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Spinocerebellar ataxias (SCAs) represent a large group of hereditary degenerative diseases of the nervous system, in particular the cerebellum, and other systems that manifest with a variety of progressive motor, cognitive, and behavioral deficits with the leading symptom of cerebellar ataxia. SCAs often lead to severe impairments of the patient's functioning, quality of life, and life expectancy. For SCAs, there are no proven effective pharmacotherapies that improve the symptoms or substantially delay disease progress, i.e., disease-modifying therapies. To study SCA pathogenesis and potential therapies, animal models have been widely used and are an essential part of pre-clinical research. They mainly include mice, but also other vertebrates and invertebrates. Each animal model has its strengths and weaknesses arising from model animal species, type of genetic manipulation, and similarity to human diseases. The types of murine and non-murine models of SCAs, their contribution to the investigation of SCA pathogenesis, pathological phenotype, and therapeutic approaches including their advantages and disadvantages are reviewed in this paper. There is a consensus among the panel of experts that (1) animal models represent valuable tools to improve our understanding of SCAs and discover and assess novel therapies for this group of neurological disorders characterized by diverse mechanisms and differential degenerative progressions, (2) thorough phenotypic assessment of individual animal models is required for studies addressing therapeutic approaches, (3) comparative studies are needed to bring pre-clinical research closer to clinical trials, and (4) mouse models complement cellular and invertebrate models which remain limited in terms of clinical translation for complex neurological disorders such as SCAs. [ABSTRACT FROM AUTHOR]

R.A. Fisher's 1922 paper On the dominance ratio has a strong claim to be the foundation paper for modern population genetics. It greatly influenced subsequent work by Haldane and Wright, and contributed 3 major innovations to the study of evolution at the genetic level. First, the introduction of a general model of selection at a single locus, which showed how variability could be maintained by heterozygote advantage. Second, the use of the branching process approach to show that a beneficial mutation has a substantial chance of loss from the population, even when the population size is extremely large. Third, the invention of the concept of a probability distribution of allele frequency, caused by random sampling of allele frequencies due to finite population size, and the first use of a diffusion equation to investigate the properties of such a distribution. Although Fisher was motivated by an inference that later turned out to lack strong empirical support (a substantial contribution of dominance to quantitative trait variability), and his use of a diffusion equation was marred by a technical mistake, the paper introduced concepts and methods that pervade much subsequent work in population genetics. [ABSTRACT FROM AUTHOR]

In the last decade there has been a revolution in terms of genetic findings in neurodevelopmental disorders (NDDs), with many discoveries critical for understanding their aetiology and pathophysiology. Clinical trials in single-gene disorders such as fragile X syndrome highlight the challenges of investigating new drug targets in NDDs. Incorporating a developmental perspective into the process of drug development for NDDs could help to overcome some of the current difficulties in identifying and testing new treatments. This paper provides a summary of the proceedings of the 'New Frontiers Meeting' on neurodevelopmental disorders organised by the European College of Neuropsychopharmacology in conjunction with the Innovative Medicines Initiative-sponsored AIMS-2-TRIALS consortium. It brought together experts in developmental genetics, autism, NDDs, and clinical trials from academia and industry, regulators, patient and family associations, and other stakeholders. The meeting sought to provide a platform for focused communication on scientific insights, challenges, and methodologies that might be applicable to the development of CNS treatments from a neurodevelopmental perspective. Multidisciplinary translational consortia to develop basic and clinical research in parallel could be pivotal to advance knowledge in the field. Although implementation of clinical trials for NDDs in paediatric populations is widely acknowledged as essential, safety concerns should guide each aspect of their design. Industry and academia should join forces to improve knowledge of the biology of brain development, identify the optimal timing of interventions, and translate these findings into new drugs, allowing for the needs of users and families, with support from regulatory agencies. [ABSTRACT FROM AUTHOR]

