Feasibility of snapshot testing using wearable sensors to detect cardiorespiratory illness (COVID infection in India).

The COVID-19 pandemic has challenged the current paradigm of clinical and community-based disease detection. We present a multimodal wearable sensor system paired with a two-minute, movement-based activity sequence that successfully captures a snapshot of physiological data (including cardiac, respiratory, temperature, and percent oxygen saturation). We conducted a large, multi-site trial of this technology across India from June 2021 to April 2022 amidst the COVID-19 pandemic (Clinical trial registry name: International Validation of Wearable Sensor to Monitor COVID-19 Like Signs and Symptoms; NCT05334680; initial release: 04/15/2022).

The Face and Features of RNU4-2: A New, Common, Recognizable, Yet Hidden Neurodevelopmental Disorder.

Background: RNU4-2 is a newly identified, noncoding gene responsible for a significant proportion of individuals with neurodevelopmental disorders (NDDs). Diagnosis is hampered by the inability of commonly employed clinical testing methods, including exome sequencing and currently formulated multigene panels, to detect variants in the noncoding region. The relatively high prevalence of this condition, predicted to affect thousands of undiagnosed children with NDDs, makes it even more relevant to have better tools to facilitate diagnosis.

Durable Muscle Extracellular Matrix Engineered with Adhesive Phenolic Moieties for Effective Skeletal Muscle Regeneration in Muscle Atrophy.

Muscle atrophy detrimentally impacts health and exacerbates physical disability, leading to increased mortality. In particular, sarcopenia, aging-related degenerative muscle loss, necessitates urgent remedies. Current approaches for treating muscle atrophy include exercise and nutrition, while drug exploration remains in its early stages.

Mapping extrachromosomal DNA amplifications during cancer progression.

To understand the role of extrachromosomal DNA (ecDNA) amplifications in cancer progression, we detected and classified focal amplifications in 8,060 newly diagnosed primary cancers, untreated metastases and heavily pretreated tumors. The ecDNAs were detected at significantly higher frequency in untreated metastatic and pretreated tumors compared to newly diagnosed cancers. Tumors from chemotherapy-pretreated patients showed significantly higher ecDNA frequency compared to untreated cancers.

Next-gen spinal cord injury clinical trials: lessons learned and opportunities for future success.

Despite promising basic science discoveries and a surge in clinical trials, the quest for effective treatments that restore neurological function after spinal cord injury lags on. While "failed" in a conventional sense, emerging solutions to longstanding challenges represent promising steps towards a future with effective interventions. In this personal view, we highlight clinical trials implementing new solutions and their impact on the field.

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.

Practical Approach to Longitudinal Neurologic Care of Adults With X-Linked Adrenoleukodystrophy and Adrenomyeloneuropathy.

Although X-linked adrenoleukodystrophy (ALD) has historically been considered a childhood disease managed by pediatric neurologists, it is one of the most common leukodystrophies diagnosed in adulthood. An increase in both male and female adults reaching diagnosis due to familial cases identified by state newborn screening panels and more widespread use of genetic testing results in a large cohort of presymptomatic or early symptomatic adults. This population is in urgent need of standardized assessments and follow-up care.