bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigation of SARS-CoV-2 Epsilon Variant and Hospitalization Status by Genomic Surveillance in a Single Large Health System During the 2020-2021 Winter Surge in Southern California
Authors: Yang Shangxin , Hemarajata Peera , Hilt Evann E , Price Travis K , Garner Omai B , Green Nicole M
Published: October 2021

Objectives

This study aimed to assess whether the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Epsilon variant (B.1.429/427) is more virulent, leading to more hospitalization and more severe disease requiring intensive care unit (ICU) admission.

Methods

SARS-CoV-2 genomic surveillance was performed on respiratory samples from 231 unique patients, collected at a single large health system in Southern California between November 2020 and March 2021 during the winter surge.

Results

The frequencies of the Epsilon variant among outpatients, hospitalized patients, and ICU patients were indifferent.

Conclusions

Our study suggests that the Epsilon variant is not associated with increased hospitalization and ICU admission.
Searching for robust associations with a multi-environment knockoff filter
Authors: Li S , Sesia M , Romano Y , Candès E , Sabatti C
Published: October 2021

In this article we develop a method based on model-X knockoffs to find conditional associations that are consistent across environments, while controlling the false discovery rate. The motivation for this problem is that large datasets may contain numerous associations that are statistically significant and yet misleading, as they are induced by confounders or sampling imperfections. However, associations replicated under different conditions may be more interesting. In fact, sometimes consistency provably leads to valid causal inferences even if conditional associations do not. Although the proposed method is widely applicable, in this paper we highlight its relevance to genome-wide association studies, in which robustness across populations with diverse ancestries mitigates confounding due to unmeasured variants. The effectiveness of this approach is demonstrated by simulations and applications to UK Biobank data.
Perceptions of injectable therapies with cardiovascular benefit: an ACNAP survey of healthcare professionals to explore facilitators and barriers
Authors: Khatib Rani , Angus Neil , Hansen Tina B , Lambrinou Ekaterini , Vellone Ercole , Khan Mutiba , Lee Geraldine A
Published: October 2021

Aims

Injectable medicines are increasingly used to manage risk factors for cardiovascular (CV) events, such as dyslipidaemia and diabetes. These include proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists. Little is known about perceptions of injectable therapies among CV healthcare professionals (HCPs). This study explores their views to identify relevant facilitators and barriers to the use of injectables with CV benefit.

Methods and results

A 22-question survey was distributed internationally via online channels. In total, 192 anonymous responses were received (43.7% physicians, 32.6% nurses, 16.8% pharmacists, 6.8% others). Among respondents with experience of these medicines, 69.1% had used an injectable PCSK9 inhibitor and 67.0% had used an injectable GLP-1 receptor agonist. Commonly raised issues were resource problems (36.5%), lack of knowledge among colleagues (32.3%), paperwork (32.3%), and lack of patient knowledge (28.1%). Key barriers respondents felt made patients decline these treatments were fear of injection (56.6%), lack of awareness or education (26.4%), and administration issues (15.1%); potential reasons for discontinuation included side effects (46.4%), perceived lack of benefit (28.6%), and local reactions (21.4%). The main topics around injectables requiring further support included managing non-adherent patients (16.2%), troubleshooting with patients (16.2%), and educating colleagues about injectables (12.2%). Preferred educational methods to support HCPs were face-to-face training (43.5%) and online learning (26.1%); favoured formats were based on role playing and case studies.

Conclusion

Healthcare professionals highlighted various potential barriers to initiation, continuation, and adherence with injectable therapies in CV medicine. Although some require healthcare system changes, many could be addressed through simple measures based primarily on enhanced training and support for patients and HCPs.
The Growing Socioeconomic Gap in Lifetime Social Security Retirement Benefits: Current and Future Retirees
Authors: Tamborini Christopher R , Reznik Gayle L , Iams Howard M , Couch Kenneth A
Published: October 2021

Objectives

Increasing socioeconomic disparities, including in life expectancy, have important implications for the U.S. Social Security program. This study examined inter- and intracohort trends in Social Security retirement benefits, paying special attention to how lifetime benefit trajectories by socioeconomic circumstance shift across cohorts encompassing current and future retirees.

Methods

Using a dynamic microsimulation model based on representative survey data linked to administrative records, we developed a set of cohort-specific projections that estimate monthly and lifetime Social Security retirement benefits for retirees spanning the early baby boom (1945–1954) to Generation X (1965–1974) cohorts.

Results

We found a widening socioeconomic gap in projected monthly and lifetime benefits for men and women, especially on a lifetime basis. This divergence is associated with stagnation of benefit levels among lower socioeconomic status groups coupled with upward shifts among higher strata groups. Distributional changes are linked with increasing differential mortality, but other factors also likely play a role such as rising education premiums, growing earnings inequality, and changes in women’s work and relationship histories.

Discussion

Widening mortality differentials can lead to distributional changes in the U.S. Social Security program. Microsimulation methodology lends insights into how the socioeconomic gap in monthly and lifetime benefit distributions may change among future older Americans in the context of differential mortality and other demographic changes. Moving forward in time, these complex patterns could offset some of the progressivity built into the system.
Older Adult Mortality From COVID-19: Food Access as a Determinant Within a Socio-ecological Framework
Authors: Sharma Andy
Published: October 2021

Background and Objectives

Low access to food can have an adverse impact on health yet there is limited research on how it is related to coronavirus disease 2019 (COVID-19). The objective of this study was to (a) better understand how inadequate food access was associated with older adult mortality from COVID-19 and (b) determine the spatial distribution of mortality from low food access utilizing a socio-ecological framework.