Background: Global estimates for cholera annually approximate 4 million cases worldwide with 95,000 deaths. Recent outbreaks, including Haiti and Yemen, are reminders that cholera is still a global health concern. Cholera outbreaks can rapidly induce high death tolls by overwhelming the capacity of health facilities, especially in remote areas or areas of civil unrest. Recent studies demonstrated that stool specimens preserved on filter paper facilitate molecular analysis of Vibrio cholerae in resource limited settings. Specimens preserved in a rapid, low-cost, safe and sustainable manner for sequencing provides previously unavailable data about circulating cholera strains. This may ultimately provide new information to shape public policy response on cholera control and elimination. Methodology/Principal findings: Whole genome sequencing (WGS) recovered close to a complete sequence of the V. cholerae O1 genome with satisfactory genome coverage from stool specimens enriched in alkaline peptone water (APW) and V. cholerae culture isolates, both spotted on filter paper. The minimum concentration of V. cholerae DNA sufficient to produce quality genomic information was 0.02 ng/μL. The genomic data confirmed the presence or absence of genes of epidemiological interest, including cholera toxin and pilus loci. WGS identified a variety of diarrheal pathogens from APW-enriched specimen spotted filter paper, highlighting the potential for this technique to explore the gut microbiome, potentially identifying co-infections, which may impact the severity of disease. WGS demonstrated that these specimens fit within the current global cholera phylogenetic tree, identifying the strains as the 7th pandemic El Tor. Conclusions: WGS results allowed for mapping of short reads from APW-enriched specimen and culture isolate spotted filter papers this provided valuable molecular epidemiological sequence information on V. cholerae strains from remote, low-resource settings. These results identified the presence of co-infecting pathogens while providing rare insight into the specific V. cholerae strains causing outbreaks in cholera-endemic areas. [ABSTRACT FROM AUTHOR]

Background: The gut microbiome is an important determinant of health and disease in preterm infants. Objectives: The objective of this article was to share our current protocol for other neonatal intensive care units to potentially expand their existing protocols, aiming to characterize the relationship between the intestinal microbiome and health outcomes in preterm infants. Methods : This prospective, longitudinal study planned to recruit 160 preterm infants born <32 weeks gestational age or weighing <1,500 g and admitted to one of two Level III/IV neonatal intensive care units. During the neonatal intensive care unit period, the primary measures included events of early life pain/stress, gut microbiome, host genetic variations, and neurobehavioral assessment. During follow-up visits, gut microbiome; pain sensitivity; and medical, growth, and developmental outcomes at 4, 8-12, and 18-24 months corrected age were measured. Discussion : As of February 14, 2020, 214 preterm infants have been recruited. We hypothesize that infants who experience greater levels of pain/stress will have altered gut microbiome, including potential adverse outcomes such as necrotizing enterocolitis and host genetic variations, feeding intolerance, and/or neurodevelopmental impairments. These will differ from the intestinal microbiome of preterm infants who do not develop these adverse outcomes. To test this hypothesis, we will determine how alterations in the intestinal microbiome affect the risk of developing necrotizing enterocolitis, feeding intolerance, and neurodevelopmental impairments in preterm infants. In addition, we will examine the interaction between the intestinal microbiome and host genetics in the regulation of intestinal health and neurodevelopmental outcomes. [ABSTRACT FROM AUTHOR]

The article offers information on the retraction of papers from a genetics journal due to concerns about informed consent for study participants, particularly from ethnic minorities in China.

Paper birch (Betula papyrifera Marsh) is an ecologically valuable species with a broad geographic distribution across the North America. Its diversity, versatility and enduring nature make it an ideal candidate for a selective breeding program in this region. However, an understanding of the genecology of this species is fundamental to deploy it successfully. Ten paper birch provenances were collected from British Columbia (BC, Canada) and northern Idaho (USA) along elevational transects to determine whether observed bud flush phenology was due to genetics and /or environmental variation or their interaction. Seedlings were grown at three different nurseries: University of Idaho (46°44'N), Landing (50°17'N) and Little Forestry (54°00'N) and planted in a randomized single tree interlocking block design in three common gardens at Sandpoint, ID (48°13'N), Skimikin, BC (50°45'N) and Red Rock, BC (53°45'N). Results indicate that variation in the timing of bud flush is a complex interaction among local genetic characteristics and environmental conditions of the growing site. Birch bud flush followed a general geographic trend where provenances at the southern common garden (Sandpoint) required less time (Day of Year, DoY) and fewer growing degree days (GDD) compared to central (Skimikin) and northern (Red Rock) common gardens. Although there were significant differences in the timing of bud flush among provenances along an elevational gradient, none of the regions showed the expected linear elevational cline, trends were inconsistent. Further, birch bud flush was significantly influenced by nursery displacement effects in the initial year of establishment but disappeared within three years. These results provide an opportunity to characterize bud flush phenology of paper birch and would be useful for improving operational paper birch seed transfer programs in BC. [ABSTRACT FROM AUTHOR]

