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The proposed project will support the Royal Government of Cambodia in its commitment to reduce Gender-based Violence (GBV) line with Sustainable Development Goal (SDG) 5 on gender equality, specifically to eliminate all forms of violence against all women and girls in the public and private spheres, through proven and novel approaches across the continuum of prevention, mitigation, and response.

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.

The proposed Northern China Agriculture and Food Ecosystem Net Zero Transformation Project (project) will support the PRC to achieve its climate commitment through catalyzing financing and strengthening institutional capacity for net zero transformation in agriculture and food ecosystem.

The noises made by organisms like ants and worms as they move around in the soil can be used to assess whether an ecosystem is in good shape

The New Horizons mission to Pluto, now zooming out of the Kuiper belt, has made a discovery that could upend what we know about where the solar system ends

New blood tests can reveal whether your immune system is fighting fit by looking at the balance of different immune cells, but there may be a simpler way of gauging your immune health

A mathematical proof shows that some quantum states can resist nature’s tendency to disorder – but only under very specific conditions

Title: Newborns' Immune Systems Ramp Up After Birth
Category: Health News
Created: 8/24/2018 12:00:00 AM
Last Editorial Review: 8/27/2018 12:00:00 AM

Title: Monitoring System for Underage Tobacco Sales Falls Short: Study
Category: Health News
Created: 8/29/2018 12:00:00 AM
Last Editorial Review: 8/30/2018 12:00:00 AM

Title: What Are the Main Parts of the Male Reproductive System?
Category: Diseases and Conditions
Created: 7/7/2022 12:00:00 AM
Last Editorial Review: 7/7/2022 12:00:00 AM

Background

Immature lung development and respiratory morbidity place preterm-born children at high risk of long-term pulmonary sequelae. This systematic review and meta-analysis aims to quantify lung function in preterm-born children and identify risk factors for a compromised lung function.

Background

Severe asthma significantly impacts a minority of children with asthma, leading to frequent symptoms, hospitalisations and potential long-term health consequences. However, accurate global data on severe asthma epidemiology is lacking. This study aims to address this gap, providing data on severe asthma epidemiology, regional differences and associated comorbidities.

Background

People living with serious respiratory illness experience a high burden of symptoms. This review aimed to determine whether multicomponent services reduce symptoms in people with serious illness related to respiratory disease.

Background

In adults with serious respiratory illness, fatigue is prevalent and under-recognised, with few treatment options. The aim of this review was to assess the impact of graded exercise therapy (GET) on fatigue in adults with serious respiratory illness.

Background

In adults with serious respiratory illness, breathlessness is prevalent and associated with reduced health-related quality of life. The aim of this review was to assess the impact of breathing techniques on breathlessness in adults with serious respiratory illness.

Background

People living with serious respiratory illness experience a high burden of distressing symptoms. Although opioids are prescribed for symptom management, they generate adverse events, and their benefits are unclear.

Most studies of genome organization have focused on intrachromosomal (cis) contacts because they harbor key features such as DNA loops and topologically associating domains. Interchromosomal (trans) contacts have received much less attention, and tools for interrogating potential biologically relevant trans structures are lacking. Here, we develop a computational framework that uses Hi-C data to identify sets of loci that jointly interact in trans. This method, trans-C, initiates probabilistic random walks with restarts from a set of seed loci to traverse an input Hi-C contact network, thereby identifying sets of trans-contacting loci. We validate trans-C in three increasingly complex models of established trans contacts: the Plasmodium falciparum var genes, the mouse olfactory receptor "Greek islands," and the human RBM20 cardiac splicing factory. We then apply trans-C to systematically test the hypothesis that genes coregulated by the same trans-acting element (i.e., a transcription or splicing factor) colocalize in three dimensions to form "RNA factories" that maximize the efficiency and accuracy of RNA biogenesis. We find that many loci with multiple binding sites of the same DNA-binding proteins interact with one another in trans, especially those bound by factors with intrinsically disordered domains. Similarly, clustered binding of a subset of RNA-binding proteins correlates with trans interaction of the encoding loci. We observe that these trans-interacting loci are close to nuclear speckles. These findings support the existence of trans-interacting chromatin domains (TIDs) driven by RNA biogenesis. Trans-C provides an efficient computational framework for studying these and other types of trans interactions, empowering studies of a poorly understood aspect of genome architecture.

