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Breakfast Might Be Good for a Child's Emotional Health, Too

Title: Breakfast Might Be Good for a Child's Emotional Health, Too
Category: Health News
Created: 8/24/2022 12:00:00 AM
Last Editorial Review: 8/24/2022 12:00:00 AM




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8 Reasons You Are Not Losing Weight on Keto

Title: 8 Reasons You Are Not Losing Weight on Keto
Category: Health and Living
Created: 8/26/2022 12:00:00 AM
Last Editorial Review: 8/26/2022 12:00:00 AM




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How Long Do Potatoes Last? Raw, Cooked, and More

Title: How Long Do Potatoes Last? Raw, Cooked, and More
Category: Health and Living
Created: 8/26/2022 12:00:00 AM
Last Editorial Review: 8/26/2022 12:00:00 AM




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Fasting Diet Could Help Folks With Type 2 Diabetes

Title: Fasting Diet Could Help Folks With Type 2 Diabetes
Category: Health News
Created: 7/26/2022 12:00:00 AM
Last Editorial Review: 7/26/2022 12:00:00 AM




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Poliovirus Discovered in New York Wastewater

Title: Poliovirus Discovered in New York Wastewater
Category: Health News
Created: 8/12/2022 12:00:00 AM
Last Editorial Review: 8/15/2022 12:00:00 AM




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Pious Parasites: Medieval Monks Battled Nasty Gut Germs

Title: Pious Parasites: Medieval Monks Battled Nasty Gut Germs
Category: Health News
Created: 8/19/2022 12:00:00 AM
Last Editorial Review: 8/19/2022 12:00:00 AM




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Monkeypox Cases May Finally Be Ebbing, With Declines Seen in Europe, WHO Says

Title: Monkeypox Cases May Finally Be Ebbing, With Declines Seen in Europe, WHO Says
Category: Health News
Created: 8/25/2022 12:00:00 AM
Last Editorial Review: 8/25/2022 12:00:00 AM




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Scientists Design Skin Patch That Takes Ultrasound Images

Title: Scientists Design Skin Patch That Takes Ultrasound Images
Category: Health News
Created: 7/29/2022 12:00:00 AM
Last Editorial Review: 7/29/2022 12:00:00 AM




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Want That Pill to Work Fast? Your Body Position Matters

Title: Want That Pill to Work Fast? Your Body Position Matters
Category: Health News
Created: 8/17/2022 12:00:00 AM
Last Editorial Review: 8/17/2022 12:00:00 AM




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Are Skin Rashes Contagious?

Title: Are Skin Rashes Contagious?
Category: Diseases and Conditions
Created: 8/10/2015 12:00:00 AM
Last Editorial Review: 8/5/2022 12:00:00 AM




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Nerve Block Plus Lidocaine Clears Psoriasis in Small Study

Title: Nerve Block Plus Lidocaine Clears Psoriasis in Small Study
Category: Health News
Created: 8/15/2022 12:00:00 AM
Last Editorial Review: 8/16/2022 12:00:00 AM




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As Pandemic Eases, It's Boom Times for Cosmetic Surgeons

Title: As Pandemic Eases, It's Boom Times for Cosmetic Surgeons
Category: Health News
Created: 8/24/2022 12:00:00 AM
Last Editorial Review: 8/24/2022 12:00:00 AM




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COVID Crisis Has Stalled Fight Against HIV/AIDS

Title: COVID Crisis Has Stalled Fight Against HIV/AIDS
Category: Health News
Created: 7/28/2022 12:00:00 AM
Last Editorial Review: 7/29/2022 12:00:00 AM




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Experimental Drug May Ease Hot Flashes

Title: Experimental Drug May Ease Hot Flashes
Category: Health News
Created: 6/13/2022 12:00:00 AM
Last Editorial Review: 6/14/2022 12:00:00 AM




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How to Manage Menopause Symptoms After Breast Cancer

Title: How to Manage Menopause Symptoms After Breast Cancer
Category: Diseases and Conditions
Created: 7/7/2022 12:00:00 AM
Last Editorial Review: 7/7/2022 12:00:00 AM




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Do You Use Mouthwash Before or After Brushing?

