. The presence of genes encoding GS2 has been expanded to Cycadopsida gymnosperms, which suggests the origin of this gene in a common ancestor of Cycadopsida, Ginkgoopsida and angiosperms. GS1a genes have been identified in all gymnosperms, basal angiosperms and some Magnoliidae species. Previous studies in conifers and the gene expression profiles obtained in ginkgo and magnolia in the present work could explain the absence of GS1a in more recent angiosperm species (e.g., monocots and eudicots) due to the redundant roles of GS1a and GS2 in photosynthetic cells. Altogether, the results provide a better understanding of the evolution of plant GS isoenzymes and their physiological roles, which is valuable for improving crop nitrogen use efficiency and productivity.
TheEscherichia coli serSgene promoter region overlaps with therarAgene
Authors: Jain Kanika , Stanage Tyler H. , Wood Elizabeth A. , Cox Michael M.
Published: November 2021

Deletion of the entire gene encoding the RarA protein ofEscherichia coliresults in a growth defect and additional deficiencies that were initially ascribed to a lack of RarA function. Further work revealed that most of the effects reflected the presence of sequences in therarAgene that affect expression of the downstream gene,serS.TheserSgene encodes the seryl aminoacyl-tRNA synthetase. Decreases in the expression ofserScan trigger the stringent response. The sequences that affectserSexpression are located in the last 15 nucleotides of therarAgene.
Epidermal Growth Factor Receptor Inhibition Prevents Caveolin-1-dependent Calcifying Extracellular Vesicle Biogenesis
Authors: Nik Amirala Bakhshian , Ng Hooi Hooi , Sun Patrick , Iacoviello Francesco , Shearing Paul R. , Bertazzo Sergio , Mero Deniel , Khomtchouk Bohdan B. , Hutcheson Joshua D.
Published: November 2021

Chronic kidney disease (CKD) increases the risk of cardiovascular disease, including vascular calcification, leading to higher mortality. Release of calcifying extracellular vesicles (EVs) by vascular smooth muscle cells (VSMCs) promotes the ectopic mineralization of vessel walls. Caveolin-1 (CAV1) protein plays a key role in genesis of calcifying EVs in VSMCs. Epidermal growth factor receptor (EGFR) co-localizes with and influences the intracellular trafficking of CAV1. Using a diet-induced mouse model of CKD, we measured serum EGFR and assessed the potential of EGFR inhibition to prevent vascular calcification. Mice with CKD developed widespread vascular calcification, which associated with increased serum levels of EGFR. We computationally analyzed 7651 individuals in the Multi-Ethnic Study of Atherosclerosis (MESA) and Framingham cohorts to assess potential correlations between coronary artery calcium and single nucleotide polymorphisms (SNPs) associated with elevated serum levels of EGFR. Individuals in the MESA and Framingham cohorts with SNPs associated with increased serum EGFR exhibit elevated coronary artery calcium. In both the CKD mice and human VSMC culture, EGFR inhibition significantly reduced vascular calcification by mitigating the release of CAV1-positive calcifying EVs. EGFR inhibition also increased bone mineral density in CKD mice. Given that EGFR inhibitors exhibit clinical safety and efficacy in other pathologies, the current data suggest that EGFR may be an ideal target to prevent pathological vascular calcification.
A chemical screen for suppressors of dioxygenase inhibition in a yeast model of familial paraganglioma
Authors: Beimers William , Braun Megan , Schwinefus Kaleb , Pearson Keenan , Wilbanks Brandon , Maher L. James
Published: November 2021

A fascinating class of familial paraganglioma (PGL) neuroendocrine tumors is driven by loss of the tricarboxylic acid (TCA) cycle enzyme succinate dehydrogenase (SDH) resulting in succinate accumulation as an oncometabolite, and other metabolic derangements. Here we exploit aS. cerevisiaeyeast model of SDH loss where accumulating succinate, and possibly reactive oxygen species, poison a dioxygenase enzyme required for sulfur scavenging. Using this model we performed a chemical suppression screen for compounds that relieve dioxygenase inhibition. After testing 1280 pharmaceutically-active compounds we identified meclofenoxate HCL, and its hydrolysis product, dimethylaminoethanol (DMAE), as suppressors of dioxygenase intoxication in SDH-loss cells. We show that DMAE acts to alter metabolism so as to normalize the succinate:2-ketoglutarate ratio, improving dioxygenase function. This work raises the possibility that oncometabolite effects might be therapeutically suppressed by drugs that rewire metabolism to reduce the flux of carbon into pathological metabolic pathways.
Field Testing of a Decision Support Tool for Acute Appendicitis using an Online Randomized Experimental Design
Authors: Rosen Joshua E. , Flum David R. , Davidson Giana H. , Liao Joshua M.
Published: November 2021

