Structure-Based Optimization of Pyridone α-Ketoamides as Inhibitors of the SARS-CoV-2 Main Protease.

The main protease M is a clinically validated target to treat infections by the coronavirus SARS-CoV-2. Among the first reported M inhibitors was the peptidomimetic α-ketoamide , whose cocrystal structure with M paved the way for multiple lead-finding studies. We established structure-activity relationships for the series by modifying residues at the P1', P3, and P4 sites.

Correction: Healthy lifestyle behaviors are major predictors of mental wellbeing during COVID-19 pandemic confinement: A study on adult Arabs in higher educational institutions.

[This corrects the article DOI: 10.1371/journal.pone.

Screens and Preschools: The Bilingual English Language Learner Assessment as a Curriculum-Compliant Digital Application.

Background/objectives: The increase in digital tools in early childhood education highlights the need for evidence-based assessments that support cognitive development and align with educational requirements and technological advances. This study contributes to the evaluation of the Bilingual English Language Learner Assessment (BELLA), designed to enhance early learning through curriculum-aligned tasks in preschool-aged children.

Methods: Data were collected from 17 schools, including 506 preschool children, using a mixed-model approach to assess BELLA's capacity to appraise early numeracy, literacy, science, and social/emotional development.

Why is the Omicron main protease of SARS-CoV-2 less stable than its wild-type counterpart? A crystallographic, biophysical, and theoretical study of the free enzyme and its complex with inhibitor 13b-K.

During the continuing evolution of SARS-CoV-2, the Omicron variant of concern emerged in the second half of 2021 and has been dominant since November that year. Along with its sublineages, it has maintained a prominent role ever since. The Nsp5 main protease (M) of the Omicron virus is characterized by a single dominant mutation, P132H.

Assessing Cognitive Skills in Early Childhood Education Using a Bilingual Early Language Learner Assessment Tool.

In this article, we propose that basic cognitive skills may be fostered and assessed in early childhood educational (pre-K) settings using a technology-based approach to assessment. BELLA (Bilingual English Language Learner Assessment), designed for use with both monolingual (English or Spanish speaking) and bilingual (English and Spanish speaking) children, is designed to attend to cognitive skill development in addition to (pre-)academic knowledge. Specifically, BELLA assesses analytical, creative, and practical thinking in 3-5-year-old children through unique item content and delivery.

Systemic sclerosis associated with primary sclerosing cholangitis and hyperthyroidism: a case report.

The association between systemic sclerosis and other immune-mediated diseases such as primary sclerosing cholangitis and hyperthyroidism should be suspected in case the patient presents with similar symptoms. A 43-year-old woman presented to the hospital with progressive jaundice, dark urine, dyspnoea, fatigue, generalized arthralgia, weight loss, and amenorrhoea. In addition, she was diagnosed with systemic sclerosis seven years ago.

Synchronous primary gastric and renal tumors: a case report.

Synchronous multiple primary cancers of the stomach and kidney are very rare, only 45 cases of synchronous multiple primary cancers of the stomach and kidney had been reported in the literature up until 2020. Thus far, no particular risk factors have been identified. We present a case of synchronous multiple primary cancers of the stomach and kidney in a 67-year-old female presenting with a 3-month history of vomiting and abdominal pain.

A Complex Intrachromosomal Rearrangement Disrupting in a Family with Popliteal Pterygium and Van der Woude Syndromes.

Clefts of the lip and/or palate (CL/P) are considered the most common form of congenital anomalies occurring either in isolation or in association with other clinical features. Van der woude syndrome (VWS) is associated with about 2% of all CL/P cases and is further characterized by having lower lip pits. Popliteal pterygium syndrome (PPS) is a more severe form of VWS, normally characterized by orofacial clefts, lower lip pits, skin webbing, skeletal anomalies and syndactyly of toes and fingers.

The association between sleep disturbances and blood pressure variability: a review of the literature.

Study Objectives: Sleep disturbances are an underrecognized public health issue that results in various adverse outcomes and disturbed quality of life. Blood pressure variability (BPV) is an emerging entity in assessing cardiovascular disease risk and accumulating evidence suggests that BPV is closely associated with end-organ damage. This review aims to explore the association between sleep disturbances and BPV.

Bored, Distracted, and Confused: Emotions That Promote Creativity and Learning in a 28-Month-Old Child Using an iPad.

Digital technology is increasingly becoming a part of daily life, including the lives of children. Portable digital devices are omnipresent and integrated into activities that did not previously require them. The related skills are often referred to as 21st-century skills, constituting a new type of literacy: digital literacy.

From Repurposing to Redesign: Optimization of Boceprevir to Highly Potent Inhibitors of the SARS-CoV-2 Main Protease.

The main protease (M) of the betacoronavirus SARS-CoV-2 is an attractive target for the development of treatments for COVID-19. Structure-based design is a successful approach to discovering new inhibitors of the M. Starting from crystal structures of the M in complexes with the Hepatitis C virus NS3/4A protease inhibitors boceprevir and telaprevir, we optimized the potency of the alpha-ketoamide boceprevir against the M by replacing its P1 cyclobutyl moiety by a γ-lactam as a glutamine surrogate.

Genetic Background of Antimicrobial Resistance in Multiantimicrobial-Resistant Isolates from Feces of Healthy Broiler Chickens in Tunisia.

Multiantimicrobial-resistant isolates are a global human health problem causing increasing morbidity and mortality. Genes encoding antimicrobial resistance are mainly harbored on mobile genetic elements (MGEs) such as transposons and plasmids as well as integrons, which enhance their rapid spread. The aim of this study was to characterize 83 multiantimicrobial-resistant isolates recovered from healthy broiler chickens.

