bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy of endoscopic therapy for T1b esophageal cancer and construction of prognosis prediction model: a retrospective cohort study
Authors: Fan Xiangli , Wang Jing , Xia Lingling , Qiu Hu , Tian Yuanyuan , Zhangcai Yutian , Luo Xixi , Gao Yuelan , Li Chen , Wu Yong , Zhao Wensi , Chen Jiamei , Shi Wei , Yuan Jingping , Ke Shaobo , Chen Yongshun
Published: May 2023

Background:

The efficacy of endoscopic therapy on the long-term survival outcomes of T1b oesophageal cancer (EC) is unclear, this study was designed to clarify the survival outcomes of endoscopic therapy and to construct a model for predicting the prognosis in T1b EC patients.

Methods:

This study was performed using the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2017 of patients with T1bN0M0 EC. Cancer-specific survival (CSS) and overall survival (OS) were compared between endoscopic therapy group, esophagectomy group and chemoradiotherapy group, respectively. Stabilized inverse probability treatment weighting was used as the main analysis method. The propensity score matching method and an independent dataset from our hospital were used as sensitivity analysis. The least absolute shrinkage and selection operator regression (Lasso) was employed to sift variables. A prognostic model was then established and was verified in two external validation cohorts.

Results:

The unadjusted 5-year CSS was 69.5% (95% CI, 61.5–77.5) for endoscopic therapy, 75.0% (95% CI, 71.5–78.5) for esophagectomy and 42.4% (95% CI, 31.0–53.8) for chemoradiotherapy. After stabilized inverse probability treatment weighting adjustment, CSS and OS were similar in endoscopic therapy and esophagectomy groups (P=0.32, P=0.83), while the CSS and OS of chemoradiotherapy patients were inferior to endoscopic therapy patients (P<0.01, P<0.01). Age, histology, grade, tumour size, and treatment were selected to build the prediction model. The area under the curve of receiver operating characteristics of 1, 3, and 5 years in the validation cohort 1 were 0.631, 0.618, 0.638, and 0.733, 0.683, 0.768 in the validation cohort 2. The calibration plots also demonstrated the consistency of predicted and actual values in the two external validation cohorts.

Conclusion:

Endoscopic therapy achieved comparable long-term survival outcomes to esophagectomy for T1b EC patients. The prediction model developed performed well in calculating the OS of patients with T1b EC.
Effects of very low carbohydrate ketogenic diets on skeletal health
Authors: Best Cora M. , Hsu Simon
Published: May 2023

Purpose of review

Very low carbohydrate ketogenic diet (KD) therapy has been associated with skeletal demineralization in children with drug-resistant epilepsy, but the cause of this association is unclear. Recently, interest in the KD has grown owing to its potential benefits for other illnesses including cancer, type 2 diabetes, obesity, and polycystic kidney disease. Summaries of the best available evidence regarding effects of a KD on skeletal health are lacking.

Recent findings

Recent rodent studies found that a KD can harm the growing skeleton, which corroborates most but not all studies in pediatric patients. Proposed mechanisms include chronic metabolic acidosis and depressed osteoanabolic hormones. Relative to other weight-reducing diets, a weight-reducing KD for treatment of obesity and/or type 2 diabetes in adults has not been associated with adverse skeletal effects. By contrast, recent evidence suggests that adaptation to a eucaloric KD may impair bone remodeling in elite adult athletes. Discrepancies in the literature may relate to differences between study populations and in diet formulation.

Attention to skeletal health is warranted when using KD therapy given the uncertainty in the literature and suggestive harms in certain populations. Future research should focus on potential mechanisms of injury.
Developing the Blueprint for Youth Suicide Prevention
Authors: Gorzkowski Hamilton Julie , Horowitz Lisa M. , Standley Corbin J. , Ryan Patrick C. , Wei August X. , Lau May , Yu Moutier Christine
Published: May 2023

Suicide and suicidal behavior among youth and young adults are a major public health crisis, exacerbated by the COVID-19 pandemic and demonstrated by increases in suicidal ideation and attempts among youth. Supports are needed to identify youth at risk and intervene in safe and effective ways. To address this need, the American Academy of Pediatrics and the American Foundation for Suicide Prevention, in collaboration with experts from the National Institute of Mental Health, developed the Blueprint for Youth Suicide Prevention (Blueprint) to translate research into strategies that are feasible, pragmatic, and actionable across all contexts in which youth live, learn, work, and play. In this piece, we describe the process of developing and disseminating the Blueprint. Through a summit and focus meetings, cross-sectoral partners convened to discuss the context of suicide risk among youth; explore the landscape of science, practice, and policy; build partnerships; and identify strategies for clinics, communities, and schools—all with a focus on health disparities and equity. These meetings resulted in 5 major takeaways: (1) suicide is often preventable; (2) health equity is critical to suicide prevention; (3) individual and systems changes are needed; (4) resilience should be a key focus; and (5) cross-sectoral partnerships are critical. These meetings and takeaways then informed the content of the Blueprint, which discusses the epidemiology of youth and young adult suicide and suicide risk, including health disparities; the importance of a public health framework; risk factors, protective factors, and warning signs; strategies for clinical settings, strategies for community and school settings; and policy priorities. Following the process description, lessons learned are also discussed, followed by a call to action for the public health community and all who serve and support youth. Finally, key steps to establishing and sustaining partnerships and implications for policy and practice are discussed.
Partial central anterior reconstruction of the auricle with one-stage combined retroauricular flaps
Authors: Poissonnet Gilles , Poissonnet Valentine , Dassonville Olivier , Bozec Alexandre , Culié Dorian
Published: May 2023

