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Host anti-viral factors are essential for controlling SARS-CoV-2 infection but remain largely unknown due to the biases of previous large-scale studies toward pro-viral host factors. To fill in this knowledge gap, we performed a genome-wide CRISPR dropout screen and integrated analyses of the multi-omics data of the CRISPR screen, genome-wide association studies, single-cell RNA-seq, and host-virus proteins or protein/RNA interactome. This study has uncovered many host factors that were missed by previous studies, including the components of V-ATPases, ESCRT, and N-glycosylation pathways that modulated viral entry and/or replication. The cohesin complex was also identified as a novel anti-viral pathway, suggesting an important role of three-dimensional chromatin organization in mediating host-viral interaction. Furthermore, we discovered an anti-viral regulator KLF5, a transcriptional factor involved in sphingolipid metabolism, which was up-regulated and harbored genetic variations linked to the COVID-19 patients with severe symptoms. Our results provide a resource for understanding the host anti-viral network during SARS-CoV-2 infection and may help develop new countermeasure strategies.The newly emerged BA.2.75 SARS-CoV-2 variant exhibits an alarming 9 additional mutations in its spike (S) protein compared to the ancestral BA.2 variant. Here we examine the neutralizing antibody escape of BA.2.75 in mRNA-vaccinated and BA.1-infected individuals, as well as the molecular basis underlying functional changes in the S protein. Notably, BA.2.75 exhibits enhanced neutralization resistance over BA.2, but less than the BA.4/5 variant. The G446S and N460K mutations of BA.2.75 are primarily responsible for its enhanced resistance to neutralizing antibodies. The R493Q mutation, a reversion to the prototype sequence, reduces BA.2.75 neutralization resistance. The mutational impact is consistent with their locations in common neutralizing antibody epitopes. Further, the BA.2.75 variant shows enhanced cell-cell fusion over BA.2, driven largely by the N460K mutation, which enhances S processing. Structural modeling revealed a new receptor contact introduced by N460K, supporting a mechanism of potentiated receptor utilization and syncytia formation.Despite unprecedented global sequencing and surveillance of SARS-CoV-2, timely identification of the emergence and spread of novel variants of concern (VoCs) remains a challenge. Several million raw genome sequencing runs are now publicly available. We sought to survey these datasets for intrahost variation to study emerging mutations of concern. We developed iSKIM ("intrahost SARS-CoV-2 k-mer identification method") to relatively quickly and efficiently screen the many SARS-CoV-2 datasets to identify intrahost mutations belonging to lineages of concern. Certain mutations surged in frequency as intrahost minor variants just prior to, or while lineages of concern arose. The Spike N501Y change common to several VoCs was found as a minor variant in 834 samples as early as October 2020. This coincides with the timing of the first detected samples with this mutation in the Alpha/B.1.1.7 and Beta/B.1.351 lineages. Using iSKIM, we also found that Spike L452R was detected as an intrahost minor variant as early as September 2020, prior to the observed rise of the Epsilon/B.1.429/B.1.427 lineages in late 2020. iSKIM rapidly screens for mutations of interest in raw data, prior to genome assembly, and can be used to detect increases in intrahost variants, potentially providing an early indication of novel variant spread.Direct human physical contact accelerates COVID-19 transmission. Smartphone mobility data has been an emerging data source to reveal fine-grained human mobility, which can be used to estimate the intensity of physical contact surrounding different locations. Our study applied smartphone mobility data to simulate the second wave spreading of COVID-19 in January 2021 in three major metropolitan statistical areas (Columbia, Greenville, and Charleston) in South Carolina, United States. https://www.selleckchem.com/products/kn-62.html Based on the simulation, the number of historical county-level COVID-19 cases was allocated to neighborhoods (Census blockgroups) and points of interest (POIs), and the transmission rate of each allocated place was estimated. The result reveals that the COVID-19 infections during the study period mainly occurred in neighborhoods (86%), and the number is approximately proportional to the neighborhood’s population. Restaurants and elementary and secondary schools contributed more COVID-19 infections than other POI categories. The simulation results for the coastal tourism Charleston area show high transmission rates in POIs related to travel and leisure activities. The results suggest that the neighborhood-level infectious controlling measures are critical in reducing COVID-19 infections. We also found that the households of lower socioeconomic status may be an umbrella against infection due to fewer visits to places such as malls and restaurants associated with their low financial status. Control measures should be tailored to different geographic locations since transmission rates and infection counts of POI categories vary among metropolitan areas.Background Since the onset of the recent COVID-19 pandemic, there have been growing concerns regarding multisystem inflammatory syndrome in children (MIS-C). This study aims to describe the clinico-epidemiological profile and challenges in management of MIS-C in low-middle income countries by highlighting the Kenyan experience. Methods A retrospective study at the Aga Khan University Hospital Nairobi, Avenue Hospital Kisumu and Kapsabet County Referral Hospital was undertaken to identify cases of MIS-C. A detailed chart review using the World Health Organization (WHO) data collection tool was adapted to incorporate information on socio-demographic details and treatment regimens. Findings Twenty children with MIS-C were identified across the three facilities. Seventy percent of the children were male (14 of 20). COVID-19 PCR testing was done for five children and only one was positive. The commonest clinical symptoms were fever (90%), tachycardia (80%), prolonged capillary refill (80%), oral mucosal changes (65%) and peripheral cutaneous inflammation (50%). Four children required admission into the critical care unit for ventilation support and inotropic support. Cardiac evaluation was available for six patients four of whom had myocardial dysfunction, three had valvulitis and one had pericarditis. Immunoglobulin therapy was availed to two children and systemic steroids provided for three children. There were no documented mortalities. Interpretation We describe the first case series of MIS-C in East and Central Africa. Majority of suspected cases of MIS-C did not have access to timely COVID-19 PCR testing and other appropriate evaluations which highlights the iniquity in access to diagnostics and treatment.Pregnant women are at greater risk of adverse outcomes, including mortality, as well as obstetrical complications resulting from COVID-19. However, pregnancy-specific changes that underlie such worsened outcomes remain unclear. Herein, we profiled the plasma proteome of pregnant and non-pregnant COVID-19 patients and controls and showed alterations that display a dose-response relationship with disease severity; yet, such proteomic perturbations are dampened during pregnancy. In both pregnant and non-pregnant state, the proteome response induced by COVID-19 showed enrichment of mediators implicated in cytokine storm, endothelial dysfunction, and angiogenesis. Shared and pregnancy-specific proteomic changes were identified pregnant women display a tailored response that may protect the conceptus from heightened inflammation, while non-pregnant individuals display a stronger response to repel infection. Furthermore, the plasma proteome can accurately identify COVID-19 patients, even when asymptomatic or with mild symptoms. This study represents the most comprehensive characterization of the plasma proteome of pregnant and non-pregnant COVID-19 patients.
To evaluate SARS-CoV-2 variants we isolated SARS-CoV-2 temporally during the pandemic starting with first appearance of virus in the Western hemisphere near Seattle, WA, USA, and isolated each known major variant class, revealing the dynamics of emergence and complete take-over of all new cases by current Omicron variants. We assessed virus neutralization in a first-ever full comparison across variants and evaluated a novel monoclonal antibody (Mab). We found that convalescence greater than 5-months provides little-to-no protection against SARS-CoV-2 variants, vaccination enhances immunity against variants with the exception of Omicron BA.1, and paired testing of vaccine sera against ancestral virus compared to Omicron BA.1 shows that 3-dose vaccine regimen provides over 50-fold enhanced protection against Omicron BA.1 compared to a 2-dose regimen. We also reveal a novel Mab that effectively neutralizes Omicron BA.1 and BA.2 variants over clinically-approved Mabs. Our observations underscore the need for continued vaccination efforts, with innovation for vaccine and Mab improvement, for protection against variants of SARS-CoV-2.