Title: Do You Use Mouthwash Before or After Brushing?
Category: Health and Living
Created: 8/5/2022 12:00:00 AM
Last Editorial Review: 8/5/2022 12:00:00 AM




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There's More MS in Northern Countries. Now, Researchers Find New Reason Why

Title: There's More MS in Northern Countries. Now, Researchers Find New Reason Why
Category: Health News
Created: 8/25/2022 12:00:00 AM
Last Editorial Review: 8/25/2022 12:00:00 AM




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Yeast infections vs. STDs in Men and Women

Title: Yeast infections vs. STDs in Men and Women
Category: Diseases and Conditions
Created: 1/8/2020 12:00:00 AM
Last Editorial Review: 7/29/2022 12:00:00 AM




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Vaccines Have Slashed Rates of HPV Infection in Young American Women

Title: Vaccines Have Slashed Rates of HPV Infection in Young American Women
Category: Health News
Created: 8/22/2022 12:00:00 AM
Last Editorial Review: 8/23/2022 12:00:00 AM




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Being Social May Be Key to 'Sense of Purpose' as You Age

Title: Being Social May Be Key to 'Sense of Purpose' as You Age
Category: Health News
Created: 7/12/2022 12:00:00 AM
Last Editorial Review: 7/12/2022 12:00:00 AM




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Bedsores Can Cause Serious Harm — Are U.S. Nursing Homes Hiding Cases?

Title: Bedsores Can Cause Serious Harm — Are U.S. Nursing Homes Hiding Cases?
Category: Health News
Created: 8/17/2022 12:00:00 AM
Last Editorial Review: 8/18/2022 12:00:00 AM




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Stay Independent of Asthma, Allergies This July 4th

Title: Stay Independent of Asthma, Allergies This July 4th
Category: Health News
Created: 7/1/2022 12:00:00 AM
Last Editorial Review: 7/1/2022 12:00:00 AM




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How to Get Rid of Mucus in My Chest Fast

Title: How to Get Rid of Mucus in My Chest Fast
Category: Diseases and Conditions
Created: 6/22/2022 12:00:00 AM
Last Editorial Review: 6/22/2022 12:00:00 AM




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Mastoiditis

Title: Mastoiditis
Category: Diseases and Conditions
Created: 1/4/2018 12:00:00 AM
Last Editorial Review: 7/30/2022 12:00:00 AM




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Australia's Current Flu Season Is Tough: Will America's Be the Same?

Title: Australia's Current Flu Season Is Tough: Will America's Be the Same?
Category: Health News
Created: 8/4/2022 12:00:00 AM
Last Editorial Review: 8/5/2022 12:00:00 AM




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How Do I Increase Serotonin?

Title: How Do I Increase Serotonin?
Category: Diseases and Conditions
Created: 5/24/2021 12:00:00 AM
Last Editorial Review: 7/5/2022 12:00:00 AM




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What Are 4 Symptoms of Seasonal Affective Disorder?

Title: What Are 4 Symptoms of Seasonal Affective Disorder?
Category: Diseases and Conditions
Created: 12/10/2021 12:00:00 AM
Last Editorial Review: 7/6/2022 12:00:00 AM




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Study Casts Doubt on 'Chemical Imbalance' Theory of Depression

Title: Study Casts Doubt on 'Chemical Imbalance' Theory of Depression
Category: Health News
Created: 8/9/2022 12:00:00 AM
Last Editorial Review: 8/9/2022 12:00:00 AM




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Evidence-based management of symptoms in serious respiratory illness: what is in our toolbox?

Extract

Living with a respiratory illness requires patients to manage a wide range of symptoms, many of which will worsen as a disease progresses. Breathlessness is a hallmark feature of respiratory conditions, occurring in almost all individuals with COPD and interstitial lung disease (ILD) [1, 2]. Cough is present in 78% of people with ILD and is frequently distressing, with physical, social and emotional impacts [1, 3].




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Impaired lung function and associated risk factors in children born prematurely: a systematic review and meta-analysis

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.

Methods

We searched MEDLINE, Embase, Cochrane Library, Web of Science and Scopus for relevant studies published on preterm cohorts born since 1990. Studies comparing forced expiratory volume in 1 s (FEV1) in preterm-born children aged ≥5 years to term-born controls or normative data were included. Study quality was assessed using the Newcastle–Ottawa Scale for cohort studies. Standardised mean differences in FEV1 and secondary spirometry outcomes per study were pooled using meta-analysis. The impact of different demographic and neonatal variables on studies’ FEV1 effect sizes was investigated by meta-regression analyses. Certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations framework.