Basal cell carcinomas of the central anterior area of the auricle, limited to the antihelix and scapha without peripheral infiltration of the helix, are not uncommon. Surgical resection is rarely transfixing but the resection of the underlying cartilage is often required. The complex anatomy of the ear, and the lack of local tissue available makes its reparation challenging. Defects of anthelix and scapha require special reconstructive techniques, taking into account skin structure and the three-dimensional architecture of the ear. Usually, the reconstruction consists of full-thickness skin grafting, or anterior transposition flap requiring an extended skin resection. We describe a one-stage technique that uses a pedicled retroauricular skin flap turned over the anterior defect, followed by immediate closure of the donor site with a transposition or a bilobed retroauricular skin flap. The one-stage combined retroauricular flaps reparation optimizes cosmetic outcome, reduces risks of successive surgeries.
Size rather than complexity of sexual ornaments prolongs male metamorphosis and explains sexual size dimorphism in sepsid flies
Authors: Rajaratnam Gowri , Lui Gerald , Su Kathy F. Y. , Chew Martin S. J. , Ang Yuchen , Puniamoorthy Nalini , Rohner Patrick T. , Blanckenhorn Wolf U. , Meier Rudolf
Published: May 2023

Male sexual ornaments often evolve rapidly and are thought to be costly, thus contributing to sexual size dimorphism. However, little is known about their developmental costs, and even less about costs associated with structural complexity. Here, we quantified the size and complexity of three morphologically elaborate sexually dimorphic male ornaments that starkly differ across sepsid fly species (Diptera: Sepsidae): (i) male forelegs range from being unmodified, like in most females, to being adorned with spines and large cuticular protrusions; (ii) the fourth abdominal sternites are either unmodified or are converted into complex
de novo
appendages; and (iii) male genital claspers range from small and simple to large and complex (e.g. bifurcated). We tracked the development of 18 sepsid species from egg to adult to determine larval feeding and pupal metamorphosis times of both sexes. We then statistically explored whether pupal and adult body size, ornament size and/or ornament complexity are correlated with sex-specific development times. Larval growth and foraging periods of male and female larvae did not differ, but the time spent in the pupal stage was
ca
5% longer for sepsid males despite emerging 9% smaller than females on average. Surprisingly, we found no evidence that sexual trait complexity prolongs pupal development beyond some effects of trait size. Evolving more complex traits thus does not incur developmental costs at least in this system.
Revealing the roles of egg darkness and nest similarity for a cryptic parasite egg versus host's cognition: an alternate coevolutionary trajectory
Authors: Yang Canchao , Ye Ping , Wu Neng , Yao Xiaogang , Liang Wei
Published: May 2023

As a text-book example of coevolution, the escalating interactions between egg mimicry by parasitic cuckoos and egg recognition by their hosts constitute a key battlefield for parasitism and anti-parasitism strategies. However, some parasite–host systems have deviated from this coevolutionary trajectory because some cuckoos do not lay mimetic eggs, while the hosts do not recognize them, even under the high costs of parasitism. The cryptic egg hypothesis was proposed to explain this puzzle, but the evidence to date is mixed and the relationship between the two components of egg crypticity, egg darkness (dim egg coloration) and nest similarity (similarity to host nest appearance), remains unknown. Here, we developed a ‘field psychophysics’ experimental design to dissect these components while controlling for undesired confounding factors. Our results clearly show that both egg darkness and nest similarity of cryptic eggs affect recognition by hosts, and egg darkness plays a more influential role than nest similarity. This study provides unambiguous evidence to resolve the puzzle of absent mimicry and recognition in cuckoo–host systems and explains why some cuckoo eggs were more likely to evolve dim coloration rather than similarity to host eggs or host nests.
A 2200-year record of Andean Condor diet and nest site usage reflects natural and anthropogenic stressors
Authors: Duda Matthew P. , Grooms Christopher , Sympson Lorenzo , Blais Jules M. , Dagodzo Daniel , Feng Wenxi , Hayward Kristen M. , Julius Matthew L. , Kimpe Linda E. , Lambertucci Sergio A. , Layton-Matthews Daniel , Lougheed Stephen C. , Massaferro Julieta , Michelutti Neal , Pufahl Peir K. , Vuletich April , Smol John P.
Published: May 2023

