bluuebunny/crossref_metadata_2025 huggingface dataset:
Petitions by Creditors
Authors: French Derek
Published: October 2021

Creditors may petition concurrently for the winding up of a partnership and the winding up or bankruptcy of a member or former member of the partnership. It must state how the petitioner came to be a creditor, merely describing the petitioner as ‘creditor’ is not sufficient. A creditor of a private company may apply under the Companies Act 2006, s 758, if the company has contravened the prohibition on public offers by private companies. If a company fails to comply with a statutory demand within 21 days, it will be deemed to be unable to pay its debts, and the claimant may present a winding-up petition. The Court of Appeal held that there should be no order as to costs up to the time the petition was served, but the company should pay the petitioner’s costs thereafter. The onus is on the company to show why it should not be ordered to pay the petitioner’s costs.
Petitions by Contributories
Authors: French Derek
Published: October 2021

Only an insolvent partnership can be wound up on a member’s petition under IPO 1994, but, in practice, almost all contributories’ petitions to wind up registered companies relate to solvent companies. A winding-up petition should not be used as a means of putting pressure on a company to meet the petitioner’s demands in relation to allotment of shares. If the partnership has eight or more members, any member may petition under article 9. If the partnership has fewer than eight members, by IA 1986, s 221A(2) inserted by IPO 1994, Petitions can be presented under article 10 for the winding up of a partnership and the winding up or bankruptcy of every one of its members only by a member of the partnership and only if all the members consent to orders being made against them. Any person liable to contribute to the assets of a registered company in the event of its being wound up is one of the company’s contributories.
Linear response theory and damped modes of stellar clusters
Authors: Fouvry Jean-Baptiste , Prunet Simon
Published: October 2021

Because all stars contribute to its gravitational potential, stellar clusters amplify perturbations collectively. In the limit of small fluctuations, this is described through linear response theory, via the so-called response matrix. While the evaluation of this matrix is somewhat straightforward for unstable modes (i.e. with a positive growth rate), it requires a careful analytic continuation for damped modes (i.e. with a negative growth rate). We present a generic method to perform such a calculation in spherically symmetric stellar clusters. When applied to an isotropic isochrone cluster, we recover the presence of a low-frequency weakly damped ℓ = 1 mode. We finally use a set of direct N-body simulations to test explicitly this prediction through the statistics of the correlated random walk undergone by a cluster’s density centre.
Identification of novel therapeutic targets for histone 3 mutated children’s brain tumour, using unique tumour cell surface proteomic signatures
Authors: Snary Anya , Grundy Richard , Layfield Rob , Rahman Ruman , Haque Farhana
Published: October 2021

Aims

Improvements in the treatments for childhood and adolescent brain tumours, High-Grade Glioma (pHGG) and Diffuse Intrinsic Pontine Glioblastoma (DIPG), have not advanced much and they continue to carry a very poor prognosis. These brain tumours are now defined by mutations affecting histone 3 proteins, indeed 80% of DIPGs harbour histone H3.1 and H3.3 K27M somatic mutations whilst 30% of pHGGs exhibit H3.3 G34R or G34V mutations. We hypothesized that the histone 3 mutant tumours will have distinct mutation specific surfactome (cell membrane proteins) signature.

Method

We therefore analysed the cell surface proteomics of pHGG and DIPG, in order to identify novel targets for therapy. We have at first isolated the cell membrane fractions from a range of patient cells carrying different histone 3 mutations (G34R, G34V), relative to wild type histone 3. A comparative quantitative mass-spectrometry analyses of these cell surface membrane fractions is then performed.

Results

The results obtained to date demonstrated unique differential cell membrane expression patterns which correlated to specific mutation type. For example, increased expression of Ras-related proteins Rab-3, Rab-3D is detected only in histone H3.3-G34R mutated cell line in comparison.

Conclusion

Identification and analyses of these unique cell membrane proteins’ association with specific in H3.3 mutation in pHGG, will help to identify precise mutation specific therapeutic targets, benefiting the patients to receive therapy based on tumour’s molecular signature.
Excessive new origin firing underlies selective glioma stem cell cytotoxicity induced by replication stress response inhibition
Authors: Clough Emily , Strathdee Karen , Carruthers Ross
Published: October 2021

Aims

Glioblastoma (GBM) is a treatment refractory cancer of extreme unmet need which exhibits treatment resistance due to a subpopulation of GBM cancer stem cells which have constitutive DNA damage response activation driven by elevated replication stress (RS). RS response inhibition is potently cytotoxic to GSC, however mechanistic understanding will be key to biomarker discovery and successful clinical translation.

We investigated response to combined ATR and PARP inhibition (CAiPi) to gain mechanistic insight and inform biomarker development.

Method

A panel of patient-derived GBM cell lines were cultured as stem enriched (GSCs) or stem depleted (bulk), to characterise response to combined ATR inhibition (VE821 5μM) and PARP inhibition (Olaparib 1μM), by CellTiter-Glo viability assay.

Mechanistic investigations included immunofluorescence of 53BP1 nuclear bodies and DNA fibre analysis. Studies into the importance of PARP trapping included another PARPi Veliparib (1μM), and investigations into inhibition of origin firing used the CDK inhibitor Roscovitine.