Results

We identified 42 studies with unique cohorts including 4743 preterm children and 9843 controls. Median gestational age in the studies was 28.0 weeks and age at assessment ranged from 6.7 to 16.7 years. Preterm children had lower FEV1 than controls (–0.58 sd, 95% CI –0.69– –0.47 sd, p<0.001) resulting in a relative risk of 2.9 (95% CI 2.4–3.4) for abnormal outcome, with high certainty of evidence. FEV1 was significantly associated with gestational age, birthweight, bronchopulmonary dysplasia and invasive mechanical ventilation in univariate meta-regression analyses (R2=36–96%).

Conclusion

This systematic review shows robust evidence of impaired lung function in preterm-born children with a high certainty of evidence.




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Epidemiology of severe asthma in children: a systematic review and meta-analysis

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.

Methods

We conducted a rigorous systematic review and meta-analysis following a registered protocol (PROSPERO CRD42023472845). We searched PubMed, Scopus and Web of Science for cohort or cross-sectional studies published since 2003, evaluating severe asthma incidence and prevalence in children. Study quality and risk of bias were assessed using STROBE guidelines.

Results

Nine studies investigating European children with asthma (aged 5–18 years) were included in the meta-analysis. No significant publication bias was found. The overall severe asthma prevalence in children with asthma was 3% (95% CI 1–6; I2=99.9%; p<0.001), with no significant difference between males and females. Prevalence estimates varied significantly depending on the diagnostic criteria used (Global Initiative for Asthma: 6%; European Respiratory Society/American Thoracic Society: 1%; other: 3%). Because none of the examined studies were prospectively designed, incidence rates could not be determined.

Conclusions

This systematic review and meta-analysis provide the first robust assessment of severe asthma prevalence among European children. Our findings underscore the need for comprehensive research to address knowledge gaps in severe asthma, including determining incidence rates, standardising definitions, investigating regional differences and evaluating comorbidities and treatment strategies.




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Noninvasive diagnostic modalities and prediction models for detecting pulmonary hypertension associated with interstitial lung disease: a narrative review

Pulmonary hypertension (PH) is highly prevalent in patients with interstitial lung disease (ILD) and is associated with increased morbidity and mortality. Widely available noninvasive screening tools are warranted to identify patients at risk for PH, especially severe PH, that could be managed at expert centres. This review summarises current evidence on noninvasive diagnostic modalities and prediction models for the timely detection of PH in patients with ILD. It critically evaluates these approaches and discusses future perspectives in the field. A comprehensive literature search was carried out in PubMed and Scopus, identifying 39 articles that fulfilled inclusion criteria. There is currently no single noninvasive test capable of accurately detecting and diagnosing PH in ILD patients. Estimated right ventricular pressure (RVSP) on Doppler echocardiography remains the single most predictive factor of PH, with other indirect echocardiographic markers increasing its diagnostic accuracy. However, RVSP can be difficult to estimate in patients due to suboptimal views from extensive lung disease. The majority of existing composite scores, including variables obtained from chest computed tomography, pulmonary function tests and cardiopulmonary exercise tests, were derived from retrospective studies, whilst lacking validation in external cohorts. Only two available scores, one based on a stepwise echocardiographic approach and the other on functional parameters, predicted the presence of PH with sufficient accuracy and used a validation cohort. Although several methodological limitations prohibit their generalisability, their use may help physicians to detect PH earlier. Further research on the potential of artificial intelligence may guide a more tailored approach, for timely PH diagnosis.




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Epidemiology of bronchiectasis

Bronchiectasis is a chronic respiratory disease characterised by permanent enlargement of the airways associated with cough, sputum production and a history of pulmonary exacerbations. In the past few years, incidence and prevalence of bronchiectasis have increased worldwide, possibly due to advances in imaging techniques and disease awareness, leading to increased socioeconomic burden and healthcare costs. Consistently, a mortality increase in bronchiectasis patient cohorts has been demonstrated in certain areas of the globe, with mortality rates of 16–24.8% over 4–5 years of follow-up. However, heterogeneity in epidemiological data is consistent, as reported prevalence in the general population ranges from 52.3 to more than 1000 per 100 000. Methodological flaws in the designs of available studies are likely to underestimate the proportion of people suffering from this condition worldwide and comparisons between different areas of the globe might be unreliable due to different assessment methods or local implementation of the same method in different contexts. Differences in disease severity associated with diverse geographical distribution of aetiologies, comorbidities and microbiology might explain an additional quota of heterogeneity. Finally, limited access to care in certain geographical areas is associated with both underestimation of the disease and increased severity and mortality. The aim of this review is to provide a snapshot of available real-world epidemiological data describing incidence and prevalence of bronchiectasis in the general population. Furthermore, data on mortality, healthcare burden and high-risk populations are provided. Finally, an analysis of the geographical distribution of determinants contributing to differences in bronchiectasis epidemiology is offered.