Introduction:

High-quality primary care can reduce avoidable emergency department visits and emergency hospitalizations. The availability of electronic medical record (EMR) data and capacities for data storage and processing have created opportunities for predictive analytics. This systematic review examines studies which predict emergency department visits, hospitalizations, and mortality using EMR data from primary care.

The analysis of extractables and leachables and subsequent risk assessment is an important aspect of the determination of biocompatibility for many medical devices. Leachable chemicals have the potential to pose a toxicological risk to patients, and therefore it is required that they be adequately characterized and assessed for potential safety concerns. One important consideration in the assessment of leachables is the choice of a suitable simulating solvent intended to replicate the use condition for the device and its biological environment. This aspect of study design is especially difficult for blood-contacting medical devices due to the complexity of simulating the biological matrix. This publication reports a comparison of the extracting power of different binary solvent mixtures and saline in comparison with whole blood for a bloodline tubing set connected to a hemodialyzer. Ten different known extractables, spanning a range of physicochemical properties and molecular weights, were quantified. The results indicated that for low-molecular-weight analytes, a suitable exaggeration for whole blood can be obtained using a low-concentration ethanol/water mixture (20%), and in general, extracted quantity increases with the concentration of alcohol cosolvent. For polyvinylpyrrolidone, the opposite trend was observed, as solubility of the polymer was found to decrease with increasing alcohol concentration, resulting in lower extracted quantities at high alcohol concentrations. Analysis of ethanol/water concentrations in the extract solutions post extraction indicated no change in solvent composition.

Drug–drug interaction (DDI) assessment of therapeutic peptides is an evolving area. The industry generally follows DDI guidelines for small molecules, but the translation of data generated with commonly used in vitro systems to in vivo is sparse. In the current study, we investigated the ability of advanced human hepatocyte in vitro systems, namely HepatoPac, spheroids, and Liver-on-a-chip, to assess potential changes in regulation of CYP1A2, CYP2B6, CYP3A4, SLCO1B1, and ABCC2 in the presence of selected therapeutic peptides, proteins, and small molecules. The peptide NN1177, a glucagon and GLP-1 receptor co-agonist, did not suppress mRNA expression or activity of CYP1A2, CYP2B6, and CYP3A4 in HepatoPac, spheroids, or Liver-on-a-chip; these findings were in contrast to the data obtained in sandwich cultured hepatocytes. No effect of NN1177 on SLCO1B1 and ABCC2 mRNA was observed in any of the complex systems. The induction magnitude differed across the systems (e.g., rifampicin induction of CYP3A4 mRNA ranged from 2.8-fold in spheroids to 81.2-fold in Liver-on-a-chip). Small molecules, obeticholic acid and abemaciclib, showed varying responses in HepatoPac, spheroids, and Liver-on-a-chip, indicating a need for EC₅₀ determinations to fully assess translatability data. HepatoPac, the most extensively investigated in this study (3 donors), showed high potential to investigate DDIs associated with CYP regulation by therapeutic peptides. Spheroids and Liver-on-a-chip were only assessed in one hepatocyte donor and further evaluations are required to confirm their potential. This study establishes an excellent foundation toward the establishment of more clinically-relevant in vitro tools for evaluation of potential DDIs with therapeutic peptides.