Paper mulberry, Broussonetia papyrifera (L.) L’Hér. ex Vent. (Moraceae), a dioecious species, was transported by humans from Taiwan to the islands of Remote Oceania. Its introduction and cultivation in Remote Oceania was intentional due to its cultural importance as a fiber source for barkcloth textiles. The aim of this study was to explore the genetic diversity and structure of paper mulberry populations within Remote Oceania in order to infer dispersal patterns that may reflect past human interaction among island groups. We present the integrated analysis of 380 samples (313 contemporary and 67 herbarium specimens) collected in Near and Remote Oceania. Genetic characterization was based on a set of ten microsatellites developed for B. papyrifera and complemented with the analysis of the ribosomal internal transcribed spacer ITS-1 sequence, a sex marker and the chloroplast ndhF–rpl32 intergenic spacer. Microsatellite data identify a total of 64 genotypes, despite this being a clonally propagated crop, and show three major dispersal hubs within Remote Oceania, centered on the islands of Fiji, Tonga, and Pitcairn. Of 64 genotypes identified, 55 correspond to genotypes associated to female-sexed plants that probably descend from plants introduced by the prehistoric Austronesian-speaking voyagers. The ratio of accessions to genotypes between herbarium and contemporary samples, suggests recent loss of genetic diversity. In addition to the chloroplast haplotypes described previously, we detected two new haplotypes within Remote Oceania both originating in Taiwan. This is the first study of a commensal species to show genetic structuring within Remote Oceania. In spite of the genetic bottleneck, the presence of only one sex, a timespan of less than 5000 years, and asexual propagation of this crop in Remote Oceania, we detect genetic diversity and regional structuring. These observations suggest specific migration routes between island groups within Remote Oceania. [ABSTRACT FROM AUTHOR]

Fertility treatment enables involuntary childless people to have genetically related children, something that, for many, is a valuable life project. In this paper, I respond to two sets of objections that have been raised against expanding state‐funded fertility treatment provision for existing treatments, such as in vitro fertilisation (IVF), and against funding new treatments, such as uterine transplantation (UTx). Following McTernan, I refer to the first set of objections as the 'one good among many' objection. It purports that it is unjustifiable for the state to prioritise the funding of the life project of becoming a parent through fertility treatment provision over the funding of other life projects that people might have. Following Lotz, I refer to the second set of objections as the 'norm‐legitimation' objection. It maintains that the provision of costly forms of fertility treatment, such as UTx, would legitimise problematic social norms concerning genetic relatedness, reproduction and parenting, and that states should not engage in such a legitimation. In response to these objections, I defend the view that (reproductive) preferences ought to be taken more seriously when discussing fertility treatment provision and parental projects, and that not doing so can be costly, especially for women. The approach defended in this paper seeks to avoid disregarding and policing preferences and to reconcile their fulfilment with political projects aimed at improving the material and social conditions of sub‐fertile people: people who, for social or biological reasons (or an intersection of the two), are unable to reproduce unassisted. [ABSTRACT FROM AUTHOR]

Understanding biological mechanisms is fundamental for improving animal production and health to meet the growing demand for high-quality protein. As an emerging biotechnology, single-cell transcriptomics has been gradually applied in diverse aspects of animal research, offering an effective method to study the gene expression of high-throughput single cells of different tissues/organs in animals. In an unprecedented manner, researchers have identified cell types/subtypes and their marker genes, inferred cellular fate trajectories, and revealed cell‒cell interactions in animals using single-cell transcriptomics. In this paper, we introduce the development of single-cell technology and review the processes, advancements, and applications of single-cell transcriptomics in animal research. We summarize recent efforts using single-cell transcriptomics to obtain a more profound understanding of animal nutrition and health, reproductive performance, genetics, and disease models in different livestock species. Moreover, the practical experience accumulated based on a large number of cases is highlighted to provide a reference for determining key factors (e.g., sample size, cell clustering, and cell type annotation) in single-cell transcriptomics analysis. We also discuss the limitations and outlook of single-cell transcriptomics in the current stage. This paper describes the comprehensive progress of single-cell transcriptomics in animal research, offering novel insights and sustainable advancements in agricultural productivity and animal health. [ABSTRACT FROM AUTHOR]