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Patient-managed interventions for adults with bronchiectasis: evidence, challenges and prospects

Bronchiectasis is a chronic lung condition which is characterised by recurrent chest infections, chronic sputum production and cough, and limited exercise tolerance. While bronchiectasis may be caused by various aetiologies, these features are shared by most patients with bronchiectasis regardless of the cause. This review consolidates the existing evidence on patient-managed interventions for adults with bronchiectasis, while also outlining areas for future research. Airway clearance techniques and hyperosmolar agents are key components of the bronchiectasis management and consistently recommended for clinical implementation. Questions around their prescription, such as optimal sequence of delivery, are still to be answered. Pulmonary rehabilitation and exercise are also recommended for patients with bronchiectasis. Relatively strong evidence underpins this recommendation during a clinically stable stage of the disease, although the role of pulmonary rehabilitation following an exacerbation is still unclear. Additionally, self-management programmes feature prominently in bronchiectasis treatment, yet the lack of consensus regarding their definition and outcomes presents hurdles to establishing a cohesive evidence base. Moreover, cough, a cardinal symptom of bronchiectasis, warrants closer examination. Although managing cough in bronchiectasis may initially appear risky, further research is necessary to ascertain whether strategies employed in other respiratory conditions can be safely and effectively adapted to bronchiectasis, particularly through identifying patient responder populations and criteria where cough may not enhance airway clearance efficacy and its control is needed. Overall, there is a growing recognition of the importance of patient-managed interventions in the bronchiectasis management. Efforts to improve research methodologies and increase research funding are needed to further advance our understanding of these interventions, and their role in optimising patient care and outcomes.




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Dynamic dysregulation of retrotransposons in neurodegenerative diseases at the single-cell level [RESOURCES]

Retrotransposable elements (RTEs) are common mobile genetic elements comprising ~42% of the human genome. RTEs play critical roles in gene regulation and function, but how they are specifically involved in complex diseases is largely unknown. Here, we investigate the cellular heterogeneity of RTEs using 12 single-cell transcriptome profiles covering three neurodegenerative diseases, Alzheimer's disease (AD), Parkinson's disease, and multiple sclerosis. We identify cell type marker RTEs in neurons, astrocytes, oligodendrocytes, and oligodendrocyte precursor cells that are related to these diseases. The differential expression analysis reveals the landscape of dysregulated RTE expression, especially L1s, in excitatory neurons of multiple neurodegenerative diseases. Machine learning algorithms for predicting cell disease stage using a combination of RTE and gene expression features suggests dynamic regulation of RTEs in AD. Furthermore, we construct a single-cell atlas of retrotransposable elements in neurodegenerative disease (scARE) using these data sets and features. scARE has six feature analysis modules to explore RTE dynamics in a user-defined condition. To our knowledge, scARE represents the first systematic investigation of RTE dynamics at the single-cell level within the context of neurodegenerative diseases.




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PWAS Hub for exploring gene-based associations of common complex diseases [RESOURCES]

PWAS (proteome-wide association study) is an innovative genetic association approach that complements widely used methods like GWAS (genome-wide association study). The PWAS approach involves consecutive phases. Initially, machine learning modeling and probabilistic considerations quantify the impact of genetic variants on protein-coding genes’ biochemical functions. Secondly, for each individual, aggregating the variants per gene determines a gene-damaging score. Finally, standard statistical tests are activated in the case-control setting to yield statistically significant genes per phenotype. The PWAS Hub offers a user-friendly interface for an in-depth exploration of gene–disease associations from the UK Biobank (UKB). Results from PWAS cover 99 common diseases and conditions, each with over 10,000 diagnosed individuals per phenotype. Users can explore genes associated with these diseases, with separate analyses conducted for males and females. For each phenotype, the analyses account for sex-based genetic effects, inheritance modes (dominant and recessive), and the pleiotropic nature of associated genes. The PWAS Hub showcases its usefulness for asthma by navigating through proteomic-genetic analyses. Inspecting PWAS asthma-listed genes (a total of 27) provide insights into the underlying cellular and molecular mechanisms. Comparison of PWAS-statistically significant genes for common diseases to the Open Targets benchmark shows partial but significant overlap in gene associations for most phenotypes. Graphical tools facilitate comparing genetic effects between PWAS and coding GWAS results, aiding in understanding the sex-specific genetic impact on common diseases. This adaptable platform is attractive to clinicians, researchers, and individuals interested in delving into gene–disease associations and sex-specific genetic effects.