Research Design and Methods

This study area was the larger Midwest, a region of the United States, which included the following states: Minnesota, Wisconsin, Iowa, Illinois, Indiana, Michigan, Ohio, and Pennsylvania. Data were aggregated from multiple sources at the county-level. Because the spatial data used in this study violated several assumptions of the global regression framework, geographically weighted regression (GWR) was employed.

Results

Results from GWR revealed low access to food was positively associated with mortality from COVID-19 for older adults but the association varied in (a) magnitude and (b) significance across the larger Midwest. More specifically, the socio-ecological framework suggested low access to food, female-headed households, and percentage Hispanic played a meaningful role in explaining older adult mortality for the western region of the larger Midwest. This was not as evident for the eastern portion.

Discussion and Implications

Such a finding calls attention to the importance of capturing the local context when devising policies to reduce mortality for older adults from COVID-19. Regional policymakers can collaborate with public health professionals when applying these results to formulate local action plans that recognize variations across geographic space.
Anomaly upon Anomaly: The 1951 Convention and State Disintegration
Authors: Reyhani Adel-Naim
Published: October 2021

This article draws the attention of refugee law scholarship to a troubling anomaly. It first illustrates how the 1951 Refugee Convention is fundamentally concerned with symptomatically addressing the casting out of refugees from the State-based international order by resolving their anomalous legal status. It then demonstrates, based on the Libyan example, that when confronted with State disintegration, the law fails to do justice to its original purpose. In reflecting on the significance of this phenomenon of ‘anomaly upon anomaly’, the article suggests an exploration of State-transcending models of jurisdiction.
Vaginal Microbiome Components as Correlates of Cervical Human Papillomavirus Infection
Authors: Andrade Pessoa Morales Julia , Marconi Camila , El-Zein Mariam , Ravel Jacques , da Silva Pinto Gabriel Victor , Silveira Rosana , Lima Moises Diogode , de Carvalho Newton Sergio , Alves Rosane Ribeiro Figueiredo , de Lima Parada Cristina Maria Garcia , Leite Sandra Helena Morais , Villa Luisa L , Franco Eduardo L , da Silva Marcia Guimarães
Published: October 2021

Background

Interplay between vaginal microbiome and human papillomavirus (HPV) remains unclear, partly due to heterogeneity of microbiota.

Methods

We used data from 546 women enrolled in a cross-sectional study in 5 Brazil. We genotyped vaginal samples for HPV and sequenced V3–V4 region of 16S rRNA gene for vaginal microbiome analysis. We used stepwise logistic regression to construct 2 linear scores to predict high-risk HPV (hrHPV) positivity: one based exclusively on presence of individual bacterial taxa (microbiome-based [MB] score) and the other exclusively on participants’ sociodemographic, behavioral, and clinical (SBC) characteristics. MB score combined coefficients of 30 (of 116) species. SBC score retained 6 of 25 candidate variables. We constructed receiver operating characteristic curves for scores as hrHPV correlates and compared areas under the curve (AUC) and 95% confidence intervals (CI).

Results

Overall, prevalence of hrHPV was 15.8%, and 26.2% had a Lactobacillus-depleted microbiome. AUCs were 0.8022 (95% CI, .7517–.8527) for MB score and 0.7027 (95% CI, .6419–.7636) for SBC score (P = .0163).

Conclusions

The proposed MB score is strongly correlated with hrHPV positivity—exceeding the predictive value of behavioral variables—suggesting its potential as an indicator of infection and possible value for clinical risk stratification.
Association of Immunoglobulin G3 Hinge Region Length Polymorphism With Cerebral Malaria in Ghanaian Children
Authors: Kyei-Baafour Eric , Kusi Kwadwo A , Arthur Fareed K N , Sarkodie-Addo Tracy , Theisen Michael , Dodoo Daniel , Adu Bright
Published: October 2021

Cerebral malaria (CM) may cause death or long-term neurological damage in children, and several host genetic risk factors have been reported. Malaria-specific immunoglobulin (Ig) G3 antibodies are crucial to human immune response against malaria. The hinge region of IgG3 exhibits length polymorphism (with long [L], medium [M], and short [S] alleles), which may influence its functionality. We studied IgG3 hinge region length polymorphisms in 136 Ghanaian children with malaria. Using logistic regression models, we found that children with the recessive MM allotype encoding medium IgG3 hinge region length had an increased risk of CM (adjusted odds ratio, 6.67 [95% confidence interval,1.30–34.32]; P=.004) . This has implications for future epidemiological studies on CM.
Severe Drug-Induced Liver Injury in the Military: A Retrospective Review
Authors: Ordway Sarah , Sadowski Brett , Driggers Kathryn E , Kwok Ryan
Published: October 2021

Objectives

Drug-induced liver injury (DILI) is a significant cause of morbidity and mortality. Establishing a diagnosis is challenging due to the broad differential diagnosis of liver injury. We retrospectively reviewed patients with severe idiosyncratic DILI at Walter Reed National Military Medical Center in order to define the scope and patterns of injury in the military population.

Methods

Using the military health database, we identified a total of 110 patients who had an International Classification of Disease (ICD)-10 code for toxic liver injury in the electronic medical record at Walter Reed National Military Medical Center between 2016 and 2019. Each patient record was reviewed, and all pertinent data for included patients were recorded into a database for analysis.