Background

Mounting evidence from randomized controlled trials have shown that antibiotics can be a safe and effective treatment for appendicitis. Patients and surgeons must work together to choose the optimal treatment approach for each patient based on their own preferences and values. We developed a novel decision support tool (DST) to facilitate shared decision making for appendicitis. The effect of this DST on decisional outcomes remains unknown.

Methods

We conducted an online randomized field test in at-risk individuals comparing the DST to a standard infographic as a control. Individuals were randomized 3:1 to the DST (intervention) or infographic (control). The primary outcome was the total decisional conflict scale (DCS) score measured before and after exposure to the DST. Secondary outcomes included between-group DCS scores, and between group comparisons of the acceptability of DST or infographic.

Results

180 individuals were included in the study after quality control checks. Total DCS scores decreased significantly after viewing the DST (59.0 to 14.6, p<0.001) representing movement from a state of high to low decisional conflict. Individuals exposed to the DST reported higher acceptability ratings (3.7 vs. 3.3, p<0.001) and had more individuals who would completely agreed that they would be willing to try antibiotics (45% vs. 21%, p=0.008).

Conclusions

The novel appendicitis DST significantly decreased decisional conflict in this online randomized field test. Users rated the tool as highly acceptable and expressed increased willingness to consider antibiotics as a treatment approach after viewing it.

Study Funding

This work was supported by the National Institute of Diabetes and Digestive and Kidney Diseases [grant number T32DK070555]; and a generous gift from Marty and Linda Ellison. The development of aspects of the decision support tool was funded by the Patient Centered Outcomes Research Institute. The funding sources had no role in the study design, collection, analysis, or interpretation of data, in the writing of the manuscript or in the decision to submit for publication.
Time varying association between deprivation, ethnicity and SARS-CoV-2 infections in England: a space-time study
Authors: Padellini Tullia , Jersakova Radka , Diggle Peter J. , Holmes Chris , King Ruairidh E. , Lehmann Brieuc C. L. , Mallon Ann-Marie , Nicholson George , Richardson Sylvia , Blangiardo Marta
Published: November 2021

Background

Ethnically diverse and socio-economically deprived communities have been differentially affected by the COVID-19 pandemic in the UK.

Method

Using a multilevel regression model we assess the time-varying association between SARS-CoV-2 infections and areal level deprivation and ethnicity. We separately consider weekly test positivity rate (number of positive tests over the total number of tests) and estimated unbiased prevalence (proportion of individuals in the population who would test positive) at the Lower Tier Local Authority (LTLA) level. The model also adjusts for age, urbanicity, vaccine uptake and spatio-temporal correlation structure.

Findings

Comparing the least deprived and predominantly White areas with most deprived and predominantly non-White areas over the whole study period, the weekly positivity rate increases by 13% from 2·97% to 3·35%. Similarly, prevalence increases by 10% from 0·37% to 0·41%. Deprivation has a stronger effect until October 2020, while the effect of ethnicity becomes slightly more pronounced at the peak of the second wave and then again in May-June 2021. Not all BAME groups were equally affected: in the second wave of the pandemic, LTLAs with large South Asian populations were the most affected, whereas areas with large Black populations did not show increased values for either outcome during the entire period under analysis.

Interpretation

At the area level, IMD and BAME% are both associated with an increased COVID-19 burden in terms of prevalence (disease spread) and test positivity (disease monitoring), and the strength of association varies over the course of the pandemic. The consistency of results across the two outcome measures suggests that community level characteristics such as deprivation and ethnicity have a differential impact on disease exposure or susceptibility rather than testing access and habits.

Fundings

EPSRC, MRC, The Alan Turing Institute, NIH, UKHSA, DHSC, NIHR
Prevalence of and risk factors for burnout and occupational stress among couriers: A systematic review
Authors: Wei Hua , Li Shugang , Li Sheng , O’Toole Thomas , Yu Mengke , Armitage Christopher J. , Chandola Tarani , Whelan Pauline , Xu Yan , van Tongeren Martie
Published: November 2021

Objective

To estimate the prevalence of burnout and occupational stress (OS) among couriers and to identify the main risk factors.

