bluuebunny/crossref_metadata_2025 huggingface dataset:
Mesenchymal Stromal Cell Mitochondrial Transfer as a Cell Rescue Strategy in Regenerative Medicine: A Review of Evidence in Preclinical Models
Authors: Tan Yu Ling , Eng Sue Ping , Hafez Pezhman , Abdul Karim Norwahidah , Law Jia Xian , Ng Min Hwei
Published: July 2022

Mesenchymal stromal cells (MSC) have excellent clinical potential and numerous properties that ease its clinical translation. Mitochondria play a crucial role in energy metabolism, essential for cellular activities, such as proliferation, differentiation, and migration. However, mitochondrial dysfunction can occur due to diseases and pathological conditions. Research on mitochondrial transfer from MSCs to recipient cells has gained prominence. Numerous studies have demonstrated that mitochondrial transfer led to increased adenosine triphosphate (ATP) production, recovered mitochondrial bioenergetics, and rescued injured cells from apoptosis. However, the complex mechanisms that lead to mitochondrial transfer from healthy MSCs to damaged cells remain under investigation, and the factors contributing to mitochondrial bioenergetics recovery in recipient cells remain largely ambiguous. Therefore, this review demonstrates an overview of recent findings in preclinical studies reporting MSC mitochondrial transfer, comprised of information on cell sources, recipient cells, dosage, route of administration, mechanism of transfer, pathological conditions, and therapeutic effects. Further to the above, this research discusses the potential challenges of this therapy in its clinical settings and suggestions to overcome its challenges.
Characterization and Molecular Mapping of a Gene Conferring High-Temperature Adult-Plant Resistance to Stripe Rust Originally from Aegilops ventricosa
Authors: Li Yuxiang , Liu Lu , Wang Meinan , Ruff Travis , See Deven R. , Hu Xiaoping , Chen Xianming
Published: July 2022

Wheat near-isogenic line AvSYr17NIL carrying Yr17, originally from Aegilops ventricosa for all-stage resistance to Puccinia striiformis f. sp. tritici, also shows nonrace-specific, high-temperature adult-plant (HTAP) resistance to the stripe rust pathogen. To separate and identify the HTAP resistance gene, seeds of AvSYr17NIL were treated with ethyl methanesulfonate. Mutant lines with only HTAP resistance were obtained, and one of the lines, M1225, was crossed with the susceptible recurrent parent Avocet S (AvS). Field responses of the F2 plants and F3 lines, together with the parents, were recorded at the adult-plant stage in Pullman and Mount Vernon, WA under natural P. striiformis f. sp. tritici infection. The parents and the F4 population were phenotyped with a Yr17-virulent P. striiformis f. sp. tritici race in the adult-plant stage under the high-temperature profile in the greenhouse. The phenotypic results were confirmed by testing the F5 population in the field under natural P. striiformis f. sp. tritici infection. The F2 data indicated a single recessive gene, temporarily named YrM1225, for HTAP resistance. The F4 lines were genotyped with Kompetitive allele-specific PCR markers converted from single-nucleotide polymorphism markers polymorphic between M1225 and AvS. The HTAP resistance gene was mapped on the short arm of chromosome 2A in an interval of 7.5 centimorgans using both linkage and quantitative trait locus mapping approaches. The separation of the HTAP resistance gene from Yr17 should improve the understanding and utilization of the different types of resistance.
Genomic Analysis and Development of Infectious Clone of a Novel Carlavirus Infecting Blueberry
Authors: Villamor D. E. V. , Mejia A. Sierra , Martin R. R. , Tzanetakis I. E.
Published: July 2022

A new blueberry virus was discovered using high-throughput sequencing. Using sequence identity values, phylogenetics, and serological and biological properties, we propose the virus, putatively named blueberry virus S (BluVS), to be a distinct species within the genus Carlavirus (family Betaflexiviridae). The genome was analyzed in depth, and an infectious clone was developed to initiate studies on virus pathogenicity. Agroinfiltration of the binary vector construct produced severe systemic symptoms in Nicotiana occidentalis. Back-inoculation using sap from agroinfiltrated N. occidentalis produced identical symptoms to the recipient plants ( N. occidentalis), and virus purification yielded flexuous carlavirus-like particles. However, unlike blueberry scorch virus (BlScV), BluVS caused symptomless infection in Chenopodium quinoa and reacted weakly to BlScV antibodies in an enzyme-linked immunosorbent assay. Collectively, the results provide evidence for the distinct speciation of BluVS. The availability of an infectious clone provides tools for future studies on the biology of the virus.
Nurse Faculty Administrators’ Experiences of Communication, Cooperation, Coordination, and Collaboration During Educational Disruption
Authors: Krouse Anne M. , McLaughlin Kristen A. , Rossi Rose , Powell Mary , Black-Dorn Wendy , Mariani Bette , Patterson Barbara J.
Published: July 2022

AIM

The primary purposes of the study were to describe nurse faculty administrators’ experiences of rapid transition and disruption in nursing education during the COVID-19 pandemic.

BACKGROUND

The disruption and shift to remote learning for nursing education programs posed challenges for these administrators.

METHOD

A descriptive survey methodology with a convenience sample was used with the Four Cs of Disaster Partnering framework.