ABSTRACTIntroduction:Since the health information system (HIS) in public health care services in Serbia was introduced in 2009, it has gradually expanded. However, it is unclear how well the HIS components have developed and the whole system’s stage of maturity.Method:In June–September 2021, a maturity assessment of the Serbian HIS was conducted for the first time using the HIS Stages of Continuous Improvement (SOCI) toolkit. The toolkit measures HIS status across 5 HIS domains: leadership and governance, management and workforce, information and communication technology (ICT), standards and interoperability, and data quality and use. The domains were further divided into 13 components and 39 subcomponents whose maturity stage was assessed on a 5-point Likert scale, indicating the level of development: (1) emerging/ad hoc; (2) repeatable; (3) defined; (4) managed; and (5) optimized. The toolkit was applied in a working group of 32 professionals and experts who were engaged in developing the new national eHealth strategy and action plan.Results:The overall maturity score of the Serbian HIS was 1.6, which indicates a low level. The highest baseline score (2) was given to the standards and interoperability domain, and the lowest (1.1) was given to ICT infrastructure. The remaining 3 domains (leadership and governance, Management and Workforce, and Data Quality and Use) were similarly rated (1.7, 1.7, and 1.6, respectively).Conclusion:A baseline assessment of the maturity level of Serbian HIS indicates that the majority of components are between the emerging/ad hoc stage and repeatable, which represent isolated, ad hoc efforts, with some basic processes in place and existing and accessible policies. This exercise provided an opportunity to address identified weaknesses in the upcoming national eHealth strategy.

ABSTRACTIntroduction:Health risks associated with short interpregnancy intervals, coupled with women’s desires to avoid pregnancy following childbirth, underscore the need for effective postpartum family planning programs. The antenatal period provides an opportunity to intervene; however, evidence is limited on the effectiveness of interventions aimed at reaching women in the antenatal period to increase voluntary postpartum family planning in low- and middle-income countries (LMICs). This systematic review aimed to identify and describe interventions in LMICs that attempted to increase postpartum contraceptive use via contacts with pregnant women in the antenatal period.Methods:Studies published from January 2012 to July 2022 were considered if they were conducted in LMICs, evaluated an intervention delivered during the antenatal period, were designed to affect postpartum contraceptive use, were experimental or quasi-experimental, and were published in French or English. The main outcome of interest was postpartum contraceptive use within 1 year after birth, defined as the use of any method of contraception at the time of data collection. We searched EMBASE, Global Health, and Medline and manually searched the reference lists from studies included in the full-text screening.Results:We double-screened 771 records and included 34 reports on 31 unique interventions in the review. Twenty-three studies were published from 2018 on, with 21 studies conducted in sub-Saharan Africa. Approximately half of the study designs (n=16) were randomized controlled trials, and half (n=15) were quasi-experimental. Interventions were heterogeneous. Among the 24 studies that reported on the main outcome of interest, 18 reported a positive intervention effect, with intervention recipients having greater contraceptive use in the first year postpartum.Conclusion:While the studies in this systematic review were heterogeneous, the findings suggest that interventions that included a multifaceted package of initiatives appeared to be most likely to have a positive effect.

Glioblastoma (GBM) is a disease of the whole brain, with infiltrative tumor cells protected by an intact blood-brain barrier (BBB). GBM has a poor prognosis despite aggressive treatment, in part due to the lack of adequate drug permeability at the BBB. Standard of care GBM therapies include radiation and cytotoxic chemotherapy that lead to DNA damage. Subsequent activation of DNA damage response (DDR) pathways can induce resistance. Various DDR inhibitors, targeting the key regulators of these pathways such as ataxia telangiectasia mutated and Rad3-related (ATR), are being explored as radio- and chemosensitizers. Elimusertib, a novel ATR kinase inhibitor, can prevent repair of damaged DNA, increasing efficacy of DNA-damaging cytotoxic therapies. Robust synergy was observed in vitro when elimusertib was combined with the DNA-damaging agent temozolomide; however, we did not observe improvement with this combination in in vivo efficacy studies in GBM orthotopic tumor-bearing mice. This in vitro–in vivo disconnect was explored to understand factors influencing central nervous system (CNS) distribution of elimusertib and reasons for lack of efficacy. We observed that elimusertib is rapidly cleared from systemic circulation in mice and would not maintain adequate exposure in the CNS for efficacious combination therapy with temozolomide. CNS distribution of elimusertib is partially limited by P-glycoprotein efflux at the BBB, and high binding to CNS tissues leads to low levels of pharmacologically active (unbound) drug in the brain. Acknowledging the potential for interspecies differences in pharmacokinetics, these data suggest that clinical translation of elimusertib in combination with temozolomide for treatment of GBM may be limited.