Understanding how animals respond to large-scale environmental changes is difficult to achieve because monitoring data are rarely available for more than the past few decades, if at all. Here, we demonstrate how a variety of palaeoecological proxies (e.g. isotopes, geochemistry and DNA) from an Andean Condor (Vultur gryphus) guano deposit from Argentina can be used to explore breeding site fidelity and the impacts of environmental changes on avian behaviour. We found that condors used the nesting site since at least approximately 2200 years ago, with an approximately 1000-year nesting frequency slowdown fromca1650 to 650 years before the present (yr BP). We provide evidence that the nesting slowdown coincided with a period of increased volcanic activity in the nearby Southern Volcanic Zone, which resulted in decreased availability of carrion and deterred scavenging birds. After returning to the nest siteca650 yr BP, condor diet shifted from the carrion of native species and beached marine animals to the carrion of livestock (e.g. sheep and cattle) and exotic herbivores (e.g. red deer and European hare) introduced by European settlers. Currently, Andean Condors have elevated lead concentrations in their guano compared to the past, which is associated with human persecution linked to the shift in diet.
Water and foodborne pathogens isolated from children in a hospital system reveal extensive resistance against commonly used Penicillin-type antibiotics
Authors: Awuor Silas Onyango , Omwenga Eric O. , Mariita Richard M. , Musila Jonathan M. , Mbeke Alexander , Musyoka Thommas M.
Published: May 2023

Diarrhoea diseases are the second leading cause of death among under five children. The situation being worsened by emergence of multi-drug resistant enteric bacteria which are becoming a major global medical and public health problem. This study aimed at identifying the common diarrhoea causing bacteria, their antibiotic susceptibility patterns in under five children. With consent from parents or guardians, total of 196 under five children seeking between January to June 2016 were included in this study. Stool samples were collected and cultured required, followed by biochemical tests using standard procedures. Susceptibility tests were conducted using various conventional antibiotics. Of the total 63.8% children were from pediatric OPD and wards while 36.2% from pediatric emergency department. Participants comprised of 53.6% males and 46.4% females. Total of 21.9% enteric bacterial pathogens were identified, 12.8% of which were confirmed to be E. coli, 5.6% Shigella spp., and the remaining 3.6% were Salmonella spp. All the isolated E. coli, Shigella and Salmonella spp. were susceptible against Ceftriaxone. Results from E. coli screening revealed that 56% and 52% were resistant against Amoxicillin and Ampicillin respectively. The study revealed concerning distribution of antibiotic resistance of bacteria in under 5 children.
The impact of COVID-19 healthcare practice on the prevalence of bacteria from door handles at the University of Port Harcourt Teaching Hospital and its multi drug resistance implication
Authors: Edi Deinmo , Ejiohuo Ovinuchi , Ordinioha Best
Published: May 2023

Background

High contact points in healthcare facilities, such as door knobs, operate as reservoirs for microorganisms and as a channel for the transmission of nosocomial diseases. The COVID-19 pandemic led to an increase in hospital infection risk due to the highly infectious nature of the virus. However, due to strict COVID-19 health regulations, sanitary and hygienic conditions in healthcare facilities were greatly improved.

Objective

This study assesses the occurrence and prevalence of bacteria on toilet door handles on health facilities using the University of Port Harcourt Teaching Hospital in Nigeria as a case study and its multi drug resistant implication.

Method

Assessment of experimental data from our study on hospital door knobs in different locations. We examined the hospital COVID-19 protocol, infection level, and overall sanitary condition during the pandemic year in 2020.

Result

The results show that despite the occurrence of pathogenic microorganisms, there is a reduction in the prevalence of multidrug resistant bacteria strains. This is an indication that certain key aspects of hospital covid-19 protocols should be maintained and encouraged. Simple practices such as constant disinfection of surfaces, hand hygiene, and contactless doors should be standards in healthcare facilities.

Conclusion

The COVID-19 pandemic has emphasized the need to limit the spread of hospital-acquired diseases (HCAIs), particularly those brought on by bacteria that are multidrug resistant. This study on door handles can be used as an environmental microbiological surveillance in cases of suspected outbreak investigations. This can check sanitary conditions in hospitals and also checkmate the prevalence of multidrug resistant bacteria in healthcare facilities.
A Review of the Inter-laboratory Variability of Caspofungin Minimum Inhibitory Concentrations for Nakaseomyces glabrata isolates
Authors: Ali Saied , Collison Meadhbh , McNicholas Sinead , McDermott Sinead
Published: May 2023

Background:
The use of automated broth-microdilution systems for caspofungin antifungal susceptibility testing (AST) for Nakaseomyces glabrata is prone to high inter-laboratory variation. We aim to review caspofungin minimum inhibitory concentrations (MICs) of clinically significant N.glabrata isolates, as reported locally and compare with reference laboratory results for the same isolate.
Methods:
All clinically significant N.glabrata isolates from 2019-2021 inclusive were reviewed. Caspofungin MICs were obtained locally using the VITEK2 system and strains were referred to the Mycology Reference Laboratory for confirmatory testing via E-Tests. MICs were compared using categorical and essential agreement.
Results:
Of the forty-one isolates reviewed, marked discrepancies were noted in interpretative breakpoints between assays, producing 16 Minor and Major Category Errors. Categorical agreement was found to be 22%, with the VITEK2 over-estimating resistance. Doubling dilution differences revealed an essential agreement of 61% within ±1 log2 dilution.  
Conclusion:
Performing caspofungin AST using broth-microdilution methods is prone to high inter-laboratory variation, and potentially results in the mis-classification of susceptible isolates as highlighted in our study. The use of E-tests has been shown to be highly reliable and not prone to inter-laboratory variation. It may be worthwhile looking into adopting a similar testing approach locally from an economic and patient-centred view.
Allorhizobium sonneratiae sp. nov., an endophytic bacterium isolated from the root of Sonneratia apetala
Authors: Li Fei , Yu Lian , Su Xin-Ying , Wang Qiao-Zhen , Huang Shu-Shi , Qin Xian-Ling , Tuo Li
Published: May 2023