Results

Twenty-seven out of 110 patients with a diagnostic code for toxic liver injury met inclusion criteria for severe idiosyncratic DILI. Nine cases were caused by supplements, including 5 active duty service members using synthetic anabolic steroids or preworkout supplements. The majority of patients were men and one-third were serving on active duty. The ranges of liver enzyme elevation and patterns of liver injury widely varied.

Conclusion

Military service members are at particularly high risk for DILI given the frequent use of over-the-counter and other unregulated strength- and performance-enhancing supplements. These injuries not only have significant medical consequences but can profoundly impact military readiness and mission capability. Diagnosis of DILI among active duty service members requires a strong index of suspicion, and inquiry regarding all ingestions is crucial. Educating physicians, providers, and policy makers on the risks of supplement-induced liver injury among service members is crucial. These data will facilitate additional studies exploring susceptibility to severe idiosyncratic DILI among the military population.
Gravitational wave signature of proto-neutron star convection: I. MHD numerical simulations
Authors: Raynaud Raphaël , Cerdá-Durán Pablo , Guilet Jérôme
Published: October 2021

Gravitational waves provide a unique and powerful opportunity to constrain the dynamics in the interior of proto-neutron stars during core collapse supernovae. Convective motions play an important role in generating neutron stars magnetic fields, which could explain magnetar formation in the presence of fast rotation. We compute the gravitational wave emission from proto-neutron star convection and its associated dynamo, by post-processing three-dimensional MHD simulations of a model restricted to the convective zone in the anelastic approximation. We consider two different proto-neutron star structures representative of early times (with a convective layer) and late times (when the star is almost entirely convective). In the slow rotation regime, the gravitational wave emission follows a broad spectrum peaking at about three times the turnover frequency. In this regime, the inclusion of magnetic fields slightly decreases the amplitude without changing the spectrum significantly compared to a non-magnetized simulation. Fast rotation changes both the amplitude and spectrum dramatically. The amplitude is increased by a factor of up to a few thousands. The spectrum is characterized by several peaks associated with inertial modes, whose frequency scales with the rotation frequency. Using simple physical arguments, we derive scalings that reproduce quantitatively several aspects of these numerical results. We also observe an excess of low-frequency gravitational waves, which appears at the transition to a strong field dynamo characterized by a strong axisymmetric toroidal magnetic field. This signature of dynamo action could be used to constrain the dynamo efficiency in a proto-neutron star with future gravitational wave detections.
Prevalence of BRAFV600 in glioma and use of BRAF Inhibitors in patients with BRAFV600 mutation-positive glioma: systematic review
Authors: Andrews Lily J , Thornton Zak A , Saincher Saanwalshah S , Yao Ian Y , Dawson Sarah , McGuinness Luke A , Jones Hayley E , Jefferies Sarah , Short Susan C , Cheng Hung-Yuan , McAleenan Alexandra , Higgins Julian P T , Kurian Kathreena M
Published: October 2021

Background

Detailed prevalence estimates of BRAFV600 mutations and BRAF inhibitor (BRAFi) treatment responses in V600-mutant glioma will inform trial development.

Methods

Our systematic review analyzed overall prevalence of BRAFV600 mutations in glioma and BRAFi treatment response.

Results

Based on 13 682 patients in 182 publications, the prevalence of BRAFV600 in epithelioid glioblastoma (eGBM) was 69% [95% CI: 45–89%]; pleomorphic xanthoastrocytoma (PXA): 56% [48–64%] anaplastic pleomorphic xanthoastrocytoma (aPXA): 38% [23–54%], ganglioglioma (GG): 40% [33–46%], and anaplastic ganglioglioma (aGG): 46% [18–76%]. Prevalence in astroblastoma was 24% [8–43%], desmoplastic infantile astrocytoma (DIA): 16% [0–57%], subependymal giant cell astrocytoma (SEGA): 8% [0–37%], dysembryoplastic neuroepithelial tumor (DNET): 3% [0–11%], diffuse astrocytoma (DA): 3% [0–9%], and pilocytic astrocytoma (PA): 3% [2–5%]. We reviewed 394 V600-mutant gliomas treated with BRAFi from 130 publications. One hundred and twenty-nine pediatric low-grade gliomas showed 4 (3.1%) complete response (CR); 53 (41.1%) partial response (PR); 64 (49.6%) stable disease (SD) and 8 (6.2%) progressive disease (PD). 25 pediatric high-grade gliomas showed CR; PR; SD; PD in 4 (16.0%); 10 (40.0%), 4 (16.0%); and 7 (28.0%) respectively. Thirty-nine adult low-grade gliomas showed CR; PR; SD; PD of 4 (10.3%); 17 (43.6%); 16 (41.0%) and 2 (5.1%) respectively. Ninety-seven adult high-grade gliomas showed CR; PR; SD; PD of 6 (6.2%); 31 (32.0%); 27 (27.8%); and 33 (34.0%) respectively.