Results

Responses to CAiPi in a panel of primary paired GBM GSCs vs differentiated progeny were heterogenous. CAiPi is selectively GSC cytotoxic in a subpopulation of tumours. DNA fibre analysis identified increased new origin firing with PARPi, which was correlated with increased PARP trapping. Inhibition of origin firing by exposure to roscovitine rescued the CAiPi cytotoxic phenotype, suggesting origin firing has an important role in selective GSC cytotoxicity.

A population of treatment-sensitive GSCs with increased numbers of 53BP1 nuclear bodies in G1 phase with CAiPi were identified, indicative of under-replication of DNA in S phase.

Conclusion

Selective GSC cytotoxicity is induced by CAiPi via dysregulation of replication, by both DNA under-replication resulting in DNA lesions, and the novel finding of increased new origin firing in GSC due to PARPi.
Characteristics of glioblastoma long-term survivors
Authors: Ali Tamara , Olubajo Farouk , Rathi Nitika , Pal Piyali , Jenkinson Michael , Brodbelt Andrew
Published: October 2021

Aims

Glioblastoma (GBM) is the commonest and most aggressive primary malignant brain tumour in adults. A small number of patients survive for >5 years and are referred to as long-term survivors (LTS). This study aimed to quantify and characterise GBM LTS in a single large UK centre.

Method

A retrospective observational cohort study was performed. Patients diagnosed with GBM in a single UK centre between 2000–2011 (inclusive) who survived >5 years from diagnosis were included. Histopathological samples were re-examined as per the WHO 2016 classification criteria and tested for molecular biomarkers including MGMT promoter methylation, IDH1/2 mutations, 1p19q codeletion and ATRX. Demographic, imaging, treatment and outcome data were collected.

Results

1130 patients diagnosed with GBM were identified, 30 of whom survived for >5 years. Twenty-three were re-confirmed as GBM histologically and seven were reclassified as anaplastic oligodendroglioma or anaplastic astroctyoma. Median overall survival for this cohort was 6.2 years. We report a 2% 5-year survival, and a 0.7% 7-year survival. LTS-associated factors were younger age (<65 years old), frontal unilateral tumours, maximal management (surgery and chemoradiotherapy), good post-operative performance status (WHO <2), MGMT promoter methylation and IDH1/2 mutation.

Conclusion

A small subset of GBM patients survive for >5 years. Most still succumb to the disease, implying 5-year survival is not indicative of a cure. On applying current molecular markers, a quarter of previously diagnosed glioblastoma in this LTS population were revised to be WHO grade III gliomas.
Glioblastoma cytotoxicity conferred through dual disruption of endolysosomal homeostasis by Vacquinol-1
Authors: Kwak Dongoh , Hammarström Lars G J , Haraldsson Martin , Ernfors Patrik
Published: October 2021

Background

Increased membrane trafficking is observed in numerous cancer types, including glioblastoma. Targeting the oncogenic driven acquired alterations in membrane trafficking by synthetic cationic amphiphilic small molecules has recently been shown to induce death of glioblastoma cells, although the molecular targets are unknown.

Methods

The mechanism of action of the cationic amphiphilic drug Vacquinol-1 (Vacq1)-induced cytotoxicity was investigated using cell biology, biochemistry, functional experiments, chemical biology, unbiased antibody-based post-translation modification profiling, and mass spectrometry-based chemical proteomic analysis on patient-derived glioblastoma cells.

Results

Vacq1 induced two types of abnormal endolysosomal vesicles, enlarged vacuoles and acidic vesicle organelles (AVOs). Mechanistically, enlarged vacuoles were formed by the impairment of lysosome reformation through the direct interaction and inhibition of calmodulin (CaM) by Vacq1, while AVO formation was induced by Vacq1 accumulation and acidification in the endosomal compartments through its activation of the v-ATPase. As a consequence of v-ATPase activation, cellular ATP consumption markedly increased, causing cellular energy shortage and cytotoxicity. This effect of Vacq1 was exacerbated by its inhibitory effects on calmodulin, causing lysosomal depletion and a failure of acidic vesicle organelle clearance.

Conclusion

Our study identifies the targets of Vacq1 and the mechanisms underlying its selective cytotoxicity in glioblastoma cells. The dual function of Vacq1 sets in motion a glioblastoma-specific vicious cycle of ATP consumption resulting in cellular energy crisis and cell death.
Shorter Duration and Lower Quality Sleep Have Widespread Detrimental Effects on Developing Functional Brain Networks in Early Adolescence
Authors: Brooks Skylar J , Katz Eliot S , Stamoulis Catherine
Published: October 2021

