Elevated genetic risk for multiple sclerosis emerged in steppe pastoralist populations.

Multiple sclerosis (MS) is a neuro-inflammatory and neurodegenerative disease that is most prevalent in Northern Europe. Although it is known that inherited risk for MS is located within or in close proximity to immune-related genes, it is unknown when, where and how this genetic risk originated. Here, by using a large ancient genome dataset from the Mesolithic period to the Bronze Age, along with new Medieval and post-Medieval genomes, we show that the genetic risk for MS rose among pastoralists from the Pontic steppe and was brought into Europe by the Yamnaya-related migration approximately 5,000 years ago.

100 ancient genomes show repeated population turnovers in Neolithic Denmark.

Major migration events in Holocene Eurasia have been characterized genetically at broad regional scales. However, insights into the population dynamics in the contact zones are hampered by a lack of ancient genomic data sampled at high spatiotemporal resolution. Here, to address this, we analysed shotgun-sequenced genomes from 100 skeletons spanning 7,300 years of the Mesolithic period, Neolithic period and Early Bronze Age in Denmark and integrated these with proxies for diet (C and N content), mobility (Sr/Sr ratio) and vegetation cover (pollen).

The selection landscape and genetic legacy of ancient Eurasians.

The Holocene (beginning around 12,000 years ago) encompassed some of the most significant changes in human evolution, with far-reaching consequences for the dietary, physical and mental health of present-day populations. Using a dataset of more than 1,600 imputed ancient genomes, we modelled the selection landscape during the transition from hunting and gathering, to farming and pastoralism across West Eurasia. We identify key selection signals related to metabolism, including that selection at the FADS cluster began earlier than previously reported and that selection near the LCT locus predates the emergence of the lactase persistence allele by thousands of years.

The evolutionary dynamics of local adaptations under genetic rescue is determined by mutational load and polygenicity.

Inbred populations often suffer from increased mutational load and reduced fitness due to lower efficacy of purifying selection in groups with small effective population sizes. Genetic rescue (GR) is a conservation tool that is studied and deployed with the aim of increasing the fitness of such inbred populations by assisted migration of individuals from closely related outbred populations. The success of GR depends on several factors-such as their demographic history and distribution of dominance effects of mutations-that may vary across populations.

Repeated origins, widespread gene flow, and allelic interactions of target-site herbicide resistance mutations.

Causal mutations and their frequency in agricultural fields are well-characterized for herbicide resistance. However, we still lack understanding of their evolutionary history: the extent of parallelism in the origins of target-site resistance (TSR), how long these mutations persist, how quickly they spread, and allelic interactions that mediate their selective advantage. We addressed these questions with genomic data from 19 agricultural populations of common waterhemp (), which we show to have undergone a massive expansion over the past century, with a contemporary effective population size estimate of 8 x 10.

Case Series: Hypercalcemia From Granulomatous Silicosis Developing After COVID-19 Infection.

Hypercalcemia is one of the most commonly encountered laboratory abnormalities in clinical medicine. Various causes have been well established. However, it is likely that the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), may be a newly found cause of this frequent finding, especially amongst those with a history of cosmetic surgery, specifically by means of silicone injection.

Detecting Selection in Multiple Populations by Modeling Ancestral Admixture Components.

One of the most powerful and commonly used approaches for detecting local adaptation in the genome is the identification of extreme allele frequency differences between populations. In this article, we present a new maximum likelihood method for finding regions under positive selection. It is based on a Gaussian approximation to allele frequency changes and it incorporates admixture between populations.

Rare Adult Subtype of Rhabdomyosarcoma, a Common Childhood Soft Tissue Carcinoma.

Rhabdomyosarcoma is a malignant soft tissue sarcoma of primitive mesenchymal cells, showing varying degrees of striated skeletal muscle cell differentiation. It is a very common cancer of childhood and adolescence, but rarely seen in the adult population. Here, we present a case of a 33-year-old male presented with a poorly differentiated desmin positive alveolar rhabdomyosarcoma in the left arm.

A Case of IgG4-Related Kidney Disease Developing While on Steroid Treatment for Autoimmune IgG4 Pancreatitis.

IgG4 (immunoglobulin G4)-related systemic disease is an autoimmune process affecting multiple organ systems. This inflammatory process can present as but not limited to pancreatitis, cholangitis, or unspecified kidney disease. In this case, our patient developed IgG4-related kidney disease while already on a prolonged steroid course for IgG4-related pancreatitis.

Delayed hemodialysis in COVID-19: Case series with literature review.

Background: Increased incidence of kidney injury has been seen in patients with COVID-19. However, less is known about COVID-19 susceptibility and outcomes in end-stage renal disease (ESRD) patients on hemodialysis (HD). Reduced angiotensin-converting enzyme 2 (ACE-2) from SARS-CoV-2 binding and increased angiotensin II (Ang-II) activity have been suggested as mechanisms for COVID-19 renal pathophysiology.