Conclusions

BRAFV600 prevalence is highest in eGBM, PXA, aPXA, GG, aGG, and lower in astroblastoma, DIA, SEGA, DNET, DA, and PA. Our data provide the rationale for adjuvant clinical trials of BRAFi in V600-mutant glioma.
Do Place-Based Policies Promote Local Innovation and Entrepreneurship?*
Authors: Tian Xuan , Xu Jiajie
Published: October 2021

This paper explores how a prominent place-based policy in China, the national high-tech zones, affects local innovation output and entrepreneurial activities. Making use of staggered establishments of national high-tech zones in various Chinese cities, we find that the establishment of national high-tech zones has positive effects on local innovation output and entrepreneurial activities. A number of additional tests suggest that the effects appear causal. Access to finance, reductions in administrative burdens, and talent cultivation are three plausible underlying economic channels. Our paper sheds new light on the evaluation of the effectiveness of China’s place-based policies.
Evaluating liability in the supervising physician, PA, and employer relationship
Authors: Hickman Kevin A.
Published: October 2021

Emerging case law demonstrates that physicians who collaborate with physician assistants (PAs), as well as the entity that employs the physician and PA, are facing allegations of liability. The allegations of liability arise from the actions of the PA, inaction of the physician, and failure to meet the regulatory requirements for the oversight of PA practice. In some instances, the physician and employer struggle to meet the complex state regulatory requirements that govern the relationship(s) between the PA and the physician. A review of case law demonstrated that courts generally assign liability for the actions of the PA to the PA, but liability to the physician and employer for failure to meet the statutory requirements for oversight of the PA. All stakeholders must use the lessons learned from case law to mitigate physician and employer liability.
Sclerosing Microcystic Adenocarcinoma: A Case Report and Review of Literature
Authors: Erkilic Suna , Uzun Evren
Published: October 2021

Sclerosing microcystic adenocarcinoma is an extremely rare tumor that was described by Mills et al in 2016 and occurs in the head and neck region. There are 8 cases published with this terminology in the English language literature. Here, we present a 59-year-old female patient with sclerosing microcystic adenocarcinoma in the anterolateral tongue and review the previously reported 8 cases. Most of the reported cases are in females and localized to the tongue. This tumor mimics microcystic adnexal carcinoma, which is a cutaneous-based malignant tumor. The tumor in the present case was composed of cells that were arranged in nests or gland-like structures, with had ductular differentiation in a densely sclerotic stroma. The diagnosis of sclerosing microcystic adenocarcinoma may be difficult because of its paucicellular histomorphology. Surgical margins can be problematic to assess. Several salivary gland tumors should be included in the differential diagnosis, such as adenoid cystic carcinoma, polymorphic adenocarcinoma, and mucoepidermoid carcinoma. The role of immunohistochemistry in this differential diagnosis is limited. Therefore, the diagnosis depends on routine histology.
Primary Peritoneal Ependymoma: A Case Report and Literature Review
Authors: Vazzano Jennifer L. , Swanson Benjamin J. , Wakely Paul E.
Published: October 2021

Extra-axial ependymoma is a rare neoplasm. Reported anatomic sites include the ovary, para-ovarian tissues, pelvis, paracervical soft tissue, lung, omentum, small bowel, and posterior mediastinum. Primary peritoneal ependymomas are extremely rare. We report such an example in a 58-year-old woman who presented with abdominal pain, bloating, and history of a 70-lb weight loss over the prior year. Computed tomography scan showed a 20-cm pelvic mass extending into the abdomen and a 3.5-cm peritoneal-based right hepatic lobe/diaphragm mass. Histologic examination of the pelvic mass revealed an ovarian mucinous cystadenoma. The peritoneal mass showed a highly cellular solid neoplasm containing perivascular pseudorosettes and true ependymal rosettes. Tumor cell nuclei were rounded, oval, and elongated with coarse, granular chromatin and occasional small nucleoli. Mitoses were rare. Immunophenotype showed positive staining with bcl-2 and GFAP and scattered staining with keratins MNF116, CAM5.2, and cytokeratin AE1/AE3, along with chromogranin and EMA, but negative staining with inhibin, HMB45, SOX10, TLE-1, CD10, synaptophysin, Olig2, CD34, CD117, STAT-6, smooth muscle actin, and S-100. Conventional cytogenetic analysis showed normal chromosomes. Foundation One molecular profiling showed no actionable mutations. Ependymoma is an entity that rarely exists outside the central neuraxis having no connection with its central nervous system counterpart. Pathologic diagnosis is based primarily on presence of unequivocal ependymal differentiation.
Mucinous Cystic Neoplasm of the Liver With Associated Neuroendocrine Carcinoma: A Case Report
Authors: Kongsgaard Ane , Brudvik Kristoffer Watten , Syversveen Trygve , Reims Henrik M.
Published: October 2021

Mucinous cystic neoplasms (MCNs) of the liver are relatively rare tumors that constitute less than 5% of liver cysts and are subcategorized into low/intermediate- and high-grade lesions based on the degree of epithelial dysplasia. An associated invasive carcinoma component occurs in 6% of cases, usually as adenocarcinoma with tubular growth. The liver is a frequent metastatic site for neuroendocrine carcinomas (NECs), whereas primary hepatic NECs are extremely rare. We present the case of a 63-year-old woman with a history of choledochal cyst, who now presented with abdominal pain. Computed tomography showed a multilocular cystic lesion in the liver. The cyst was surgically enucleated, and the histological examination revealed an MCN with low-grade dysplasia, with an associated invasive large cell NEC. To our knowledge, this is the first report in the literature of a biliary MCN with associated NEC.
UHRF1, NSUN2, and NEIL1 were Detected as Clinical Biomarker Candidates in Prostate Adenocarcinoma with Potential Roles in Disease Pathogenesis
Authors: Kahyaoğulları Buse Nur , Demircan Turan
Published: October 2021