RESULTS

The findings revealed that key elements of the Four Cs framework played a role in the successful adaptation to new learning environment realities. Time was an overarching finding. Connectedness with faculty, staff, and students was a significant challenge.

CONCLUSION

The application of the Four Cs of Disaster Partnering framework demonstrated utility for examining academic nurse administrators’ preparedness.
Maternal and Perinatal Outcomes Associated With the Omicron Variant of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection
Authors: Seasely Angela R. , Blanchard Christina T. , Arora Nitin , Battarbee Ashley N. , Casey Brian M. , Dionne-Odom Jodie , Leal Sixto M. , Moates Derek B. , Sinkey Rachel G. , Szychowski Jeff M. , Tita Alan T. , Subramaniam Akila
Published: July 2022

Two years into the coronavirus disease 2019 (COVID-19) pandemic, we have now seen three main variant waves. We performed a retrospective cohort study of all pregnant patients with COVID-19 at our institution from March 22, 2020, to February 26, 2022, to evaluate disease severity and perinatal outcomes among the variants. Patients were categorized as pre-Delta (March 22, 2020–May 31, 2021), Delta (July 1, 2021–December 15, 2021), or Omicron (December 16, 2021– February 26, 2022) based on variant tracking from the Centers for Disease Control and Prevention and genotype sequencing at our institution. There were fewer cases of severe–critical disease (1.8% Omicron vs 13.3% pre-Delta and 24.1% Delta) and adverse perinatal outcomes during the Omicron wave compared with the pre-Delta and Delta waves.
Two-year outcome comparison of custom versus conventional total knee (TKA) implants: a retrospective cohort study
Authors: Passano Brandon , Lee Ji Won , Gallagher Brian , Desale Sameer , Boucher Henry R.
Published: July 2022

Background:

Custom implants have drawn increasing interest from surgeons seeking the promise of improved coronal alignment, decreased operative time, and improved outcomes. Currently, there is no clear evidence to support those claims. This study sought to investigate whether utilization of custom implants and instrumentation would lead to a greater improvement in two-year patient-reported outcomes compared with conventional total knee arthroplasty (TKA).

Methods:

This is a retrospective cohort study of 287 knees that underwent either custom TKA (n=150) or conventional TKA (n=137). Primary outcome measures included changes in Oxford Knee Score (OKS) and Short-Form 12 (SF-12) mental and physical component scores at preoperative versus 2-year follow-up. A mixed effects model was utilized to make comparisons between improvements in score. The complication and revision rates were compared.

Results:

There was a significant improvement in all three patient-reported outcome measures from preoperative to 2-year follow-up in both the custom and conventional instrumentation group. There were no significant differences in the magnitude of improvement between the custom and conventional groups for OKS, SF-12 mental, or SF-12 physical (P=0.07, 0.19, and 0.13, respectively) at 2-year follow-up. There were no significant differences in the complication rate (P=0.69) or revision rate (P=0.60) at 2-year follow-up.

Conclusions:

At a minimum follow-up of 2 years, the authors found no significant differences in patient-reported outcome measures including the OKS, SF-12 mental and physical scores between custom and conventional TKAs. Additionally, there were no significant differences in complication or revision rates.

Level of Evidence:

Level III
Patient-Related Functional Outcomes After Robotic-Assisted Rectal Surgery Compared With a Laparoscopic Approach: A Systematic Review and Meta-analysis
Authors: Flynn Julie , Larach Jose T. , Kong Joseph C.H. , Waters Peadar S. , McCormick Jacob J. , Warrier Satish K. , Heriot Alexander
Published: July 2022

BACKGROUND:

Robotic surgery has gained significant momentum in rectal cancer surgery. Most studies focus on short-term and oncological outcomes, showing similar outcomes to laparoscopic surgery. Increasing survivorship mandates greater emphasis on quality of life and long-term function.

OBJECTIVE:

This study aimed to compare quality of life and urinary, sexual, and lower GI functions between robotic and laparoscopic rectal surgeries.

DATA SOURCES:

A systematic search of Medline, PubMed, Embase, Clinical Trials Register, and Cochrane Library–identified articles comparing robotic with laparoscopic rectal resections was performed.

MAIN OUTCOME MEASURES:

The outcome measures were quality of life and urinary, sexual, and GI functions between robotic and laparoscopic rectal resection patient groups. Where comparable data were available, results were pooled for analysis.

RESULTS:

The initial search revealed 1777 papers; 101 were reviewed in full, and 14 studies were included for review. Eleven assessed male sexual function; 7 favored robotic surgery, and the remaining studies showed no significant difference. Pooled analysis of 5 studies reporting rates of male sexual dysfunction at 12 months showed significantly lower rates after robotic surgery (OR, 0.51; p = 0.043). Twelve studies compared urinary function. Six favored robotic surgery, but in 2 studies, a difference was seen at 6 months but not sustained at 12 months. Pooled analysis of 4 studies demonstrated significantly better urinary function scores at 12 months after robotic surgery (OR, 0.26; p = 0.016). Quality of life and GI function were equivalent, but very little data exist for these parameters.

LIMITATIONS:

A small number of studies compare outcomes between these groups; only 2 are randomized. Different scoring systems limit comparisons and pooling of data.