Sleep is critical for cognitive health, especially during complex developmental periods such as adolescence. However, its effects on maturating brain networks that support cognitive function are only partially understood. We investigated the impact of shorter duration and reduced quality sleep, common stressors during development, on functional network properties in early adolescence—a period of significant neural maturation, using resting-state functional magnetic resonance imaging from 5566 children (median age = 120.0 months; 52.1% females) in the Adolescent Brain Cognitive Development cohort. Decreased sleep duration, increased sleep latency, frequent waking up at night, and sleep-disordered breathing symptoms were associated with lower topological efficiency, flexibility, and robustness of visual, sensorimotor, attention, fronto-parietal control, default-mode and/or limbic networks, and with aberrant changes in the thalamus, basal ganglia, hippocampus, and cerebellum (P < 0.05). These widespread effects, many of which were body mass index-independent, suggest that unhealthy sleep in early adolescence may impair neural information processing and integration across incompletely developed networks, potentially leading to deficits in their cognitive correlates, including attention, reward, emotion processing and regulation, memory, and executive control. Shorter sleep duration, frequent snoring, difficulty waking up, and daytime sleepiness had additional detrimental network effects in nonwhite participants, indicating racial disparities in the influence of sleep metrics.
Characterization and Aggressiveness of Take-All Root Rot Pathogens Isolated from Symptomatic Bermudagrass Putting Greens
Authors: Stephens Cameron M. , Gannon Travis W. , Cubeta Marc A. , Sit Tim L. , Kerns James P.
Published: October 2021

Take-all root rot is a disease of ultradwarf bermudagrass putting greens caused by Gaeumannomyces graminis (Gg), Gaeumannomyces sp. (Gx), Gaeumannomyces graminicola (Ggram), Candidacolonium cynodontis (Cc), and Magnaporthiopsis cynodontis (Mc). Many etiological and epidemiological components of this disease remain unknown. Improving pathogen identification and our understanding of the aggressiveness of these pathogens along with growth at different temperatures will advance our knowledge of disease development to optimize management strategies. Take-all root rot pathogens were isolated from symptomatic bermudagrass root and stolon pieces from 16 different golf courses. Isolates of Gg, Gx, Ggram, Cc, and Mc were used to inoculate ‘Champion’ bermudagrass in an in planta aggressiveness assay. Each pathogen was also evaluated at 10, 15, 20, 25, 30, and 35°C to determine growth temperature optima. Infected plant tissue was used to develop a real-time PCR high-resolution melt assay for pathogen detection. This assay was able to differentiate each pathogen directly from infected plant tissue using a single primer pair. In general, Ggram, Gg, and Gx were the most aggressive while Cc and Mc exhibited moderate aggressiveness. Pathogens were more aggressive when incubated at 30°C compared with 20°C. While they grew optimally between 24.4 and 27.8°C, pathogens exhibited limited growth at 35°C and no growth at 10°C. These data provide important information on this disease and its causal agents that may improve take-all root rot management.
The Autophagy Genes ChATG4 and ChATG8 Are Required for Reproductive Development, Virulence, and Septin Assembly in Cochliobolus heterostrophus
Authors: Yu Huilin , Jia Wantong , Xiao Kunqin , Jiao Wenli , Zhang Xianghui , Pan Hongyu
Published: October 2021

Autophagy is a highly conserved degrading process that is crucial for cell growth and development in eukaryotes, especially when they face starvation and stressful conditions. To evaluate the functions of Atg4 and Atg8 in mycelial growth, asexual and sexual development, and virulence in Cochliobolus heterostrophus, ΔChatg4 and ΔChatg8 mutants were generated by gene replacement. Strains deleted for ChATG4 and ChATG8 genes showed significant changes in vegetative growth and development of conidia and ascospores compared with the wild-type strain. The autophagy process was blocked and virulence was reduced dramatically in ΔChatg4 and ΔChatg8 mutants. In addition, deletion of ChATG4 and ChATG8 disordered Cdc10 subcellular localization and formation of septin rings. The direct physical interaction between ChAtg4 and ChAtg8 was detected by yeast two-hybrid assay, and ChAtg4-GFP was dispersed throughout the cytoplasm, although GFP-ChAtg8 appeared as punctate structures. All phenotypes were restored in complemented strains. Taken together, these findings indicate that ChATG4 and ChATG8 are crucial for autophagy to regulate fungal growth, development, virulence, and localization of septin in C. heterostrophus.
Ninety-Day Readmission Rates in a Geriatric Hip Fracture Population, From a Bundled Care Payment Initiative Perspective
Authors: Bair Jeffrey M. , O'Mara Gardner Kristin , Tank Jason C. , Georgiadis Gregory M. , Redfern Roberta E.
Published: October 2021

Objective:

To determine the incidence of hospital readmission in a geriatric hip fracture population within 90 days.

Methods:

Analysis of patients ≥60 years of age presenting with a fragility fracture of the hip from a prospective geriatric hip fracture program registry was performed. Demographics, diagnoses, treatments, complications, hospital events, and readmission for any cause within 30 and 90 days were collected. Readmission events were categorized as defined by Bundled Care Payment Initiative (BCPI)/Care for Joint Replacement payment model.

Results:

The population included 305 patients. All-cause readmission at 30 and 90 days was 11.5% and 19.7%, respectively. Surgical site infection or prosthesis failure accounted for 2.6% of 90 days readmissions. Application of the BCPI rules identified 44 of 60 readmitted patients (73.3%) with causes attributable to the surgical event: medical (0.7%), hospital (12.1%), and mechanical (2.6%). Death within 30 days was the largest contributor to hospital-related events.

Conclusions:

This study identified a 90-day readmission rate of nearly 20% in patients with geriatric fragility fractures. Application of the BCPI definitions currently used in the Care for Joint Replacement payment model will result in more readmissions being attributed to the index surgical event than classically considered. If bundled payment models remain the future, further investigation of this population's risk factors for readmission is needed in light of these findings.