Method

We followed PRISMA guidelines to search studies published in English and Chinese databases before February 2022.

Results

The search yielded 15 (7 English and 8 Chinese) papers, 12 of which studied Chinese couriers, and three studied French, Israeli and Malaysian couriers. Twelve studies reported OS using various validated measurement tools, and six reported burnout using adapted versions of Maslach Burnout Inventory. Only four included studies suggested cut-off points to define the condition, hence we used the midpoint of the scales to estimate the prevalence (the proportion of the cases that were above the midpoint). The estimated prevalence of burnout (or a dimension of burnout) among couriers ranged from 20% to 73% (median=33%). The prevalence of OS (or a dimension of OS) ranged from 7% to 90% (median=40%). Twelve studies reported risk factors for burnout or OS; the main ones were physical demands, customer behaviour and a range of working and employment conditions, such as employment precarity and financial insecurity. Job resources (i.e. social support and decision latitude) and organizational support had mitigating effects.

Conclusions

Burnout and OS are relatively high among couriers. Interventions to prevent or reduce burnout in this occupation are currently limited. The use of platform technology to shift risks, intensify work and tighten managerial controls could be a potential work-related stressor for app-based couriers but remains a knowledge gap.
Biochemical and Immunological Predictors of Non-healing in Individuals with Early-stage Diabetic Foot Ulcers
Authors: Raghavan Jayashree Vijaya , Sagar Shruthi Ksheera , Dorai Vinod Kumar , Samuel Rebecca Diya , Arunachalam Priyanka , Chaluvanarayana H C , Belahalli Pavan , Kalpana S R , Jhunjhunwala Siddharth
Published: November 2021

Objective

The goal of this study was to identify biochemical and immunological parameters from the blood as predictors of non-healing in early-stage diabetic foot ulcers.

Research Design and Methods

We performed a cross-sectional prospective cohort study among individuals with early-stage foot ulcers visiting the Karnataka Institute of Endocrinology Research over a 2.5-year period. Histopathological, biochemical, and immunological data (a total of 31 parameters) from 52 individuals were collected and analyzed to determine if predictors of non-healing may be identified. Data analysis was performed using traditional univariate analyses as well as univariate and multivariable logistic regression.

Results

Individual histopathological and biochemical parameters did not show any differences between healed and non-healed individuals. However, conventional univariate analysis and univariate logistic regression analysis showed that the expression of the cell-surface proteins CD63, HLA-DR and CD11b on monocytes (CD14+) was significantly lower in non-healed individuals, but with moderate discriminative ability as assessed by area under the curve (AUC) of Receiver Operating Characteristics (ROC) curve. In comparison, a multivariable logistic regression model identified four of the 31 parameters to be salient predictors and demonstrated high discrimination ability with an AUC of ROC value of 0.87. Among the four identified parameters, LDL cholesterol (OR 18.83, CI 18.83-342) and cell-surface expression of CD63 on monocytes (OR 0.12, CI 0.12-0.45) were significant.

Conclusion

Through this study we conclude that LDL cholesterol and cell-surface expression of CD63 on monocytes are strong positive and negative predictors of non-healing, respectively, in individuals with early-stage DFU. Following validation in a larger cohort, these parameters may be used by the clinician for early identification of non-healers.
Probabilistic classification learning in amnesia.
Authors: Knowlton B J , Squire L R , Gluck M A
Published: November 2021

Amnesic patients and control subjects participated in a study of probabilistic classification learning. In each of three tasks, four different cues were each probabilistically associated with one of two outcomes. On each trial, the cues could appear alone or in combination with other cues and subjects selected the outcome they thought was correct. Feedback was provided after each trial. In each task, the amnesic patients learned gradually to associate the cues with the appropriate outcome at the same rate as control subjects, improving from 50% correct to approximately 65% correct. Presumably because the cue-outcome associations were probabilistic, declarative memory for the outcomes of specific trials was not as useful for performance as the information gradually accrued across trials. Nevertheless, declarative memory does appear to make a contribution to performance when training is extended beyond approximately 50 trials, because with further training control subjects eventually outperformed the amnesic patients. It was also demonstrated that performance on the probabilistic classification task was not the result of holding knowledge of cue-outcome associations in short-term memory, because both control subjects and amnesic patients demonstrated significant savings when testing was interrupted by a 5-min delay (experiment 2). Probabilistic classification learning appears to provide an analog in human subjects for the habit learning tasks that can be acquired normally by animals with hippocampal lesions.
Low-frequency stimulation erases LTP through an NMDA receptor-mediated activation of protein phosphatases.
Authors: O'Dell T J , Kandel E R
Published: November 2021