A novel endophytic bacterium, designated strain BGMRC 0089T, was isolated from a surface-sterilized root of Sonneratia apetala. Cells were observed to be Gram-negative, rod-shaped and motile with polar flagella. Strain BGMRC 0089T was found to grow optimally at 28–30 °C, pH 7.0–8.0 and in the presence of 1 % (w/v) NaCl. Strain BGMRC 0089T contained ubiquinone Q-10 and the predominant fatty acid was summed feature 8. The polar lipid profile of strain BGMRC 0089T was found to contain diphosphatidylglycerol, phosphatidylglycerol, phosphatidylmonomethylethanolamine and phosphatidylethanolamine. Based on the results of 16S rRNA gene analysis, this isolate has the closest phylogenetic relationships with

Rhizobium lemnae

L6-16T (96.5 %) and

Allorhizobium oryziradicis

N19T (96.4 %). Average nucleotide identity, amino acid identity and digital DNA–DNA hybridization values of the isolate with the type strains of the genera

Rhizobium

and

Allorhizobium

were below 84.6, 73.9 and 22.1  %, respectively. Analysis the 4.55 Mb draft genome of strain BGMRC 0089T revealed several plant-associated genes, which may play important roles for the plant in the adaptation to the mangrove habitat. Based on its distinct phylogenetic, phenotypic and chemotaxonomic characteristics, strain BGMRC 0089T is proposed to represent a novel

Allorhizobium

species, for which the name Allorhizobium sonneratiae sp. nov. is proposed (type strain BGMRC 0089T=DSM 100171T=MCCC 1K04805T).
The Impact of Peripartum Floor Lockdowns on Newborn Safety
Authors: Neshek Barbara , Bryant David Ray , Hruska Justin , Gupta Deepak
Published: May 2023

Background

For the safety of newborns, infrastructural lockdown of peripartum floors may be imperative.

Materials and Methods

Cumulative data with no identifiers at all was collected from Midas Incident Reporting System reports and Security Logs reports for comparing incidence of newborn abductions four year-period (2015-2018) before the institution of lockdown with four year-period (2019-2022) since the institution of lockdown.

Results

During the entire eight years, there was not a single incident of newborn abduction reported in Midas Incident Reporting System and Security Logs.

Conclusion

The absent incidence of newborn abductions before and since peripartum floors’ lockdown should not deter keeping safety protocols enhanced and potential loopholes closed thus preemptively treating lax human factors while protecting precious and vulnerable newborns during their stay in peripartum floors.
Multi-Omic Factor Analysis uncovers immunological signatures with pathophysiologic and clinical implications in coronary syndromes
Authors: Pekayvaz Kami , Losert Corinna , Knottenberg Viktoria , van Blokland Irene V. , Oelen Roy , Groot Hilde E. , Benjamins Jan Walter , Brambs Sophia , Kaiser Rainer , Eivers Luke , Polewka Vivien , Escaig Raphael , Joppich Markus , Janjic Aleksandar , Popp Oliver , Petzold Tobias , Zimmer Ralf , Enard Wolfgang , Saar Kathrin , Mertins Philipp , Huebner Norbert , van der Harst Pim , Franke Lude H. , van der Wijst Monique G. P. , Massberg Steffen , Heinig Matthias , Nicolai Leo , Stark Konstantin
Published: May 2023

Acute and chronic coronary syndromes (ACS and CCS) are leading causes of mortality. Inflammation is considered to be a key pathogenic driver, but immune states in humans and their clinical implications remain poorly understood. We hypothesized that Multi-Omic blood analysis combined with Multi-Omic Factor Analysis (MOFA) might uncover hidden sources of variance providing pathophysiological insights linked to clinical needs. Here, we compile a single cell longitudinal dataset of the circulating immune states in ACS & CCS (13x103clinical & Multi-Omic variables, n=117 subjects, n=838 analyzed samples) from two independent cohorts. Using MOFA, we identify multilayered factors, characterized by distinct classical monocyte and CD4+& CD8+T cell states that explain a large proportion of inter-patient variance. Three factors either reflect disease course or predict outcome in coronary syndromes. The diagnostic performance of these factors reaches beyond established biomarkers highlighting the potential use of MOFA as a novel tool for multilayered patient risk stratification.
Sex and age-dependent alterations of drug consumption during the COVID-19 lockdown in Spain: Lessons learned for the future
Authors: Lorente Jesús David , Forte Anabel , Cuitavi Javier , Verdú Francesc , Hipólito Lucía
Published: May 2023

