y

Is Syphilis 100% Curable?

Title: Is Syphilis 100% Curable?
Category: Diseases and Conditions
Created: 7/15/2022 12:00:00 AM
Last Editorial Review: 7/15/2022 12:00:00 AM




y

Erectile Dysfunction (ED, Impotence)

Title: Erectile Dysfunction (ED, Impotence)
Category: Diseases and Conditions
Created: 12/31/1997 12:00:00 AM
Last Editorial Review: 7/25/2022 12:00:00 AM




y

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




y

Is Chlamydia Contagious?

Title: Is Chlamydia Contagious?
Category: Diseases and Conditions
Created: 5/28/2015 12:00:00 AM
Last Editorial Review: 8/1/2022 12:00:00 AM




y

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




y

tobramycin

Title: tobramycin
Category: Medications
Created: 8/2/2022 12:00:00 AM
Last Editorial Review: 8/2/2022 12:00:00 AM




y

Tramadol vs. Hydrocodone

Title: Tramadol vs. Hydrocodone
Category: Medications
Created: 4/24/2017 12:00:00 AM
Last Editorial Review: 8/5/2022 12:00:00 AM




y

Cyclobenzaprine vs. Xanax (alprazolam)

Title: Cyclobenzaprine vs. Xanax (alprazolam)
Category: Medications
Created: 6/6/2019 12:00:00 AM
Last Editorial Review: 8/25/2022 12:00:00 AM




y

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




y

U.S. Hospitals Are Getting Safer for Patients, Study Finds

Title: U.S. Hospitals Are Getting Safer for Patients, Study Finds
Category: Health News
Created: 7/20/2022 12:00:00 AM
Last Editorial Review: 7/20/2022 12:00:00 AM




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AHA News: How You Feel About Aging Could Affect Health. Here's How to Keep the Right Attitude.

Title: AHA News: How You Feel About Aging Could Affect Health. Here's How to Keep the Right Attitude.
Category: Health News
Created: 8/19/2022 12:00:00 AM
Last Editorial Review: 8/19/2022 12:00:00 AM




y

You Could Live 9 Years Longer in Hawaii Than in Mississippi, New Data Shows

Title: You Could Live 9 Years Longer in Hawaii Than in Mississippi, New Data Shows
Category: Health News
Created: 8/23/2022 12:00:00 AM
Last Editorial Review: 8/23/2022 12:00:00 AM




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Steps to Long Life: Short Walk Each Day Helps Folks Over 85

Title: Steps to Long Life: Short Walk Each Day Helps Folks Over 85
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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Get Moving! Any Sports Can Lower Seniors' Odds of Early Death

Title: Get Moving! Any Sports Can Lower Seniors' Odds of Early Death
Category: Health News
Created: 8/25/2022 12:00:00 AM
Last Editorial Review: 8/26/2022 12:00:00 AM




y

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




y

Salicylate Sensitivity Causes, Symptoms, and Foods to Avoid

Title: Salicylate Sensitivity Causes, Symptoms, and Foods to Avoid
Category: Health and Living
Created: 7/8/2022 12:00:00 AM
Last Editorial Review: 7/8/2022 12:00:00 AM




y

Health Care Plans Keep Allergy Rescue Injectors Pricey for Some

Title: Health Care Plans Keep Allergy Rescue Injectors Pricey for Some
Category: Health News
Created: 7/15/2022 12:00:00 AM
Last Editorial Review: 7/15/2022 12:00:00 AM




y

Looking for Reliable Hay Fever Advice? It's Probably Not on YouTube

Title: Looking for Reliable Hay Fever Advice? It's Probably Not on YouTube
Category: Health News
Created: 8/16/2022 12:00:00 AM
Last Editorial Review: 8/16/2022 12:00:00 AM




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When Removing a Big Kidney Stone, Get the Little Ones, Too

Title: When Removing a Big Kidney Stone, Get the Little Ones, Too
Category: Health News
Created: 8/11/2022 12:00:00 AM
Last Editorial Review: 8/11/2022 12:00:00 AM




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Organ From Live Donor Best When Child Needs New Kidney

Title: Organ From Live Donor Best When Child Needs New Kidney
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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Kidneys' Resilience May Depend on Your Gender, Study Finds

Title: Kidneys' Resilience May Depend on Your Gender, Study Finds
Category: Health News
Created: 8/22/2022 12:00:00 AM
Last Editorial Review: 8/22/2022 12:00:00 AM




y

What Is the Main Cause of Leaky Gut, and How Do You Fix It?