In the CA1 region of adult guinea pig hippocampal slices, long trains of theta frequency (5 Hz) stimulation produced a small enhancement of basal synaptic transmission but depressed the strength of synaptic transmission at synapses that had recently undergone long-term potentiation (LTP). Five hertz stimulation delivered immediately prior to high-frequency stimulation also inhibited the subsequent induction of LTP. The depression of potentiated synapses by 5 Hz stimulation (depotentiation) was blocked by 2-amino-5-phosphonovalerate and was observed only during the early phases of LTP. Furthermore, the protein phosphatase inhibitors okadaic acid and calyculin A blocked both depotentiation and the ability of 5 Hz stimulation to inhibit subsequent LTP, suggesting that protein phosphatases are involved in the ability of 5 Hz stimulation to modulate synaptic plasticity in the CA1 region of the hippocampus.
7-Nitro indazole, a neuron-specific nitric oxide synthase inhibitor, produces amnesia in the chick.
Authors: Hölscher C
Published: November 2021

7-Nitro indazole (7-NI), which is selective for the neuronal isoform of nitric oxide synthase (NOS), was tested in a passive avoidance task in the chick. Injection of 50 mg/kg i.p. pretraining had amnesic effects for the task when tested 30 min, 2 or 24 hr after training. Injections post-training had no effect. Because 7-NI does not inhibit the endothelial isoform of NOS, it does not affect blood vessel relaxation, as nonspecific inhibitors do. This effect on blood vessels could explain the amnestic effects produced by nonspecific NOS inhibitors. The results support the theory that NO is a neuronal transmitter that is important in processes of synaptic plasticity and learning.
Crystal structures of metallocene complexes with uranium–germanium bonds
Authors: Tarlton Michael L. , Kelley Steven P. , Walensky Justin R.
Published: November 2021

The first structural examples of complexes with uranium–germanium bonds are presented, namely, bis[3,5-bis(trifluoromethyl)phenyl-2κC
1](hydrido-2κH)(iodido-1κI)bis[1,1(η5)-pentamethylcyclopentadienyl]germaniumuranium(Ge—U), [GeU(C10H15)2(C8H3F6)2HI], and bis[3,5-bis(trifluoromethyl)phenyl-2κC
1](fluorido-1κI)(hydrido-2κH)bis[1,1(η5)-pentamethylcyclopentadienyl]germaniumuranium(Ge—U), [GeU(C10H15)2(C8H3F6)2FH]. The two complexes both have a long U—Ge bond [distances of 3.0428 (7) and 3.0524 (7) Å].
Labelling or not: influence of food retailer's approaching the expiration date labelling on consumers' patronage intention
Authors: Tang Yifan , Kuang Yiting , Li Han , Cao Binbin , Qing Ping
Published: November 2021

Purpose

The purpose of this paper is to investigate the influence of food retailer's Approaching the Expiration Date (AED) labelling on consumers' retailer-related response. Specifically, the main effect of food retailer's AED labelling on consumers' patronage intention, the mediation effect of food retailer's concern for consumers and the boundary condition of this effect are explored. The selected context of research is that food retailers are reluctant to stick an AED label on nearly expired food due to negative effect on selling them.

Design/methodology/approach

Two separate pretests and two separate experiments have been conducted to investigate the influence of food retailer's AED labelling on patronage intention. Pretest 1 develops the stimulus material of food retailer's AED labelling. Study 1 investigates the influence of AED labelling on patronage intention and mediation effect of consumers' perception of retailer's concern for consumers. Pretest 2 develops the stimulus material of government regulation on food retailer's AED labelling. Study 2 explores the boundary condition of the positive effect, namely the moderation effect of whether retailer's AED labelling is voluntary or mandatory.

Findings

The main findings of this research highlight the positive influence of food retailer's AED labelling on consumers' patronage intention. In addition, the current research reveals the underlying mechanism food retailer's concern for consumers and the boundary condition whether the AED labelling is voluntary or mandatory.