In order to reduce the spread of COVID-19, lockdown has been one of the most implemented measures worldwide. Spain had one of the harshest lockdowns in Europe, impacting the social and psychological health of the population. The aim of this paper is to study how the lockdown has affected drug consumption patterns and the extent to which age and sex are influential factors. We have developed an online survey in which people were asked about their consumption of alcohol, marihuana, cocaine, and sedative and tranquilizers before and during the COVID-19 lockdown. Data revealed a general reduction in the consumption of all the drugs surveyed. Interestingly, when data was analysed by sex or age, we detected alterations in the consumption patterns depending on these variables that were of special relevance in the case of alcohol, marihuana and non-prescription sedatives and tranquilizers. Our data revealed a general decrease in the use of these drugs in the case of young adults, revealing that their use is strongly linked to social life, whereas the middle-aged population has experienced alterations in their consumption patterns, whereby their use has increased to daily. In addition, the use of non-prescription sedatives and tranquilizers has increased in specific populations. In conclusion, our data reveals important alterations during the lockdown in the consumption pattern of both legal and illegal drugs (sex and age dependent) in the Spanish population, and these alterations might be considered for future national strategies of preventative actions.
Selective Enhancer Dependencies inMYC-Intact andMYC-Rearranged Germinal Center B-cell Diffuse Large B-cell Lymphoma
Authors: Iyer Ashwin R. , Gurumurthy Aishwarya , Kodgule Rohan , Aguilar Athalee R. , Saari Travis , Ramzan Abdullah , Rausch Dylan , Gupta Juhi , Hall Cody N. , Runge John S. , Weiss Matthew , Rahmat Mahshid , Anyoha Rockwell , Fulco Charles P. , Ghobrial Irene M. , Engreitz Jesse , Cieslik Marcin P. , Ryan Russell J.H.
Published: May 2023

High expression ofMYCand its target genes define a subset of germinal center B-cell diffuse large B-cell lymphoma (GCB-DLBCL) associated with poor outcomes. Half of these high-grade cases show chromosomal rearrangements between theMYClocus and heterologous enhancer-bearing loci, while focal deletions of the adjacent non-coding genePVT1are enriched inMYC-intact cases. To identify genomic drivers ofMYCactivation, we used high-throughput CRISPR-interference (CRISPRi) profiling of candidate enhancers in theMYClocus and rearrangement partner loci in GCB-DLBCL cell lines and mantle cell lymphoma (MCL) comparators that lacked common rearrangements betweenMYCand immunoglobulin (Ig) loci. Rearrangements betweenMYCand non-Ig loci were associated with unique dependencies on specific enhancer subunits within those partner loci. Notably, fitness dependency on enhancer modules within theBCL6super-enhancer (BCL6-SE) cluster regulated by a transcription factor complex of MEF2B, POU2F2, and POU2AF1 was higher in cell lines bearing a recurrentMYC::BCL6-SE rearrangement. In contrast, GCB-DLBCL cell lines withoutMYCrearrangement were highly dependent on a previously uncharacterized 3’ enhancer within theMYClocus itself (GCBME-1), that is regulated in part by the same triad of factors. GCBME-1 is evolutionarily conserved and active in normal germinal center B cells in humans and mice, suggesting a key role in normal germinal center B cell biology. Finally, we show that thePVT1promoter limitsMYCactivation by either native or heterologous enhancers and demonstrate that this limitation is bypassed by 3’ rearrangements that removePVT1from its position inciswith the rearrangedMYCgene.

Key points

CRISPR-interference screens identify a conserved germinal center B cellMYCenhancer that is essential for GCB-DLBCL lackingMYCrearrangements.

Functional profiling ofMYCpartner loci reveals principles ofMYCenhancer-hijacking activation by non-immunoglobulin rearrangements.
Richness and density jointly determine context dependence in bacterial interactions
Authors: Dooley Keven D. , Bergelson Joy
Published: May 2023

Pairwise interactions are often used to predict features of complex microbial communities due to the challenge of measuring multi-species interactions in high dimensional contexts. This assumes that interactions are unaffected by community context. Here, we used synthetic bacterial communities to investigate that assumption by observing how interactions varied across contexts. Interactions were most often weakly negative and showed clear phylogenetic signal. Community richness and total density emerged as strong predictors of interaction strength and contributed to an attenuation of interactions as richness increased. Population level and per-capita measures of interactions both displayed such attenuation, suggesting factors beyond systematic changes in population size were involved; namely, changes to the interactions themselves. Nevertheless, pairwise interactions retained some predictive value across contexts, provided those contexts were not substantially diverged in richness. These results suggest that understanding the emergent properties of microbial interactions can improve our ability to predict features of microbial communities.
Discovery and characterization of highly potent and selective covalent inhibitors of SARS-CoV-2 PLpro
Authors: Wu Jian , Vaid Tasneem M. , Kim Hoshin , Lu Jun , Demissie Robel , Lee Hyun , Fung Leslie W.-M. , Chen Jia , Xi Chenghao , Yang Zhezhou , Huang Yu , Zhang Zhantao , Zhang Jingqing , Yan Fengfeng , Johnson Michael E. , Li Min
Published: May 2023