Title: What Is the Main Cause of Leaky Gut, and How Do You Fix It?
Category: Diseases and Conditions
Created: 8/23/2022 12:00:00 AM
Last Editorial Review: 8/23/2022 12:00:00 AM




y

Digestive Enzymes Oral

Title: Digestive Enzymes Oral
Category: Medications
Created: 3/2/2005 12:00:00 AM
Last Editorial Review: 8/24/2022 12:00:00 AM




y

erythromycin

Title: erythromycin
Category: Medications
Created: 12/31/1997 12:00:00 AM
Last Editorial Review: 6/17/2022 12:00:00 AM




y

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




y

hexylresorcinol

Title: hexylresorcinol
Category: Medications
Created: 6/28/2022 12:00:00 AM
Last Editorial Review: 6/28/2022 12:00:00 AM




y

Cold, Flu, Allergy Treatments

Title: Cold, Flu, Allergy Treatments
Category: Diseases and Conditions
Created: 9/24/1999 12:00:00 AM
Last Editorial Review: 7/15/2022 12:00:00 AM




y

Is Laryngitis Contagious?

Title: Is Laryngitis Contagious?
Category: Diseases and Conditions
Created: 9/10/2015 12:00:00 AM
Last Editorial Review: 7/22/2022 12:00:00 AM




y

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




y

How Childhood Abuse Can Haunt the Senior Years

Title: How Childhood Abuse Can Haunt the Senior Years
Category: Health News
Created: 7/8/2022 12:00:00 AM
Last Editorial Review: 7/8/2022 12:00:00 AM




y

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




y

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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Treating central sleep apnoea in heart failure: is positive airway pressure and adaptive servo-ventilation in particular the gold standard?

Extract

We read with great interest the review article by Randerath et al. [1] recently published in the European Respiratory Review. We would like to congratulate the authors on this clearly structured review, which emphasises the urgent need for an increasingly differentiated view of central sleep apnoea (CSA) in the context of precision medicine.




y

The deadly dance of alveolar macrophages and influenza virus

Influenza A virus (IAV) is one of the leading causes of respiratory infections. The lack of efficient anti-influenza therapeutics requires a better understanding of how IAV interacts with host cells. Alveolar macrophages are tissue-specific macrophages that play a critical role in lung innate immunity and homeostasis, yet their role during influenza infection remains unclear. First, our review highlights an active IAV replication within alveolar macrophages, despite an abortive viral cycle. Such infection leads to persistent alveolar macrophage inflammation and diminished phagocytic function, alongside direct mitochondrial damage and indirect metabolic shifts in the alveolar micro-environment. We also discuss the "macrophage disappearance reaction", which is a drastic reduction of the alveolar macrophage population observed after influenza infection in mice but debated in humans, with unclear underlying mechanisms. Furthermore, we explore the dual nature of alveolar macrophage responses to IAV infection, questioning whether they are deleterious or protective for the host. While IAV may exploit immuno-evasion strategies and induce alveolar macrophage alteration or depletion, this could potentially reduce excessive inflammation and allow for the replacement of more effective cells. Despite these insights, the pathophysiological role of alveolar macrophages during IAV infection in humans remains understudied, urging further exploration to unravel their precise contributions to disease progression and resolution.




y

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.