Simple Summary: Myeloid-derived suppressor cells (MDSCs) are immature cells that expand in the circulation of patients with cancer, sepsis or chronic inflammation, modulate the immune response against cancer (favoring tumor onset and progression) and promote neoangiogenesis. These premises suggest that MDSCs could be involved in the pathogenesis of primary myelofibrosis (PMF) (a myeloproliferative neoplasm characterized by chronic inflammation and extensive neoangiogenesis in bone marrow and spleen). In this paper, we found that (1) MDSCs are increased both in the circulation and in the spleen of PMF patients and strongly correlate with disease progression; and (2) reduced CXCR4 expression on MDSCs along with increased plasmatic SDF-1α can be involved in their mobilization. These findings suggest that circulating MDSCs can be considered a parameter of disease severity and set MDSCs as potential new targets for cancer therapy. Primary myelofibrosis (PMF) is a myeloproliferative neoplasm characterized by a chronic inflammatory state that plays a relevant role in the disease pathogenesis (as proven by high levels of inflammatory cytokines with prognostic significance and by a persistent oxidative stress) and by extensive neoangiogenesis in bone marrow (BM) and spleen. Myeloid-derived suppressor cells (MDSCs) are immature cells that expand in patients with cancer, sepsis or chronic inflammation, favoring tumor onset and progression mainly through the decrease in immune surveillance and the promotion of neoangiogenesis. In this paper, we evaluated the presence of circulating MDSCs in PMF patients, the plasmatic factors involved in their mobilization/expansion and the correlations with laboratory, genetic and clinical parameters. The data indicated that MDSCs could have a relevant role in PMF as a new pathogenic mechanism contributing to explaining the phenotypic diversity observed during the clinical course of the disease, or a potential new target for personalized treatment. [ABSTRACT FROM AUTHOR]

• CFTR-related disorders (RD) are a group of conditions caused by CFTR protein dysfunction, but to a level of dysfuncton not satisfying the diagnostic crtieria for cystic fibrosis (CF). • This paper discusses the individual disorders, including congenital absence of the vas deferens (CAVD), diffuse bronchiectasis, chronic or acute recurrent pancreatitis, allergic bronchopulmonary aspergillosis, chronic rhinosinusitis, primary sclerosing cholangitis and aquagenic wrinkling of the palms. • The CFTR functional and genetic evidence in support of each condition being a CFTR-RD are discussed and guidance for reaching the diagnosis is provided. • Gaps in our knowledge and future areas of research, including the role of CFTR modulators, are highlighted. This is the third paper in the series providing updated information and recommendations for people with cystic fibrosis transmembrane conductance regulator (CFTR)-related disorder (CFTR-RD). This paper covers the individual disorders, including the established conditions - congenital absence of the vas deferens (CAVD), diffuse bronchiectasis and chronic or acute recurrent pancreatitis - and also other conditions which might be considered a CFTR-RD, including allergic bronchopulmonary aspergillosis, chronic rhinosinusitis, primary sclerosing cholangitis and aquagenic wrinkling. The CFTR functional and genetic evidence in support of the condition being a CFTR-RD are discussed and guidance for reaching the diagnosis, including alternative conditions to consider and management recommendations, is provided. Gaps in our knowledge, particularly of the emerging conditions, and future areas of research, including the role of CFTR modulators, are highlighted. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) is a complex disease that develops through a sequence of molecular events that are still poorly defined. This process is driven by a multitude of context-dependent genes that play different roles based on their environment. The complexity and multi-faceted nature of these genes make it difficult to study the genetic basis of IBD. The goal of this article is to review the key genes in the pathophysiology of IBD and highlight new technology that can be used in further research. This paper examines Nanostring RNA probe technology, which uses tissue analyzed without the use of enzymes, transcription, or amplification. Nanostring offers several panels of genes to test, including an inflammation panel of 234 genes. This article analyzes this panel and reviews the literature for each gene's effect in IBD for use as a framework to review the pathophysiology of the disease. The panel was narrowed to 26 genes with significant evidence of mechanistic potential in IBD, which were then categorized into specific areas of pathogenesis. These include gut barrier breakdown, inappropriate recognition of commensal bacteria, immune cell activation, proinflammatory cytokine release, and subsequent impairment of the anti-inflammatory response. The eventual goal of this paper is the creation of a customized panel of IBD genes that can be used to better understand the genetic mechanism of IBD and aid in the development of future therapies in IBD. [ABSTRACT FROM AUTHOR]