Coronavirus infections, such as the global COVID-19 pandemic, have had a profound impact on many aspects of our daily life including working style, economy, and the healthcare system. To prevent the rapid viral transmission and speed up recovery from the infection, many academic organizations and industry research labs have conducted extensive research on discovering new therapeutic options for SARS-CoV-2. Among those efforts, RNA-dependent RNA polymerase (RdRp) inhibitors such as Remdesivir, Molnupiravir and 3CLpro inhibitor such as Nirmatrelvir (Paxlovid™) have been widely used as the therapeutic options. Given the recent emergence of several new variants that caused a resurgence of the virus, it would be beneficial to discover more diverse therapeutic options with novel anti-viral mechanisms. In this regard, PLpro has been highlighted since it, along with 3CLpro, is one of the two most important proteases that are required for SARS-CoV-2 viral processing. While 3CLpro inhibitors were extensively investigated in the light of Emergency Use Authorizations of Nirmatrelvir, PLpro inhibitors have not been thoroughly investigated even preclinically. Thus, discovery efforts on antivirals acting against PLpro will be valuable. PLpro inhibitors may exert their activity by inhibiting viral replication and enhancing the host defense system through blocking virus-induced cell signaling events for evading host immune response. In this study, we report the discovery and development of two covalent irreversible PLpro inhibitors, HUP0109 and its deuterated analog DX-027, out of our quest for novel anti-COVID 19 therapeutic agents for the past two and half years. HUP0109 selectively targets the viral catalytic cleft of PLpro and covalently modifies its active site cysteine residue (C111). Promising results from preclinical evaluation suggest that DX-027 can be developed as a potential COVID-19 treatment.
Integrating gene mutation spectra from tumors and the general population with gene expression topological networks to identify novel cancer driver genes
Authors: He Dan , Li Ling , Lu Zhiya , Li Shaoying , Lan Tianjun , Liu Feiyi , Zhang Huasong , Lei Bingxi , Cooper David N. , Zhao Huiying
Published: May 2023

Background

Understanding the genetics underlying cancer development and progression is the most important goal of biomedical research to improve patient survival rates. Recently, researchers have proposed computationally combining the mutational burden with biological networks as a novel means to identify cancer driver genes. However, these approaches treated all mutations as having the same functional impact on genes and incorporated gene-gene interaction networks without considering tissue specificity, which may have hampered our ability to identify novel cancer drivers.

Methods

We have developed a framework, DGAT-cancer that integrates the predicted pathogenicity of somatic mutation in cancers and germline variants in the healthy population, with topological networks of gene expression in tumor tissues, and the gene expression levels in tumor and paracancerous tissues in predicting cancer drivers. These features were filtered by an unsupervised approach, Laplacian selection, and those selected were combined by Hotelling and Box-Cox transformations to score genes. Finally, the scored genes were subjected to Gibbs sampling to determine the probability that a given gene is a cancer driver.

Results

This method was applied to nine types of cancer, and achieved the best area under the precision-recall curve compared to three commonly used methods, leading to the identification of 571 novel cancer drivers. One of the top genes,EEF1A1was experimentally confirmed as a cancer driver of glioma. Knockdown ofEEF1A1led to a ~ 41-50% decrease in glioma size and improved the temozolomide sensitivity of glioma cells.

Conclusion

By combining the pathogenic status of mutational spectra in tumors alongside the spectrum of variation in the healthy population, with gene expression in both tumors and paracancerous tissues, DGAT-cancer has significantly improved our ability to detect novel cancer driver genes.
Building Trust in Deep Learning-based Immune Response Predictors with Interpretable Explanations
Authors: Borole Piyush , Rajan Ajitha
Published: May 2023

The ability to predict whether a peptide will get presented on Major Histocompatibility Complex (MHC) class I molecules has profound implications in designing vaccines. Numerous deep learning-based predictors for peptide presentation on MHC class I molecules exist with high levels of accuracy. However, these MHC class I predictors are treated as black-box functions, providing little insight into their decision making. To build turst in these predictors, it is crucial to understand the rationale behind their decisions with human-interpretable explanations. We present MHCXAI, eXplainable AI (XAI) techniques to help interpret the outputs from MHC class I predictors in terms of input peptide features. In our experiments, we explain the outputs of four state-of-the-art MHC class I predictors over a large dataset of peptides and MHC alleles. Additionally, we evaluate the reliability of the explanations by comparing against ground truth and checking their robustness. MHCXAI seeks to increase understanding of deep learning-based predictors in the immune response domain and build trust with validated explanations
Emergent cooperative behavior in transient compartments
Authors: Arenzon Jeferson J. , Peliti Luca
Published: May 2023