y

Antibody-mediated protection against respiratory syncytial virus in children

Respiratory syncytial virus (RSV) is a major global pathogen, causing lower respiratory tract disease in at-risk populations including young children. Antibodies form a crucial layer of protection from RSV disease, particularly in immunologically naïve infants. Such antibodies are derived from the mother via transplacental transfer and breast milk, but may be particularly low in high-risk infants such as those born preterm. Maternally derived antibodies can now be supplemented by the administration of anti-RSV monoclonal antibodies, while a rising wave of maternal and paediatric vaccine strategies are approaching. The implementation of these prophylactics may profoundly decrease the healthcare burden of RSV. In this article, we review the role of antibody-mediated immunity in protecting children from RSV. We focus on maternally derived antibodies as the main source of protection against RSV and study factors that influence the scale of this transfer. The role of passive and active prophylactic approaches in protecting infants against RSV are discussed and knowledge gaps in our understanding of antibody-mediated protection against RSV are identified.




y

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.




y

The ageing of people living with cystic fibrosis: what to expect now?

The prognosis of people with cystic fibrosis (pwCF) has improved dramatically with the introduction of cystic fibrosis transmembrane conductance regulator (CFTR) modulators (CFTRm). The ageing of the cystic fibrosis (CF) population is changing the disease landscape with the emergence of different needs and increasing comorbidities related to both age and long-term exposure to multiple treatments including CFTRm. Although the number of pwCF eligible for this treatment is expected to increase, major disparities in care and outcomes still exist in this population. Moreover, the long-term impact of the use of CFTRm is still partly unknown due to the current short follow-up and experience with their use, thus generating some uncertainties. The future spread and initiation of these drugs at an earlier stage of the disease is expected to reduce the systemic burden of systemic inflammation and its consequences on health. However, the prolonged life expectancy is accompanied by an increasing burden of age-related comorbidities, especially in the context of chronic disease. The clinical manifestations of the comorbidities directly or indirectly associated with CFTR dysfunction are changing, along with the disease dynamics and outcomes. Current protocols used to monitor slow disease progression will need continuous updates, including the composition of the multidisciplinary team for CF care, with a greater focus on the needs of the adult population.




y

Multicomponent services for symptoms in serious respiratory illness: a systematic review and meta-analysis

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.

Methods

Electronic databases were searched to identify randomised controlled trials (RCTs) evaluating multicomponent services that enrolled patients due to symptoms, rather than underlying disease, and provided at least one nonpharmacological intervention. The primary outcome was chronic breathlessness and secondary outcomes were health-related quality of life (HRQoL), cough, fatigue and adverse events. At least two authors independently screened studies, assessed risk of bias and extracted data.

Results

Five RCTs, involving 439 patients, were included. In comparison to usual care, multicomponent services improved breathlessness mastery (Chronic Respiratory Questionnaire (CRQ) mastery scale, mean difference (MD) 0.43 points, 95% CI 0.20–0.67, three RCTs, 327 participants) and HRQoL (CRQ total score, MD 0.24 points, 95% CI 0.04–0.40, two RCTs, 237 participants). Fatigue did not improve with multicomponent services and no studies evaluated cough. No serious adverse events were reported. The one study evaluating mortality found increased survival in those accessing a multicomponent service. The certainty of evidence was very low, mainly due to detection and reporting bias.

Conclusion

Multicomponent services improve breathlessness mastery and HRQoL, with minimal risk. These findings support the use of multicomponent symptom-directed services for people living with serious respiratory illness.




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The effect of graded exercise therapy on fatigue in people with serious respiratory illness: a systematic review

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.

Methods

Electronic databases were searched to identify randomised controlled trials (RCTs) testing GET (involving incremental increases in exercise from an established baseline) in adults with serious respiratory illness. The primary outcome was fatigue and secondary outcomes were health-related quality of life (HRQoL) and adverse events. Two authors independently screened for inclusion, evaluated risk of bias and extracted data.