Time-Restricted Feeding and Aerobic Performance in Elite Runners: Ramadan Fasting as a Model.

A distance runner's performance is generally limited by energy availability when competing or training. Modifying meal frequency and timing by abstaining from eating or drinking, from dawn to dusk, during Ramadan fasting is hypothesized to induce hypohydration and reduced caloric and nutrient intake. The purpose of this study was to investigate the impact of Ramadan fasting on runners' performances.

Structural Features of a Full-Length Ubiquitin Ligase Responsible for the Formation of Patches at the Plasma Membrane.

Plant U-box armadillo repeat (PUB-ARM) ubiquitin (Ub) ligases have important functions in plant defense through the ubiquitination of target proteins. Defense against pathogens involves vesicle trafficking and the formation of extracellular vesicles. The PUB-ARM protein SENESCENCE ASSOCIATED UBIQUITIN E3 LIGASE1 (SAUL1) can form patches at the plasma membrane related to tethering multi-vesicular bodies (MVBs) to the plasma membrane.

Epidemiology and management of hypertension among refugees in the Middle East: a review of the literature.

This review aims to explore the burden of hypertension among refugees in the Middle East by reporting its prevalence, risk factors and access to care. A comprehensive literature search was performed using Web of Science, Ovid MEDLINE, PubMed, SCOPUS, CINHAL+, WHO Regional Office for the Eastern Mediterranean (EMRO) and United Nations High Commissioner for Refugees (UNHCR) on articles spanning from 1948 until 2020. Most studies were cross-sectional in design.

Healthy lifestyle behaviors are major predictors of mental wellbeing during COVID-19 pandemic confinement: A study on adult Arabs in higher educational institutions.

Background: In the past infectious diseases affected the quality of lifestyle during home confinement. The study conducted examines the influence of home confinement during the COVID-19 pandemic outbreak on lifestyle, mental wellbeing, nutritional status, and sleeping pattern.

Method: An online multicategorical questionnaire was distributed to collect demographic information combined with the following tools: Food Frequency Questionnaire (FFQ), International Physical Activity Questionnaire (IPAQ), WHO-5 wellbeing score, and Pittsburgh Sleep Quality Index (PSQI).

Associated with Hyperphosphatasia with Mental Retardation Plays a Novel Role in Brain Morphogenesis and Neuronal Wiring at Early Development.

Recessive mutations in Post-GPI attachment to proteins 3 () cause the rare neurological disorder hyperphosphatasia with mental retardation syndrome 4 type (HPMRS4). Here, we report a novel homozygous nonsense mutation in (c.265C>T-p.

[Sclerosing rhabdomyosarcoma of the parotid gland: Unusual location of a rare mesenchymal tumor].

Rhabdomyosarcoma is a malignant mesenchymal tumour with skeletal muscle differentiation. Its sclerosing variant is a rare entity, which is described in the latest WHO edition of soft tissues in association with the spindle cell subtype, with which it shares clinical, morphological and cytogenetic features. Cytogenetic advances have allowed a prognostic approach to fusiform/sclerosing cell rhabdomyosarcoma by individualizing 3 different genomic prognostic groups.

Occurrence of plasmid-mediated quinolone resistance determinants among Escherichia coli strains isolated from animals in Tunisia: Specific pathovars acquired qnr genes.

Objectives: The aim of this study was to characterise Escherichia coli strains harbouring plasmid-mediated quinolone resistance (PMQR) genes recovered from various samples (n = 116) from healthy and diarrhoeic animals in Tunisia.

Methods: All nalidixic acid-resistant E. coli isolates were screened for the presence of PMQR genes.

Metatypical Basal Cell Carcinoma: A 6-Year Retrospective Study.

Metatypical basal cell carcinoma (MBCC) represents a high-risk type of cutaneous tumor and has characteristics similar to basal cell carcinoma and squamous cell carcinoma. We report a retrospective study of 13 patients who presented with cervicofacial MBCC. Our study found an increased prevalence of aggressive clinicohistologic features and showed disease recurrences in more than one-third of the patients; therefore, we conclude that MBCC is an aggressive variant that requires a complex surgical approach for achieving a stable and complete remission.

Diverse Escherichia coli pathovars of phylogroups B2 and D isolated from animals in Tunisia.

Introduction: The virulent Escherichia coli strains responsible for extraintestinal infections were mainly belonged to B2 and D phylogroups. However, no past studies have determinate via the presence of virulence genes the frequency of E. coli pathovars recovered from animals housed in farms in Tunisia.

HHV8/EBV Coinfection Lymphoproliferative Disorder: Rare Entity with a Favorable Outcome.

HHV8/EBV-associated germinotropic lymphoproliferative disorder (GLD) is a challenging diagnosis given its rarity, the particular clinical presentation, and the lack of expression of markers usually used in establishing hematopoietic lineage. We report a new case of HHV8/EBV GLD in an immunocompetent 78-year-old woman. The diagnosis was made in an incidentally discovered lymphadenopathy.

Antimicrobial drug resistance and genetic properties of Salmonella enterica serotype Enteritidis circulating in chicken farms in Tunisia.

This study focused on 77 isolates of Salmonella enterica serotype Enteritidis collected during 2009 to 2013 from healthy and sick chickens and environmental farm samples in Tunisia. Resistance to 14 antimicrobials and the encoding genes were analyzed. 66, 26, 6.

Metastatic Squamous Cell Carcinoma of the Stomach.

Primary squamous cell carcinoma of the stomach is very rare. Its pathogenesis is unclear and the treatment strategy is controversial. We report an agressive primary squamous cell carcinoma of the stomach with liver and lung metastases in a 55-year-old man.