Prostate cancer (PCa) is the most commonly diagnosed cancer in men. Expanding evidence suggests a significant association between cancer progression and RNA modifications. However, our knowledge of the link between m5C and hm5C pathways with PCa is limited. Therefore, we aimed to explore the diagnostic and prognostic values of m5C and hm5C regulators in PCa. In this study, genetic alterations in m5C and hm5C regulators were identified using publicly available databases. Differentially expressed genes in these pathways between tumor and nontumor samples, correlation among m5C and hm5C pathway members, and prognostic value of the regulators were evaluated. Furthermore, enrichment of gene ontology (GO) terms and KEGG pathways was carried out. Obtained results unveiled the mRNA level differences as the key genetic alterations for m5C and hm5C regulators between tumor and nontumor samples. UHRF1, TET3, and NEIL1 were significantly upregulated in tumor samples compared to nontumor ones, whereas EGR1 was significantly downregulated. UHRF1, DNMT1, NSUN2, NSUN4, C1orf77, C3orf37, WDR77, NEIL1, and TDG genes were identified as candidate prognostic markers of overall survival. The upregulated genes in patient samples with genetic alterations in m5C and hm5C pathways enriched cell cycle-related processes. In summary, our findings suggest that the m5C and hm5C regulators might play a role in PRAD development by activation of proliferation, and the UHRF1, NSUN2, and NEIL1 genes have the potential to be utilized as clinical biomarkers.
Optimizing Social Distancing Policies: A Dynamic Programming Approach for Coupled High and Low Risk Populations
Authors: Dai Peng , Vardavas Raffaele , Nowak Sarah A. , Suen Sze-chuan
Published: October 2021

Background

Decision makers may use social distancing to reduce transmission between risk groups in a pandemic scenario like Covid-19. However, it may result in both financial, mental, and social costs. Given these tradeoffs, it is unclear when and who needs to social distance over the course of a pandemic when policies are allowed to change dynamically over time and vary across different risk groups (e.g., older versus younger individuals face different Covid-19 risks). In this study, we examine the optimal time to implement social distancing to optimize social utility, using Covid-19 as an example.

Methodology

We propose using a Markov decision process (MDP) model that incorporates transmission dynamics of an age-stratified SEIR compartmental model to identify the optimal social distancing policy for each risk group over time. We parameterize the model using population-based tracking data on Covid-19 within the US. We compare results of two cases: allowing the social distancing policy to vary only over time, or over both time and population (by risk group). To examine the robustness of our results, we perform sensitivity analysis on patient costs, transmission rates, clearance rates, mortality rates.

Results

Our model framework can be used to effectively evaluate dynamic policies while disease transmission and progression occurs. When the policy cannot vary by subpopulation, the optimal policy is to implement social distancing for a limited duration at the beginning of the epidemic; when the policy can vary by subpopulation, our results suggest that some subgroups (older adults) may never need to socially distance. This result may occur because older adults occupy a relatively small proportion of the total population and have less contact with others even without social distancing.

Conclusion

Our results show that the additional flexibility of allowing social distancing policies to vary over time and across the population can generate substantial utility gain even when only two patient risk groups are considered. MDP frameworks may help generate helpful insights for policymakers. Our results suggest that social distancing for high-contact but low-risk individuals (e.g., such as younger adults) may be more beneficial in some settings than doing so for low-contact but high-risk individuals (e.g., older adults).
A biological variation-based approach to the day-to-day changes of D-dimer, Fibrinogen, and Ferritin levels that are crucial in the clinical course of COVID-19 in healthy smokers and non-smokers
Authors: Balci Aydın , Düz Muhammed Emin , Menekşe Elif
Published: October 2021

Objective

D-dimer, ferritin, and fibrinogen parameters in COVID-19 patients are essential, particularly in inpatients and intensive care unit patients. It is vital to know the changes that occur due to the biological structure of the person than the disease effect in these tests in order to manage the fatal disease better.

Method

Blood samples were taken on the first, third, and fifth days from 30 healthy volunteers, 15 of whom were smokers, 15 were non-smokers, and D-dimer, ferritin, and fibrinogen tests were studied with repeated measurements. After the data processed for normality and homogeneity and removing extreme values, CVA, CVI, CVG, CVT, RCV, II, I%, B%, TE% values were calculated via a full nested ANOVA design, according to Callum G, Fraser, and EFLM.

Results

CVI and CVG values of D-dimer were calculated as 49.07% and 40.69% for all individuals, 49.26% and 27.71% for smokers, 48.80% and 51.67% for non-smokers, respectively. In terms of fibrinogen, the same analyzes for all individuals were calculated as 11.18% and 10.62%, 3.25% and 20.17% for smokers, 9.11% and 6.79% for non-smokers, respectively. The same analyzes for ferritin were calculated as 23.74% and 63.31% for all individuals, 34.98% and 35.24% for smokers, 30.53% and 74.87% for non-smokers, respectively.