We introduce a minimal model of multilevel selection on structured populations, considering the interplay between game theory and population dynamics. Through a bottleneck process, finite groups are formed with cooperators and defectors sampled from an infinite pool. After the fragmentation, these transient compartments grow until the carrying capacity is attained. Eventually, all compartments are merged, well mixed and the whole process is repeated. We show that cooperators, even if interacting only through mean-field intra-group interactions that favor defectors, may perform well because of the inter-group competition and the size diversity among the compartments. These cycles of isolation and coalescence may therefore be important in maintaining diversity among different species or strategies and may help to understand the underlying mechanisms of the scaffolding processes in the transition to multicellularity.
Evaluation of Expanded 2-Aminobenzothiazole Library for Inhibition ofPseudomonas aeruginosaVirulence Phenotypes
Authors: Fihn Conrad A. , Lembke Hannah K. , Gaulin Jeffrey , Bouchard Patricia , Villarreal Alex R. , Penningroth Mitchell R. , Crone Kathryn K. , Vogt Grace A. , Gilbertsen Adam J. , Ayotte Yann , Couthino de Oliveira Luciana , Serrano-Wu Michael H. , Drouin Nathalie , Hung Deborah T. , Hunter Ryan C. , Carlson Erin E.
Published: May 2023

Bacterial resistance to antibiotics is a rapidly increasing threat to human health. New strategies to combat resistant organisms are desperately needed. One potential avenue is targeting two-component systems, which are the main bacterial signal transduction pathways used to regulate development, metabolism, virulence, and antibiotic resistance. These systems consist of a homodimeric membrane-bound sensor histidine kinase, and a cognate effector, the response regulator. The high sequence conservation in the catalytic and adenosine triphosphate-binding (CA) domain of histidine kinases and their essential role in bacterial signal transduction could enable broad-spectrum antibacterial activity. Through this signal transduction, histidine kinases regulate multiple virulence mechanisms including toxin production, immune evasion, and antibiotic resistance. Targeting virulence, as opposed to development of bactericidal compounds, could reduce evolutionary pressure for acquired resistance. Additionally, compounds targeting the CA domain have the potential to impair multiple two-component systems that regulate virulence in one or more pathogens. We conducted structure-activity relationship studies of 2-aminobenzothiazole-based inhibitors designed to target the CA domain of histidine kinases. We found these compounds have anti-virulence activities inPseudomonas aeruginosa, reducing motility phenotypes and toxin production associated with the pathogenic functions of this bacterium.
Evolution and genetics of accessory gland transcriptome divergence betweenDrosophila melanogasterand D.simulans
Authors: Majane Alex C. , Cridland Julie M. , Begun David J.
Published: May 2023

Studies of allele-specific expression in interspecific hybrids have provided important insights into gene-regulatory divergence and hybrid incompatibilities. Many such investigations in Drosophila have used transcriptome data from whole animals or gonads, however, regulatory divergence may vary widely among species, sex, and tissues. Thus, we lack sufficiently broad sampling of tissues to be confident about the general principles of regulatory divergence. Here we seek to fill some of these gaps in the literature by characterizing regulatory evolution and hybrid misexpression in a somatic male sex organ, the accessory gland, in F1 hybrids betweenDrosophila melanogasterandD. simulans.The accessory gland produces seminal fluid proteins, which play an important role in male and female fertility and may be subject to adaptive divergence due to male-male or male-female interactions. We find thattransdifferences are relatively more abundant thancis, in contrast to most of the interspecific hybrid literature, though large effect-sizetransdifferences are rare. Seminal fluid protein genes have significantly elevated levels of expression divergence and tend to be regulated through bothcisandtransdivergence. We find limited misexpression in this organ compared to other Drosophila studies. As in previous studies, male-biased genes are overrepresented among misexpressed genes and are much more likely to be underexpressed. ATAC-Seq data show that chromatin accessibility is correlated with expression differences among species and hybrid allele-specific expression. This work identifies unique regulatory evolution and hybrid misexpression properties of the accessory gland and suggests the importance of tissue-specific allele-specific expression studies.
Generation Z, tourism and hospitality: the legacy of COVID-19
Authors: Morrone Domenico , Tarulli Annunziata , Silvestri Raffaele , Santovito Savino
Published: May 2023

Purpose

As Generation Z (Gen Z) represents one of the most important segments in the travel and tourism sector, the present work aims to analyse Gen Z's behaviour in a post-pandemic scenario. In particular, the present work deepens the factors that may influence future accommodation choices.

Design/methodology/approach

This study uses data from a web-based questionnaire targeting Italian tourists belonging to Generation Z, reaching 221 complete responses. After the statistical analysis of the sample, an exploratory factor analysis (EFA) was then carried out.

Findings

Data provided evidence about the main factors affecting Gen Z tourist choices. In particular, these young consumers are positively influenced by the information (especially from institutional and verifiable sources), more flexible purchase terms (e.g. full refund in case of cancellation due to contagion of the coronavirus disease 2019 (COVID-19) and digital payments) and structure features (e.g. cleanliness, sanitisation, digitalisation and sustainability).

Originality/value

This work attempts to contribute to the academic literature by looking at the tourism experience from Gen Z's perspective. From this angle, this work underlines the influence some factors exert on the final accommodation choice, especially in the presence of exogenous events. Moreover, as this study focusses on a post-pandemic scenario, the study seeks to provide valuable indications, both at the theoretical and managerial level, for the tourism sector to boost the sector's recovery and prepare the sector to face similar events.
The dark side of high-performance work systems and self-sacrificial leadership: an empirical examination
Authors: Bai Peipei , Heidarian Ghaleh Hossein , Chang Huikun , Li Longzhen , Pak Jongwook
Published: May 2023

Purpose

The study aims to offer a nuanced, fine-grained understanding of how the relationship between high-performance work systems (HPWSs) and negative employee outcomes can be attenuated under self-sacrificial leadership (SSL).