Nitric oxide (NO) from endothelial NO synthase importantly contributes to vascular homeostasis. Reduced NO production or increased scavenging during disease conditions with oxidative stress contribute to endothelial dysfunction and NO deficiency. In addition to the classical enzymatic NO synthases (NOS) system, NO can also be generated via the nitrate-nitrite-NO pathway. Dietary and pharmacological approaches aimed at increasing NO bioactivity, especially in the cardiovascular system, have been the focus of much research since the discovery of this small gaseous signaling molecule. Despite wide appreciation of the biological role of NOS/NO signaling, questions still remain about the chemical nature of NOS-derived bioactivity. Recent studies show that NO-like bioactivity can be efficiently transduced by mobile NO-ferroheme species, which can transfer between proteins, partition into a hydrophobic phase, and directly activate the soluble guanylyl cyclase-cGMP-protein kinase G pathway without intermediacy of free NO. Moreover, interaction between red blood cells and the endothelium in the regulation of vascular NO homeostasis have gained much attention, especially in conditions with cardiometabolic disease. In this review we discuss both classical and nonclassical pathways for NO generation in the cardiovascular system and how these can be modulated for therapeutic purposes.

Anorectal malformations (ARMs) constitute a group of congenital defects of the gastrointestinal and urogenital systems. They affect males and females, with an estimated worldwide prevalence of 1 in 5000 live births. These malformations are clinically heterogeneous and can be part of a syndromic presentation (syndromic ARM) or as a nonsyndromic entity (nonsyndromic ARM). Despite the well-recognized heritability of nonsyndromic ARM, the genetic etiology in most patients is unknown. In this study, we describe three siblings with diverse congenital anomalies of the genitourinary system, anemia, delayed milestones, and skeletal anomalies. Genome sequencing identified a novel, paternally inherited heterozygous Caudal type Homeobox 2 (CDX2) variant (c.722A > G (p.Glu241Gly)), that was present in all three affected siblings. The variant identified in this family is absent from population databases and predicted to be damaging by most in silico pathogenicity tools. So far, only two other reports implicate variants in CDX2 with ARMs. Remarkably, the individuals described in these studies had similar clinical phenotypes and genetic alterations in CDX2. CDX2 encodes a transcription factor and is considered the master regulator of gastrointestinal development. This variant maps to the homeobox domain of the encoded protein, which is critical for interaction with DNA targets. Our finding provides a potential molecular diagnosis for this family's condition and supports the role of CDX2 in anorectal anomalies. It also highlights the clinical heterogeneity and variable penetrance of ARM predisposition variants, another well-documented phenomenon. Finally, it underscores the diagnostic utility of genomic profiling of ARMs to identify the genetic etiology of these defects.