Disentangling selection on genetically correlated polygenic traits via whole-genome genealogies.

We present a full-likelihood method to infer polygenic adaptation from DNA sequence variation and GWAS summary statistics to quantify recent transient directional selection acting on a complex trait. Through simulations of polygenic trait architecture evolution and GWASs, we show the method substantially improves power over current methods. We examine the robustness of the method under stratification, uncertainty and bias in marginal effects, uncertainty in the causal SNPs, allelic heterogeneity, negative selection, and low GWAS sample size.

Outpatient Antibiotic Prescribing Patterns for Adult End-Stage Renal Disease Patients in New York State.

Background: Infections are important complications of end-stage renal disease (ESRD) with few studies having investigated oral antibiotic use. Inappropriate antibiotic prescribing can contribute to multidrug-resistant organisms and Clostridioides difficile infections seen in ESRD. This study investigates antibiotic prescribing practices in ESRD across New York State (NYS).

An approximate full-likelihood method for inferring selection and allele frequency trajectories from DNA sequence data.

Most current methods for detecting natural selection from DNA sequence data are limited in that they are either based on summary statistics or a composite likelihood, and as a consequence, do not make full use of the information available in DNA sequence data. We here present a new importance sampling approach for approximating the full likelihood function for the selection coefficient. Our method CLUES treats the ancestral recombination graph (ARG) as a latent variable that is integrated out using previously published Markov Chain Monte Carlo (MCMC) methods.

Human Disease Variation in the Light of Population Genomics.

Identifying the causes of similarities and differences in genetic disease prevalence among humans is central to understanding disease etiology. While present-day humans are not strongly differentiated, vast amounts of genomic data now make it possible to study subtle patterns of genetic variation. This allows us to trace our genomic history thousands of years into the past and its implications for the distribution of disease-associated variants today.

Physiological and Genetic Adaptations to Diving in Sea Nomads.

Understanding the physiology and genetics of human hypoxia tolerance has important medical implications, but this phenomenon has thus far only been investigated in high-altitude human populations. Another system, yet to be explored, is humans who engage in breath-hold diving. The indigenous Bajau people ("Sea Nomads") of Southeast Asia live a subsistence lifestyle based on breath-hold diving and are renowned for their extraordinary breath-holding abilities.

Diversity of Translation Initiation Mechanisms across Bacterial Species Is Driven by Environmental Conditions and Growth Demands.

The Shine-Dalgarno (SD) sequence motif is frequently found upstream of protein coding genes and is thought to be the dominant mechanism of translation initiation used by bacteria. Experimental studies have shown that the SD sequence facilitates start codon recognition and enhances translation initiation by directly interacting with the highly conserved anti-SD sequence on the 30S ribosomal subunit. However, the proportion of SD-led genes within a genome varies across species and the factors governing this variation in translation initiation mechanisms remain largely unknown.

Survival after Metastasectomy for Metastatic Urothelial Carcinoma: A Systematic Review and Meta-Analysis.

Cisplatin-based combination chemotherapy is standard treatment for metastatic urothelial carcinoma; however, the vast majority of patients experience disease progression. As systemic therapy alone is rarely curative for the treatment of metastatic urothelial cancer, not only are new therapies needed but also refinement of general treatment principles. Herein, we conducted a systematic review and meta-analysis to explore the role of metastasectomy in metastatic urothelial carcinoma.

Decisional outcomes following use of an interactive web-based decision aid for prostate cancer screening.

Informed decision-making tools are recommended for men considering prostate cancer screening. We evaluated the extent to which use of an interactive, web-based decision aid was associated with decisional and screening outcomes. Participants (N = 253) were 57 (7.

Bedside Ultrasonography for Arteriovenous Fistula Cannulation.

Difficulty in accessing a new arteriovenous fistula (AVF) is a common technical issue in hemodialysis patients, which often leads to interventional radiology and/or vascular surgery referral. As a consequence, the patient who needs dialysis may require a temporary dialysis catheter with its known potential complications. We present a case where bedside ultrasonography facilitated successful cannulation of a difficult AVF.

High blood pressure in dialysis patients: cause, pathophysiology, influence on morbidity, mortality and management.

Dialysis is initiated in a patient with End stage renal disease. The recent guidelines suggest the initiation of dialysis when symptoms and signs of kidney failure are present and not merely a decrease in GFR. The most common complication postdialysis is the occurrence of hypotension.

Tissue plasminogen activator versus heparin for locking dialysis catheters: A systematic review.

Background And Objectives: Hemodialysis catheters are commonly used when renal replacement therapy is initiated. These catheters have significant complications. Among "locking" solutions used in an attempt to decrease these complications is recombinant tissue plasminogen activator (rt-PA).