CONCLUSIONS:

The limited available data suggest that robotic rectal cancer resection improves male sexual and urinary functions when compared with laparoscopy, but there is no difference in quality of life or GI function. Future studies should report all facets of functional outcomes using standardized scoring systems.
Limb Fasciotomy for COVID-19 Patients: Is the Chance to Cut a Chance to Cure?
Authors: Holzmer Stephanie W. , Walsh Catherine A. , Mohiuddin Waseem , Sharpe Frances E.
Published: July 2022

Based on the findings of two consecutive cases of upper extremity compartment syndrome encountered at our institution, we hypothesize that the presence of compartment syndrome in the unstable COVID-19 patient may be associated with high mortality and low limb salvage rates. A literature search was conducted with key search terms, including “compartment syndrome, fasciotomy, COVID, and coronavirus.” Articles describing patients with a confirmed COVID-19 diagnosis who developed extremity compartment syndrome were included in our study. The primary outcome investigated was patient survival. Secondary outcomes included limb survival and limb salvage. Limb salvage was calculated in patients who survived to time of discharge, whereas limb survival was counted for all patients. We then added our two cases to the findings reported in our literature to determine current overall limb salvage and patient survival rates. Our review of the literature yielded six case reports of ten extremities that developed compartment syndrome in the COVID-19 positive patient. Overall survival was four of six patients (67%). The overall limb survival rate at the time of hospital discharge was three of 10 (30%). With the addition of our two cases, overall survival was four of eight (50%) and overall limb survival rate was three of 12 (25%). Furthermore, with inclusion of our two cases, the patient survival rate of hemodynamically unstable patients was only three of seven (43%). The development of compartment syndrome in the unstable COVID-19 patient may be a harbinger of death, and the decision to proceed with operative intervention is challenging, complex, and in some cases must prioritize life over limb.
Role of inwardly rectifying K+ channel 5.1 (Kir5.1) in the regulation of renal membrane transport
Authors: Lin Dao-Hong , Duan Xin-Peng , Zheng Jun-Ya , Wang Wen-Hui
Published: July 2022

Purpose of review

Kir5.1 interacts with Kir4.2 in proximal tubule and with Kir4.1 in distal convoluted tubule (DCT), connecting tubule (CNT) and cortical collecting duct (CCD) to form basolateral-K+-channels. Kir4.2/Kir5.1 and Kir4.1/Kir5.1 play an important role in regulating Na+/HCO3
--transport of the proximal tubule and Na+/K+ -transport in the DCT/CNT/CCD. The main focus of this review is to provide an overview of the recent development in the field regarding the role of Kir5.1 regulating renal electrolyte transport in the proximal tubule and DCT.

Recent findings

Loss-of-function-mutations of KCNJ16 cause a new form of tubulopathy, characterized by hypokalaemia, Na+-wasting, acid-base-imbalance and metabolic-acidosis. Abnormal bicarbonate transport induced by loss-of-function of KCNJ16-mutants is recapitulated in Kir4.2-knockout-(Kir4.2 KO) mice. Deletion of Kir5.1 also abolishes the effect of dietary Na+ and K+-intakes on the basolateral membrane voltage and NCC expression/activity. Long-term high-salt intake or high-K+-intake causes hyperkalaemic in Kir5.1-deficient mice.

Kir4.2/Kir5.1 activity in the proximal tubule plays a key role in regulating Na+, K+ and bicarbonate-transport through regulating electrogenic-Na+-bicarbonate-cotransporter-(NBCe1) and type 3-Na+/H+-exchanger-(NHE3). Kir4.1/Kir5.1 activity of the DCT plays a critical role in mediating the effect of dietary-K+ and Na+-intakes on NCC activity/expression. As NCC determines the Na+ delivery rate to the aldosterone-sensitive distal nephron (ASDN), defective regulation of NCC during high-salt and high-K+ compromises renal K+ excretion and K+ homeostasis.
The genetic spectrum of Gitelman(-like) syndromes
Authors: Schlingmann Karl P. , de Baaij Jeroen H.F.
Published: July 2022

Purpose of review

Gitelman syndrome is a recessive salt-wasting disorder characterized by hypomagnesemia, hypokalemia, metabolic alkalosis and hypocalciuria. The majority of patients are explained by mutations and deletions in the SLC12A3 gene, encoding the Na+-Cl−-co-transporter (NCC). Recently, additional genetic causes of Gitelman-like syndromes have been identified that should be considered in genetic screening. This review aims to provide a comprehensive overview of the clinical, genetic and mechanistic aspects of Gitelman(-like) syndromes.

Recent findings

Disturbed Na+ reabsorption in the distal convoluted tubule (DCT) is associated with hypomagnesemia and hypokalemic alkalosis. In Gitelman syndrome, loss-of-function mutations in SLC12A3 cause impaired NCC-mediated Na+ reabsorption. In addition, patients with mutations in CLCKNB, KCNJ10, FXYD2 or HNF1B may present with a similar phenotype, as these mutations indirectly reduce NCC activity. Furthermore, genetic investigations of patients with Na+-wasting tubulopathy have resulted in the identification of pathogenic variants in MT-TI, MT-TF, KCNJ16 and ATP1A1. These novel findings highlight the importance of cell metabolism and basolateral membrane potential for Na+ reabsorption in the DCT.

