The project is closely aligned with (i) ADB's Strategy 2030's operational priorities on gender equality, environment, climate resilience and disaster risk management, rural development and food security, and institutional strengthening; (ii) Sustainable Development Goals on economic growth, social inclusion and environmental protection; and (iii) ADB's Water Sector Directional Guide that aims for poverty reduction, gender equality, climate resilience, food security, and capacity building.

The project will be aligned with the following impacts: (i) modern public health service system ensuring well-being of all Thais in an effective, fair, sufficient, and sustainable manner developed; and (ii) UHC, including access to essential health care services, sustained. The outcome is: access to quality public hospital services by all in selected provinces improved.

Devices that let people with paralysis walk and talk are rapidly improving. Some see a future in which we alter memories and download skills – but major challenges remain

As a major type of structural variants, tandem duplication plays a critical role in tumorigenesis by increasing oncogene dosage. Recent work has revealed that noncoding enhancers are also affected by duplications leading to the activation of oncogenes that are inside or outside of the duplicated regions. However, the prevalence of enhancer duplication and the identity of their target genes remains largely unknown in the cancer genome. Here, by analyzing whole-genome sequencing data in a non-gene-centric manner, we identify 881 duplication hotspots in 13 major cancer types, most of which do not contain protein-coding genes. We show that the hotspots are enriched with distal enhancer elements and are highly lineage-specific. We develop a HiChIP-based methodology that navigates enhancer–promoter contact maps to prioritize the target genes for the duplication hotspots harboring enhancer elements. The methodology identifies many novel enhancer duplication events activating oncogenes such as ESR1, FOXA1, GATA3, GATA6, TP63, and VEGFA, as well as potentially novel oncogenes such as GRHL2, IRF2BP2, and CREB3L1. In particular, we identify a duplication hotspot on Chromosome 10p15 harboring a cluster of enhancers, which skips over two genes, through a long-range chromatin interaction, to activate an oncogenic isoform of the NET1 gene to promote migration of gastric cancer cells. Focusing on tandem duplications, our study substantially extends the catalog of noncoding driver alterations in multiple cancer types, revealing attractive targets for functional characterization and therapeutic intervention.

Clinical reports suggest that the most effective strategies for managing opioid use disorder comprise a comprehensive treatment program of both pharmacological and nonpharmacological approaches. However, the conditions under which these combinations are most effective are not well characterized. This study examined whether the presence of an alternative reinforcer could alter the efficacy of Food and Drug Administration–approved opioid antagonist or agonist medications, as well as the nonopioid flumazenil, in decreasing oxycodone choice self-administration in nonhuman primates. Adult squirrel monkeys (n = 7; four females) responded under concurrent second-order fixed-ratio (FR)-3(FR5:S);TO45s schedules of reinforcement for intravenous oxycodone (0.1 mg/kg) or saline on one lever and 30% sweetened condensed milk or water on the other. Doses of naltrexone (0.00032–1.0 mg/kg), nalbuphine (0.32–10 mg/kg), buprenorphine (0.0032–0.032 mg/kg), methadone (0.32–1.0 mg/kg), or flumazenil (1–3.2 mg/kg) were administered intramuscularly prior to oxycodone self-administration sessions that occurred with either milk or water as the alternative. Naltrexone, a μ-opioid receptor antagonist, was >30-fold more potent when milk was available compared with water and abolished oxycodone intake (injections/session) while concomitantly increasing milk deliveries at the highest dose tested. Pretreatment with the low-efficacy μ-agonist nalbuphine was most effective in the presence of milk compared with water, decreasing oxycodone preference to <50% of control values. The higher efficacy μ-agonists, methadone and buprenorphine, and the benzodiazepine antagonist flumazenil did not appreciably alter the reinforcing potency of oxycodone under either condition. These results suggest that antagonist medications used in combination with alternative reinforcers may be an effective strategy to curtail opioid abuse–related behaviors.

BACKGROUND AND PURPOSE:

A cleftlike nonenhancing hypointensity was observed repeatedly in the pituitary gland at the adenohypophysis/neurohypophysis border on contrast-enhanced 3D fat-saturated T1-MPRAGE using clinical 7T MRI. Our primary goal was to assess the prevalence of this finding. The secondary goals were to evaluate the frequency of other incidental pituitary lesions, MRI artifacts, and their effect on pituitary imaging on the contrast-enhanced 3D fat-saturated T1 MPRAGE at 7T.

Devices that let people with paralysis walk and talk are rapidly improving. Some see a future in which we alter memories and download skills – but major challenges remain

The Indian pharmaceutical industry is advocating for enhanced fire safety measures and improved insurance coverage for employees working in pharmaceutical facilities.

Mar 13, 2024

David Kearn argues that even in the absence of restrictive resource and budgetary constraints, a focus on identifying and achieving concrete objectives that will position the United States and its allies to effectively deter aggression in critical regional flashpoints should be the priority given the stressed nature of the defense industrial base and the nuclear enterprise.

Chase launches new Ultimate Rewards website offering customers enhanced, personalized rewards.

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The French tax authority has announced that it will modify and extend a scheme that allows employers to pay workers tax-free bonuses.

Hong Kong's Legislative Council has passed a bill to implement a series of amendments to the Inland Revenue Ordinance.

Hong Kong's Legislative Council has passed a bill to implement a series of amendments to the Inland Revenue Ordinance.

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Common gut microbe called Blastocystis might play a surprising role in how our diet impacts our health, a new study suggests. The research, led by a team

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The expansion of insurance coverage under the Affordable Care Act (ACA) correlated with a rise in patient admissions to accredited cancer hospitals in Pennsylvania (!--ref1--).

You may not have even been acquainted to the thought of social media management in recent past, however in today’s world you will hear it spoken of from presumably every one. A number of us use this expression as we have a...

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