We isolated SARS-CoV-2 temporally starting with emergence of virus in the Western hemisphere. Neutralization analyses across all variant lineages show that vaccine-boost regimen provides protection against Omicron BA.1. We reveal a Mab that protects against Omicron BA.1 and BA.2 variants.
We isolated SARS-CoV-2 temporally starting with emergence of virus in the Western hemisphere. Neutralization analyses across all variant lineages show that vaccine-boost regimen provides protection against Omicron BA.1. We reveal a Mab that protects against Omicron BA.1 and BA.2 variants.The COVID-19 pandemic has resulted in extensive surveillance of the genomic diversity of SARS-CoV-2. Sequencing data generated as part of these efforts can also capture the diversity of the SARS-CoV-2 virus populations replicating within infected individuals. To assess this within-host diversity of SARS-CoV-2 we quantified low frequency (minor) variants from deep sequence data of thousands of clinical samples collected by a large urban hospital system over the course of a year. Using a robust analytical pipeline to control for technical artefacts, we observe that at comparable viral loads, specimens from patients hospitalized due to COVID-19 had a greater number of minor variants than samples from outpatients. Since individuals with highly diverse viral populations could be disproportionate drivers of new viral lineages in the patient population, these results suggest that transmission control should pay special attention to patients with severe or protracted disease to prevent the spread of novel variants.
Airborne transmission is one of the major routes contributing to the spread of SARS-CoV-2. Successful aerosol transmission occurs when people release respiratory particles carrying infectious virus in the fine aerosol size range. It remains poorly understood how infection influences the physiological host factors that are integral to this process. Here we assessed the changes in breathing, exhaled droplets, and released virus early after infection with the Alpha and Delta variants in the Syrian hamster. Infection with the two variants led to only nuanced differences in viral tissue titers, disease severity, or shedding magnitude. Both variants led to a short window of detectable virus in the air between 24 h and 48 h, which was poorly reflected by upper respiratory shedding measured in oropharyngeal swabs. The loss of viable air samples coincided with changes in airway constriction as measured by whole body plethysmography, and a decrease of fine aerosols produced in the 1-10 μm aerodynamic diameter range. We found that male sex was associated with greater viral replication in the upper respiratory tract and virus shedding in the air.

