bluuebunny/crossref_metadata_2025 huggingface dataset:
Laparoscopic Ventral Mesh Rectopexy (LVMR) for Internal and External Rectal Prolapse: An Analysis of 122 Consecutive Patients
Authors: Shin Jae-Won , Hong Kwang-Dae , Lee Doo-Han , Kim Do-Sun , Lee Doo-Seok
Published: February 2021

Background:

Even though several reports have been published on the results of laparoscopic ventral mesh rectopexy (LVMR) in Asia, there are few mid-term or long-term results of LVMR. The authors aimed to evaluate the results of LVMR in patients with internal rectal prolapse (IRP) external rectal prolapse (ERP).

Materials and Methods:

From September 2013 to January 2019, 122 patients with IRP (n=48) or ERP (n=74) underwent LVMR. Constipation and fecal incontinence (FI) scores were evaluated using the Cleveland Clinic Florida score preoperatively and postoperatively. The questionnaire for the change of obstructed defecation or FI symptoms after surgery was also administered to grade the results as cured, improved, unchanged, or worsened for each survey.

Results:

The mean age of the patients was 61.9 years. The mean operation time was 116.5 minutes, and the mean hospital stay was 5.1 days. The mean follow-up was 42.1 months. There were no mesh-related complications. Eight patients (10.7%) among the ERP group required additional surgery for recurrent full-thickness prolapse. Eleven patients (14.7%) who had mucosal prolapse within 2 cm underwent stapled hemorrhoidopexy after LVMR. In the postoperative 6-month period, the overall constipation score (7.12) significantly improved compared with the preoperative score (13.03) (P<0.001), whereas the FI score significantly improved after surgery (12.16 to 8.92; P<0.001).

Conclusion:

LVMR is a feasible and safe technique and favorable recurrence for ERP. Functional outcomes of obstructed defecation and FI were improved and the satisfaction of LVMR was high after the surgery. LVMR can be considered a recommended surgical option to treat ERP and IRP.
Endoscopic Vacuum Therapy (EVT) for Persistent Duodenal Stump Dehiscence After Upper Gastrointestinal Surgery in Selected Patients: A Tertiary Referral Center Case Series
Authors: Mutignani Massimiliano , Dioscoridi Lorenzo , Massad Mutaz , Bonato Giulia , Pugliese Francesco , Cintolo Marcello , Forti Edoardo
Published: February 2021

Introduction:

The usefulness of endoscopic vacuum therapy (EVT) in the setting of postoperative gastrointestinal leaks is widely described. On this basis, we would like to focus a specific application of EVT: the dehiscence of the duodenal stump after upper gastrointestinal surgery. Standard EVT is not applicable in these cases because of technical limitations (length of overtube and devices). However, vacuum stimulates the healing of leaks and fistulas through granulation tissue’s formation and would be effective also in this setting.

Materials and Methods:

Between October 2019 and January 2020, 7 consecutive patients (4 M, 3 F, 62±9 y old) affected by duodenal stump’s dehiscence were endoscopically treated by the placement of a large-bore (14 to 18 Ch) suction tube across the wall’s defect into the peritoneal cavity. Continuous aspiration at −80/−100 mm Hg was applied. Clinical success was established both by fluoroscopic check injecting contrast medium from the tube to verify the fistula’s closure and by abdominal computed tomography scan to exclude residual fluid collections.

Results:

Technical and clinical success were achieved in all the patients. The suction tube was maintained in site for 12±5 days in continuous aspiration. The drainage’s output became null in 2±1 days without any intra-abdominal residual fluid collection. The principle of this technique is to let the duodenal walls’ stump to collapse on the intraluminal part of the tube (with subsequent mucosal intussusception into the holes of the tube itself) creating a sort of vacuum-packed barrier to interrupt the outflow of enteric materials into the fistula’s path. It guarantees the fistula’s closure by the gradual formation of granulation tissue.

Conclusions:

The present technique offers a safe and viable endoscopic alternative to treat duodenal stump’s leaks after upper gastrointestinal surgery.
Emerging carbapenem-resistant Klebsiella pneumoniae sequence type 16 causing multiple outbreaks in a tertiary hospital in southern Vietnam
Authors: Nguyen To Nguyen Thi , Nguyen Phuong Luong Nha , Le Ngan Thi Quynh , Nguyen Lan Phu Huong , Duong Thuy Bich , Ho Nghia Dang Trung , Nguyen Quynh Pham Nhu , Pham Trung Duc , Tran Anh Tuan , The Hao Chung , Nguyen Hien Huu , Nguyen Chau Van Vinh , Thwaites Guy E. , Rabaa Maia A. , Pham Duy Thanh
Published: February 2021

The emergence of carbapenem resistance in

Klebsiella pneumoniae

represents a major global public health concern. Nosocomial outbreaks caused by multidrug-resistant

K. pneumoniae

are commonly reported to result in high morbidity and mortality due to limited treatment options. Between October 2019 and January 2020, two concurrent high-mortality nosocomial outbreaks occurred in a referral hospital in Ho Chi Minh City, Vietnam. We performed genome sequencing and phylogenetic analysis of eight

K. pneumoniae

isolates from infected patients and two environmental isolates for outbreak investigation. We identified two outbreaks caused by two distinct lineages of the international sequence type (ST) 16 clone, which displayed extensive drug resistance, including resistance to carbapenem and colistin. Carbapenem-resistant ST16 outbreak strains clustered tightly with previously described ST16