Design/methodology/approach

Hierarchical linear modeling (HLM) was used to test the proposed multilevel model on a sample of 37 first-line managers (FLMs) and 209 employees working in a large Chinese company.

Findings

The results showed that HPWS is positively related to emotional exhaustion and turnover intention. Most conspicuously, the authors found that such adverse effects of HPWS are mitigated with a high level of SSL.

Practical implications

The dark side of HPWS can be alleviated if practitioners complement their practices with sufficient support for employees. Particularly, FLMs who exhibit subordinate-serving attitudes consider followers' well-being and provide them with resources can lessen the high pressure of HPWS in pursuit of performance enhancement.

Originality/value

Prior studies on the relationships between HPWS and employee outcomes have produced somewhat mixed results. This study extended the current discourse by explicating instead why HPWS could potentially impair employee outcomes and how the negative effects of HPWS can be mitigated under positive leader behaviors.
How does restaurant experienscape affect solo diners' emotions and dining satisfaction in Korea?
Authors: Im Soo Yeon , Seo Sunhee
Published: May 2023

Purpose

This study aims to explore the role of restaurant experienscape in affecting diners' emotions and satisfaction with solo dining, considering the moderating role of solo dining willingness and public self-consciousness (PSC).

Design/methodology/approach

In total, 403 Korean customers who had dined alone at restaurants in the past three months participated in this study. Structural equation modeling, including multiple group analysis, was conducted to examine the hypotheses.

Findings

The dining atmosphere influenced solo diners' positive emotions but not their negative emotions. Responses from other guests and the interactional fairness of employees affected solo diners' negative emotions but not their positive emotions. Food sensory influences both positive and negative emotions. This study found that PSC significantly moderated the effect of the dining atmosphere on positive emotions, and solo dining willingness significantly moderated the impact of food sensory on positive emotions.

Practical implications

This study suggests that restaurant managers should pay close attention to providing fair service to all customers by training and educating employees because the unfair treatment that solo diners receive from employees affects focal customers' negative emotions.

Originality/value

The experienscape model was applied to the solo dining context based on Mehrabian and Russell's (1974) stimulus–organism–response paradigm and Pizam and Tasci's (2019) experienscape concept, which reflects the growing trend in solo dining.
Virtual communication adoption by educational leaders: moderating role of perceived risk and benefits
Authors: Gupta Saurabh , Mathur Nidhi
Published: May 2023

Purpose

The objective of this study was to analyse the effects of major determinants on VCT adoption intention among higher educational leaders. Also, this study aims to investigate how perceived risk and perceived benefits influence the educational leaders, VCT actual use intention.

Design/methodology/approach

The authors used the online survey method to collect the 440 responses through purposive sampling procedure. Structural equation modelling (SEM) technique and Multi Group Analysis procedure were used to test the proposed model and moderating effects.

Findings

The findings revealed that all the four determinants (PE, EE, SI and FC) based on UTAUT model have positive and significant effects on intention to use VCT. Besides this there is a significant and positive effect of intention to use VCT on actual usage of VCT by the educational leaders. The moderating effect of perceived risk and perceived benefits on actual usage of virtual communication also found significant.

Research limitations/implications

This paper makes its contribution to the literature related to virtual communication technology adoption by including two moderator variables (perceived risk and benefits) that are expected to affect educational leaders' actual usage of VCT. The results can also help researchers and practitioners better understanding the factors that influence higher educational leaders to adopt VCT.

Originality/value

This study proposed a model incorporating the perceived risk and perceived benefits in the UTAUT model to predict the actual use of VCT. The study endeavours to investigate the moderating effects of perceived risk and perceived benefits between ITUVCT and AUVCT in Indian educational context.
Application of microcredentials to validate human capabilities in a large telecommunications organisation: strategic transformation to a future-ready workforce
Authors: Bowles Marcus , Brooks Benjamin , Curnin Steven , Anderson Helen
Published: May 2023

Purpose

The value of transverse skills, including human capabilities, has been acknowledged for a significant period of time by major organisations such as UNESCO and the World Economic Forum. This paper reports on the application of microcredentials linked to the Human Capability Framework in a major telecommunications organisation that has a vision to establish a baseline to develop the levels of capability for both individual employees and the entire workforce. In this case study, capability is evidenced through learning and applied performance specified in a microcredential that carries a credit-entry score into higher education qualifications. The value of the microcredentials lies not in recognising learning outcomes; rather, it lies in an individual's ability to validate their full potential, open sustainable employment opportunities and prepare for emergent new roles.

Design/methodology/approach

This commentary offers a case study of how a major Australian telecommunications organisation implemented microcredentials that are aligned to the Human Capability Framework Standards reference model.

Findings

The approach in this case study demonstrates how a company that confidently invests in non-traditional learning approaches that increase the value of human capital can tangibly grow the capacity of the workforce to deliver not only its strategy but also its cultural values.

Originality/value

The multi-award-winning model described in this case study is novel and clearly informs current research and thinking addressing this topic.