Conclusion

Changes in D-dimer measurements every other day in healthy individuals can be observed depending on the biological characteristics of the individuals, and the population-based reference interval may be insufficient for clinical evaluation. Each individual should be evaluated within himself/herself. When evaluating the results of ferritin and fibrinogen in non-smoking individuals, it should be taken into account that significant differences may occur between individuals. Besides, it should be kept in mind that there may be significant changes due to biological variation in the repeated measurements of ferritin every other day.
Impact of valganciclovir therapy on severe IRIS-Kaposi Sarcoma mortality: an open-label, parallel, randomized controlled-trial
Authors: Volkow Patricia , Galán Leslie Chávez , Ramón-Luing Lucero , Cruz-Velazquez Judith , Cornejo-Juárez Patricia , Sada-Ovalle Isabel , Pérez-Padilla Rogelio , Beda Islas-Muñoz
Published: October 2021

Introduction

High HHV-8 viral load (VL) in Kaposi Sarcoma (KS) has been associated with severe Immune reconstitution inflammatory syndrome (S-IRIS-KS), which can occur after initiating cART, and is linked with high mortality particularly in patients with pulmonary involvement. We investigate if valganciclovir initiated before cART decreases HHV-8 VL and assess if it reduces the incidence of S-IRIS-KS and its attributable mortality.

Methods

Open-label parallel-group randomized clinical trial in AIDS cART naïve patients with disseminated KS (DKS) as defined by at least two of the following: pulmonary, lymph-node or gastrointestinal involvement, lymphedema, or ≥30 skin lesions. In the experimental group (EG), patients were randomized to valganciclovir 900 mg BID four weeks before cART and continued until week-48; in the control group (CG), cART was initiated on week-0. Non-severe-IRIS-KS was defined as: increase in number of lesions plus ≥one log10 HIV-VL decrease or ≥50 cells/mm3 increase or ≥2-fold rise in baseline CD4+cells. S-IRIS-KS was defined as abrupt clinical worsening of KS lesions and/or fever after ruling out another infection following cART initiation, and at least three of the following: thrombocytopenia, anemia, hyponatremia, or hypoalbuminemia.

Results

40 patients were randomized and 37 completed the study. In the ITT analysis, the overall mortality did not differ between groups. In the per-protocol analyses, the difference showed a trend for higher S-IRIS-KS mortality in the CG 3/19 (15.7%), compared to EG 0/18 (p=0.07). The incidence of S-IRIS KS was significantly lower in the EG; two patients, one each had S-IRIS-KS episode (0.038 per 100 patient-days) compared to CG group, four patients developed 12 S-IRIS-KS episodes (0.21 per 100 patient-days); incidence rate of 0.09 (95% CI 0.02-0.5 p=0.006). Mortality in patients with pulmonary KS was significantly lower in EG, 3/4 in CG vs 0/5 in EG. S-IRIS-KS was associated with higher HHV-8-VL; IL6 and CRP; valganciclovir was protective. Of survivors at week 48, 82% achieved >80% remission. No difference was found between groups in the number of non-S-IRIS-KS events.

Conclusions

Valganciclovir significantly reduced the episodes of S-IRIS-KS although attributable KS mortality was lower in the EG the difference was not significant (p=0.07). Mortality was significantly lower in EG patients with pulmonary KS.

NIH Clinical Trails ID NCT03296553.
Race/ethnicity in relation to incident primary open-angle glaucoma characterized by autonomously determined visual field loss patterns
Authors: Kang Jae H. , Wang Mengyu , Frueh Lisa , Rosner Bernard , Wiggs Janey L. , Elze Tobias , Pasquale Louis R.
Published: October 2021

Purpose

We used an autonomous algorithm to classify incident visual field (VF) loss patterns in primary open-angle glaucoma (POAG). Subsequently, we compared racial differences in the risk of these regional VF loss patterns.

Design/Participants

Participants (n=209,036) from the Nurses’ Health Study (NHS) (follow-up: 1980-2018); NHS2 (1989-2019); and Health Professionals Follow-up Study (HPFS; 1986-2018), aged ≥40 years and free of glaucoma.

Methods

Demographics, medical and lifestyle information was assessed on biennial questionnaires. Incident POAG cases (n=1946) with reproducible Humphrey VF loss were confirmed with medical records. The total deviation information of the earliest reliable VF for each eye with POAG (n=2564) was extracted, and a statistical learning method was used to identified optimal solutions for regional vision loss patterns. Each POAG eye was assigned the VF pattern (“archetype”) based on the highest weighting coefficient.

Multivariable-adjusted hazard ratios (HRs) for POAG of various archetypes and 95% confidence intervals (CIs) were estimated using per-eye Cox proportional hazards models. Covariates included cohort, age, glaucoma family history, socioeconomic status, lifestyle parameters, number of eye exams during follow-up, and medical conditions. False discovery rate (FDR) was used for multiple comparisons.

Main outcome measures

POAG based on VF patterns.

Results

Mean age was 58 years; 1.3% were Black, 1.2% were Asian, 1.1% were Hispanic-White and 96.4% were non-Hispanic White. We identified 14 archetypes: 1 representing no VF loss, 9 of early loss and 4 of advanced loss patterns. Compared to non-Hispanic Whites, Blacks were at significantly higher risk of POAG with early VF loss archetypes collectively (Blacks: HR=1.96, 95% CI=1.46, 2.63) and at even higher risk for POAG with advanced loss archetypes collectively (Blacks: HR=6.07, 95% CI=3.61, 10.21; p=0.0002 for the two estimates being different); no differences were observed for Asians or Hispanic Whites. For individual VF archetypes, Hispanic-Whites had FDR-significant higher risks of POAG of archetypes showing early paracentral defects and advanced superior loss while Blacks had FDR-significant higher risks of all advanced loss archetypes and 3 early loss patterns, including early paracentral defects.