K. pneumoniae

from other hospitals in Vietnam, suggesting local persistence and transmission of this particular clone in this setting. We found environmental isolates from a hospital bed and blood pressure cuff that were genetically linked to an outbreak case cluster, confirming the potential of high-touch surfaces as sources for nosocomial spread of

K. pneumoniae

. Further, we found colistin resistance caused by disruption of the mgrB gene by an ISL3-like element, and carbapenem resistance mediated by a transferable IncF/bla
OXA-181 plasmid carrying the ISL3-like element. Our study highlights the importance of coordinated efforts between clinical and molecular microbiologists and infection control teams to rapidly identify, investigate and contain nosocomial outbreaks. Routine surveillance with advanced sequencing technology should be implemented to strengthen hospital infection control and prevention measures.
Epidemiological analysis of pneumococcal strains isolated at Yangon Children’s Hospital in Myanmar via whole-genome sequencing-based methods
Authors: Yamaguchi Masaya , Win Hpoo Pwint Myo , Higashi Kotaro , Ono Masayuki , Hirose Yujiro , Motooka Daisuke , Okuzaki Daisuke , Aye Mya Mya , Htun Moh Moh , Thu Hlaing Myat , Kawabata Shigetada
Published: February 2021

Streptococcus pneumoniae

causes over one million deaths from lower respiratory infections per annum worldwide. Although mortality is very high in Southeast Asian countries, molecular epidemiological information remains unavailable for some countries. In this study, we report, for the first time, the whole-genome sequences and genetic profiles of pneumococcal strains isolated in Myanmar. We isolated 60 streptococcal strains from 300 children with acute respiratory infection at Yangon Children’s Hospital in Myanmar. We obtained whole-genome sequences and identified the species, serotypes, sequence types, antimicrobial resistance (AMR) profiles, virulence factor profiles and pangenome structure using sequencing-based analysis. Average nucleotide identity analysis indicated that 58 strains were

S. pneumoniae

and the other 2 strains were

Streptococcus mitis

. The major serotype was 19F (11 strains), followed by 6E (6B genetic variant; 7 strains) and 15 other serotypes; 5 untypable strains were also detected. Multilocus sequence typing analysis revealed 39 different sequence types, including 11 novel ones. In addition, genetic profiling indicated that AMR genes and mutations spread among pneumococcal strains in Myanmar. A minimum inhibitory concentration assay indicated that several pneumococcal strains had acquired azithromycin and tetracycline resistance, whereas no strains were found to be resistant against levofloxacin and high-dose penicillin G. Phylogenetic and pangenome analysis showed various pneumococcal lineages and that the pneumococcal strains contain a rich and mobile gene pool, providing them with the ability to adapt to selective pressures. This molecular epidemiological information can help in tracking global infection and supporting AMR control in addition to public health interventions in Myanmar.
Detection of cytosine methylation in Burkholderia cenocepacia by single-molecule real-time sequencing and whole-genome bisulfite sequencing
Authors: Vandenbussche Ian , Sass Andrea , Van Nieuwerburgh Filip , Pinto-Carbó Marta , Mannweiler Olga , Eberl Leo , Coenye Tom
Published: February 2021

Research on prokaryotic epigenetics, the study of heritable changes in gene expression independent of sequence changes, led to the identification of DNA methylation as a versatile regulator of diverse cellular processes. Methylation of adenine bases is often linked to regulation of gene expression in bacteria, but cytosine methylation is also frequently observed. In this study, we present a complete overview of the cytosine methylome in

Burkholderia cenocepacia

, an opportunistic respiratory pathogen in cystic fibrosis patients. Single-molecule real-time (SMRT) sequencing was used to map all 4mC-modified cytosines, as analysis of the predicted MTases in the

B. cenocepacia

genome revealed the presence of a 4mC-specific phage MTase, M.BceJII, targeting GGCC sequences. Methylation motif GCGGCCGC was identified, and out of 6850 motifs detected across the genome, 2051 (29.9 %) were methylated at the fifth position. Whole-genome bisulfite sequencing (WGBS) was performed to map 5mC methylation and 1635 5mC-modified cytosines were identified in CpG motifs. A comparison of the genomic positions of the modified bases called by each method revealed no overlap, which confirmed the authenticity of the detected 4mC and 5mC methylation by SMRT sequencing and WGBS, respectively. Large inter-strain variation of the 4mC-methylated cytosines was observed when

B. cenocepacia

strains J2315 and K56-2 were compared, which suggests that GGCC methylation patterns in

B. cenocepacia

are strain-specific. It seems likely that 4mC methylation of GGCC is not involved in regulation of gene expression but rather is a remnant of bacteriophage invasion, in which methylation of the phage genome was crucial for protection against restriction-modification systems of

B. cenocepacia

.
Synchronizability predicts effective responsive neurostimulation for epilepsy prior to treatment
Authors: Scheid Brittany H. , Bernabei John M. , Khambhati Ankit N. , Jeschke Jay , Bassett Danielle S. , Becker Danielle , Davis Kathryn A. , Lucas Tim , Doyle Werner , Chang Edward F. , Friedman Daniel , Rao Vikram R. , Litt Brian
Published: February 2021