Altogether, these findings extend the genetic spectrum of Gitelman-like electrolyte alterations. Genetic testing of patients with hypomagnesemia and hypokalemia should cover a panel of genes involved in Gitelman-like syndromes, including the mitochondrial genome.
Utilization of Phone Simulations to Assess Competency Within Nursing Education
Authors: Wilbeck Jennifer , Cross Lacey , Weaver Angela , Kennedy Betsy B.
Published: July 2022

Background:

Phone simulations offer educators unique opportunities for teaching and assessment with reduced scheduling and location barriers.

Problem:

Challenges to learner assessments are multifaceted, including decreased availability of clinical sites, preceptors, and, at times, clinical instructors.

Approach:

This article describes the creation and implementation of diverse phone simulations at multiple levels of nursing education and provides suggestions for broader replication and adaptation.

Outcomes:

Phone simulations are easily implemented, well received, and helpful in assessing student learning and progression. At the generalist level, telephone SBAR (situation, background, assessment, and recommendation) simulations promote essential communication skills imperative in the delivery of safe and effective care. For advanced practice learners, phone simulations are easily applied across multiple populations and specialties. Guided reflections following simulation offer learners an opportunity to immediately self-remediate.

Conclusions:

Phone simulations provide adaptable opportunities to support learning and assess knowledge and competency within educational and clinical settings.
Functional Status and Hospital Readmission After Pediatric Critical Disease: A Year Follow-Up
Authors: Dattein Peiter Ana Paula , Wohlgemuth Schaan Camila , Campos Camila , Knisspell de Oliveira Jéssica , Vieira Rosa Nathalia , da Silva Rodrigues Rayane , dos Santos de Moraes Larissa , Luisa Lukrafka Janice , Salatti Ferrari Renata
Published: July 2022

Objectives:

To evaluate the association between pediatric functional status at hospital discharge after PICU admission and hospital readmission within 1 year.

Design:

Prospective longitudinal study.

Setting:

Two PICUs in tertiary hospitals in South Brazil.

Patients:

Children and adolescents admitted to the PICU.

Interventions:

None.

Measurements and Main Results:

We evaluated the following: clinical and sociodemographic characteristics, functional status using the Functional Status Scale—Brazil (FSS-Brazil) at baseline and at hospital discharge, and hospital readmission within 1 year. Hospital readmission risk was associated with possible related factors using Cox regression to estimate the hazard ratio (HR). A total of 196 patients completed the follow-up. At hospital discharge, 39.3% of children had some degree of decline in FSS-Brazil, and 38.3% had at least one nonelective hospital readmission within 1 year. FSS-Brazil rating at hospital discharge was associated with the risk of hospital readmission within 1 year (HR, 1.698; 95% CI, 1.016–2.838).

Conclusion:

FSS-Brazil rating at hospital discharge, age, and length of stay were associated with greater hazard of nonelective hospital readmission within 1 year of discharge.
Natural killer cells during acute HIV-1 infection: clues for HIV-1 prevention and therapy
Authors: Alrubayyi Aljawharah , Rowland-Jones Sarah , Peppa Dimitra
Published: July 2022

Despite progress in preexposure prophylaxis, the number of newly diagnosed cases with HIV-1 remains high, highlighting the urgent need for preventive and therapeutic strategies to reduce HIV-1 acquisition and limit disease progression. Early immunological events, occurring during acute infection, are key determinants of the outcome and course of disease. Understanding early immune responses occurring before viral set-point is established, is critical to identify potential targets for prophylactic and therapeutic approaches. Natural killer (NK) cells represent a key cellular component of innate immunity and contribute to the early host defence against HIV-1 infection, modulating the pathogenesis of acute HIV-1 infection (AHI). Emerging studies have identified tools for harnessing NK cell responses and expanding specialized NK subpopulations with adaptive/memory features, paving the way for development of novel HIV-1 therapeutics. This review highlights the knowns and unknowns regarding the role of NK cell subsets in the containment of acute HIV-1 infection, and summarizes recent advances in selectively augmenting NK cell functions through prophylactic and therapeutic interventions.
Characterization and rank assignment criteria for the anaerobic fungi (Neocallimastigomycota)
Authors: Elshahed Mostafa S. , Hanafy Radwa A. , Cheng Yanfen , Dagar Sumit S. , Edwards Joan E. , Flad Veronika , Fliegerová Kateřina Olša , Griffith Gareth W. , Kittelmann Sandra , Lebuhn Michael , O'Malley Michelle A. , Podmirseg Sabine Marie , Solomon Kevin V. , Vinzelj Julia , Young Diana , Youssef Noha H.
Published: July 2022

Establishing a solid taxonomic framework is crucial for enabling discovery and documentation efforts. This ensures effective communication between scientists as well as reproducibility of results between laboratories, and facilitates the exchange and preservation of biological material. Such framework can only be achieved by establishing clear criteria for taxa characterization and rank assignment. Within the anaerobic fungi (phylum Neocallimastigomycota), the need for such criteria is especially vital. Difficulties associated with their isolation, maintenance and long-term storage often result in limited availability and loss of previously described taxa. To this end, we provide here a list of morphological, microscopic, phylogenetic and phenotypic criteria for assessment and documentation when characterizing newly obtained Neocallimastigomycota isolates. We also recommend a polyphasic rank-assignment scheme for novel genus-, species- and strain-level designations for newly obtained Neocallimastigomycota isolates.
Microbe Profile: Nitrosopumilus maritimus
Authors: Kraft Beate , Canfield† Donald E.
Published: July 2022

