Predictive risk models for COVID-19 patients using the multi-thresholding meta-algorithm.

This study aims to develop a Machine Learning model to assess the risks faced by COVID-19 patients in a hospital setting, focusing specifically on predicting the complications leading to Intensive Care Unit (ICU) admission or mortality, which are minority classes compared to the majority class of discharged patients. We operate within a multiclass framework comprising three distinct classes, and address the challenge of dataset imbalance, a common source of model bias. To effectively manage this, we introduce the Multi-Thresholding meta-algorithm (MTh), an innovative output-level methodology that extends traditional thresholding from binary to multiclass classification.

HIV-1 Reverse Transcriptase Error Rates and Transcriptional Thresholds Based on Single-strand Consensus Sequencing of Target RNA Derived From In Vitro-transcription and HIV-infected Cells.

Nucleotide incorporation and lacZ-based forward mutation assays have been widely used to determine the accuracy of reverse transcriptases (RTs) in RNA-dependent DNA polymerization reactions. However, they involve quite complex and laborious procedures, and cannot provide accurate error rates. Recently, NGS-based methods using barcodes opened the possibility of detecting all errors introduced by the RT, although their widespread use is limited by cost, due to the large size of libraries to be sequenced.

Partial repair causes permanent defects in papillary structure and function after reversal of urinary obstruction.

Unlabelled: Urinary obstruction causes injury to the renal papilla and leads to defects in the ability to concentrate urine which predisposes to progressive kidney injury. However, the regenerative capacity of the papilla after reversal of obstruction is poorly understood. To address this, we developed a mouse model of reversible urinary obstruction which is characterized by extensive papillary injury, followed by a robust regeneration response and complete histological recovery over a 3- month period.

Discovery of Thiophene Derivatives as Potent, Orally Bioavailable, and Blood-Brain Barrier-Permeable Ebola Virus Entry Inhibitors.

The endemic nature of the Ebola virus disease in Africa underscores the need for prophylactic and therapeutic drugs that are affordable and easy to administer. Through a phenotypic screening employing viral pseudotypes and our in-house chemical library, we identified a promising hit featuring a thiophene scaffold, exhibiting antiviral activity in the micromolar range. Following up on this thiophene hit, a new series of compounds that retain the five-membered heterocyclic scaffold while modifying several substituents was synthesized.

Unprecedented selectivity for homologous lectin targets: differential targeting of the viral receptors L-SIGN and DC-SIGN.

DC-SIGN (CD209) and L-SIGN (CD209L) are two C-type lectin receptors (CLRs) that facilitate SARS-CoV-2 infections as viral co-receptors. SARS-CoV-2 manipulates both DC-SIGN and L-SIGN for enhanced infection, leading to interest in developing receptor antagonists. Despite their structural similarity (82% sequence identity), they function differently.

SARS-CoV-2 M inhibitor identification using a cellular gain-of-signal assay for high-throughput screening.

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2, SARS2) is responsible for the COVID-19 pandemic and infections that continue to affect the lives of millions of people worldwide, especially those who are older and/or immunocompromised. The SARS2 main protease enzyme, M (also called 3C-like protease, 3CL), is a bona fide drug target as evidenced by potent inhibition with nirmatrelvir and ensitrelvir, the active components of the drugs Paxlovid and Xocova, respectively. However, the existence of nirmatrelvir and ensitrelvir-resistant isolates underscores the need to develop next-generation drugs with different resistance profiles and/or distinct mechanisms of action.

Effect of Preoperative Mitral Regurgitation on LVAD Outcomes in Patients with Elevated Pulmonary Vascular Resistance.

Purpose: In patients with end-stage heart failure who undergo left ventricular assist device (LVAD) implantation, higher pulmonary vascular resistance (PVR) is associated with higher right heart failure rates and ineligibility for heart transplant. Concomitant mitral regurgitation (MR) could potentially worsen pulmonary hemodynamics and lead to worse outcomes; however, its effects in this patient population have not been specifically examined.

Methods: Using an institutional database spanning November 2003 to August 2017, we retrospectively identified patients with elevated PVR who underwent LVAD implantation.

Caregiver-specific quality measures for home- and community-based services: Environmental scan and stakeholder priorities.

Although family caregivers are increasingly recognized for their essential role in helping vulnerable adults live in the community for as long as possible, their priorities and perspectives have not been well-integrated into quality assessments of home- and community-based services (HCBS). Our overall goal was to identify measurement gaps to guide monitoring and improve HCBS. Caregiver-specific measurement priorities were identified during a multi-level stakeholder engagement process that included 34 Veterans, 24 caregivers, and 39 facility leaders, clinicians, and staff across four VA healthcare systems.