Level of Evidence:

Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Removal of Antibiotic Cement-Coated Interlocking Nails
Authors: Abalkhail Talal B , Elhessy Ahmed H , Conway Janet D.
Published: October 2021

Objectives:

To report the outcomes of antibiotic cement-coated interlocking nail (ACCIN) removal, detail a removal technique that mitigates debonding of coating, and describe how to address occurrences intraoperatively.

Design:

Retrospective case series.

Setting:

Level II trauma center.

Patients:

Twenty-eight patients who underwent ACCIN removal between January 2014 and August 2019.

Intervention:

Removal of ACCINs that were coated using the silicone tubing method.

Main Outcome Measurements:

Successful removal of the nail with intact antibiotic coating.

Results:

A total of 42 ACCIN removals were included in this study. Successful ACCIN removal was achieved in 37 cases (88.1%), with debonding in only 5 cases (11.9%). Eight nails (19%) required 1 additional removal procedure, and 3 nails (7.1%) required 2 additional removal procedures. The main reasons for the additional procedures were nonunion and persistent infection.

Conclusions:

ACCIN insertion and removal can be challenging. The proper technique of coating and insertion can facilitate later removal. Removal of knee-long fusion rods can be more challenging.

Level of Evidence:

Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Using Reformatted Axial Computed Tomography Images in Isolation Will Miss Narrow S1 Transsacral Screw Corridors
Authors: Hadeed Michael , Woods David , Koerner Jason , Strage Katya , Chu Xiangquan , Simon Violette , Mauffrey Cyril , Parry Joshua A.
Published: October 2021

Objective:

To evaluate S1 transsacral (TS) corridors on reformatted and nonreformatted computed tomography (CT) images to determine which most reliably identifies narrow corridors.

Design:

Retrospective cohort.

Setting:

Level 1 trauma center.

Patients:

Two hundred forty-five patients with operative pelvic ring injuries.

Intervention:

CT scan review.

Main Outcome Measurements:

Preoperative CT scans were evaluated to determine the width of the S1 TS corridor on standard axial nonreformatted (ANR), axial reformatted (AR), and coronal reformatted images. Sensitivity and specificity of each format to detect a narrow corridor (<10 mm on AR or coronal reformatted) were calculated. Patients with S1 TS screws were evaluated to determine the rate of screw breach with narrow corridors.

Results:

The axial width of the S1 TS corridor was consistently smaller on ANR versus AR images (mean difference 1.4mm, 95% confidence interval 1.1–1.5). The corridor width on ANR images was on average 86% of the AR measurement. ANR images had the highest sensitivity and specificity (100% and 98%) for detecting S1 TS corridors <10 mm. Fifty-three S1 TS screws were placed in corridors ranging 10–23 mm on AR images and 7–19 mm on ANR images. Four (57%) of the 7 screws placed in corridors less than 10 mm in width on ANR images breached the sacral cortex.

Conclusion:

Using ANR images to measure the S1 TS corridor consistently measured smaller widths than AR images and identified all narrow corridors. A high rate of screw breach was noted with screw placement in narrow corridors.

Level of Evidence:

Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.
Therapeutic Drug Monitoring of the Echinocandin Antifungal Agents: Is There a Role in Clinical Practice? A Position Statement of the Anti-Infective Drugs Committee of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology
Authors: Kim Hannah Yejin , Baldelli Sara , Märtson Anne-Grete , Stocker Sophie , Alffenaar Jan-Willem , Cattaneo Dario , Marriott Deborah J.E.
Published: October 2021

Purpose:

Reduced exposure to echinocandins has been reported in specific patient populations, such as critically ill patients; however, fixed dosing strategies are still used. The present review examines the accumulated evidence supporting echinocandin therapeutic drug monitoring (TDM) and summarizes available assays and sampling strategies.

Methods:

A literature search was conducted using PubMed in December 2020, with search terms such as echinocandins, anidulafungin, caspofungin, micafungin, or rezafungin with pharmacology, pharmacokinetics (PKs), pharmacodynamics (PDs), drug–drug interactions, TDM, resistance, drug susceptibility testing, toxicity, adverse drug reactions, bioanalysis, chromatography, and mass spectrometry. Data on PD/PD (PK/PD) outcome markers, drug resistance, PK variability, drug–drug interactions, assays, and TDM sampling strategies were summarized.

Results:

Echinocandins demonstrate drug exposure–efficacy relationships, and maximum concentration/minimal inhibitory concentration ratio (Cmax/MIC) and area under the concentration–time curve/MIC ratio (AUC/MIC) are proposed PK/PD markers for clinical response. The relationship between drug exposure and toxicity remains poorly clarified. TDM could be valuable in patients at risk of low drug exposure, such as those with critical illness and/or obesity. TDM of echinocandins may also be useful in patients with moderate liver impairment, drug–drug interactions, hypoalbuminemia, and those undergoing extracorporeal membrane oxygenation, as these conditions are associated with altered exposure to caspofungin and/or micafungin. Assays are available to measure anidulafungin, micafungin, and caspofungin concentrations. A limited-sampling strategy for anidulafungin has been reported.