Conclusion

Among health professionals, compared to non-Hispanic-Whites, Blacks and Hispanic-Whites had higher risks of incident POAG with central and advanced VF loss.
In silico modeling and interactive profiling of BPH resistant R genes with elicitor molecules of rice planthoppers
Authors: Premachandran Krishnamanikumar , Srinivasan Thanga Suja
Published: October 2021

Brown planthopper resistant NBS-LRR specific R genes (Bph9, Bph14, Bph18, Bph26) have been reported in rice. BPH specific R genes were clustered with other R genes of rice on chromosome 12 (Bph9, Bph18, Bph26) and 3 (Bph14). Motif analysis of BPH specific R genes showed the predominant motifs as CC, NBS and LRR regions. Bph9, Bph18 and Bph26 R genes exhibited high degree of sequence similarity in their CC and NBS region and are considered as functional alleles of BPH resistance at chromosome 12. LRR region of BPH genes were interacting with the elicitor molecules of planthoppers and are the potential lignad binding site. Bph14 exhibited more number of LRR repeats and were interacting efficiently with all the tested salivary elictor molecules of planthoppers. Bph18 with no LRR region exhibited reduced interaction efficiency with the tested elicitor molecules of planthoppers. Our in silico studies confirms that Bph14 R gene resistance protein to be a promising candidate for providing broad spectrum resistance against planthoppers of rice. The study further provides new avenues to investigate the mechanism of receptor-ligand recognition and signaling mechanism against rice planthoppers.
Virtual reality intervention alleviates dyspnea in patients recovering from COVID pneumonia
Authors: Sophie Betka , Alan Kannape Oliver , Jemina Fasola , Florian Lance , Sylvain Cardin , Aline Schmid , Thomas Similowski , Marina Soccal Paola , Bruno Herbelin , Dan Adler , Olaf Blanke
Published: October 2021

Background

Immersive virtual reality (iVR)-based digital therapeutics (DTx) are gaining clinical attention in the field of pain management. Based on known analogies between pain and dyspnea, we investigated the effects of visual-respiratory feedback, on persistent dyspnea in patients recovering from COVID-19 pneumonia.

Methods

We performed a controlled, randomized, single-blind, cross-over clinical study to evaluate an iVR-based intervention to alleviate dyspnea in patients recovering from COVID-19 pneumonia. Included patients reported persistent dyspnea (≥5 on a 10-point scale) and preserved cognitive function (MoCA>24). Assignment was random and concealed. Patients received synchronous (intervention) or asynchronous (control) feedback of their breathing, embodied via a gender-matched virtual body. Outcomes were assessed using questionnaires and breathing recordings. COVVR is registered with ClinicalTrials.gov (NCT04844567).

Findings

Study enrollment was open between November 2020 and April 2021. Twenty-six patients were enrolled (27% women; age: median=55, interquartile range (IQR)=18). Data were available for 24 of 26 patients. The median (IQR) rating on a 7-point Likert-scale of breathing comfort improved from 1(2) at baseline, to 2(1) for synchronous feedback, but remained unchanged at 1(1.5) for asynchronous feedback (p<0.05) between iVR conditions). Moreover, 91.2% of all patients were satisfied with the intervention (p<0.0001) and 66.7% perceived it as beneficial for their breathing (p<0.05). No adverse events were reported.

Interpretation

Based on these findings, our iVR-based DTx presents a feasible and safe respiratory rehabilitation tool that improves breathing comfort in patients recovering from COVID-19 infection presenting with persistent dyspnea. Future research should investigate the DTx’s generalizability to persistent dyspnea with other etiologies and its potential for preventing chronification.

Funding

Marie Sklodowska-Curie Individual Fellowship (H2020-MSCA-IF-2019 894111/ RESPVR), Bertarelli Foundation
Fungal auxin is a quorum-based modulator of blast disease severity
Authors: Dong Lihong , Shen Qing , Chen Cheng-yen , Shen Lizheng , Yang Fan , Naqvi Naweed I. , Deng Yi Zhen
Published: October 2021

Auxin is an important phytohormone regulating plant growth and development, and can also be produced by microbial pathogens including the rice-blast fungusMagnaporthe oryzae. However, the detailed biosynthesis pathway, biological function(s), and cellular distribution of such fungal auxin inM. oryzaeremain largely unknown. Here, we report a sequential accumulation of intrinsic auxin in the three conidial cells, the infection structure (appressorium), and the invasive hyphae inM. oryzae. Such fungus-derived auxin was also secreted out and perceived by the host plants. A mitochondria-associated Indole-3-pyruvate decarboxylase, Ipd1, is essential for auxin/Indole-3-acetic acid biosynthesis inM. oryzae. Theipd1Δ was defective in pathogenicity whereas overexpression ofIPD1led to enhanced virulence in rice. Chemical inhibition of fungal IAA biosynthesis, or its increase via external supplementation decreased or increased the severity of blast disease, respectively, in a dose-dependent manner. Furthermore, the IAA produced and secreted byM. oryzaegoverned the incidence and severity of blast disease in a quorum-dependent manner. Appressorium formation, conidial cell death critical for appressorium function, and the transcription of infection-related genes,MPG1andINV1, directly correlated with cell density and/or IAA levels within the conidial population at the early stages of pathogenic development. Overall, our study revealed that the severity of blast disease is regulated via quorum sensing with intrinsic IAA serving as an associated signal transducer in rice blast.
Excessive inflammatory and metabolic responses to acute SARS-CoV-2 infection are associated with a distinct gut microbiota composition
Authors: Albrich Werner C. , Ghosh Tarini Shankar , Ahearn-Ford Sinead , Mikaeloff Flora , Lunjani Nonhlanhla , Forde Brian , Suh Noémie , Kleger Gian-Reto , Pietsch Urs , Frischknecht Manuel , Garzoni Christian , Forlenza Rossella , Horgan Mary , Sadlier Corinna , Negro Tommaso Rochat , Pugin Jérôme , Wozniak Hannah , Cerny Andreas , Neogi Ujjwal , O’Toole Paul W. , O’Mahony Liam
Published: October 2021

Protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and associated clinical sequelae requires well-coordinated metabolic and immune responses that limit viral spread and promote recovery of damaged systems. In order to understand potential mechanisms and interactions that influence coronavirus disease 2019 (COVID-19) outcomes, we performed a multi-omics analysis on hospitalised COVID-19 patients and compared those with the most severe outcome (i.e. death) to those with severe non-fatal disease, or mild/moderate disease, that recovered. A distinct subset of 8 cytokines and 140 metabolites in sera identified those with a fatal outcome to infection. In addition, elevated levels of multiple pathobionts and lower levels of protective or anti-inflammatory microbes were observed in the faecal microbiome of those with the poorest clinical outcomes. Weighted gene correlation network analysis (WGCNA) identified modules that associated severity-associated cytokines with tryptophan metabolism, coagulation-linked fibrinopeptides, and bile acids with multiple pathobionts. In contrast, less severe clinical outcomes associated with clusters of anti-inflammatory microbes such asBifidobacteriumorRuminococcus, short chain fatty acids (SCFAs) and IL-17A. Our study uncovered distinct mechanistic modules that link host and microbiome processes with fatal outcomes to SARS-CoV-2 infection. These features may be useful to identify at risk individuals, but also highlight a role for the microbiome in modifying hyperinflammatory responses to SARS-CoV-2 and other infectious agents.
Vulnerable workers and the demise of adult education in England
Authors: Wallis Emma , Nacua Lizel , Winterton Jonathan
Published: October 2021

Purpose

This paper reviews changing government policy on adult education in England over the past 20 years and the funding regimes affecting adult and community learning and union-led learning, which play a major role in learning opportunities for socially excluded adults.

Design/methodology/approach

A review and analysis of extant literature, informed by previous involvement in the sector and ongoing collaborations.

Findings

Two decades ago, adult education in England provided a variety of learning opportunities for people who either had limited qualifications or who needed to reskill for whatever reason. Access to those opportunities has been reduced just when it is most needed.

Research limitations/implications

This is a review and viewpoint paper based on experience in England, the limitations of which are discussed in the concluding section. Notwithstanding the institutional specificities of adult education in England, many of the implications are generic and have wider relevance beyond this country context.

Practical implications

Economic recovery post-coronavirus (COVID) and Brexit will require more access to adult education so people can prepare for labour market re-integration. The practical implication of extending provision in adult education to support labour market integration of vulnerable workers is relevant to most countries.

Originality/value

This paper takes a holistic view of adult education, with particular attention to adult and community learning and union-led learning.
Efficacy of empiric antibiotic management of septic olecranon bursitis without bursal aspiration in emergency department patients
Authors: Beyde Adrian , Thomas Alexa L. , Colbenson Kristina M. , Sandefur Benjamin J. , Kisirwan Imtithal , Mullan Aidan F. , O’Driscoll Shawn W. , Campbell Ronna L.
Published: October 2021

Objectives

Many guidelines for septic olecranon bursitis recommend aspiration of the bursa prior to initiation of antimicrobial therapy despite the absence of robust clinical data to support this practice and known risk of aspiration complications. Our objective was to describe outcomes associated with empiric antibiotic therapy without bursal aspiration among emergency department (ED) patients with suspected septic olecranon bursitis.

Methods

We conducted a retrospective observational cohort study of patients presenting to an academic ED from January 1, 2011, to December 31, 2018, with olecranon bursitis. The health record was reviewed to assess patient characteristics and outcomes within 6 months of the ED visit. Olecranon bursitis was considered “suspected septic” if the patient was treated with antibiotics. The primary outcome of interest was complicated versus uncomplicated bursitis resolution. Uncomplicated resolution was defined as bursitis resolution without subsequent bursal aspiration, surgery, or hospitalization.

Results

During the study period, 264 ED patients were evaluated for 266 cases of olecranon bursitis. The median age was 57 years and 85% were men. Four (1.5%) patients had bursal aspiration during their ED visit, 39 (14.7%) were admitted to the hospital, 76 (28.6%) were dismissed without antibiotic therapy, and 147 (55.3%) were dismissed with empiric antibiotic therapy for suspected septic olecranon bursitis. Among these 147 patients, 134 had follow‐up available including 118 (88.1%, 95% confidence interval [CI] = 81.1%–92.8%) with an uncomplicated resolution, eight (6.0%, 95% CI = 2.8%–11.8%) who underwent subsequent bursal aspiration, and nine (6.7%, 95% CI = 3.3%–12.7%) who were subsequently admitted for inpatient antibiotics.

Conclusions

Eighty‐eight percent of ED patients with suspected septic olecranon bursitis treated with empiric antibiotics without aspiration had resolution without need for subsequent bursal aspiration, hospitalization, or surgery. Our findings suggest that empiric antibiotics without bursal aspiration may be a reasonable initial approach to ED management of select patients with suspected septic olecranon bursitis.