Despite the success of responsive neurostimulation (RNS) for epilepsy, clinical outcomes vary significantly and are hard to predict. The ability to forecast clinical response to RNS therapy before device implantation would improve patient selection for RNS surgery and could prevent a costly and ineffective intervention. Determining and validating biomarkers predictive of RNS response is difficult, however, due to the heterogeneity of the RNS patient population and clinical procedures; large, multi-center datasets are needed to quantify patient variability and to account for stereotypy in the treatment paradigm of any one center. Here we use a distributed, cloud-based pipeline to analyze a federated dataset of intracranial EEG recordings, collected prior to RNS surgery, from a retrospective cohort of 30 patients across three major epilepsy centers. Based on recent work modelling the controllability of distributed brain networks, we hypothesize that broader brain network connectivity, beyond the seizure onset zone, can predict RNS response. We demonstrate how intracranial EEG recordings can be leveraged through network analysis to uncover biomarkers that predict response to RNS therapy. Our findings suggest that peri-ictal changes in synchronizability, a global network metric shown to accurately predict outcome from resective epilepsy surgery, can distinguish between good and poor RNS responders under the current RNS therapy guidelines (area under the receiver operating characteristic curve of 0.75). Furthermore, this study also provides a proof-of-concept roadmap for multicenter collaboration where practical considerations impede sharing datasets fully across centers.
COVID-19 in pregnancy – characteristics and outcomes of pregnant women admitted to hospital because of SARS-CoV-2 infection in the Nordic countries
Authors: Engjom Hilde , Aabakke Anna JM , Klungsøyr Kari , Svanvik Teresia , Äyräs Outi , Jonasdottir Eva , Thurn Lars , Jones Elin , Pettersson Karin , Nyfløt Lill Trine , Al-Zirqi Iqbal , Vangen Siri , Júlíusson Pétur B. , Källén Karin , Gissler Mika , Krebs Lone
Published: February 2021

Introduction

Population-based studies about the consequences of SARS-CoV-2 infection (COVID-19) in pregnancy are few and have limited generalizability to the Nordic population and health care systems.

Material and method

This study examines pregnant women with COVID-19 in the five Nordic countries. Pregnant women were included if they were admitted to hospital between March 1 and June 30, 2020 and had a positive SARS-CoV-2 PCR test 14 days or fewer prior to the admission. Cause of admission was classified as obstetric or COVID-19 related.

Results

In the study areas, 214 pregnant women with a positive test were admitted to hospital, of which 56 women needed hospital care due to COVID-19. The rate of admission due to COVID-19 was 0.4 per 1000 deliveries in Denmark, Finland, and Norway and 3.8 per 1000 deliveries in the Swedish regions. Women hospitalized because of COVID-19 were more frequently obese (P< 0.001) and had migrant background (P< 0.001) compared to the total population of women who delivered in 2018. Twelve women (21.4%) needed intensive care. Preterm delivery (n=12, 25%,P< 0.001) and cesarean delivery (n=21, 43,8%,P< 0.001) were more frequent in women with COVID-19 compared to the women who delivered in 2018. No maternal deaths, stillbirths or neonatal deaths were reported.

Conclusions

The risk of admission due to severe COVID-19 disease in pregnancy was low in the Nordic countries. A fifth of the women required intensive care and we observed higher rates of preterm and cesarean deliveries. National public health policies appear to have had an impact on the rates of admission due to severe COVID-19 disease in pregnancy. Nordic collaboration is important in collecting robust data and assessing rare outcomes.

Key Message

Risk of hospital admission due to COVID-19 infection among pregnant women was low in the Nordic countries, but varied between the countries, which is most likely related to different national public health strategies.
Expression of ACE2 receptor, soluble ACE2, Angiotensin I, Angiotensin II and Angiotensin (1-7), is modulated in COVID-19 patients
Authors: Osman Ikram Omar , Melenotte Cléa , Brouqui Philippe , Million Matthieu , Lagier Jean-Christophe , Parola Philippe , Stein Andréas , Scola Bernard La , Meddeb Line , Mege Jean-Louis , Raoult Didier , DEvaux Christian A.
Published: February 2021

Although SARS-CoV-2 is primarily a pulmonary-tropic virus, it is nonetheless responsible for multi-organ failure in patients with severe forms of COVID-19, particularly those with hypertension or cardiovascular disease. Infection requires virus binding to the angiotensin I converting enzyme 2 (ACE2) monocarboxypeptidase, a regulator of blood pressure homeostasis through its ability to catalyze the proteolysis of Angiotensin II (AngII) into Ang(1-7). Although assumed, it had not been proven so far whether the SARS-CoV-2 replication in COVID-19 patients could modulate the expression of the ACE2 receptor and/or the AngII plasma levels. We demonstrate here, that in COVID-19 patients the ACE2 mRNA expression is markedly reduced in circulating blood cells. This ACE2 gene dysregulation mainly affects the monocytes which also show a lower expression of membrane ACE2 protein. Moreover, a significant decrease in soluble ACE2 plasma levels is observed in COVID-19 patients, whereas the concentration of sACE2 returns to normal levels in patients recovered from COVID-19. In the plasma of COVID-19 patients, we also found an increase in AngI and AngII. On the other hand, the plasma levels of Ang(1-7) remains almost stable in COVID-19 patients. Despite the Ang(1-7) presence in the plasma of COVID-19 patients it seems insufficient to prevent the effects of massive AngII accumulation. These are the first direct evidence that the SARS-CoV-2 may affect the expression of blood pressure regulators with possible harmful consequences on COVID-19 outcome.
Population-Based Study of anti-SARS-CoV-2, Social Distancing and Government Responses in Joinville, Brazil
Authors: Diegoli Henrique , Conzatti Vivianne Samara , Mazin Suleimy Cristina , Safanelli Juliana , Chiaradia Dellatorre Louise Domenguini , Bett Keli , Radtke Roselaine Elisa , Wollmann Giulia Murillo , Lima Helbert do Nascimento , de França Paulo Henrique Condeixa , da Silva Jean Rodrigues
Published: February 2021