BackgroundMost people with type 2 diabetes receive treatment in primary care by GPs who are not specialised in diabetes. Thus, it is important to uncover the most essential information needs regarding type 2 diabetes in general practice.AimTo identify information needs related to type 2 diabetes for GPs.Design and settingSystematic review focused on literature relating to Western countries.MethodMEDLINE, Embase, PsycInfo and CINAHL were searched from inception to January 2024. Two researchers conducted the selection process, and citation searches were performed to identify any relevant articles missed by the database search. Quality appraisal was conducted with the Mixed Methods Appraisal Tool. Meaning units were coded individually, grouped into categories, and then studies were summarised within the context of these categories using narrative synthesis. An evidence map was created to highlight research gaps.ResultsThirty-nine included studies revealed eight main categories and 36 subcategories of information needs. Categories were organised into a comprehensive hierarchical model of information needs, suggesting ‘Knowledge of guidelines’ and ‘Reasons for referral’ as general information needs alongside more specific needs on ‘Medication’, ‘Management’, ‘Complications’, ‘Diagnosis’, ‘Risk factors’, and ‘Screening for diabetes’. The evidence map provides readers with the opportunity to explore the characteristics of the included studies in detail.ConclusionThis systematic review provides GPs, policymakers, and researchers with a hierarchical model of information and educational needs for GPs, and an evidence map showing gaps in the current literature. Information needs about clinical guidelines and reasons for referral to specialised care overlapped with needs for more specific information.

PURPOSE

Chest pain frequently poses a diagnostic challenge for general practitioners (GPs). Utilizing risk stratification tools might help GPs to rule out acute coronary syndrome (ACS) and make appropriate referral decisions. We conducted a systematic review of studies evaluating risk stratification tools for chest pain in primary care settings, both with and without troponin assays. Our aims were to assess the performance of tools for ruling out ACS and to provide a comprehensive review of the current evidence.

Over the past decades the zebrafish has emerged as an excellent model organism with which to study the biology of all glial cell types in nervous system development, plasticity, and regeneration. In this review, which builds on the earlier work by Lyons and Talbot in 2015, we will summarize how the relative ease to manipulate the zebrafish genome and its suitability for intravital imaging have helped understand principles of glial cell biology with a focus on oligodendrocytes, microglia, and astrocytes. We will highlight recent findings on the diverse properties and functions of these glial cell types in the central nervous system and discuss open questions and future directions of the field.

A national review of social work in Scotland has been launched in a bid to address ‘systemic racism’ within the sector.

The technology will deliver enhanced day-to-day and major incident response capability

Stroll on down to Uncle Capcom's garage, girls and boys, because it's time to meddle with a cat's voicebox, ride a combat peacock and meticulously injure a vast, blubbery teddybear. By which I mean, the Monster Hunter Wilds beta is now live on Steam through to 4th November at 2.59am GMT. That's 2.59am sharp. If you're hurrying along at 3am on Monday absolutely desperate to polish the aesthetics of a small enslaved catperson, you can sod off and play Dragon Age: The Veilguard instead.

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"Never read the comments," is a truth much-rehearsed by senior games journalists, but I have long since levelled-up past this axiom and entered into a new world of benevolent narcissism. I always read the comments, for all commenters are my children. They exist to glorify and preserve me in my dotage. True, occasionally my children say things like "I think your writing and opinions are appalling, and that you deserve to be repeatedly run over by a herd of deer", but it is the nature of children to rebel.

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Let’s try and get you up to speed on the fascinating oddity that is simulation game Ecosystem, on the off chance that Nate's coverage of it hasn't stuck with you like an unwelcome brain parasite you’re nonetheless unwilling to get removed for fear of the lingering emptiness it might cause (he once described an eel as “a quaver with erectile dysfunction”). Broadly speaking, this game is Spore’s evolutionary-biology-degree-having cousin. It’s been in early access for about three years now, but with the latest "Crustacean" update, it’s just hit 1.0. Once again, carcinization has come for all things.

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To transport our planet across the universe, we would need to bring the whole solar system to sustain life on Earth – on this episode of Dead Planets Society, our hosts contemplate how to shepherd all that baggage on this scenic journey

Exoplanets in binary star systems usually orbit both stars, but astronomers have now spotted three planets orbiting one or the other star in a pair

Astronomers listened for radio signals emanating from planets in the TRAPPIST-1 system, but found no evidence of any interplanetary communications

The books, TV, games and more that New Scientist staff have enjoyed this week