Nitrosopumilus maritimus

is a marine ammonia-oxidizing archaeon with a high affinity for ammonia. It fixes carbon via a modified hydroxypropionate/hydroxybutyrate cycle and shows weak utilization of cyanate as a supplementary energy and nitrogen source. When oxygen is depleted,

N. maritimus

produces its own oxygen, which may explain its regular occurrence in anoxic waters. Several enzymes of the ammonia oxidation and oxygen production pathways remain to be identified.
Inferring transcriptional bursting kinetics from single-cell snapshot data using a generalized telegraph model
Authors: Luo Songhao , Zhang Zhenquan , Wang Zihao , Yang Xiyan , Chen Xiaoxuan , Zhou Tianshou , Zhang Jiajun
Published: July 2022

Motivation

Gene expression has inherent stochasticity resulting from transcription’s burst manners. Single-cell snapshot data can be exploited to rigorously infer transcriptional burst kinetics, using mathematical models as blueprints. The classical telegraph model (CTM) has been widely used to explain transcriptional bursting with Markovian assumptions (i.e., exponentially distributed dwell time in ON and OFF states). However, growing evidence suggests that the gene-state dwell times are nonexponential, as gene-state switching is a multi-step process in organisms. Therefore, interpretable non-Markovian mathematical models and efficient statistical inference methods are urgently required in investigating transcriptional burst kinetics.

Results

We develop an interpretable and tractable model, the generalized telegraph model (GTM), to carve transcriptional bursting that allows arbitrary dwell-time distributions, rather than exponential distributions, to be incorporated into the ON and OFF switching process. Based on the GTM, we propose an inference method for transcriptional bursting kinetics using an approximate Bayesian computation framework (BayesGTM). BayesGTM demonstrates efficient and scalable estimation of burst frequency and burst size on synthetic data. Further, the application of BayesGTM to genome-wide data from mouse embryonic fibroblasts reveals that CTM would overestimate burst frequency and underestimate burst size. In conclusion, the GTM and the corresponding BayesGTM are effective tools to infer dynamic transcriptional bursting from static single-cell snapshot data.
Clinical utility of repurposing a short course of hepatitis C drugs for COVID19. A randomized controlled study
Authors: Yakoot Mostafa , Eysa Basem , Gouda Essam , Helmy Sherine A , Elsayed Mahmoud R , Elrouby Ola , Mohamed Amal , Reyad Ehab , Fawzi Mohamed M , Elmandouh Safaa , Abdellatif Wessam , Zidan Ahmed A , Adel Abd-Elmoniem , Hassany Mohamed
Published: July 2022

BACKGROUND

Preliminary data suggests a potential therapeutic benefit for the hepatitis C drugs, sofosbuvir (SOF) and daclatasvir (DCV) for the treatment of COVID-19. We aim to evaluate efficacy of a short course of dual sofosbuvir/daclatasvir in patients with COVID-19.

METHODS

Eighty-nine consecutive eligible patients were randomly assigned to two treatment groups. The experimental group was treated with the standard of care (SOC) therapy in addition to one 400 mg tablet sofosbuvir and one 60 mg daclatasvir daily for 10 days; while the control group was treated with the SOC therapy alone. Baseline clinical data was measured and followed up for 21 days. Data was compared between the two treatment groups.

RESULTS

The proportion of cumulative clinical recovery in the experimental group at day 21 was numerically greater than the control group (40/44 (91%; 95%CI: 78.8-96.4%) versus 35/45 (77.8%; CI 63.7-87.5%)). The Hazard Ratio (HR) for time to clinical recovery adjusted for baseline severity, using a Cox-regression model was statistically significant: HR: 1.59 (95%CI: 1.001-2.5). Concordantly, the experimental group also showed trends for greater improvement in the mean 8-points ordinal scale score, the severity of lung lesions score and the case fatality rate (4.5% versus 11.1%). No serious or severe adverse events were reported in both groups.

CONCLUSION

This study supports potential benefit and safety of sofosbuvir combined with daclatasvir when given early in the treatment of COVID-19. We hope to encourage further large sized, multinational studies to confirm the results.

HIGHLIGHTS

Preliminary data suggests a potential therapeutic benefit for the hepatitis C drugs, sofosbuvir (SOF) and daclatasvir (DCV) for the treatment of COVID-19.

Eighty-nine COVID-19 patients were randomly assigned to either treatment with SOC plus a short course of combined SOF/DCV therapy or SOC therapy alone.

The Hazard Ratio (HR) for time to clinical recovery adjusted for baseline severity showed statistical significance: HR: 1.59 (95%CI: 1.001-2.5). Concordantly, all other efficacy endpoints showed numerical trends for greater improvement in the experimental group including the case fatality rate (4.5% versus 11.1%). No serious or severe adverse events were reported in both groups.

