Discovery of Novel Pyrido[2,3-b]Pyrazine Human Cytomegalovirus Polymerase Inhibitors with Broad Spectrum Antiherpetic Activity and Reduced hERG Inhibition.

The development of non-nucleoside inhibitors targeting human cytomegalovirus (HCMV) polymerase presents a promising approach for enhancing therapeutic treatment for patients with sustained HCMV viremia. A series of non-nucleoside HCMV DNA polymerase inhibitors with various substitution groups at 2-postition of the novel pyrido[2,3-b]pyrazine core was synthesized and investigated. The study focused on optimizing HCMV polymerase inhibition while minimizing off-target inhibition of human ether-à-go-go (hERG) ion channel.

Predictive modeling for breast cancer classification in the context of Bangladeshi patients by use of machine learning approach with explainable AI.

Breast cancer has rapidly increased in prevalence in recent years, making it one of the leading causes of mortality worldwide. Among all cancers, it is by far the most common. Diagnosing this illness manually requires significant time and expertise.

Peptidomimetic nitrile warheads as SARS-CoV-2 3CL protease inhibitors.

Tragically, the death toll from the COVID-19 pandemic continues to rise, and with variants being observed around the globe new therapeutics, particularly direct-acting antivirals that are easily administered, are desperately needed. Studies targeting the SARS-CoV-2 3CL protease, which is critical for viral replication, with different peptidomimetics and warheads is an active area of research for development of potential drugs. To date, however, only a few publications have evaluated the nitrile warhead as a viral 3CL protease inhibitor, with only modest activity reported.

Peptidomimetic α-Acyloxymethylketone Warheads with Six-Membered Lactam P1 Glutamine Mimic: SARS-CoV-2 3CL Protease Inhibition, Coronavirus Antiviral Activity, and Biological Stability.

Recurring coronavirus outbreaks, such as the current COVID-19 pandemic, establish a necessity to develop direct-acting antivirals that can be readily administered and are active against a broad spectrum of coronaviruses. Described in this Article are novel α-acyloxymethylketone warhead peptidomimetic compounds with a six-membered lactam glutamine mimic in P1. Compounds with potent SARS-CoV-2 3CL protease and viral replication inhibition were identified with low cytotoxicity and good plasma and glutathione stability.

Developing eHealth in neonatal care to enhance parents' self-management.

Background: Discharge from a neonatal care unit is often experienced as a vulnerable time for parents. By communicating through digital technology, it may be possible to improve the support for parents and thereby make the transition from hospital to home less stressful.

Aim: To develop an eHealth device supporting the transition from hospital to home for parents with a preterm-born child in Sweden using participatory design.

Social Jetlag and Its Association With Screen Time and Nighttime Texting Among Adolescents in Sweden: A Cross-Sectional Study.

The discrepancy between social and biological clock due to sleep and wake up time difference across weekdays and weekends is referred as social jetlag. The overall aim of this study is to test whether there is an association between both screen time and nighttime texting and social jetlag among 13- to 15-year-old adolescents in Sweden. This study included a cross-sectional survey in which data were collected from all schools with grades 7 and 8 in four municipalities in southern Sweden.

Comprehensive in vitro characterization of PD-L1 small molecule inhibitors.

Blockade of the programmed cell death 1 (PD-1)/programmed cell death-ligand 1 (PD-L1) interaction has emerged as a powerful strategy in cancer immunotherapy. Recently, there have been enormous efforts to develop potent PD-1/PD-L1 inhibitors. In particular, Bristol-Myers Squibb (BMS) and Aurigene Discovery Technologies have individually disclosed several promising PD-1/PD-L1 inhibitors, whose detailed experimental data are not publicly disclosed.

Association of Depressive Symptoms with Consumption of Analgesics among Adolescents.

Purpose: To investigate the prevalence of depressive symptoms, pain (headaches and stomachaches), and analgesic consumption in addition to the association between depressive symptoms and analgesic consumption among adolescents.

Design And Methods: This cross-sectional study was conducted in southern Sweden. The survey was distributed among students in grade 8 (aged 13-15 years, n = 878).

Reproductive biology of Nemipterus japonicus (Bloch, 1791) from the coastal waters of Bintulu (South China Sea), Sarawak, Malaysia.

Samples of threadfin breams Nemipterus japonicus were collected from a village in Kuala Nyalau and a fish landing centre at Bintulu from April 2013 to March 2014. A total of 360 individuals of N. japonicus (214 male and 146 female) were used in this reproductive study.

Inner shell as variation key of local hard clam Meretrix spp.