Conclusions:

Echinocandin TDM should be considered in patients at known risk of suboptimal drug exposure. However, for implementing TDM, clinical validation of PK/PD targets is needed.
Piggyback Photochromic Contact Lens for Visual Rehabilitation and Photophobia Management in Traumatic Aniridia
Authors: Miyoshi Letícia H. , Hollaender Marianna A. , Giglio Veronica B. , Villela Flavio F. , Alves Milton R.
Published: October 2021

We report herein a case of fitting with a photochromic silicone hydrogel contact lens under a rigid gas-permeable lens (piggyback system) for photophobia and low vision correction after traumatic aniridia and aphakia. A 40-year-old woman was referred to our practice for contact lens fitting in her right eye, which was left aphakic after an open globe injury. She also presented traumatic aniridia in the right eye, and her left eye had been previously eviscerated. A successful fitting was obtained with a photochromic silicone hydrogel (senofilcon A) contact lens, with a Dk/t of 121 × 10−9, under an aspheric design, +13.00 D rigid gas-permeable lens. The patient displayed visual acuity and contrast sensitivity improvement and reported decreased photophobia.
Occam's razor dulled: the occurrence of multiple genetic diagnoses
Authors: Linscott Kristin B. , Cassady Jennifer A. , Robin Nathaniel H.
Published: October 2021

Purpose of review

A single genetic diagnosis, especially from the analysis of a limited number of genes, may not signal the end of a diagnostic odyssey. When a patient with a genetic syndrome presents with symptoms that are not usually associated with their disease phenotype, additional genetic testing is warranted.

Recent findings

Although multiple co-existing genetic diagnoses may sound unlikely, many recent studies and case reports have demonstrated that this scenario is more common than expected. Studies involving whole exome and genome sequencing have identified a frequency of multiple genetic diagnoses and have identified clinical findings that make a second diagnosis more likely, which we have seen reflected in recent cases from our own clinic and consult service. These include multisystem disease, consanguinity, well described aneuploidies with rare or new symptoms, and complex structural chromosomal anomalies which may include multiple chromosomes and breakpoints that disrupt gene function.

Identifying a second diagnosis can have vast implications for patient management and counseling. Patients can be followed with appropriate medical screening and early interventions to support optimal child development. Furthermore, the patient's family can be impacted by ending the diagnostic odyssey, providing testing for other at-risk family members, and offering prenatal options.
Uterus transplantation: the importance of uterine natural killer cells
Authors: Lucander Aaron C.K. , Porrett Paige M.
Published: October 2021

Purpose of review

Murine studies have established that uterine natural killer (uNK) cells are critical regulators of normal placentation and fetal development in mammals. However, the biology of uNK cells in humans remains poorly understood. This ignorance represents a costly knowledge gap, as disordered placentation is thought to underpin a variety of pregnancy complications that impact maternal and neonatal health. In the context of uterus transplantation (UTx), uNK cells are anticipated to play a critical role within the allograft. Here, we review the current understanding of uNK cells in pregnancy biology and explore how this critically important cell population may contribute to pregnancy and graft outcomes in uterus transplant recipients.

Recent findings

Recent studies have characterized differences in NK cell populations between anatomic compartments in humans. In the endometrium, at least five phenotypically and functionally distinct subpopulations of uNK cells have been identified, with research into mechanisms regulating their differentiation and function currently underway.

Further elucidating uNK cell biology has the potential to influence the outcomes of pregnancy and UTx and benefit human health. UTx is a unique opportunity to study uNK cell biology and may shed light on mechanisms by which immunological tolerance is established at the maternal–fetal interface.
Women's Mental Health and Wellbeing in the Interconception Period
Authors: Leiferman Jenn A. , Jewell Jennifer S. , Huberty Jennifer L. , Lee-Winn Angela E.
Published: October 2021

Purpose:

Promoting women's health during the interconception period is critical for the health of future pregnancies.

Methods:

This was a cross-sectional study to better understand interconception mental health and wellbeing using a convenience sample of women recruited on social media who completed an online survey.

Results:

Women who participated in the survey (N = 146) were 1 to 4 years since last pregnancy, primarily non-Hispanic White (81.2%), with an average age of 30 years (SD = 5.0; range = 19-47 years); 20% were insured by Medicaid. Depression, anxiety, stress, social support, mindfulness, and resilience were assessed. Approximately 22.9% reported depressive symptomatology, 18.8% symptoms of anxiety, 6.5% high stress, and 52.9% moderate stress. These patterns differed across years after giving birth, with percentages peaking for depressive symptoms during the first to second year (χ2 = 9.81, p = 0.007), and anxiety symptoms peaking after the third year (χ2 = 7.28, p = 0.026). Women reported moderate scores on wellbeing measures, with resilience scores decreasing as years since last pregnancy increased (F = 3.24, p = 0.042). Less than 25% reported that a provider discussed depressed mood during the interconception period.