SOF/DCV therapy might be beneficial when given early in the treatment of COVID-19.
Efficacy of the AZD1222 (ChAdOx1 nCoV-19) COVID-19 Vaccine Against SARS-CoV-2 Variants of Concern
Authors: Koen Anthonet L. , Izu Alane , Baillie Vicky , Kwatra Gaurav , Cutland Clare L. , Fairlie Lee , Padayachee Sherman D. , Dheda Keertan , Barnabas Shaun L. , Bhorat Qasim Ebrahim , Briner Carmen , Ahmed Khatija , Bhikha Sutika , Bhiman Jinal N. , Plessis Jeanine du , Esmail Aliasgar , Horne Elizea , Hwa Shi-Hsia , Oommen-Jose Aylin , Lambe Teresa , Laubscher Matt , Malahleha Mookho , Benade Gabriella , McKenzie Shakeel , Oelofse Suzette , Patel Faeezah , Pillay Sureshnee , Rhead Sarah , Rodel Hylton , Taoushanis Carol , Tegally Houriiyah , Thombrayil Asha , Villafana Tonya L. , Gilbert Sarah , Pollard Andrew J. , Madhi Shabir A.
Published: July 2022

In this South African phase 1/2b study, we demonstrated vaccine efficacy (VE) of two doses of AZD1222 for asymptomatic and symptomatic SARS-CoV-2 infection: 90.6% against wild-type and 77.1% against the Delta variant ≥9 months after vaccination. VE against infection with the Beta variant, which preceded circulation of Delta, was 6.7%.

Clinical trial identifier

CT.govNCT04444674
AFM-based force spectroscopy unravels the stepwise-formation of a DNA transposition complex driving multi-drug resistance dissemination
Authors: Fernandez Maricruz , Shkumatov Alexander V. , Liu Yun , Stulemeijer Claire , Derclaye Sylvie , Efremov Rouslan G. , Hallet Bernard , Alsteens David
Published: July 2022

Transposon Tn4430 belongs to a widespread family of bacterial transposons, the Tn3 family, which plays a prevalent role in the dissemination of antibiotic resistance among pathogens. So far, the molecular mechanisms underlying the replicative transposition of these elements are still poorly understood. Here, we use force-distance curve-based atomic force microscopy to probe the binding of the TnpA transposase of Tn4430 to DNA molecules containing one or two transposon ends and to extract the thermodynamic and kinetic parameters of transposition complex assembly. Comparing wild-type TnpA with previously isolated deregulated TnpA mutants supports a stepwise pathway for transposition complex formation and activation during which TnpA first binds to a single transposon end and then undergoes a structural transition that enables it to bind the second end co-operatively and to become activated for transposition catalysis. Our study thus provides an unprecedented approach to probe the dynamic of a complex DNA processing machinery at the single-particle level.
Primate simplexviruses differ in tropism for macaque cells
Authors: Hofmann-Winkler Heike , Siregar Abdul Rahman , Rodriguez Polo Ignacio , Esiyok Nesil , Gärtner Sabine , Behr Rüdiger , Pöhlmann Stefan , Winkler Michael
Published: July 2022

Primate simplexviruses are closely related neurotropic herpesviruses, which are largely apathogenic in their respective host species. However, cross-species transmission of Macacine alphaherpesvirus 1 (McHV1, also termed Herpes B virus) from rhesus macaques to humans can cause fatal encephalomyelitis. In contrast, closely related viruses, such as Cercopithecine alphaherpesvirus 2 (CeHV2, also termed simian agent 8) or Papiine alphaherpesvirus 2 (PaHV2, also termed herpesvirus papio 2), have not been linked to human disease and are believed to be largely apathogenic in humans. Here, we investigated whether McHV1, PaHV2 and CeHV2 differ in their capacity to infect non-human primate (NHP) and human cells. For comparison, we included the human simplexviruses HSV1 and HSV2 in our analyses. All five viruses replicated efficiently in cell lines of human and African green monkey origin and McHV1 and PaHV2 also showed robust replication in rhesus macaque cell lines. In contrast, replication of HSV1, HSV2 and CeHV2 in cell lines of rhesus macaque origin was inefficient. These results demonstrate a previously unappreciated partial resistance of certain rhesus macaque cell lines to HSV1/HSV2/CeHV2 infection and reveal similarities between cell tropism of McHV1 and PaHV2 that might be relevant for risk assessment.
Fibronectin deficiency in newborn mice leads to cyst formation in the kidney
Authors: Hermann Kristina , Seibold Silke , Skoczynski Kathrin , Buchholz Bjoern , Tamm Ernst R. , Herrnberger-Eimer Leonie
Published: July 2022

Purpose

The ubiquitously expressed glycoprotein fibronectin (FN) is a central component of the fibrillar extracellular matrix (ECM) that is found in multiple sites throughout the body including the peritubular interstitium of the kidney. To learn more about the specific role(s) of FN in the kidney we generated and investigated FN-deficient mice.

Methods

We generated CAGG-Cre-ER™/Fnfl/fl mice which carry floxed Fn alleles and ubiquitously express Cre-recombinase after tamoxifen treatment. Newborn pups were treated with tamoxifen eye drops (2.5 mg/mL) to induce FN deficiency. Conditional deletion of Fn was confirmed by quantitative real-time PCR, Western blot analysis and immunohistochemistry. The expression patterns of Fn were analyzed by in situ hybridization. Kidneys were investigated by light microscopy and immunohistochemistry.