Results

76 RCTs were included with 3309 participants, most with a diagnosis of COPD or asthma. Reductions in fatigue measured by the Chronic Respiratory Disease Questionnaire fatigue domain score were demonstrated following GET consisting of aerobic with/without resistance training (mean difference (MD) 0.53 points, 95% CI 0.41–0.65, 11 RCTs, 624 participants) and GET using resistance training alone (MD 0.58 points, 95% CI 0.21–0.96, two RCTs, 82 participants) compared with usual care. Although the mean effect exceeded the minimal important difference, the lower end of the confidence intervals did not always exceed this threshold so the clinical significance could not be confirmed. GET consistently improved HRQoL in people with a range of chronic respiratory diseases on multiple HRQoL measures. No serious adverse events related to GET were reported.

Conclusion

GET may improve fatigue alongside consistent improvements in HRQoL in people with serious respiratory illness. These findings support the use of GET in the care of people with serious respiratory illness.




y

Breathing techniques to reduce symptoms in people with serious respiratory illness: a systematic review

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.

Methods

Electronic databases were searched to identify randomised controlled trials testing breathing techniques (techniques that aim to alter the respiratory pattern, excluding respiratory muscle training) in people with serious respiratory illness. The primary outcome was breathlessness and secondary outcomes were health-related quality of life and adverse events. Two authors independently screened for inclusion, evaluated risk of bias and extracted data.

Results

73 randomised controlled trials were included with 5479 participants, most with COPD or asthma. Breathing exercises (pursed lip and/or diaphragmatic breathing) reduced breathlessness measured by the modified Medical Research Council scale compared to usual care (mean difference (MD) –0.40 points, 95% CI –0.70– –0.11, eight studies, n=323), although the effect did not exceed the minimal important difference. Yoga breathing also improved modified Medical Research Council score compared to usual care (MD –1.05 points, 95% CI –2.45–0.35, three studies, n=175). Breathing techniques consistently improved health-related quality of life in people with COPD and asthma on multiple health-related quality of life measures in comparison to usual care, with effects that generally exceeded the minimal important difference. No adverse events related to breathing techniques were reported.

Conclusion

Breathing techniques may improve breathlessness, and consistently improve health-related quality of life, in people with serious respiratory illness. These findings support the use of breathing exercises in the care of people with serious respiratory illness.




y

Opioids for the palliation of symptoms in people with serious respiratory illness: a systematic review and meta-analysis

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.

Methods

We examined the efficacy and safety of opioids for symptom management in people with serious respiratory illness. Embase, MEDLINE and the Cochrane Central Register of Controlled Trials were searched up to 11 July 2022. Reports of randomised controlled trials administering opioids to treat symptoms in people with serious respiratory illness were included. Key exclusion criteria included <80% of participants having a nonmalignant lung disease. Data were extracted regarding study characteristics, outcomes of breathlessness, cough, health-related quality of life (HRQoL) and adverse events. Treatment effects were pooled using a generic inverse variance model with random effects. Risk of bias was assessed using the Cochrane Risk of Bias tool version 1.

Results

Out of 17 included trials, six were laboratory-based exercise trials (n=70), 10 were home studies measuring breathlessness in daily life (n=788) and one (n=18) was conducted in both settings. Overall certainty of evidence was "very low" to "low". Opioids reduced breathlessness intensity during laboratory exercise testing (standardised mean difference (SMD) –0.37, 95% CI –0.67– –0.07), but not breathlessness measured in daily life (SMD –0.10, 95% CI –0.64–0.44). No effects on HRQoL (SMD –0.42, 95% CI –0.98–0.13) or cough (SMD –1.42, 95% CI –3.99–1.16) were detected. In at-home studies, opioids led to increased frequency of nausea/vomiting (OR 3.32, 95% CI 1.70–6.51), constipation (OR 3.08, 95% CI 1.69–5.61) and drowsiness (OR 1.37, 95% CI 1.01–1.86), with serious adverse events including hospitalisation and death identified.

Conclusions

Opioids improved exertional breathlessness in laboratory exercise studies, but did not improve breathlessness, cough or HRQoL measured in daily life at home. There were significant adverse events, which may outweigh any benefits.