Background

The city of Joinville had been mildly affected by the COVID-19 pandemic until June 2020. This study aimed to longitudinally assess the prevalence of exposure to the virus and social distancing practices in the local population.

Methods

A randomized selection of households stratified by region was created. From June 15 to August 7, 2020, a dweller was randomized in each household, answered a questionnaire, and performed a test for the detection of SARS-CoV-2 antibodies. The prevalence of positive tests was calculated for each week and adjusted for the test’s sensitivity and specificity.

Results

The adjusted proportion of positive results increased from 1.4% in the first week (margin of error [ME] 0% to 2.87%) to 13.38% in the eighth week (ME 10.22% to 16.54%). Among the 213 participants that tested positive, 55 (25.82%) were asymptomatic. Only 37 (17.37%) sought medical consultation for any symptom. Among the 77 (36.15%) that were leaving home to work or study, only 18 (23.38%) stopped due to any symptom. The proportion that referred going to bars, restaurants, or making non-essential shopping decreased from 20.56% in the first week to 8.61% during the peak of diagnoses.

Conclusion

The low proportion of participants that sought medical consultation or stopped leaving home indicates strategies directed to isolate only those symptomatic reach a low proportion of infected patients.
Contractile cell apoptosis regulates airway smooth muscle remodeling in asthma
Authors: Fraga-Iriso Rebeca , Amor-Carro Óscar , Brienza Nadia S. , Núñez-Naveira Laura , Lema-Costa Beatriz , González-Barcala Francisco Javier , Bazús-González Teresa , Montero-Martínez Carmen , López-Viña Antolín , Torrego Alfons , Plaza Vicente , Martínez-Rivera Carlos , Hamid Qutayba , Martin James G. , Berger Patrick , Ramos-Barbón David
Published: February 2021

Rationale

Investigations on the mechanisms of airway smooth muscle remodeling, a prominent asthma feature contributing to its clinical manifestations and severity, have largely focused on its hyperplastic growth. Conversely, limited data and virtually no translational research have been produced on a plausible role of apoptosis in the homeostasis and remodeling of airway smooth muscle.

Objectives

We aimed at demonstrating an involvement of apoptosis, an essential regulator of organ structure and cell turnover, in the pathophysiology of airway smooth muscle remodeling in asthma.

Methods

Murine experimental asthma was modeled to analyze airway hyperresponsiveness, contractile tissue remodeling and apoptosis detection outcomes at early and late cutoffs, and under pharmacological inhibition of apoptosis by employing a caspase blocker. Clinical investigation followed through analyses on human bronchial biopsies.

Results

Airway hyperresponsiveness and contractile tissue remodeling were already established in early experimental asthma, and a subsequent upregulation of apoptosis limited the airway contractile tissue growth. Caspase inhibition elicited chaotic pulmonary mechanics and an unusual growth of airway smooth muscle that was structurally disorganized. In bronchial biopsies, airway smooth muscle increased from controls through subjects with intermittent and persistent moderate and severe asthma. Cleaved poly-ADP ribose polymerase (c-PARP, a byproduct of caspase activity) was increased in severe asthma.

Conclusions

Apoptosis is involved in airway contractile cell turnover and in shaping the size, structure and proper function of the airway smooth muscle layer. Apoptosis inhibitors may complicate concomitant asthma, whereas agents favouring airway contractile cell apoptosis may provide a novel pipeline of therapeutic development.

Key messages

How normal airway smooth muscle structure is preserved, and whether counteracting responses to remodeling are elicited in asthma, are outstanding questions not probed in vivo nor in the clinical setting.

In this work, combined investigations on murine experimental asthma and human bronchial biopsies show that airway contractile cell apoptosis is involved in the homeostasis of airway smooth muscle, and apoptotic activity is upregulated as part of the remodeling process of this tissue in asthma.

