Drug Interaction Studies of Cabamiquine:Ganaplacide Combination against Hepatic .

New antimalarial combination therapies with novel modes of action are required to counter the emergence and spread of drug resistance against existing therapeutics. Here, we present a study to evaluate the preventive activity of a combination of clinical antimalarial drug candidates, cabamiquine and ganaplacide, that have multistage activity against the liver and blood stages of infection. Cabamiquine (DDD107498, M5717) inhibits parasite protein synthesis, and ganaplacide (KAF156) inhibits protein trafficking, blocks the establishment of new permeation pathways, and causes endoplasmic reticulum expansion.

Cryptosporidium PI(4)K inhibitor EDI048 is a gut-restricted parasiticidal agent to treat paediatric enteric cryptosporidiosis.

Diarrhoeal disease caused by Cryptosporidium is a major cause of morbidity and mortality in young and malnourished children from low- and middle-income countries, with no vaccine or effective treatment. Here we describe the discovery of EDI048, a Cryptosporidium PI(4)K inhibitor, designed to be active at the infection site in the gastrointestinal tract and undergo rapid metabolism in the liver. By using mutational analysis and crystal structure, we show that EDI048 binds to highly conserved amino acid residues in the ATP-binding site.

DETECTION OF CF. , AND IN CERVIDS OF THE SCOTTISH HIGHLANDS, UNITED KINGDOM.

Outbreaks of suspected tick-borne disease (redwater fever) have been reported in captive deer of the Scottish Highlands. In this pilot study, polymerase chain reaction and amplicon sequencing were used to detect tick-borne pathogens in opportunistically collected blood and spleen samples from 63 (healthy, n = 44; diseased, n = 19) cervids, and 45 questing and feeding ticks () from the outbreak sites in 2021-2022. Potentially pathogenic species were detected in deer but not identified in ticks, was detected in both deer and ticks, and was detected in ticks but not in deer.

Modified failproof physics-informed neural network framework for fast and accurate optical fiber transmission link modeling.

Physics-informed neural networks (PINNs) have recently emerged as an important and ground-breaking technique in scientific machine learning for numerous applications including in optical fiber communications. However, the vanilla/baseline version of PINNs is prone to fail under certain conditions because of the nature of the physics-based regularization term in its loss function. The use of this unique regularization technique results in a highly complex non-convex loss landscape when visualized.

Utilization of clinical practice guidelines for cancer care in routine practice and during the coronavirus disease 2019 pandemic in India.

Aim: The coronavirus disease 2019 (COVID-19) pandemic affected cancer service delivery and the feasibility of following the standard treatment guidelines. The present paper describes the use of clinical care guidelines for cancer management in routine practice and the approach adopted towards cancer care during the COVID-19 pandemic in India.

Methods: A web-based survey was done in 107 hospitals (including public and private health facilities) that hosted Hospital-Based Cancer Registries under the National Cancer Registry Programme.