Clinical Implications:

Our findings revealed high prevalence and temporal patterns of depressive and anxiety symptoms during the interconception period, identifying a need for nurses to continue to follow-up with their patients about mental health concerns well after the traditionally defined 1 year postpartum. Further investigation of women's mental health and wellbeing and their unique needs during the interconception period is warranted.
Racial Disparities in Stillbirth Risk Factors among non-Hispanic Black Women and non-Hispanic White Women in the United States
Authors: Henry Carrie J. , Higgins Melinda , Carlson Nicole , Song Mi-Kyung
Published: October 2021

Introduction:

Historically, stillbirth risk factors are more prevalent among non-Hispanic Black women than non-Hispanic White women, including age < 20, lower formal educational attainment, prepregnancy obesity, smoking, hypertension, diabetes, short interpregnancy interval, small for gestational age newborn, late prenatal care, and previous cesarean birth. We examined whether these disparities have changed since 2011 and identified a group of risk factors that differed between Black women and White women when accounting for correlations among variables.

Methods:

In a random sample of 315 stillbirths from the National Center for Health Statistics' 2016 fetal death data, Black women and White women were compared for each risk factor using t-tests or chi-square tests. Variables with p ≤ .20 were analyzed using multivariate analysis of variance.

Results:

In this sample, Black women experiencing stillbirth were less likely to have a Bachelor's degree (12.94% vs. 28.49%, p = .04), and more likely to be obese (44.5% vs. 29.1%, p = .01) than White women. Multivariate analysis accounting for correlations among variables showed a group of risk factors that differed between Black women and White women: age < 20, lower education, prepregnancy obesity, hypertension (chronic and pregnancy-associated), nulliparity before stillbirth, and earlier gestation.

Clinical Implications:

Less formal education, obesity, age <20, hypertension, chronic and pregnancy-associated, nulliparity, and earlier gestation are important to consider in multilevel stillbirth prevention interventions to decrease racial disparity in stillbirth. Respectfully listening to women and taking their concerns seriously is one way nurses and other health care providers can promote equity in health outcomes for childbearing women.
Quinolone-resistant uropathogenic E. coli: is there a relation between qnr genes, gyrA gene target site mutation and biofilm formation?
Authors: Sultan Amira M. , Amer Ghada F. , Nabiel Yasmin
Published: October 2021

Introduction. The resistance to quinolone reported in uropathogenic

Escherichia coli

(UPEC) is commonly caused by mutations in the target site encoding genes such as the gyrA gene. Bacterial plasmids carrying resistance genes such as qnr genes can also transfer resistance. Biofilms produced by UPEC can further aid the development of resistant urinary tract infections (UTIs).

Hypothesis. Biofilm production is associated with higher prevalence of quinolones resistance genetic determinants.

Aim. To detect the prevalence of qnr genes and gyrA gene mutation among quinolone-resistant UPEC and to investigate the relation between these genetic resistance determinants and biofilm production.

Methodology. Catheterized urine samples were collected from 420 patients with evidence of UTIs and processed using standard techniques. Isolated UPEC were screened for quinolone resistance using an antimicrobial susceptibility test. Biofilm production among quinolone-resistant isolates was detected using the tissue culture plate method. All quinolone-resistant isolates were screened for qnr genes (qnrA, qnrB and qnrS) by multiplex PCR and for gyrA gene mutation by PCR-RFLP.

Results. Two hundred and sixty-four UPEC isolates were detected from 420 processed urine samples. Out of the identified 264 UPEC, 123 (46.6 %) isolates were found to be quinolone-resistant, showing resistance to 1 or more of the tested quinolones. Of the 123 quinolone-resistant UPEC detected, 71(57.7 %) were biofilm producers. The qnr genes were detected among 62.6 % of the quinolone-resistant UPEC, with an estimated prevalence of 22.8, 32.5 and 37.4 % for qnrA, qnrB and qnrS genes, respectively. Additionally, the gyrA gene mutation was identified among 53.7 % of the quinolone-resistant isolates. We reported a significant association between biofilm production and the presence of qnrA, qnrB and qnrS genes. Furthermore, the gyrA gene mutation was significantly associated with biofilm-producing isolates. The coexistence of qnr genes, gyrA gene mutation and biofilm production was demonstrated in almost 40 % of the quinolone-resistant isolates.

Conclusions. A significantly higher prevalence of qnr genes (qnrA, qnrB and qnrS) as well as the gyrA gene mutation was found among biofilm-forming UPEC. The reported coexistence of these different resistance mechanisms could aggravate quinolone resistance. Therefore, monitoring of resistance mechanisms and a proper stewardship programme are necessary.
DNA binding and gene regulatory functions of MSMEG_2295, a repressor encoded by the dinB2 operon of Mycobacterium smegmatis
Authors: Patra Madhu Manti , Ghosh Poulami , Sengupta Shreya , Das Gupta Sujoy K.
Published: October 2021