Apoptosis arises as a key regulator of the size and structure of the airway smooth muscle layer. This concept draws implications for clinical practice and drug development.
Novel SARS-CoV-2 spike variant identified through viral genome sequencing of the pediatric Washington D.C. COVID-19 outbreak
Authors: LoTempio Jonathan , Billings Erik , Draper Kyah , Ralph Christal , Moshgriz Mahdi , Duong Nhat , Bard Jennifer Dien , Gai Xiaowu , Wessel David , DeBiasi Roberta L. , Campos Joseph M. , Vilain Eric , Delaney Meghan , Michael Drew G.
Published: February 2021

The SARS-CoV-2 virus has emerged as a global pandemic, severely impacting everyday life. Significant resources have been dedicated towards profiling the viral genome in the adult population. We present an analysis of viral genomes acquired from pediatric patients presenting to Children’s National Hospital in Washington D.C, including 24 with primary SARS CoV2 infection and 3 with Multisystem Inflammatory Syndrome in Children (MIS-C) undergoing treatment at our facility. Viral genome analysis using next generation sequencing indicated that approximately 81% of the analyzed strains were of the GH clade, 7% of the cases belonged to the GR clade, and 12% of the cases belonged to S, V, or G clades. One sample, acquired from a neonatal patient, presented with the highest viral RNA load of all patients evaluated at our center. Viral sequencing of this sample identified a SARS-CoV-2 spike variant, S:N679S. Analysis of data deposited in the GISAID global database of viral sequences shows the S:N679S variant is present in eight other sequenced samples within the US mid-Atlantic region. The similarity of the regional sequences suggests transmission and persistence of the SARS-CoV-2 variant within the Capitol region, raising the importance of increasing the frequency of SARS-CoV-2 genomic surveillance.

IMPORTANCE

A variant in the SARS-CoV-2 spike protein was identified in a febrile neonate who was hospitalized with COVID-19. This patient exhibited the highest viral RNA load of any COVID-19 patient tested at our center. Viral sequencing identified a spike protein variant, S:N679S, which is proximal to the cleavage site at residue 681. The SARS-CoV-2 surface spike is a protein trimer (three subunits) which serves as the key target for antibody therapies and vaccine development. Study of viral sequences from the GISAID database revealed eight related sequences from the US mid-Atlantic region. The identification of this variant in a very young patient, its critical location in the spike polyprotein, and the evidence that it has been detected in other patients in our region underscores the need for increased viral sequencing to monitor variant prevalence and emergence, which may have a direct impact on recommended public health measures and vaccination strategies.
Methylation scores for smoking, alcohol consumption, and body mass index and risk of seven types of cancer
Authors: Dugué Pierre-Antoine , Yu Chenglong , Hodge Allison M , Wong Ee Ming , Joo JiHoon E , Jung Chol-Hee , Schmidt Daniel , Makalic Enes , Buchanan Daniel D , Severi Gianluca , English Dallas R , Hopper John L , Milne Roger L , Giles Graham G , Southey Melissa C
Published: February 2021

Methylation marks of exposure to health risk factors may be useful markers of cancer risk as they might better capture current and past exposures than questionnaires, and reflect different individual responses to exposure. We used data from seven case-control studies nested within the Melbourne Collaborative Cohort Study of blood DNA methylation and risk of colorectal, gastric, kidney, lung, prostate and urothelial cancer, and B-cell lymphoma (N cases=3,123). Methylation scores (MS) for smoking, body mass index (BMI), and alcohol consumption were calculated based on published data as weighted averages of methylation values. Rate ratios (RR) and 95% confidence intervals for association with cancer risk were estimated using conditional logistic regression and expressed per standard deviation increase of the MS, with and without adjustment for health-related confounders. The contribution of MS to discriminate cases from controls was evaluated using the area under the curve (AUC). After confounder adjustment, we observed: large associations (RR∼1.5-1.7) with lung cancer risk for smoking MS; moderate associations (RR∼1.2-1.3) with urothelial cancer risk for smoking MS and with mature B-cell neoplasm risk for BMI and alcohol MS; moderate to small associations (RR∼1.1-1.2) for BMI and alcohol MS with several cancer types and cancer overall. Generally small AUC increases were observed after inclusion of several MS in the same model (colorectal, gastric, kidney, urothelial cancers: +3%; lung cancer: +7%; B-cell neoplasms: +8%). Methylation scores for smoking, BMI, and alcohol consumption show independent associations with cancer risk, and may provide some improvements in risk prediction.
Disruption of nuclear architecture as a cause of COVID-19 induced anosmia
Authors: Zazhytska Marianna , Kodra Albana , Hoagland Daisy A. , Fullard John F. , Shayya Hani , Omer Arina , Firestein Stuart , Gong Qizhi , Canoll Peter D. , Goldman James E. , Roussos Panos , tenOever Benjamin R. , Overdevest Jonathan B. , Lomvardas Stavros
Published: February 2021

Olfaction relies on a coordinated partnership between odorant flow and neuronal communication. Disruption in our ability to detect odors, or anosmia, has emerged as a hallmark symptom of infection with SARS-CoV-2, yet the mechanism behind this abrupt sensory deficit remains elusive. Here, using molecular evaluation of human olfactory epithelium (OE) from subjects succumbing to COVID-19 and a hamster model of SARS-CoV-2 infection, we discovered widespread downregulation of olfactory receptors (ORs) as well as key components of their signaling pathway. OR downregulation likely represents a non-cell autonomous effect, since SARS-CoV-2 detection in OSNs is extremely rare both in human and hamster OEs. A likely explanation for the reduction of OR transcription is the striking reorganization of nuclear architecture observed in the OSN lineage, which disrupts multi-chromosomal compartments regulating OR expression in humans and hamsters. Our experiments uncover a novel molecular mechanism by which a virus with a very selective tropism can elicit persistent transcriptional changes in cells that evade it, contributing to the severity of COVID-19.
Improving germline transmission efficiency in chimeric chickens using a multi-stage injection approach
Authors: Naseri Danial , Dormiani Kianoush , Hajian Mehdi , Jafarpour Farnoosh , Forouzanfar Mahboobeh , Karimi Naeimeh , Nasr-Esfahani Mohammad Hossein
Published: February 2021