Results

The expression analyses and immunohistochemistry showed a significant reduction of FN at postnatal day (P) 4. Loss of FN corelated with the formation of renal cysts at the corticomedullary border, which expand with increasing age. In situ hybridization demonstrated that on P4 Fn expression extends mainly from the pelvis to the corticomedullary border, whereas in 5-6 weeks old mice it is located only in the cortex. Immunohistochemistry and light microscopy showed a loosening of the renal interstitium and additionally an appearance of ECM proteins in the cysts.

Conclusion

We conclude that FN deficiency leads to the development of renal cysts, which occurs a few days after tamoxifen treatment and results in extensive loss of renal parenchyma a few weeks after birth. The results indicate an important role of FN for maintenance of kidney structure and function.
A human RNA ligase that operates via auto- and RNA-AMPylation
Authors: Yuan Yizhi , Stumpf Florian M. , Schlor Lisa A. , Schmidt Olivia P. , Huber Luisa B. , Frese Matthias , Höllmüller Eva , Scheffner Martin , Stengel Florian , Diederichs Kay , Marx Andreas
Published: July 2022

Different forms of life are known to express RNA ligases that catalyse the condensation of a 3’-hydroxy group and a 5’-terminal phosphate of RNA. No such RNA ligases have yet been identified in vertebrates. Here, we report that the hitherto uncharacterised human protein chromosome 12 open reading frame 29 (C12orf29), which we identified by a chemical proteomics approach, is a 5’-3’ RNA ligase. C12orf29 catalyses RNA ligation via auto-AMPylation of a critical lysine residue by using ATP as a cosubstrate and subsequent AMP transfer to the 5’-phosphate of an RNA substrate followed by phosphodiester bond formation. Studies at the cellular level reveal the involvement of C12orf29 in maintaining RNA integrity upon cellular stress induced by reactive oxygen species. These findings highlight the importance of RNA ligation for cellular fitness.
Gyrator-capacitor based modelling and simulation of forward converter
Authors: Koseni Hakan , Yildiz Ali Bekir
Published: July 2022

Purpose

This paper aims to propose an efficient model for analysis of power electronic circuits with integrated magnetic components.

Design/methodology/approach

The inductance modeling technique is used as the traditional method for analyzing magnetic components. This model is simple and enough to generate for individual components, that is, an inductor and a transformer. However, it becomes difficult to realize this model for the integrated magnetic structures. This paper shows an appropriate model for individual magnetic components as well as integrated magnetic components and its application to magnetically coupled DC–DC converters. Gyrator–capacitor (G–C) modeling offers a unified, reasonable way of understanding the magnetic components commonly met with in power electronics and the other disciplines.

Findings

G–C model allows any electrical and magnetic circuit to be simultaneously simulated with circuit simulators. In this regard, this paper gives a complete simulation model and analysis as an illustrative example. There is no limitation of this paper or future works. The proposed G–C model can be applied to all power electronic circuits having integrated magnetic components.

Originality/value

In the proposed model, the magnetic circuit is converted to a pure electric circuit with capacitors and controlled sources; every winding is replaced with a pair of current controlled voltage sources, namely, a gyrator.
Approaching the field of addictions through the lens of the gender perspective: emerging issues
Authors: Lainas Sotiris , Kouimtsidis Christos
Published: July 2022

Purpose

Evidence suggests that the percentage of men seeking treatment for substance use disorders and other addictive behaviours is significantly higher than that of women. This fact raises several crucial questions concerning the field of addictions. This paper aims to emphasize to the study of addiction in the light of gender studies and especially in the light of theories of dominant/hegemonic masculinity.

Design/methodology/approach

The perspective of dominant/hegemonic masculinity in the field of addictions raises a number of questions: Can the dominant/hegemonic masculinity perspective contribute to the understanding of the phenomenon of addiction? What are the implications of male-dominated and male-centred treatment services on meeting the needs of other populations? Are androcentric approaches ultimately helpful for heteronormative men? This paper investigates the emerging questions through a critical review of the literature including the disciplines of psychology, sociology and anthropology.

Findings

The perspective of hegemonic masculinity can make an important contribution to the understanding of addiction as it sheds light on a dimension that is not well researched and used in the field of addictions. The influences of the androcentric approach to addiction treatment are significant and pose problems both in accessing and serving the needs of other populations. The androcentric approach to treatment is not helpful for heteronormative men either as there is a risk of not addressing the toxic dimensions of dominant/hegemonic masculinity that are directly linked to the problem of addiction.

Research limitations/implications

This paper poses interesting research questions for further research in the field.

Practical implications

This paper raises important issues for practitioners in the field and at the same time suggests alternative perspectives on the interpretation and treatment of addiction.

Social implications

The gender perspective that should further enrich psychosocial interventions is crucial for the equal access of all people with an addiction problem to appropriate support structures.

Originality/value

Gender studies can make an important contribution to further understanding of addiction problems and to the development of effective practices for dealing with it. The fact that in substance abuse treatment programmes the vast majority of participants are heteronormative men raises a number of concerns. These concerns relate to the extent to which structures are directed at meeting the needs of these men and whether because of this orientation the needs of other populations such as heteronormative women and those who do not meet the norms of heteronormativity are left uncovered. These concerns are linked to broader considerations of the role that dominant/hegemonic masculinity plays in the aetiology of addiction and in creating barriers to help-seeking for heteronormative men themselves.
Organizational learning culture and sustainable competitive advantage: implications for organizational development specialists
Authors: Kaupa Stewart
Published: July 2022

Purpose

This study examines the impact of organizational learning culture as a strategic tool for gaining sustainable competitive advantage in the public sector.