Mechanical force activates the light-dependent channels TRP and TRPL in excised patches from the rhabdomere of Drosophila photoreceptors.

Drosophila phototransduction in light-sensitive microvilli involves a metabotropic signaling cascade. Photoisomerized rhodopsin couples to G-protein, activating phospholipase C, which cleaves phosphatidylinositol bisphosphate (PIP2) into inositol trisphosphate, diacylglycerol (DAG) and a proton. DAG is converted into phosphatidic acid by DAG-kinase and metabolized to L-linoleoyl glycerol (2-LG) by DAG-lipase.

Encorafenib and binimetinib followed by radiotherapy for patients with BRAFV600-mutant melanoma and brain metastases (E-BRAIN/GEM1802 phase II study).

Background: Encorafenib plus binimetinib (EB) is a standard-of-care treatment for advanced BRAFV600-mutant melanoma. We assessed the efficacy and safety of encorafenib plus binimetinib in patients with BRAFV600-mutant melanoma and brain metastasis (BM) and explored if radiotherapy improves the duration of response.

Methods: E-BRAIN/GEM1802 was a prospective, multicenter, single-arm, phase II trial that enrolled patients with melanoma BRAFV600-mutant and BM.

Newborn auditory brainstem response and sudden infant death syndrome.

Sudden infant death syndrome (SIDS)-the sudden and unexplained death of a seemingly healthy infant, <1 year old-may be associated with abnormalities in the brain regions that underlie breathing and arousal during sleep. While post-mortem studies suggest abnormalities in SIDS infants' brainstems, there are no studies of these infants' brainstem function before death. One way to assess the function of the brainstem is with auditory brainstem response (ABR), a routine hearing-screening method that noninvasively measures the brainstem's response to sound.

A Scoping Review to Contribute to Knowledge About Culturally Adapting Interventions for Latino Family Caregivers of Persons Living With Dementia.

Introduction: Few interventions have focused on Latino family caregivers to persons with dementia, addressing their unique needs. This review aimed to identify best practices in cultural adaptation to make recommendations for adapting interventions for Latino family caregivers of persons living with dementia.

Method: This scoping review was conducted following the Joanna Briggs Institute Scoping Review guidelines, with findings extracted and summarized from 17 studies addressing cultural adaptation.

Quick Estimation of Minimum Hearing Levels Using a Binaural Multifrequency Stimulus Paradigm: Proof of Concept.

Objectives: Objective estimation of minimum hearing levels using auditory brainstem responses (ABRs) elicited by single frequency tone-bursts presented monaurally is currently considered the gold standard. However, the data acquisition time to estimate thresholds (for both ears across four audiometric frequencies) using this method usually exceeds the sleep time (ranging between 35 and 49 minutes) in infants below 4 months, thus providing incomplete information of hearing status which in turn delays timely clinical intervention. Alternate approaches using faster rate, or tone-burst trains have not been readily accepted due to additional hardware and software requirements.

The effect of lexical triggers on Spanish-English code-switched judgment tasks.

Introduction: It has been argued that certain words can "trigger" intrasentential code-switching. While some researchers suggest that cognates establish triggering at the lexical level, others have argued that words that lack direct translations are more natural stories switch. Yet to be tested experimentally is to what extent different types of lexical items influence the acceptability of mixed utterances.

Tubular CPT1A deletion minimally affects aging and chronic kidney injury.

Kidney tubules use fatty acid oxidation (FAO) to support their high energetic requirements. Carnitine palmitoyltransferase 1A (CPT1A) is the rate-limiting enzyme for FAO, and it is necessary to transport long-chain fatty acids into mitochondria. To define the role of tubular CPT1A in aging and injury, we generated mice with tubule-specific deletion of Cpt1a (Cpt1aCKO mice), and the mice were either aged for 2 years or injured by aristolochic acid or unilateral ureteral obstruction.

Transient Synaptic Enhancement Triggered by Exogenously Supplied Monocarboxylate in Drosophila Motoneuron Synapse.

Current evidence suggests that glial cells provide C3 carbon sources to fuel neuronal activity; however, this notion has become challenged by biosensor studies carried out in acute brain slices or in vivo, showing that neuronal activity does not rely on the import of astrocyte-produced L-lactate. Rather, stimulated neurons become net lactate exporters, as it was also shown in Drosophila neurons, in which astrocyte-provided lactate returns as lipid droplets to be stored in glial cells. In this view, we investigate whether exogenously supplied monocarboxylates can support Drosophila motoneuron neurotransmitter release (NTR).