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Rapid SARS-CoV-2 surveillance using clinical, pooled, or wastewater sequence as a sensor for population change [METHODS]

The COVID-19 pandemic has highlighted the critical role of genomic surveillance for guiding policy and control. Timeliness is key, but sequence alignment and phylogeny slow most surveillance techniques. Millions of SARS-CoV-2 genomes have been assembled. Phylogenetic methods are ill equipped to handle this sheer scale. We introduce a pangenomic measure that examines the information diversity of a k-mer library drawn from a country's complete set of clinical, pooled, or wastewater sequence. Quantifying diversity is central to ecology. Hill numbers, or the effective number of species in a sample, provide a simple metric for comparing species diversity across environments. The more diverse the sample, the higher the Hill number. We adopt this ecological approach and consider each k-mer an individual and each genome a transect in the pangenome of the species. Structured in this way, Hill numbers summarize the temporal trajectory of pandemic variants, collapsing each day's assemblies into genome equivalents. For pooled or wastewater sequence, we instead compare days using survey sequence divorced from individual infections. Across data from the UK, USA, and South Africa, we trace the ascendance of new variants of concern as they emerge in local populations well before these variants are named and added to phylogenetic databases. Using data from San Diego wastewater, we monitor these same population changes from raw, unassembled sequence. This history of emerging variants senses all available data as it is sequenced, intimating variant sweeps to dominance or declines to extinction at the leading edge of the COVID-19 pandemic.




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Contrasting and combining transcriptome complexity captured by short and long RNA sequencing reads [METHODS]

Mapping transcriptomic variations using either short- or long-read RNA sequencing is a staple of genomic research. Long reads are able to capture entire isoforms and overcome repetitive regions, whereas short reads still provide improved coverage and error rates. Yet, open questions remain, such as how to quantitatively compare the technologies, can we combine them, and what is the benefit of such a combined view? We tackle these questions by first creating a pipeline to assess matched long- and short-read data using a variety of transcriptome statistics. We find that across data sets, algorithms, and technologies, matched short-read data detects ~30% more splice junctions, such that ~10%–30% of the splice junctions included at ≥20% by short reads are missed by long reads. In contrast, long reads detect many more intron-retention events and can detect full isoforms, pointing to the benefit of combining the technologies. We introduce MAJIQ-L, an extension of the MAJIQ software, to enable a unified view of transcriptome variations from both technologies and demonstrate its benefits. Our software can be used to assess any future long-read technology or algorithm and can be combined with short-read data for improved transcriptome analysis.




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Complete genomes of Asgard archaea reveal diverse integrated and mobile genetic elements [RESEARCH]

Asgard archaea are of great interest as the progenitors of Eukaryotes, but little is known about the mobile genetic elements (MGEs) that may shape their ongoing evolution. Here, we describe MGEs that replicate in Atabeyarchaeia, a wetland Asgard archaea lineage represented by two complete genomes. We used soil depth–resolved population metagenomic data sets to track 18 MGEs for which genome structures were defined and precise chromosome integration sites could be identified for confident host linkage. Additionally, we identified a complete 20.67 kbp circular plasmid and two family-level groups of viruses linked to Atabeyarchaeia, via CRISPR spacer targeting. Closely related 40 kbp viruses possess a hypervariable genomic region encoding combinations of specific genes for small cysteine-rich proteins structurally similar to restriction-homing endonucleases. One 10.9 kbp integrative conjugative element (ICE) integrates genomically into the Atabeyarchaeum deiterrae-1 chromosome and has a 2.5 kbp circularizable element integrated within it. The 10.9 kbp ICE encodes an expressed Type IIG restriction-modification system with a sequence specificity matching an active methylation motif identified by Pacific Biosciences (PacBio) high-accuracy long-read (HiFi) metagenomic sequencing. Restriction-modification of Atabeyarchaeia differs from that of another coexisting Asgard archaea, Freyarchaeia, which has few identified MGEs but possesses diverse defense mechanisms, including DISARM and Hachiman, not found in Atabeyarchaeia. Overall, defense systems and methylation mechanisms of Asgard archaea likely modulate their interactions with MGEs, and integration/excision and copy number variation of MGEs in turn enable host genetic versatility.