Originality/value

Although previous researches has explored the effect of food retailer's AED labelling on consumers' response, most of them focus on consumer purchase intention of the nearly expired food and neglect its effect on consumers' food retailer-related response. It is a need for food retailer to explore the potential positive influence of food retailer's AED labelling on consumers' patronage intention.
Mapping the intellectual structure of short food supply chains research: a bibliometric analysis
Authors: Luo Jianli , Liang Yuanxiang , Bai Yanhu
Published: November 2021

Purpose

The purpose of this paper is to identify major research topics and propose future research directions for the short food supply chains (SFSCs) by conducting a comprehensive bibliometric analysis.

Design/methodology/approach

A step-by-step literature review was performed. A total of 684 scientific papers were retrieved from Scopus, dated between 2000 and 2020. Then, content analysis was conducted based on 162 articles selected from the co-citation analysis. Bibexcel and Gephi software were employed to analyse, integrate and visualize the data.

Findings

The results of the descriptive analysis provided insights into publication trends, prominent countries, institutions and journal sources, which had not been fully captured or evaluated by previous reviews. In the citation analysis, the authors determined the highly cited papers based on the global citation. Additionally, in the co-citation analysis, the authors derived six research clusters, identified research gaps in each of six clusters and then suggested possible future research directions.

Originality/value

Although several reviews have focused on certain aspects of SFSCs, a comprehensive review has been lacking. This study is among the first to comprehensively examine the knowledge structure of SFSCs research by using rigorous bibliometric analysis. More importantly, the future lines presented here offer potential insights for SFSCs researchers and policymakers.
Addressing sustainable food management in hotels: proposing a framework and examining hotel groups
Authors: Ruiz Molina María Eugenia , Belda-Miquel Sergio , Hytti Anni , Gil-Saura Irene
Published: November 2021

Purpose

Sustainable food practices have been recognised as a key issue in efforts to improve and report sustainable tourism practices, given the importance of the social, environmental and economic impacts of the food industry throughout its entire chain of production – from farm to fork. From this standpoint, the aim of the present paper is to propose a comprehensive framework for reporting or making decisions concerning sustainable food management in hotels, taking into account the various facets of the food supply chain.

Design/methodology/approach

Several dimensions are proposed for dealing with sustainable food management, involving all aspects of food supply chains that may be relevant for hotel decision-making. Furthermore, some key criteria for creating and using indicators of different types (qualitative and quantitative) to address these various dimensions of sustainable food management are suggested. Subsequently, the proposed framework is validated with the sustainability criteria and indicators provided by the top eight hotel groups, according to the 2019 SAM Annual Corporate Sustainability Assessment.

Findings

Hotels neglect a number of aspects of sustainable food management identified in the framework. The quality and the quantity of the information provided by hotels are limited.

Practical implications

There is a need to improve sustainability in food management in the hotels under analysis in several areas. A comprehensive framework such as that proposed in this paper may be of great value in seeking to remedy this situation. It may also assist users of hotel services and communities in making more informed decisions.

Originality/value

The proposed framework may be beneficial in advancing academic debate towards a more embracing and relevant understanding of sustainable food management in hotels and on the indicators required in this regard.
A new technique for right half plane zero elimination from dynamics of a boost converter using magnetic coupling concept
Authors: Goudarzian Alireza
Published: November 2021

Purpose

Control-signal-to-output-voltage transfer function of the conventional boost converter has at least one right-half plane zero (RHPZ) in the continuous conduction mode which can restrict the open-loop bandwidth of the converter. This problem can complicate the control design for the load voltage regulation and conversely, impact on the stability of the closed-loop system. To remove this positive zero and improve the dynamic performance, this paper aims to suggest a novel boost topology with a step-up voltage gain by developing the circuit diagram of a conventional boost converter.

Design/methodology/approach

Using a transformer, two different pathways are provided for a classical boost circuit. Hence, the effect of the RHPZ can be easily canceled and the voltage gain can be enhanced which provides conditions for achieving a smaller working duty cycle and reducing the voltage stress of the power switch. Using this technique makes it possible to achieve a good dynamic response compared to the classical boost converter.

Findings

The observations show that the phase margin of the proposed boost converter can be adequately improved, its bandwidth is largely increased, due to its minimum-phase structure through RHPZ cancellation. It is suitable for fast dynamic response applications such as micro-inverters and fuel cells.

