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Background Due the computational complexity of sequence alignment algorithms, various accelerated solutions have been proposed to speedup this analysis. NVBIO is the only available GPU library that accelerates sequence alignment of high-throughput NGS data, but has limited performance. In this article we present GASAL2 , a GPU library for aligning DNA and RNA sequences that outperforms existing CPU and GPU libraries. Results The GASAL2 library provides specialized, accelerated kernels for local, global and all types of semi-global alignment. Pairwise sequence alignment can be performed with and without traceback. GASAL2 outperforms the fastest CPU-optimized SIMD implementations such as SeqAn and Parasail, as well as NVIDIA’s own GPU-based library known as NVBIO. GASAL2 is unique in performing sequence packing on GPU, which is up to 750x faster than NVBIO. Overall on Geforce GTX 1080 Ti GPU, GASAL2 is up to 21x faster than Parasail on a dual socket hyper-threaded Intel Xeon system with 28 cores and up to 13x faster than NVBIO with a query length of up to 300 bases and 100 bases, respectively. GASAL2 alignment functions are asynchronous/non-blocking and allow full overlap of CPU and GPU execution. The paper shows how to use GASAL2 to accelerate BWA-MEM, speeding up the local alignment by 20x, which gives an overall application speedup of 1.3x vs. CPU with up to 12 threads. Conclusions The library provides high performance APIs for local, global and semi-global alignment that can be easily integrated into various bioinformatics tools.

There are limited real-world data on the use of botulinum toxin type A (BoNT-A) in patients with multiple sclerosis (MS). Accordingly, this nationwide, population-based, retrospective cohort study aimed to describe BoNT-A treatment trends in patients with MS between 2014 and 2020 in France. This study extracted data from the French National Hospital Discharge Database (Programme de Médicalisation des Systèmes d’Information, PMSI) covering the entire French population. Among 105,206 patients coded with MS, we identified those who received ≥1 BoNT-A injection, administered within striated muscle for MS-related spasticity and/or within the detrusor smooth muscle for neurogenic detrusor overactivity (NDO). A total of 8427 patients (8.0%) received BoNT-A injections for spasticity, 52.9% of whom received ≥3 BoNT-A injections with 61.9% of the repeated injections administered every 3 to 6 months. A total of 2912 patients (2.8%) received BoNT-A injections for NDO, with a mean of 4.7 injections per patient. Most repeated BoNT-A injections within the detrusor smooth muscle (60.0%) were administered every 5 to 8 months. There were 585 patients (0.6%) who received both BoNT-A injections within striated muscle and the detrusor smooth muscle. Overall, our study highlights a broad range of BoNT-A treatment practices between 2014 and 2020 in patients with MS.

Following publication of the original article [1], the author requested changes to the figures 4, 7, 8, 9, 12 and 14 to align these with the text. The corrected figures are supplied below.Following publication of the original article [1], the author requested changes to the figures 4, 7, 8, 9, 12 and 14 to align these with the text. The corrected figures are supplied below.

Ciliopathies are rare genetic disorders caused by dysfunction of the primary or motile cilia. Their mode of inheritance is mostly autosomal recessive with biallelic pathogenic variants inherited from the parents. However, exceptions exist such as uniparental disomy (UPD) or the appearance of a de novo pathogenic variant in trans of an inherited pathogenic variant. These two genetic mechanisms are expected to be extremely rare, and few data are available in the literature, especially regarding ciliopathies. In this study, we investigated 940 individuals (812 families) with a suspected ciliopathy by Sanger sequencing, high-throughput sequencing and/or SNP array analysis and performed a literature review of UPD and de novo variants in ciliopathies. In a large cohort of 623 individuals (511 families) with a molecular diagnosis of ciliopathy (mainly Bardet-Biedl syndrome and Alström syndrome), we identified five UPD, revealing an inherited pathogenic variant and five pathogenic variants of de novo appearance (in trans of another pathogenic variant). Moreover, from these ten cases, we reported 15 different pathogenic variants of which five are novel. We demonstrated a relatively high prevalence of UPD and de novo variants in a large cohort of ciliopathies and highlighted the importance of identifying such rare genetic events, especially for genetic counseling.