Design/methodology/approach

The study adopted a qualitative research approach whereby data were collected from 150 public sector employees through focus groups and interviews. The study was conducted in Namibia. The data were analyzed through thematic analysis and content analysis techniques.

Findings

The study found that organizational learning culture has a significant contribution toward organizational performance. Through organizational learning employees learn the values and norms of the organization and the industry and align their behaviors to the desired levels. By so doing employees become more motivated and enthusiastic about the organization resulting in higher productivity.

Originality/value

Few studies have been done to uncover the key forces and factors that drive performance in the public sector. Hence the findings from this study will contribute to the literature and assist organizational leaders, management and practitioners in the public sector to put emphasis on creating an organizational learning culture that would motivate employees and lead to the mindset change of public servants.
Challenges facing hospital human resources during the COVID-19 pandemic: a qualitative study in Iran
Authors: Asadi Hehshmatollah , Barati Omid , Garavand Ali , Joyani Yaser , Kahkesh Masoumeh Bagheri , Afsarimanesh Nasim , Seifi Mehrdad , Shokri Azad
Published: July 2022

Purpose

This study aims to identify health workforce challenges at Iranian hospitals during the COVID-19 pandemic.

Design/methodology/approach

This was a conventional content analysis study conducted in 2020. The population consisted of the managers (heads of hospitals, managers and matrons) and staff (nurses, physicians, etc.) of eligible hospitals. The participants were selected using purposive sampling, and data saturation was achieved after 28 interviews. The data were analyzed in MAXQDA10.

Findings

In total, 28 interviews were conducted with 10 women and 18 men. The challenges of hospital human resources were categorized into five main themes and 15 sub-themes. The main themes were the shortage of human resources, burnout, the need to acquire new knowledge and skills, the employees’ health and safety and the reward system.

Originality/value

Identification of challenges faced by human resources is the first step toward preventing human force shortage and psychological problems in the personnel. Implementing the recommendations of the present study would assist the proper management of hospitals’ human resources.
Employee’s intention to share knowledge: the impacts of learning organization culture and learning goal orientation
Authors: Yoon Seung Won , Park Jong Gyu
Published: July 2022

Purpose

The purpose of this study is to examine employees' perceived influence of the learning organization culture and learning goal orientation on their knowledge sharing attitude and intention across multiple industries. In connecting these concepts, the researchers incorporated theories of the knowledge-based firm, goal orientation and reasoned action.

Design/methodology/approach

A survey was used to collect data from a total of 323 responses from eight South Korean organizations to examine the influence of organizational and individual learning factors on employees' knowledge sharing. Structural equation modeling showed that the proposed research model was supported by item internal consistency and model-fits.

Findings

Results indicated that employees' learning goal orientation, knowledge sharing attitude and learning organization culture positively influence employees' knowledge sharing intention. This study highlights that those employees are more likely to share knowledge when employees with high learning goal orientation form a positive attitude toward knowledge sharing in a learning supportive culture and structure.

Originality/value

This study added to the literature of learning organizations by identifying a strong positive connection between the learning organization culture and employees' knowledge sharing. The theoretical contribution of this study lies in which the important roles were extended that the learning goal orientation exerts on employee behaviors when they perceive the organization valuing learning.
Does the stock liquidity drive the trade credit of publicly listed firms in Saudi Arabia?
Authors: Bajaher Mohammed , Shawtari Fekri Ali
Published: July 2022

Purpose

This study aims to examine the influence of stock liquidity on the trade credit of publicly listed companies in Saudi Arabia.

Design/methodology/approach

In this study various econometric models were used to test the data of 900 firms listed in Saudi Arabia during the period of 2010–2019.

Findings

The robust results of the various econometric models indicate that firms are more willing to offer trade credit to customers when stock liquidity is greater; however, they are less likely to rely on obtaining more payables from suppliers. The findings further indicate that payables and receivables are indeed related, but not exclusively, in the sense that more payables lead to more receivables. The study also reveals a pattern of persistence in payables and receivables during the period of study.

Research limitations/implications

The sample of the present study is only made up of Saudi listed companies. Future research could extend the sample of this study taking into account listed firms in the Middle East and North Africa (MENA) region as a whole so as to gain more insights from the entire region including oil-producing and non–oil-producing countries. More studies are needed to further examine the impact of alternative options for credit access and their linkage to stock liquidity. Finally the difference in difference (DiD) method of analysis as quasi experimental method can be another extension of this research.

Practical implications

The findings would provide implications for managers and investors by recognizing the potential role of stock liquidity in affecting trade credit and understanding the association between the stock liquidity and trade credit. Management of the firms should look for the ways to enhance the stock liquidity of the firms so as to help in reducing the extreme debts usage and therefore, alternative source of funds can be available accordingly. Once the advantage of stock market is identified, firms' managers should search for chances and policies that can promote stock liquidity and hence make use of the advantages of being liquid.

Originality/value

This paper provides new evidence from the emerging market, particularly the Saudi Arabia. The attempt is one of the first in the region to broaden the knowledge about the effects of stock liquidity on trade credit. It provides market participants with insights on the role of stock liquidity in financial flexibility.