Originality/value

The introduced method is analytically studied via determining the state-space model and necessary criteria are obtained to achieve a minimum-phase structure. Practical observations of a constructed prototype for the voltage conversion from 24 V to 100 V and various load conditions are shown.
Insurers' risk management as a business process: a prospective competitive advantage or not?
Authors: Ahmed Danish , Yuantao Xie , Saeed Bhutta Umair
Published: November 2021

Purpose

Insurance companies exist to manage the risk of others, which is why they are perceived to be competitive in risk management (RM). Considering this, we investigate how different RM capabilities make insurers effective in RM. These capabilities include understanding risk and risk management (URRM), risk identification (RI), risk assessment and analysis (RAA) and risk monitoring (RMON) activities in insurance companies. In addition, the authors probe how these capabilities can jointly yield a competitive advantage for the insurance industry under the resource-based view (RBV) and dynamic capabilities perspective (DCP).

Design/methodology/approach

The authors present a latent variable RM model for the insurance industry and employ structural equation modeling (SEM) to test the hypotheses. Furthermore, the authors also conduct confirmatory factor analysis (CFA) and convergent and discriminant validity analysis for model fit and invariance testing, respectively.

Findings

The results show that insurers who investigated RM-related capabilities directly influence their risk management practices (RMPs). Moreover, improving these capabilities will make insurers more effective in managing the risks of others. Thus, RM as a business process will yield a competitive advantage for the insurance sector. The findings are supported by the theoretical insights presented by the RBV and DCP. Furthermore, the model also adheres to the convergent and discriminant validity cut-off values.

Originality/value

To the best of the authors’ knowledge, this is the first study examining insurers' RM practices as a source of a competitive advantage.
Epidemic modeling as a means to reimagine health education and policy post-COVID
Authors: Racine Elise E. , Bryson Joanna J.
Published: November 2021

Purpose

As illustrated by coronavirus disease 2019 (COVID-19), epidemic models are powerful health policy tools critical for disease prevention and control, i.e. if they are fit for purpose. How do people ensure this is the case and where does health education fit in?

Design/methodology/approach

This research takes a multidisciplinary approach combining qualitative secondary and primary data from a literature review, interviews and surveys. The former spans academic literature, grey literature and course curriculum, while the latter two involve discussions with various modeling stakeholders (educators, academics, students, modeling experts and policymakers) both within and outside the field of epidemiology.

Findings

More established approaches (compartmental models) appear to be favored over emerging techniques, like agent-based models. This study delves into how formal and informal education opportunities may be driving this preference. Drawing from other fields, the authors consider how this can be addressed.

Practical implications

This study offers concrete recommendations (course design routed in active learning pedagogies) as to how health education and, by extension, policy can be reimagined post-COVID to make better use of the full range of epidemic modeling methods available.

Originality/value

There is a lack of research exploring how these methods are taught and how this instruction influences which methods are employed. To fill this gap, this research uniquely engages with modeling stakeholders and bridges disciplinary silos to build complimentary knowledge.
The application of topological geometry to the architectural concept design process in the flow of digitalization
Authors: Thuy Nguyen Thi Minh , Thi Nguyen Dinh
Published: November 2021

Purpose

The paper aims to research the applications of topological geometry to the architectural concept design process and their combination with the modern digital technology to find novel architectural spaces and forms which are dynamic, easily adaptable to the context and surroundings.

Design/methodology/approach

The article uses the method of studying the existing literature on topological geometry and architectural design theory including design thinking, architectural design methods and architectural compositions to analyze and compare them with architectural practices and suggest new topological design tools and methods. Moreover, the paper tests the proposals with a number of preliminary design research experiments. In addition, graphic design software, parametric design, building information modeling (BIM) and digital development trends in architecture were explored and experienced to reveal the application potential of topological design thinking and methods in the trend of architectural digitization.

Findings

The paper has analyzed, synthesized and systematized the basic theories of topological geometry in order to clarify their applications in the architectural concept design process. On that basis, the paper proposes a novel topological design thinking and method for finding rich diversified architectural ideas and forms based on original invariant design constraints. Finally, the paper clarifies the combination as well as the mutual, motivating relationship between topological geometry and modern digital technologies when applied to architectural design.

Originality/value

The research contributes a novel design thinking and method based on topological geometry combined with modern digital technology to the architectural design theory. It will be a valuable tool capable of suggesting architects how to think and innovate in architecture in the era of industrial revolution 4.0.