Inequities in Coronavirus Disease 2019 (COVID-19) vaccine and booster coverage may contribute to future disparities in morbidity and mortality within and between Massachusetts (MA) communities. We conducted a population-based cross-sectional study of primary series vaccination and booster coverage 18 months into the general population vaccine rollout. We obtained public-use data on residents vaccinated and boosted by ZIP code (and by age group: 5 to 19, 20 to 39, 40 to 64, 65+) from MA Department of Public Health, as of October 10, 2022. We constructed population denominators for postal ZIP codes by aggregating census tract population estimates from the 2015-2019 American Community Survey. We excluded nonresidential ZIP codes and the smallest ZIP codes containing 1% of the state's population. We mapped variation in ZIP code-level primary series vaccine and booster coverage and used regression models to evaluate the association of these measures with ZIP code-level socioeconomic and demographic characteristics. Because age is strongly associated with COVID-19 severity and vaccine access/uptake, we assessed whether observed socioeconomic and racial/ethnic inequities persisted after adjusting for age composition and plotted age-specific vaccine and booster coverage by deciles of ZIP code characteristics. We analyzed data on 418 ZIP codes. We observed wide geographic variation in primary series vaccination and booster rates, with marked inequities by ZIP code-level education, median household income, essential worker share, and racial/ethnic composition. In age-stratified analyses, primary series vaccine coverage was very high among the elderly. However, we found large inequities in vaccination rates among younger adults and children, and very large inequities in booster rates for all age groups. In multivariable regression models, each 10 percentage point increase in \"percent college educated\" was associated with a 5.1 (95% confidence interval (CI) 3.9 to 6.3, p < 0.001) percentage point increase in primary series vaccine coverage and a 5.4 (95% CI 4.5 to 6.4, p < 0.001) percentage point increase in booster coverage. Although ZIP codes with higher \"percent Black/Latino/Indigenous\" and higher \"percent essential workers\" had lower vaccine coverage (-0.8, 95% CI -1.3 to -0.3, p < 0.01; -5.5, 95% CI -7.3 to -3.8, p < 0.001), these associations became strongly positive after adjusting for age and education (1.9, 95% CI 1.0 to 2.8, p < 0.001; 4.8, 95% CI 2.6 to 7.1, p < 0.001), consistent with high demand for vaccines among Black/Latino/Indigenous and essential worker populations within age and education groups. Strong positive associations between \"median household income\" and vaccination were attenuated after adjusting for age. Limitations of the study include imprecision of the estimated population denominators, lack of individual-level sociodemographic data, and potential for residential ZIP code misreporting in vaccination data. Eighteen months into MA's general population vaccine rollout, there remained large inequities in COVID-19 primary series vaccine and booster coverage across MA ZIP codes, particularly among younger age groups. Disparities in vaccination coverage by racial/ethnic composition were statistically explained by differences in age and education levels, which may mediate the effects of structural racism on vaccine uptake. Efforts to increase booster coverage are needed to limit future socioeconomic and racial/ethnic disparities in COVID-19 morbidity and mortality.

The growth in this literature has been facilitated by the increasing availability of national-scale air pollution concentration estimates at high geographic resolution that can be coupled with national-scale census data on sociodemographic patterns. Census data also limit the ability to conduct truly intersectional analyses or to incorporate attributes, such as sexual orientation or gender identity, that are underrepresented in the environmental justice literature (Collins et al. 2017). There is strong evidence of disparities by income or race/ethnicity in housing attributes (Adamkiewicz et al. 2011; Swope and Hernández 2019), and a modeling study demonstrated that disparities in pollutant infiltration can exacerbate disparities in ambient air pollution concentrations (Rosofsky et al. 2019).