Although different strategies have been developed to generate transgenic poultry, low efficiency of germline transgene transmission has remained a challenge in poultry transgenesis. Herein, we developed an efficient germline transgenesis method using a lentiviral vector system in chickens through multiple injections of transgenes into embryos at different stages of development. The embryo chorioallantoic membrane (CAM) vasculature was successfully used as a novel route of gene transfer into germline tissues. We established a new method of eggshell windowing for embryo manipulation at different developmental stages. Compared to the other routes of viral vector administration, the embryo’s bloodstream at Hamburger-Hamilton (HH) stages 14-15 achieved the highest rate of germline transmission (GT), 7.7%. Single injection of viral vectors into the CAM vasculature resulted in a GT efficiency of 2.7%, which was significantly higher than the 0.4% obtained by injection into embryos at the blastoderm stage. Double injection of viral vectors into the bloodstream at HH stages 14-15 and through CAM was the most efficient method for producing germline chimeras, giving a GT rate of 13.6%. The authors suggest that the new method described in this study could be efficiently used to produce transgenic poultry in virus-mediated gene transfer systems.
Archaeal extracellular vesicles are produced in an ESCRT-dependent manner and promote gene transfer and nutrient cycling in extreme environments
Authors: Liu Junfeng , Cvirkaite-Krupovic Virginija , Commere Pierre-Henri , Yang Yunfeng , Zhou Fan , Forterre Patrick , Shen Yulong , Krupovic Mart
Published: February 2021

Membrane-bound extracellular vesicles (EVs), secreted by cells from all three domains of life, transport various molecules and act as agents of intercellular communication in diverse environments. Here we demonstrate that EVs produced by a hyperthermophilic and acidophilic archaeonSulfolobus islandicuscarry not only diverse proteins but also chromosomal and plasmid DNA, and can transfer this DNA to recipient cells. Furthermore, we show that EVs can support the heterotrophic growth ofSulfolobusin minimal medium, implicating EVs in carbon and nitrogen fluxes in extreme environments. Finally, our results suggest that, similar to eukaryotes, production of EVs inS. islandicusdepends on the archaeal ESCRT machinery. Using synchronizedS. islandicuscultures, we show that EV production is linked to cell division and appears to be triggered by increased expression of ESCRT proteins during this cell cycle phase. Using a CRISPR-based knockdown system, we show that archaeal ESCRT-III and AAA+ ATPase Vps4 are required for EV production, whereas archaea-specific component CdvA appears to be dispensable. Collectively, our results suggest that ESCRT-mediated EV biogenesis has deep evolutionary roots, likely predating the divergence of eukaryotes and archaea, and that EVs play an important role in horizontal gene transfer and nutrient cycling in extreme environments.
Wing structure and neural encoding jointly determine sensing strategies in insect flight
Authors: Weber Alison I. , Daniel Thomas L. , Brunton Bingni W.
Published: February 2021

Animals rely on sensory feedback to generate accurate, reliable movements. In many flying insects, strain-sensitive neurons on the wings provide rapid feedback that enables stable flight control. While the impacts of wing structure on aerodynamic performance have been widely studied, the impacts of wing structure on sensing remain unexplored. In this paper, we show how the structural properties of the wing and encoding by mechanosensory neurons interact to jointly determine optimal sensing strategies and performance. Specifically, we examine how neural sensors can be placed effectively over a flapping wing to detect body rotation about different axes, using a computational wing model with varying flexural stiffness inspired by the hawkmothManduca sexta. A small set of mechanosensors, conveying strain information at key locations with a single action potential per wingbeat, permit accurate detection of body rotation. Optimal sensor locations are concentrated at either the wing base or the wing tip, and they transition sharply as a function of both wing stiffness and neural threshold. Moreover, the sensing strategy and performance is robust to both external disturbances and sensor loss. Typically, only five sensors are needed to achieve near-peak accuracy, with a single sensor often providing accuracy well above chance. Our results show that small-amplitude, dynamic signals can be extracted efficiently with spatially and temporally sparse sensors in the context of flight. The demonstrated interaction of wing structure and neural encoding properties points to the importance of their joint evolution.
Prisoner of War dynamics explains the time-dependent pattern of substitution rates in viruses
Authors: Ghafari Mahan , Simmonds Peter , Pybus Oliver G , Katzourakis Aris
Published: February 2021