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De novo genome assemblies of two cryptodiran turtles with ZZ/ZW and XX/XY sex chromosomes provide insights into patterns of genome reshuffling and uncover novel 3D genome folding in amniotes [RESEARCH]

Understanding the evolution of chromatin conformation among species is fundamental to elucidate the architecture and plasticity of genomes. Nonrandom interactions of linearly distant loci regulate gene function in species-specific patterns, affecting genome function, evolution, and, ultimately, speciation. Yet, data from nonmodel organisms are scarce. To capture the macroevolutionary diversity of vertebrate chromatin conformation, here we generate de novo genome assemblies for two cryptodiran (hidden-neck) turtles via Illumina sequencing, chromosome conformation capture, and RNA-seq: Apalone spinifera (ZZ/ZW, 2n = 66) and Staurotypus triporcatus (XX/XY, 2n = 54). We detected differences in the three-dimensional (3D) chromatin structure in turtles compared to other amniotes beyond the fusion/fission events detected in the linear genomes. Namely, whole-genome comparisons revealed distinct trends of chromosome rearrangements in turtles: (1) a low rate of genome reshuffling in Apalone (Trionychidae) whose karyotype is highly conserved when compared to chicken (likely ancestral for turtles), and (2) a moderate rate of fusions/fissions in Staurotypus (Kinosternidae) and Trachemys scripta (Emydidae). Furthermore, we identified a chromosome folding pattern that enables "centromere–telomere interactions" previously undetected in turtles. The combined turtle pattern of "centromere–telomere interactions" (discovered here) plus "centromere clustering" (previously reported in sauropsids) is novel for amniotes and it counters previous hypotheses about amniote 3D chromatin structure. We hypothesize that the divergent pattern found in turtles originated from an amniote ancestral state defined by a nuclear configuration with extensive associations among microchromosomes that were preserved upon the reshuffling of the linear genome.




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Mutational scanning of CRX classifies clinical variants and reveals biochemical properties of the transcriptional effector domain [RESEARCH]

The transcription factor (TF) cone-rod homeobox (CRX) is essential for the differentiation and maintenance of photoreceptor cell identity. Several human CRX variants cause degenerative retinopathies, but most are variants of uncertain significance. We performed a deep mutational scan (DMS) of nearly all possible single amino acid substitutions in CRX using a cell-based transcriptional reporter assay, curating a high-confidence list of nearly 2000 variants with altered transcriptional activity. In the structured homeodomain, activity scores closely aligned to a predicted structure and demonstrated position-specific constraints on amino acid substitution. In contrast, the intrinsically disordered transcriptional effector domain displayed a qualitatively different pattern of substitution effects, following compositional constraints without specific residue position requirements in the peptide chain. These compositional constraints were consistent with the acidic exposure model of transcriptional activation. We evaluated the performance of the DMS assay as a clinical variant classification tool using gold-standard classified human variants from ClinVar, identifying pathogenic variants with high specificity and moderate sensitivity. That this performance could be achieved using a synthetic reporter assay in a foreign cell type, even for a highly cell type-specific TF like CRX, suggests that this approach shows promise for DMS of other TFs that function in cell types that are not easily accessible. Together, the results of the CRX DMS identify molecular features of the CRX effector domain and demonstrate utility for integration into the clinical variant classification pipeline.




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AGAP duplicons associate with structural diversity at Chromosome 10q11.22 [RESEARCH]