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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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Seamless, rapid, and accurate analyses of outbreak genomic data using split k-mer analysis [METHODS]

Sequence variation observed in populations of pathogens can be used for important public health and evolutionary genomic analyses, especially outbreak analysis and transmission reconstruction. Identifying this variation is typically achieved by aligning sequence reads to a reference genome, but this approach is susceptible to reference biases and requires careful filtering of called genotypes. There is a need for tools that can process this growing volume of bacterial genome data, providing rapid results, but that remain simple so they can be used without highly trained bioinformaticians, expensive data analysis, and long-term storage and processing of large files. Here we describe split k-mer analysis (SKA2), a method that supports both reference-free and reference-based mapping to quickly and accurately genotype populations of bacteria using sequencing reads or genome assemblies. SKA2 is highly accurate for closely related samples, and in outbreak simulations, we show superior variant recall compared with reference-based methods, with no false positives. SKA2 can also accurately map variants to a reference and be used with recombination detection methods to rapidly reconstruct vertical evolutionary history. SKA2 is many times faster than comparable methods and can be used to add new genomes to an existing call set, allowing sequential use without the need to reanalyze entire collections. With an inherent absence of reference bias, high accuracy, and a robust implementation, SKA2 has the potential to become the tool of choice for genotyping bacteria. SKA2 is implemented in Rust and is freely available as open-source software.




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Theoretical framework for the difference of two negative binomial distributions and its application in comparative analysis of sequencing data [METHODS]

High-throughput sequencing (HTS) technologies have been instrumental in investigating biological questions at the bulk and single-cell levels. Comparative analysis of two HTS data sets often relies on testing the statistical significance for the difference of two negative binomial distributions (DOTNB). Although negative binomial distributions are well studied, the theoretical results for DOTNB remain largely unexplored. Here, we derive basic analytical results for DOTNB and examine its asymptotic properties. As a state-of-the-art application of DOTNB, we introduce DEGage, a computational method for detecting differentially expressed genes (DEGs) in scRNA-seq data. DEGage calculates the mean of the sample-wise differences of gene expression levels as the test statistic and determines significant differential expression by computing the P-value with DOTNB. Extensive validation using simulated and real scRNA-seq data sets demonstrates that DEGage outperforms five popular DEG analysis tools: DEGseq2, DEsingle, edgeR, Monocle3, and scDD. DEGage is robust against high dropout levels and exhibits superior sensitivity when applied to balanced and imbalanced data sets, even with small sample sizes. We utilize DEGage to analyze prostate cancer scRNA-seq data sets and identify marker genes for 17 cell types. Furthermore, we apply DEGage to scRNA-seq data sets of mouse neurons with and without fear memory and reveal eight potential memory-related genes overlooked in previous analyses. The theoretical results and supporting software for DOTNB can be widely applied to comparative analyses of dispersed count data in HTS and broad research questions.




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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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Systematic identification of interchromosomal interaction networks supports the existence of specialized RNA factories [METHODS]

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.




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Global characterization of somatic mutations and DNA methylation changes during vegetative propagation in strawberries [RESEARCH]

Somatic mutations arise and accumulate during tissue culture and vegetative propagation, potentially affecting various traits in horticultural crops, but their characteristics are still unclear. Here, somatic mutations in regenerated woodland strawberry derived from tissue culture of shoot tips under different conditions and 12 cultivated strawberry individuals are analyzed by whole genome sequencing. The mutation frequency of single nucleotide variants is significantly increased with increased hormone levels or prolonged culture time in the range of 3.3 x 10–8–3.0 x 10–6 mutations per site. CG methylation shows a stable reduction (0.71%–8.03%) in regenerated plants, and hypoCG-DMRs are more heritable after sexual reproduction. A high-quality haplotype-resolved genome is assembled for the strawberry cultivar "Beni hoppe." The 12 "Beni hoppe" individuals randomly selected from different locations show 4731–6005 mutations relative to the reference genome, and the mutation frequency varies among the subgenomes. Our study has systematically characterized the genetic and epigenetic variants in regenerated woodland strawberry plants and different individuals of the same strawberry cultivar, providing an accurate assessment of somatic mutations at the genomic scale and nucleotide resolution in plants.