Molecular clock dating is widely used to estimate timescales of phylogenetic histories and to infer rates at which species evolve. One of the major challenges with inferring rates of molecular evolution is the observation of a strong correlation between estimated rates and the timeframe of their measurements. Recent empirical analysis of virus evolutionary rates suggest that a power-law rate decay best explains the time-dependent pattern of substitution rates and that the same pattern is observed regardless of virus type (e.g.groups I-VII in the Baltimore classification). However there exists no explanation for this trend based on molecular evolutionary mechanisms. We provide a simple predictive mechanistic model of the time-dependent rate phenomenon, incorporating saturation and host constraints on the evolution of some sites. Our model recapitulates the ubiquitous power-law rate decay with a slope of −0.65 (95% HPD: −0.72, −0.52) and can satisfactorily account for the variation in inferred molecular evolutionary rates over a wide range of timeframes. We show that once the saturation of sites starts - typically after hundreds of years in RNA viruses and thousands of years in DNA viruses - standard substitution models fail to correctly estimate divergence times among species, while our model successfully re-creates the observed pattern of rate decay. We apply our model to re-date the diversification of genotypes of hepatitis C virus (HCV) to 396,000 (95% HPD: 326,000 - 425,000) years before present, a time preceding the dispersal of modern humans out of Africa, and also showed that the most recent common ancestor of sarbecoviruses dates back to 23,500 (95% HPD: 21,100 - 25,300) years ago, nearly thirty times older than previous estimates. This not only creates a radical new perspective for our understanding the origins of HCV but also suggests a substantial revision of evolutionary timescales of other viruses can be similarly achieved.
Transformations, Lineage Comparisons, and Analysis of Down to Up Protomer States of Variants of the SARS-CoV-2 Prefusion Spike Protein Including the UK Variant B.1.1.7
Authors: Peters Michael H. , Bastidas Oscar , Kokron Daniel S. , Henze Christopher E.
Published: February 2021

Monitoring and strategic response to variants in SARS-CoV-2 represents a considerable challenge in the current pandemic, as well as potentially future viral outbreaks of similar magnitude. In particular mutations and deletions involving the virion’s prefusion Spike protein have significant potential impact on vaccines and therapeutics that utilize this key structural viral protein in their mitigation strategies. In this study, we have demonstrated how dominant energetic landscape mappings (“glue points”) coupled with sequence alignment information can potentially identify or flag key residue mutations and deletions associated with variants. Surprisingly, we also found excellent homology of stabilizing residue glue points across the lineage ofβcoronavirus Spike proteins, and we have termed this as “sequence homologous glue points”. In general, these flagged residue mutations and/or deletions are then computationally studied in detail using all-atom biocomputational molecular dynamics over approximately one microsecond in order to ascertain structural and energetic changes in the Spike protein associated variants. Specifically, we examined both a theoretically-based triple mutant and the so-called UK or B.1.1.7 variant. For the theoretical triple mutant, we demonstrated through Alanine mutations, which help “unglue” key residue-residue interactions, that these three key stabilizing residues could cause the transition of Down to Up protomer states, where the Up protomer state allows binding of the prefusion Spike protein to hACE2 host cell receptors, whereas the Down state is believed inaccessible. Thus, we are able to demonstrate the importance of glue point residue identification in the overall stability of the prefusion Spike protein. For the B.1.1.7 variant, we demonstrated the critical importance of D614G and N5017 on the structure and binding, respectively, of the Spike protein. Notably, we had previously identified D614 as a key glue point in the inter-protomer stabilization of the Spike protein prior to the emergence of its mutation. The mutant D614G is a structure breaking Glycine mutation demonstrating a relatively more distal Down state RBD and a more stable conformation in general. In addition, we demonstrate that the mutation N501Y may significantly increase the Spike protein binding to hACE2 cell receptors through its interaction with Y41 of hACE2 forming a potentially strong hydrophobic residue binding pair. We note that these two key mutations, D614G and N501Y, are also found in the so-called South African (SA; B.1.351) variant of SARS-CoV-2. Future studies along these lines are, therefore, aimed at mapping glue points to residue mutations and deletions of associated prefusion Spike protein variants in order to help identify and analyze possible “variants of interest” and optimize efforts aimed at the mitigation of this current and future virions.
X-SPEC: a 70 eV to 15 keV undulator beamline for X-ray and electron spectroscopies
Authors: Weinhardt Lothar , Steininger Ralph , Kreikemeyer-Lorenzo Dagmar , Mangold Stefan , Hauschild Dirk , Batchelor David , Spangenberg Thomas , Heske Clemens
Published: February 2021

X-SPEC is a high-flux spectroscopy beamline at the KIT (Karlsruhe Institute of Technology) Synchrotron for electron and X-ray spectroscopy featuring a wide photon energy range. The beamline is equipped with a permanent magnet undulator with two magnetic structures of different period lengths, a focusing variable-line-space plane-grating monochromator, a double-crystal monochromator and three Kirkpatrick–Baez mirror pairs. By selectively moving these elements in or out of the beam, X-SPEC is capable of covering an energy range from 70 eV up to 15 keV. The flux of the beamline is maximized by optimizing the magnetic design of the undulator, minimizing the number of optical elements and optimizing their parameters. The beam can be focused into two experimental stations while maintaining the same spot position throughout the entire energy range. The first experimental station is optimized for measuring solid samples under ultra-high-vacuum conditions, while the second experimental station allows in situ and operando studies under ambient conditions. Measurement techniques include X-ray absorption spectroscopy (XAS), extended X-ray absorption fine structure (EXAFS), photoelectron spectroscopy (PES) and hard X-ray PES (HAXPES), as well as X-ray emission spectroscopy (XES) and resonant inelastic X-ray scattering (RIXS).
Theoretical and experimental investigation of protein crystal nucleation in pores and crevices
Authors: Nanev Christo , Govada Lata , Chayen Naomi E.
Published: February 2021

The nucleation ability of pores is explained using the equilibration between the cohesive energy maintaining the integrity of a crystalline cluster and the destructive energy tending to tear it up. It is shown that to get 3D crystals it is vital to have 2D crystals nucleating in the pores first. By filling the pore orifice, the 2D crystal nuclei are more stable because their peripheries are protected from the destructive action of water molecules. Furthermore, the periphery of the 2D crystal is additionally stabilized as a result of its cohesion with the pore wall. The understanding provided by this study combining theory and experiment will facilitate the design of new nucleants.
Employee development and retention of Generation-Z employees in the post-COVID-19 workplace: a conceptual framework
Authors: Jayathilake Hasaranga Dilshan , Daud Dazmin , Eaw Hooi Cheng , Annuar Nursyamilah
Published: February 2021

Purpose

The purpose of this article is to demonstrate a conceptual framework on employee development, organizational performances and retention of Generation-Z employees in the new normal environment beyond the COVID-19 pandemic.