MSMEG_2295 is a TetR family protein encoded by the first gene of a

Mycobacterium smegmatis

(Msm) operon that expresses the gene for DinB2 (MSMEG_2294), a translesion DNA repair enzyme. We have carried out investigations to understand its function by performing DNA binding studies and gene knockout experiments. We found that the protein binds to a conserved inverted repeat sequence located upstream of the dinB2 operon and several other genes. Using a knockout of MSMEG_2295, we show that MSMEG_2295 controls the expression of at least five genes, the products of which could potentially influence carbohydrate and fatty acid metabolism as well as antibiotic and oxidative stress resistance. We have demonstrated that MSMEG_2295 is a repressor by performing complementation analysis. Knocking out of MSMEG_2295 had a significant impact on pyruvate metabolism. Pyruvate dehydrogenase activity was virtually undetectable in ΔMSMEG_2295, although in the complemented strain, it was high. We also show that knocking out of MSMEG_2295 causes resistance to H2O2, reversed in the complemented strain. We have further found that the mycobacterial growth inhibitor plumbagin, a compound of plant origin, acts as an inducer of MSMEG_2295 regulated genes. We, therefore, establish that MSMEG_2295 functions by exerting its role as a repressor of multiple Msm genes and that by doing so, it plays a vital role in controlling pyruvate metabolism and response to oxidative stress.
Two regulatory factors of Vibrio cholerae activating the mannose-sensitive haemagglutinin pilus expression is important for biofilm formation and colonization in mice
Authors: Shi Mengting , Zheng Yue , Wang Xianghong , Wang Zhengjia , Yang Menghua
Published: October 2021

Vibrio cholerae

the causative agent of cholera, uses a large number of coordinated transcriptional regulatory events to transition from its environmental reservoir to the host intestine, which is its preferred colonization site. Transcription of the mannose-sensitive haemagglutinin pilus (MSHA), which aids the persistence of

V. cholerae

in aquatic environments, but causes its clearance by host immune defenses, was found to be regulated by a yet unknown mechanism during the infection cycle of

V. cholerae

. In this study, genomic expression library screening revealed that two regulators, VC1371 and VcRfaH, are able to positively activate the transcription of MSHA operon. VC1371 is localized and active in the cell membrane. Deletion of vc1371 or VcrfaH genes in

V. cholerae

resulted in less MshA protein production and less efficiency of biofilm formation compared to that in the wild-type strain. An adult mouse model showed that the mutants with vc1371 or VcrfaH deletion colonized less efficiently than the wild-type; the VcrfaH deletion mutant showed less colonization efficiency in the infant mouse model. The findings strongly suggested that the two regulators, namely VC1371 and VcRfaH, which are involved in the regulation of MSHA expression, play an important role in

V. cholerae

biofilm formation and colonization in mice.
Lack of Trust, Insufficient knowledge and Risk denial; an in-depth Understanding of Health workers Barriers to uptake of the Covid-19 vaccine at Iganga Hospital Eastern Uganda, and Mengo Hospital Kampala Uganda
Authors: Muhamadi Lubega , Edith Namulema , James Waako , Tumwesigye Nazarius Mbona , Museene Safinah Kisu , Mukakaarisa Hellen , Peterson Stefan Swartling , Ekström Anna Mia
Published: October 2021

Covid 19 Vaccine hesitancy among health workers remains a major hindrance to the governments vaccine roll out plan among health workers and other target populations in Uganda.

We conducted 12 focus group discussions and 20 in-depth interviews with health workers (vaccinated and unvaccinated) to understand barriers to vaccine acceptance in their own perspective and context in central and eastern Uganda. Reported barriers to vaccine acceptance included: gross lack of trust, fear of side effects, risk denial and insufficient information about the vaccine amidst negative publicity about the vaccine from the internet and social media platforms. Others were health system inhibition factors and religious beliefs against the vaccine.

We recommend a health work context specific information, education and dissemination strategy to create awareness, information and more knowledge about the vaccine to health workers.

We also recommend a sustained government media campaign to give more information about the vaccine and also dispel the negative publicity and misinformation about the vaccine.

Dialogue with health workers at all levels of care, positive peer influence, use of religious and opinion leaders as well as government ensuring accessibly to various Covid 19 vaccines and putting vaccine posts outside hospital settings to limit exposure to Covid patients could also increase uptake of the vaccine among health workers.
A deep learning based graph-transformer for whole slide image classification
Authors: Zheng Yi , Gindra Rushin , Betke Margrit , Beane Jennifer E. , Kolachalama Vijaya B.
Published: October 2021

Deep learning is a powerful tool for assessing pathology data obtained from digitized biopsy slides. In the context of supervised learning, most methods typically divide a whole slide image (WSI) into patches, aggregate convolutional neural network outcomes on them and estimate overall disease grade. However, patch-based methods introduce label noise in training by assuming that each patch is independent with the same label as the WSI and neglect the important contextual information that is significant in disease grading. Here we present a Graph-Transformer (GT) based framework for processing pathology data, called GTP, that interprets morphological and spatial information at the WSI-level to predict disease grade. To demonstrate the applicability of our approach, we selected 3,024 hematoxylin and eosin WSIs of lung tumors and with normal histology from the Clinical Proteomic Tumor Analysis Consortium, the National Lung Screening Trial, and The Cancer Genome Atlas, and used GTP to distinguish adenocarcinoma (LUAD) and squamous cell carcinoma (LSCC) from those that have normal histology. Our model achieved consistently high performance on binary (tumor versus normal: mean overall accuracy = 0.975 ± 0.013) as well as three-label (normal versus LUAD versus LSCC: mean accuracy = 0.932 ± 0.019) classification on held-out test data, underscoring the power of GT-based deep learning for WSI-level classification. We also introduced a graphbased saliency mapping technique, called GraphCAM, that captures regional as well as contextual information and allows our model to highlight WSI regions that are highly associated with the class label. Taken together, our findings demonstrate GTP as a novel interpretable and effective deep learning framework for WSI-level classification.
Assessment of knowledge about human papillomavirus vaccination among primary school girls in Arba Minch town, South Ethiopia, 2020. An institution-based cross-sectional study
Authors: Ukumo Eshetu Yisihak , Gebremeskel Feleke , Abebe Samuel , Minanmo Desta Markos , Ukke Gebresilasea Gendisha
Published: October 2021