A decade ago, AJPH published a special supplement on environmental justice (https://ajph.aphapublications. org/toc/ajph/101/S1), with dozens of articles addressing themes such as residential proximity to hazardous facilities, expanded risk assessment frameworks that acknowledged cumulative exposures and differential vulnerability, and perspectives on community engagement, empowerment, and capacity building.Much has changed over the past decade. The escalating burden of climate change, growing recognition of the insidiousness of racism, and political extremism have had profound influences on public health and environmental justice. Given this, we put out a call for papers on \"New Frontiers of Environmental Justice,\" soliciting articles that address novel topics, utilize innovative methods, and reflect on approaches for addressing environmental justice in the future. In the current and subsequent issues of AJPH, we present articles that grapple with some of these complex questions.This special section features complementary framing and research articles that beckon more inclusive understandings of oppression and action-oriented processes to pursue justice. For instance, Goldsmith and Bell (p. 79) explore how environmental exposures disproportionately affect the LGBTQ + (lesbian, gay, bisexual, transgender, queer or questioning, and others) population while Collins et al. (p. 54) and Gaard (p. 57) discuss the implications of an intersectional approach within environmental justice research and policy. Relatedly, McDonald etal. (p. 50) expose toxic disparities in beauty products marketed toward people of color, including LGBTQ+ members, and call for regulatory changes within the cosmetics industry.

Empathy is a core human social ability shaped by biological dispositions and caregiving experiences; yet the mechanisms sustaining maturation of the neural basis of empathy are unknown. Here, we followed eighty-four children, including 42 exposed to chronic war-related adversity, across the first decade of life, and assessed parenting, child temperament, and anxiety disorders as contributors to the neural development of empathy. At preadolescence, participants underwent magenetoencephalography while observing others’ distress. Preadolescents show a widely-distributed response in structures implicating the overlap of affective (automatic) and cognitive (higher-order) empathy, which is predicted by mother-child synchrony across childhood. Only temperamentally reactive young children growing in chronic adversity, particularly those who later develop anxiety disorders, display additional engagement of neural nodes possibly reflecting hyper-mentalizing and ruminations over the distressing stimuli. These findings demonstrate how caregiving patterns fostering interpersonal resonance, reactive temperament, and chronic adversity combine across early development to shape the human empathic brain. People’s early experiences and dispositions influence their ability to show and feel empathy. Here, using a sample of children exposed to war-related trauma, the authors examine how parenting, temperament, anxiety, and adversity affect the maturation of neural responses associated with empathy.

Most genetic variants that contribute to disease 1 are challenging to correct efficiently and without excess byproducts 2 , 3 , 4 – 5 . Here we describe prime editing, a versatile and precise genome editing method that directly writes new genetic information into a specified DNA site using a catalytically impaired Cas9 endonuclease fused to an engineered reverse transcriptase, programmed with a prime editing guide RNA (pegRNA) that both specifies the target site and encodes the desired edit. We performed more than 175 edits in human cells, including targeted insertions, deletions, and all 12 types of point mutation, without requiring double-strand breaks or donor DNA templates. We used prime editing in human cells to correct, efficiently and with few byproducts, the primary genetic causes of sickle cell disease (requiring a transversion in HBB ) and Tay–Sachs disease (requiring a deletion in HEXA ); to install a protective transversion in PRNP ; and to insert various tags and epitopes precisely into target loci. Four human cell lines and primary post-mitotic mouse cortical neurons support prime editing with varying efficiencies. Prime editing shows higher or similar efficiency and fewer byproducts than homology-directed repair, has complementary strengths and weaknesses compared to base editing, and induces much lower off-target editing than Cas9 nuclease at known Cas9 off-target sites. Prime editing substantially expands the scope and capabilities of genome editing, and in principle could correct up to 89% of known genetic variants associated with human diseases. A new DNA-editing technique called prime editing offers improved versatility and efficiency with reduced byproducts compared with existing techniques, and shows potential for correcting disease-associated mutations.