The 10q11.22 chromosomal region is a duplication-rich interval of the human genome and one of the last to be fully assembled. It carries copy number–variable genes associated with intellectual disability, bipolar disorder, and obesity. In this study, we characterized the structural diversity at this locus by analyzing 64 haploid assemblies produced by the Human Pangenome Reference Consortium. We identified 11 alternative haplotypes that differ in the copy number and/or orientation of large genomic segments, ranging from hundreds of kilobase pairs (kbp) to over one megabase pair (Mbp). We uncovered a 2.4 Mbp size difference between the shortest and longest haplotypes. Breakpoint analysis revealed that genomic instability results from nonallelic homologous recombination between segmental duplication (SD) pairs with varying similarity (94.4%–99.6%). Nonetheless, these pairs generally recombine at positions where their identity is higher (>99.6%). Recurrent inversions occur with different breakpoints within the same inverted SD pair. Inversion polymorphisms shuffle the entire SD arrangement, creating new predispositions to copy-number variations. The SD architecture is associated with a catarrhine-specific subgroup of the AGAP gene family, which likely triggered the accumulation of SDs at this locus over the past 25 million years of human evolution. Our results reveal extensive structural diversity and genomic instability at the 10q11.22 locus, and expand the general understanding of the mutational mechanisms behind SD-mediated rearrangements.




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The chromatin tapestry as a framework for neurodevelopment [MINI-REVIEW]

The neuronal nucleus houses a meticulously organized genome. Within this structure, genetic material is not simply compacted but arranged into a precise and functional 3D chromatin landscape essential for cellular regulation. This mini-review highlights the importance of this chromatin landscape in healthy neurodevelopment, as well as the diseases that occur with aberrant chromatin architecture. We discuss insights into the fundamental mechanistic relationship between histone modifications, DNA methylation, and genome organization. We then discuss findings that reveal how these epigenetic features change throughout normal neurodevelopment. Finally, we highlight single-gene neurodevelopmental disorders that illustrate the interdependence of epigenetic features, showing how disruptions in DNA methylation or genome architecture can ripple across the entire epigenome. As such, we emphasize the importance of measuring multiple chromatin architectural aspects, as the disruption of one mechanism can likely impact others in the intricate epigenetic network. This mini-review underscores the vast gaps in our understanding of chromatin structure in neurodevelopmental diseases and the substantial research needed to understand the interplay between chromatin features and neurodevelopment.




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Re: Friendship as Medicine




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Potential Drawbacks of Noninvasive Diagnostic Methods for Nonalcoholic Fatty Liver Disease

The rising obesity epidemic is a phenomenon that has gained increasing attention from health providers and health policy makers. This led to recognition of nonalcoholic fatty liver disease (MASLD). The standard for its assessment has been histologic, which is neither practical nor acceptable by patients. Subsequently, a number of noninvasive assessment methods have been developed. However, despite ease of implementation, their confounding variables do hinder their accuracy. Nonetheless, the development of the liver stiffness measurement (LSM) and incorporation of other biological parameters has minimized but not eliminated the need for liver biopsy. Imaging methods are useful in evaluation, estimation, and following the progression of steatosis and fibrosis with particular attention to controlled attenuation parameter (CAP) and MRI–Proton Density Fat Fraction (MRI-PDFF). The choices for the family physician are broad and rely on tests’ availability, cost, and patient acceptance. Great efforts have been undertaken to produce more robust and novel noninvasive markers that indicate fibrinogenesis directly in an implementable and cost-effective way.




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Be SMART About Asthma Management: Single Maintenance and Reliever Therapy

Single maintenance and reliever therapy (SMART) is an asthma treatment approach that utilizes combined inhaled corticosteroids and long-acting β-agonists for maintenance and quick relief therapy. Despite the evidence for its benefits in asthma treatment and its adoption into American and international asthma guidelines and recommendations, SMART remains a practice of some debate. This article reviews the available evidence for SMART and offers guidance for its integration into comprehensive asthma management. Overall, short-acting β-agonist-only asthma therapy regimens should be avoided, regardless of condition severity (SOR A Recommendation). Family medicine clinicians should start SMART for patients requiring either GINA Step 3 or 4 therapy, especially if they have signs of poor adherence (SOR B Recommendation). Finally, use budesonide-formoterol over other inhaled corticosteroid/long-acting β-agonist combinations when implementing SMART (SOR B Recommendation).




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Assessing Patient Readiness for Hospital Discharge, Discharge Communication, and Transitional Care Management

Background:

Discharge communication between hospitalists and primary care clinicians is essential to improve care coordination, minimize adverse events, and decrease unplanned health services use. Health-related social needs are key drivers of health, and hospitalists and primary care clinicians value communicating social needs at discharge.

Objective:

To 1) characterize the current state of discharge communications between an academic medical center hospital and primary care clinicians at associated clinics; 2) seek feedback about the potential usefulness of discharge readiness information to primary care clinicians.

Design:

Exploratory, convergent mixed methods.