Introduction

Cervical cancer is the second leading cause of cancer-related mortality among females in Ethiopia. The knowledge regarding human papillomavirus vaccination and its acceptability among adolescent girls affects the human papillomavirus vaccine uptake, however, the status of knowledge of the human papillomavirus vaccination among adolescent girls in Ethiopia, particularly in this study area is not well known. Therefore, this study aimed to determine the knowledge of human papillomavirus vaccination and associated factors among primary school girls in Arba Minch town, South Ethiopia, 2020.

Methods

A school-based cross-sectional study in which 516 school girls participated was conducted on January 24, 2020. The study participants were selected by a simple random sampling technique. A pre-tested and self-administered questionnaire was used to collect the data. Data was entered to Epi_data version 4.6 and exported to SPSS Version 23 for analysis. The logistic regression model was used to identify the statistically significant variables for knowledge of the human papillomavirus vaccination.

Results

The overall knowledge level of the study participants in this study was 71.7%. Their main information source was social media 41.74% followed by health care workers 29.69%.

Conclusions

Nearly three-fourths of the study participants were knowledgeable about human papillomavirus vaccination. The knowledge about the human papillomavirus vaccination shows a positive association with age, education level, and access to information sources, and parents’ educational status.
Public Perception of COVID-19 Vaccines on Twitter in the United States
Authors: Xie Zidian , Wang Xueting , Jiang Yan , Chen Yuhan , Huang Shengyuan , Ma Haoxuan , Anand Ajay , Li Dongmei
Published: October 2021

Background

COVID-19 vaccines play a vital role in combating the COVID-19 pandemic. Social media provides a rich data source to study public perception of COVID-19 vaccines.

Objective

In this study, we aimed to examine public perception and discussion of COVID-19 vaccines on Twitter in the US, as well as geographic and demographic characteristics of Twitter users who discussed about COVID-19 vaccines.

Methods

Through Twitter streaming Application Programming Interface (API), COVID-19-related tweets were collected from March 5th, 2020 to January 25th, 2021 using relevant keywords (such as “corona”, “covid19”, and “covid”). Based on geolocation information provided in tweets and vaccine-related keywords (such as “vaccine” and “vaccination”), we identified COVID-19 vaccine-related tweets from the US. Topic modeling and sentiment analysis were performed to examine public perception and discussion of COVID-19 vaccines. Demographic inference using computer vision algorithm (DeepFace) was performed to infer the demographic characteristics (age, gender and race/ethnicity) of Twitter users who tweeted about COVID-19 vaccines.

Results

Our longitudinal analysis showed that the discussion of COVID-19 vaccines on Twitter in the US reached a peak at the end of 2020. Average sentiment score for COVID-19 vaccine-related tweets remained relatively stable during our study period except for two big peaks, the positive peak corresponds to the optimism about the development of COVID-19 vaccines and the negative peak corresponds to worrying about the availability of COVID-19 vaccines. COVID-19 vaccine-related tweets from east coast states showed relatively high sentiment score. Twitter users from east, west and southern states of the US, as well as male users and users in age group 30-49 years, were more likely to discuss about COVID-19 vaccines on Twitter.

Conclusions

Public discussion and perception of COVID-19 vaccines on Twitter were influenced by the vaccine development and the pandemic, which varied depending on the geographics and demographics of Twitter users.
ImmunAL: a frame to identify the immunological markers for Mild Moderated Alzheimer’s Disease applying Multiplex Network Model
Authors: Sen Sagnik , Chatterjee Agneet , Maulik Ujjwal
Published: October 2021

Identification of immunological markers for neurodegenerative diseases resolve issues related to diagnostic and therapeutic. Neuro-specific cells experience disruptive mechanisms in the early stages of disease progression. The autophagy mechanism, guided by the autoantibodies, is one of the prime indicators of neurodegenerative diseases. Identifying autoantibodies can show a new direction. Detecting influential autoantibodies from relational networks viz., co-expression, co-methylation, etc. is a well-studied area. However, none of the studies have considered the functional affinity among the autoantibodies while selecting them from a relational network. In this regard, a twolayered multiplex network based framework has been proposed, whereby the layers consist co-expression and co-semantic scores. The networks have been formed using three distinct cases viz., diseased, controlled, and a combination of both. Subsequently, a random walk with restart mechanism has been applied to identify the influential autoantibodies, where layer switching probability and restart probability are 0.5 and 0.4 respectively. Next, pathway semantic network has been formed considering the autoantibody associated pathways. EPO and IL1RN, associated with a maximum number of pathways, are identified as the two most influential autoantibodies. The network also provides insights into possible molecular mechanisms during the pathogenic progression. Finally, MDPI and CNN3 are also identified as important biomarkers.

Availability

The code is available athttps://github.com/agneet42/ImmunAL