Inpatient violence poses a great risk to the health and well-being of other patients and members of staff. Previous research has shown that prevalence rates of violent behavior are particularly high in forensic psychiatric settings. Thus, the reliable identification of forensic inpatients who are particularly at risk for violent behavior is an important aspect of risk management. In the present study, we analyzed clinicians' assessments of N = 504 male and female inpatients of German forensic mental health institutions in order to identify risk factors for verbal institutional violence. Using a tree-based modeling approach, we found the following variables to be predictors of verbal aggression gender, insight into the illness, number of prior admissions to psychiatric hospitals, and insight into the iniquity of the offence. A high number of prior admissions to psychiatric hospitals seems to be a risk factor for verbal aggression amongst men whereas it showed the opposite effect amongst women. Our results highlight the importance of dynamic risk factors, such as poor insight into the own illness, in the prediction of violent incidents. With regard to future research, we argue for a stronger emphasis on nonparametric models as well as on potential interaction effects of risk and protective factors.The board of directors of a nonprofit proprietary hospital is responsible for supervising and managing major operational matters and reviewing operational results. This study investigates how hospital financial performance is influenced by director and supervisor characteristics among the board members of nonprofit proprietary hospitals in Taiwan. Data were obtained from the Division of Medical Services of the Ministry of Health and Welfare. A generalized linear model was used to evaluate 32 non-profit proprietary hospitals for the years 2006 to 2017, totaling 363 observations. The empirical results revealed a significant positive correlation between the proportion of directors with management qualifications and hospital financial performance. Moreover, the results represented that a higher proportion of board members with a medical background did not correspond to higher hospital financial performance. Although doctors accounted for the highest proportion of board members, indicating their key role in hospital management, the need for board members with management expertise cannot be ignored. Therefore, a balance between directors with management experience and medical knowledge on the board of directors is beneficial for hospital financial performance.
To assess the efficacy and safety of dexamethasone 0.7 mg implants (DEX-I) in patients with diabetic macular edema (DME) either naïve to therapy or refractory to anti-VEGF treatment, in a single-center, real-world setting.