Participants:

Primary care clinicians from Family Medicine and General Internal Medicine of an academic medical center in the US Intermountain West.

Approach:

Literature-informed REDCap survey. Semistructured interview guide developed with key informants, grounded in current literature. Survey data were descriptively summarized; interview data were deductively and inductively coded, organized by topics.

Results:

Two key topics emerged: 1) discharge communication, with interrelated topics of transitional care management and follow-up appointment challenges, and recommendations for improving discharge communication; and 2) usefulness of the discharge readiness information, included interrelated topics related to lack of shared understanding about roles and responsibilities across settings and ethical concerns related to identifying problems that may not have solutions.

Conclusions:

While reiterating perennial discharge communication and transitional care management challenges, this study reveals new evidence about how these issues are interrelated with assessing and responding to patients’ lack of readiness for discharge and unmet social needs during care transitions. Primary care clinicians had mixed views on the usefulness of discharge readiness information. We offer recommendations for improving discharge communication and transitional care management (TCM) processes, which may be applicable in other care settings.




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Colorectal Cancer Screening: A Multicomponent Intervention to Increase Uptake in Patients Aged 45-49

Purpose:

Colorectal cancer (CRC) screening is recommended starting at age 45, but there has been little research on strategies to promote screening among patients younger than 50. This study assessed the effect of a multicomponent intervention on screening completion in this age group.

Methods:

The intervention consisted of outreach to patients aged 45 to 49 (n = 3,873) via mailed fecal immunochemical test (FIT) (sent to 46%), text (84%), e-mail (53%), and the extension to this age group of an existing standing order protocol allowing primary care nurses and medical assistants to order FIT at primary care clinics in an urban safety-net system. We used segmented linear regression to assess changes in CRC screening completion trends. Patients aged 51 to 55 were included as a comparison group (n = 3,943). Data were extracted from the EHR.

Results:

The percentage of patients aged 45 to 49 who were up-to-date with CRC screening (colonoscopy in 10 years or FIT in last year) increased an average of 0.4% (95% CI 0.3, 0.6)) every 30 days before intervention rollout and 2.8% (95% CI 2.5, 3.1) after (slope difference 2.3% [95% CI 2.0, 2.7]). This difference persisted after accounting for small changes in the outcome observed in the comparison group (slope difference 1.7% [95% CI 1.2, 2.2]).

Conclusions:

These results suggest that the intervention increased CRC screening completion among patients 45 to 49. Health care systems seeking to improve CRC screening participation among patients aged 45 to 49 should consider implementing similar interventions.




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Associations Between Patient/Caregiver Trust in Clinicians and Experiences of Healthcare-Based Discrimination

Background:

Higher trust in healthcare providers has been linked to better health outcomes and satisfaction. Lower trust has been associated with healthcare-based discrimination.

Objective:

Examine associations between experiences of healthcare discrimination and patients’ and caregivers of pediatric patients’ trust in providers, and identify factors associated with high trust, including prior experience of healthcare-based social screening.

Methods:

Secondary analysis of cross-sectional study using logistic regression modeling. Sample consisted of adult patients and caregivers of pediatric patients from 11 US primary care/emergency department sites.

Results:

Of 1,012 participants, low/medium trust was reported by 26% identifying as non-Hispanic Black, 23% Hispanic, 18% non-Hispanic multiple/other race, and 13% non-Hispanic White (P = .001). Experience of any healthcare-based discrimination was reported by 32% identifying as non-Hispanic Black, 23% Hispanic, 39% non-Hispanic multiple/other race, and 26% non-Hispanic White (P = .012). Participants reporting low/medium trust had a mean discrimination score of 1.65/7 versus 0.57/7 for participants reporting high trust (P < .001). In our adjusted model, higher discrimination scores were associated with lower trust in providers (aOR 0.74, 95%CI = 0.64, 0.85). A significant interaction indicated that prior healthcare-based social screening was associated with reduced impact of discrimination on trust: as discrimination score increased, odds of high trust were greater among participants who had been screened (aOR = 1.28, 95%CI = 1.03, 1.58).

Conclusions:

Patients and caregivers reporting more healthcare-based discrimination were less likely to report high provider trust. Interventions to strengthen trust need structural antiracist components. Increased rapport with patients may be a potential by-product of social screening. Further research is needed on screening and trust.




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Physician Satisfaction Should Be the Measure of Electronic Health Record Quality for the Nation