Design/methodology/approach

With referring to the present literature and utilizing social-exchange and human needs approach, from this study, the authors illustrate a conceptual framework with democratize learning, reverse mentoring and intrepreneurship as key modifications for employee development perspective to retain Generation-Z employees and enhance organizational performance to secure the competitiveness.

Findings

Democratize learning, reverse mentoring and intrapreneurship have a significant potential impact on enhancing Generation-Z employees' development which may effect on attaining better organizational performance and employee retention. In addition, organizational performance may have a moderating effect on employee intention to stay longer.

Research limitations/implications

The proposed conceptual framework would be empirically validated in future research.

Practical implications

Based on the framework, the authors suggest approaches for Generation-Z specific retention strategies on upgrading the employee development subcategory under human resource function in terms of minimizing the disadvantages that are associated with the work from home concept in a post-COVID-19 pandemic era.

Originality/value

One of the very first studies to propose a holistic framework on employee development that subsequently impact on retaining Generation-Z employees in a pandemic situation. This article enriches the human resource management literature by explaining the novel moderating relationship that articulated from organizational performance to employee retention and focussing on Generation-Z employees (younger generation employees).
The effects of bank competition on firm R&D investment: an inverted-U relationship
Authors: Xia Yufeng , Liu Peisen
Published: February 2021

Purpose

Bank financing is an important external financing source for firm research and development (R&D) investment. This study aims to use an exponential quadratic specification to investigate the effect of bank competition on firm R&D investment and its underlying mechanisms. Moreover, this study checks bank competition’s heterogeneous effects on firm R&D investment.

Design/methodology/approach

Based on data of Chinese manufacturing firms and bank branches, this study uses the Tobit estimator, instrumental variable method and Heckman two-step approach to test the relationship between bank competition and firm R&D investment.

Findings

The results show robustness evidence of an inverted-U relationship between bank competition and firm R&D investment. Specifically, increases in bank competition promote firm R&D investment until bank competition reaches the turning point and reduce firm R&D investment after crossing the turning point. Financing costs and financial constraints can explain the inverted-U relationship between bank competition and firm R&D investment. Heterogeneity examinations reveal that R&D investment is more sensitive to bank competition in non-state-owned enterprises, small firms and high-tech firms.

Originality/value

This study contributes to the literature on the relationship between bank competition and firm innovation. The authors investigate the heterogeneity of R&D investment influenced by bank competition and depict the economic effects brought by bank competition. This study sheds light on the real effects of bank competition and the determinants of firm R&D investment in transition economies. The conclusions provide empirical evidence for reducing credit discrimination and improving capital allocation efficiency in developing countries.
Digital communication, value co-creation and customer engagement in business networks: a conceptual matrix and propositions
Authors: Sashi C.M.
Published: February 2021

Purpose

Technological innovations that resulted in the emergence and widespread adoption of digital communication in recent years have led to a surge of academic and practitioner interest in its implications for the co-creation of value and customer engagement. However, in comparison to the attention given to the study of customer engagement in consumer markets, few studies have examined its key role in business markets. This paper aims to examine the impact of digital communication on value co-creation and customer engagement in inter-organizational relationships in business networks.

Design/methodology/approach

Co-creation of value and customer engagement in business networks occurs among interconnected organizations that are partners in intermediate transactions. The paper develops a matrix of inter-organizational engagement among partners in business networks and propositions linking digital communication to value co-creation and inter-organizational engagement.

Findings

The relationships among network organizations may be characterized by the extent of relational exchange and inter-organizational bonds among them. Four types of inter-organizational engagement emerge: transactional partners, loyal partners, trusted partners and engaged partners. The partners co-create value to better satisfy customers.

Research limitations/implications

The paper is an initial attempt to develop a conceptual understanding of customer engagement in business markets and formulate propositions that can be further investigated. Networks of partner organizations co-create value, altering their input and output markets, value addition and products, permitting greater flexibility and customization in satisfying the needs of customers.

Practical implications

The ability afforded by digital communication for real-time interactive communication enables individuals from multiple departments and hierarchical positions within multiple organizations dispersed across geographic locations and industries to maintain contact, quickly and easily communicate task information, build trust and commitment in long-term relationships with network partners and provide superior customer value.

Originality/value

The paper represents a unique attempt to understand the nature of customer engagement in business markets. It discusses how digital communication alters market transactions among partner organizations in a network by facilitating changes in their make/buy decisions. It develops a matrix of inter-organizational engagement in business networks and propositions that improve understanding of the customer engagement concept and provide the foundation for strategies to better satisfy customers.