Patients diagnosed with DME and treated with DEX-I were retrospectively enrolled in the study and split in two groups naïve (Group 1,
 = 64) and refractory (Group 2,
 = 64) to treatment. Patients were evaluated at baseline, at 1 month, and every 3 months after each DEX-I implant. https://www.selleckchem.com/products/ala-gln.html Main outcome measures were change in best-corrected visual acuity (BCVA) and central macular thickness (CMT) from baseline to follow-up visits.

Significant improvements in BCVA were observed in treatment-naïve patients at 6 months following the first and second DEX-I injection (
 = 0.0023 and
 = 0.0063, respectively), with significant reductions in mean CMT at 6 months after all DEX implants. In treatment-refractory patients, mean CMT was significantly reduced from baseline to 6 months (
 < 0.05) after all DEX-I injections, although no changes were observed in BCVA.

DEX-I improved visual acuity and macular edema mostly in treatment-naïve patients, suggesting DEX-I may be a viable first-line treatment option in DME.
DEX-I improved visual acuity and macular edema mostly in treatment-naïve patients, suggesting DEX-I may be a viable first-line treatment option in DME.
Treating chronic macular edema (CME) post endophthalmitis is a challenge. Use of steroids may reactivate the infection and repeated intravitreal therapy with anti-vascular growth factor inhibitors (Anti-VEGF) puts the patient again at the risk of exacerbation of inflammation or endophthalmitis. We describe a case of CME post traumatic endophthalmitis successfully treated with topical interferon therapy.

A 34-year-old Asian Indian lady with a history of cat bite to her right eye and treated elsewhere as traumatic endophthalmitis with recurrent macular edema, presented to us 1 year after the injury. She had received anti-VEGF injection for same. Her medical history was non-contributory except for close contact with her cat. Therapeutic trials with oral doxycycline followed by oral albendazole with steroids, as well as repeated anti-VEGF therapy failed to prevent recurrence of CME. Patient's steroid responsiveness and reluctance for injections, made us to opt for a novel topical Interferon therapy. Macular edema resolved in 2 months. Interruption of interferon therapy due to COVID-lock down resulted in recurrence of the CME, which again responded well to interferon monotherapy.

Topical interferon may have a role in the treatment of inflammatory macular edema and can serve as a, safer, economical and non-invasive treatment option compared to intravitreal steroids and anti-VEGFs.
Topical interferon may have a role in the treatment of inflammatory macular edema and can serve as a, safer, economical and non-invasive treatment option compared to intravitreal steroids and anti-VEGFs.Optical coherence tomography angiography (OCTA) is a functional extension of optical coherence tomography for non-invasive in vivo three-dimensional imaging of the microvasculature of biological tissues. Several algorithms have been developed to construct OCTA images from the measured optical coherence tomography signals. In this study, we compared the performance of three OCTA algorithms that are based on the variance of phase, amplitude, and the complex representations of the optical coherence tomography signals for rodent retinal imaging, namely the phase variance, improved speckle contrast, and optical microangiography. The performance of the different algorithms was evaluated by comparing the quality of the OCTA images regarding how well the vasculature network can be resolved. Quantities that are widely used in ophthalmic studies including blood vessel density, vessel diameter index, vessel perimeter index, vessel complexity index were also compared. Results showed that both the improved speckle contrast and optical microangiography algorithms are more robust than phase variance, and they can reveal similar vasculature features while there are statistical differences in the calculated quantities.
Flow diverters (FDs) are an effective treatment for intracranial aneurysms, though not free from hemorrhagic complications. A previous study demonstrated increased vascular contractility after FD-implantation as a potential mechanism of distal complications. Our study aimed to investigate whether L-arginine medication affects vascular contractility following FD deployment in a rabbit model.