The morphology and 12 shell morphometric features proportionate to shell length were analysed between local hard clam; Meretrix lyrata, M. meretrix and M. lusoria from Sarawak, Malaysia.

Forest structure and litter production of naturally re-generated white mangrove Avicennia marina in sub-tropical estuarine coast.

The present work deals with plant structure, phenology, litter production and decomposition of mangrove Avicennia marina in the newly re-generated mangrove forest in sub-tropical coast. The natural generation in this accreted coastal land of mono-specific A. marina forest stand was prominent, with 45% seedlings and 32% saplings.

Spatial distribution of copepods along the salinity gradient of Perai river estuary, Penang, Malaysia.

Investigation on copepod communities in Perai river estuary was conducted from November 2005 to May 2006. Five stations were established for monthly sampling and were located from the river mouth to the upper reaches of the river. Copepod samples were collected from vertical tows using a standard zooplankton net.

Composition of macrobenthos in the Bakkhali channel system, Cox's Bazar with notes on soil parameter.

Macrobenthos in coastal environment that play a significant role in the food web. It could also use as a good indicator of aquatic ecosystem health. The abundance and composition of macrobenthos in Bakkhali channel system, Cox's Bazar were conducted in relation to the soil parameters.

Discovery of a series of 2-(1H-pyrazol-1-yl)pyridines as ALK5 inhibitors with potential utility in the prevention of dermal scarring.

A series of 2-(1H-pyrazol-1-yl)pyridines are described as inhibitors of ALK5 (TGFβ receptor I kinase). Modeling compounds in the ALK5 kinase domain enabled some optimization of potency via substitutions on the pyrazole core. One of these compounds PF-03671148 gave a dose dependent reduction in TGFβ induced fibrotic gene expression in human fibroblasts.

Metastatic male ductal breast cancer mimicking obstructing primary colon cancer.

Male breast cancer comprises only about 1% of all breast cancers. Commonly, sites of metastases include the central nervous system, lungs, bones, and even liver. In females, extrahepatic gastrointestinal metastases are unusual but have been reported with various clinical presentations.

(1R,2S)-4-(2-cyano-cyclohexyl-oxy)-2-trifluoromethyl-benzonitrile, a potent androgen receptor antagonist for stimulating hair growth and reducing sebum production.

Synthesis, pharmacology, and pharmacokinetic profiles of (1R, 2S)-4-(2-cyano-cyclohexyl-oxy)-2-trifluoromethyl-benzonitrile are reported. This compound demonstrated remarkable potency for stimulating hair growth in a male C3H mouse model as well as reducing sebum production in the male Syrian hamster ear model.

The discovery of glycine and related amino acid-based factor Xa inhibitors.

Herein, we report on the identification of three potent glycine and related amino acid-based series of FXa inhibitors containing a neutral P1 chlorophenyl pharmacophore. A X-ray crystal structure has shown that constrained glycine derivatives with optimized N-substitution can greatly increase hydrophobic interactions in the FXa active site. Also, the substitution of a pyridone ring for a phenylsulfone ring in the P4 sidechain resulted in an inhibitor with enhanced oral bioavailability.

A Study Directed to the Asymmetric Synthesis of the Antineoplastic Macrolide Acutiphycin under Enantioselective Acyclic Stereoselection Based on Chiral Oxazaborolidinone-Promoted Asymmetic Aldol Reactions.

A shortening of the reaction path can be realized by using a series of the chiral oxazaborolidinone-promoted aldol reaction with respect to the practical synthesis of the (+)-acutiphycin seco acid derivative 5. The linear strategy is based on the utilization of five aldol reactions with a sequence of silyl nucleophiles, 7, 8, 35, 10, and 11, in the presence of stoichiometric amounts of the promoter, 1 or 2. The construction of the relative configuration between the stereogenic centers is diastereoselectively controlled by the stereochemistry of the promoter used in the enantioselective aldol reaction, which is nearly independent of that of the substrate (promoter control).

Axillary node dissection in malignant melanoma: results and complications.

Axillary node dissection was performed in 133 patients with malignant melanoma. The nodes were histologically negative for disease in 67 patients and positive in 66 patients. Disease-free survival rate varied according to the histologic and clinical status of the nodes and to the number of the nodes involved by tumor.

Occult breast cancer in two community hospitals in New York State.

The histopathologic results of 360 consecutive preoperative needle localizations of nonpalpable breast lesions performed at two community hospitals in New York State were analyzed for comparison with national data. Seventy-eight (21.6%) samples were malignant lesions.