Notes

Germline and Somatic strains inside postmenopausal breast cancers individuals.
Heat shock proteins (HSPs), a representative family of chaperone genes, play crucial roles in malignant progression and are pursued as attractive anti-cancer therapeutic targets. Despite tremendous efforts to develop anti-cancer drugs based on HSPs, no HSP inhibitors have thus far reached the milestone of FDA approval. There remains an unmet need to further understand the functional roles of HSPs in cancer.

We constructed the network for HSPs across ~ 10,000 tumor samples from The Cancer Genome Atlas (TCGA) and ~ 10,000 normal samples from Genotype-Tissue Expression (GTEx), and compared the network disruption between tumor and normal samples. We then examined the associations between HSPs and cancer hallmarks and validated these associations from multiple independent high-throughput functional screens, including Project Achilles and DRIVE. Finally, we experimentally characterized the dual function effects of HSPs in tumor proliferation and metastasis.

We comprehensively analyzed the HSP expression landsnhibitors as well as other drugs in cancer therapy.
Alcohol use disorder (AUD) is a highly prevalent, chronic relapsing disorder with a high disease burden in the USA. Pharmacotherapy is a promising treatment method for AUD; however, the few FDA-approved medications are only modestly effective. Medications development for AUD is a high priority research area, but the cumbersome drug development process hinders many potential compounds from reaching approval. One area with major opportunities for improvement is the process of screening novel compounds for initial efficacy, also known as early phase 2 trials. Early phase 2 trials incorporate human laboratory paradigms to assess relevant clinical constructs, such as craving and subjective responses to alcohol. However, these controlled paradigms often lack the ecological validity of clinical trials. Therefore, early phase 2 trials can be more efficient and clinically meaningful if they combine the internal validity of experimental laboratory testing with the external validity of clinical trials. To that end, thhich in turn can serve as an efficient strategy for making go/no-go decisions as to whether to proceed with clinical trials.

ClinicalTrials.gov NCT04249882 . Registered on 31 January 2020.
ClinicalTrials.gov NCT04249882 . Registered on 31 January 2020.Photoaging is mainly induced by continuous exposure to sun light, causing multiple unwanted skin characters and accelerating skin aging. Adipose-derived stem cells(ADSCs) are promising in supporting skin repair because of their significant antioxidant capacity and strong proliferation, differentiation, and migration ability, as well as their enriched secretome containing various growth factors and cytokines. The identification of the mechanisms by which ADSCs perform these functions for photoaging has great potential to explore therapeutic applications and combat skin aging. We also review the basic mechanisms of UV-induced skin aging and recent improvement in pre-clinical applications of ADSCs associated with photoaging. Results showed that ADSCs are potential to address photoaging problem and might treat skin cancer. Compared with ADSCs alone, the secretome-based approaches and different preconditionings of ADSCs are more promising to overcome the current limitations and enhance the anti-photoaging capacity.
Human milk is recommended for all very low birth weight infants. Breastmilk is highly variable in nutrient content, failing to meet the nutritional demands of this group. Fortification of human milk is recommended to prevent extrauterine growth retardation and associated poor neurodevelopmental outcome. However, standard fortification with fixed dose multicomponent fortifier does not account for the variability in milk composition. Targeted fortification is a promising alternative and needs further investigation.

This randomized controlled trial will recruit preterm infants (≤ 32 weeks of gestation) within the first 7 days of life. After reaching 80 ml/kg/day of enteral feeding, patients will be randomized to receive standard fortification (HMF, Nutricia) or targeted fortification (modular components Bebilon Bialka, Nutricia-protein; Polycal, Nutricia-carbohydrates; Calogen, Nutricia-lipids). The intervention will continue until 37 weeks of post-conception age or hospital discharge. Olaparib Parents and outcome assessors will be blinded to the intervention. The primary outcome measure is velocity of weight, length, and head growth until 36 weeks post-conceptional age or discharge. Secondary outcomes include neurodevelopment at 12 months assessed with Bayley Scale of Development III, repeated at 36 months; body composition at discharge and at 4 months; and incidence of necrotizing enterocolitis, sepsis, retinopathy of prematurity, and bronchopulmonary dysplasia.

Targeted fortification has previously been shown as doable in the neonatal intensive care unit context. If it shows to improve growth and neonatal outcome, choosing the targeted fortification as a first line nutritional approach in very low birth weight infants may become a recommendation.

ClinicalTrials.gov NCT03775785 , Registered on July 2019.
ClinicalTrials.gov NCT03775785 , Registered on July 2019.
Pharmacological therapies of proven efficacy in coronavirus disease 2019 (COVID-19) are still lacking. We have identified IFNβ-1a as the most promising drug to be repurposed for COVID-19. The rationale relies on the evidence of IFNβ anti-viral activity in vitro against SARS-CoV-2 and animal models resembling SARS-CoV-2 infection and on a recent clinical trial where IFNβ was indicated as the key component of a successful therapeutic combination.

This is a randomized, controlled, open-label, monocentric, phase II trial (INTERCOP trial). One hundred twenty-six patients with positive swab detection of SARS-CoV-2, radiological signs of pneumonia, and mild-to-moderate disease will be randomized 21 to IFNβ-1a in addition to standard of care vs standard of care alone. No other anti-viral drugs will be used as part of the regimens, both in the control and the intervention arms. IFNβ-1a will be administered subcutaneously at the dose of 44 mcg (equivalent to 12 million international units) three times per week, at least 48 h apart, for a total of 2weeks.
Website: https://www.selleckchem.com/products/AZD2281(Olaparib).html