FDs were implanted in the aorta of normal rabbits (+FD, n = 10), with sham-operated aorta as controls (n = 5). L-Arginine was given in the drinking water (2.25% L-arginine hydrochloride) of half of the +FD animals (+FD/+Arg). Force contraction vascular contractility studies were performed on the aortic rings proximal and distal to the FD using an organ bath. Total eNOS, eNOS(pS1177), eNOS(pT495), COX-2, and S100A4 were quantified by western analysis on total protein lysates from aortic segments, normalizing to GAPDH.

Mean vascular contractility was 53% higher in distal relative to proximal aortic segments (P = 0.0038) in +FD animals, but were not significantly different in +FD/+Arg animals, or in sham-operated controls. The +FD animals expressed significantly reduced levels of eNOS(pS1177) than sham-operated controls (P = 0.0335), while both the +FD and +FD/+Arg groups had reduced levels of eNOS(pT495) relative to sham-operated controls (P = 0.0331 and P = 0.0311, respectively).

These results suggest that L-arginine medication reduces distal vascular contractility after FD treatment via nitric oxide production and thus might mitigate risk for downstream complications.
These results suggest that L-arginine medication reduces distal vascular contractility after FD treatment via nitric oxide production and thus might mitigate risk for downstream complications.
Late hypotony is an undesirable and challenging complication of glaucoma surgery. We describe our use of the Ologen Collagen Matrix to treat late hypotony developing after trabeculectomy.

A retrospective study performed at three eye surgery centers in Brazil.

Eighteen patients who underwent 19 eye surgeries.

Subconjunctival Ologen was implanted at the trabeculectomy sites to treat over-filtering or leaking blebs in patients experiencing late hypotony after trabeculectomy (obtained 6 months after glaucoma surgery). The primary outcome was the intraocular pressure (IOP); we gathered preoperative data records from 19 Ologen treated eyes and days 1, 7, 30, 60, and 180 postoperatively. The secondary outcomes included visual acuity and macular thickness measured via optical coherence tomography; we compared preoperative data to subsequent ones up to sixth-month-evolution.

Over the 6-month period, the IOP rose from 2.89 ± 1.59 mmHg preoperatively to 8.21 ± 3.46 mmHg (
 = 0.0001). Visual acuity improved from 0.33 ± 0.29 to 0.21 ± 0.31 LogMar (
 = 0.0013). Macular thickness fell from 325.62 ± 58.7 to 283.08 ± 47.35 µm (
 = 0.0097). We encountered two complications one related to suture dehiscence following an ocular trauma and one instance of transitory choroidal detachment.

Subconjunctival Ologen implants preserved bleb function and successfully treated post-trabeculectomy hypotony as revealed by data collected at the 6-month follow-up. Longer follow-up is necessary to confirm long-term efficacy and safety. There are no financial conflicts of interest to disclose.
Subconjunctival Ologen implants preserved bleb function and successfully treated post-trabeculectomy hypotony as revealed by data collected at the 6-month follow-up. Longer follow-up is necessary to confirm long-term efficacy and safety. There are no financial conflicts of interest to disclose.This research proposes a new medical procurement decision-making tool named Evaluation of Medical Technology Procurement (EMTP), which combines Mini-health Technology Assessment (Mini HTA) with the analytic hierarchy process (AHP), as well as the intuitionistic linguistic multi-criteria group decision model for multi-criteria decision analysis (MCDA). This tool was applied to a medical device procurement decision in a large provincial general hospital with more than 5000 beds in China as a case study. link2 Specifically, the AHP evaluation framework is first established to determine the evaluation dimensions and criteria. This goal is achieved by applying the AdHopHTA Mini-HTA template and gathering data from questionnaires completed by experts from 33 major public hospitals in Anhui Province, China. link3 The professionals within the application hospital were invited to evaluate the alternative products in a pairwise comparison and obtain a ranking of their advantages and disadvantages. This goal is achieved using the intuitionistic linguistic fuzzy model to deal with the subjectivity and uncertainty that may be present in the professional evaluation by experts in different fields.