Purpose: From a diagnostic standpoint, certain approaches to genetic screening in clinical practice remain ambiguous in the era of assisted reproduction. Even the most current guidelines do not provide definite guidance on testing protocols, leaving clinicians to carefully determine which tests best serve patients struggling with infertility. The lack of uniformity in the current practice of male fertility evaluation can prove to be quite costly, thus necessitating healthcare practitioners to carefully appraise the necessity and weigh the advantages against potential economic and psychological detriments. The objective of this review is to map the existing literature on the general topic of the clinical indications of routine karyotyping and/or AZF screening in infertile men, identify key concepts, determine where the gaps are, and lastly, provide an overview of the conclusions drawn from a body of knowledge that varies widely in terms of methodologies or disciplines. Materials and Methods: A thorough search was conducted for the published findings up until July 2023, utilizing PubMed (MEDLINE). This comprehensive search involved the use of specific search keywords, either individually or in combination. The search terms employed were as follows: “Karyotype”, "Klinefelter" or "KS" or "47,XXY", "AZF" or "Azoospermi*" and/or "microdeletion*" in the title or abstract. Once the titles and abstracts of selected articles were obtained, the complete texts of linked papers were meticulously scrutinized. Results: A total of 191 records were identified from PubMed. During screening, 161 records (84.3%) were eliminated. Finally, 30 papers were included in this scoping review, which was conducted in 18 countries. The number of sequence tag sites (STSs) used in the studies varied from 5 to 59. The rate of AZF deletions among patients with NOA ranged from 1.3% to 53%. The mean frequency was estimated to be 5.6%. The rate of YCM among patients with XXY karyotype was nil in 19 out of 30 studies (63%), whilst, in the remaining studies, the rate varied from 0.8% to 67%. Conclusion: This review provides insights into managing male infertility. The presence of spermatozoa in ejaculation and successful surgical retrieval cannot be excluded for individuals with AZFb/AZFbc microdeletions. Screening for Y chromosome microdeletions is not needed for mosaic or classic KS. Only 1% of individuals with sperm concentration exceeding 1×106 sperm/mL and less than 5×106 sperm/mL exhibit AZF microdeletions; therefore, testing referral for such populations may need reassessment. Individuals with mosaic monosomy X karyotype and certain chromosomal anomalies should be referred for AZF deletion screening. These findings have implications for male infertility management and future research. [ABSTRACT FROM AUTHOR]

Biosensors have emerged as a valuable tool with high specificity and sensitivity for fast and reliable detection of hazardous substances in drinking water. Numerous substances have been addressed using synthetic biology approaches. However, many proposed biosensors are based on living, genetically modified organisms and are therefore limited in shelf life, usability and biosafety. We addressed these issues by the construction of an extensible, cell-free biosensor. Storage is possible through freeze drying on paper. Following the addition of an aqueous sample, a highly efficient cell-free protein synthesis (CFPS) reaction is initiated. Specific allosteric transcription factors modulate the expression of ‘superfolder’ green fluorescent protein (sfGFP) depending on the presence of the substance of interest. The resulting fluorescence intensities are analyzed with a conventional smartphone accompanied by simple and cheap light filters. An ordinary differential equitation (ODE) model of the biosensors was developed, which enabled prediction and optimization of performance. With an optimized cell-free biosensor based on the Shigella flexneri MerR transcriptional activator, detection of 6 μg/L Hg(II) ions in water was achieved. Furthermore, a completely new biosensor for the detection of gamma-hydroxybutyrate (GHB), a substance used as date-rape drug, was established by employing the naturally occurring transcriptional repressor BlcR from Agrobacterium tumefaciens. [ABSTRACT FROM AUTHOR]

The paper mulberry is one of the multifunctional tree species in agroforestry systems and is also commonly utilized in traditional medicine in China and other Asian countries. However, little is known about its molecular genetics, which hinders research on and exploitation of this valuable resource. To discern the correlation between gene expression and the essential properties of the paper mulberry, we performed a transcriptomics analysis, assembling a total of 37,725 unigenes from 54,638,676 reads generated by RNA-seq. Among these, 22,692 unigenes showed greater than 60% similarity with genes from other species. The lengths of 13,566 annotated unigenes were longer than 1,000 bp. Functional clustering analysis with COG (Cluster of Orthologous Groups) revealed that 17,184 unigenes are primarily involved in transcription, translation, signal transduction, carbohydrate metabolism, secondary metabolism, and energy metabolism. GO (Gene Ontology) annotation suggests enrichment of genes encoding antioxidant activity, transporter activity, biosynthesis, metabolism and stress response, with a total of 30,659 unigenes falling in these categories. KEGG (Kyoto Encyclopedia of Genes and Genomes) metabolic pathway analysis showed that 7,199 unigenes are associated with 119 metabolic pathways. In addition to the basic metabolism, these genes are enriched for plant pathogen interaction, flavonoid metabolism and other secondary metabolic processes. Furthermore, differences in the transcriptomes of leaf, stem and root tissues were analyzed and 7,233 specifically expressed unigenes were identified. This global expression analysis provided novel insights about the molecular mechanisms of the biosynthesis of flavonoid, lignin and cellulose, as well as on the response to biotic and abiotic stresses including the remediation of contaminated soil by the paper mulberry. [ABSTRACT FROM AUTHOR]

Amphimeriasis, a fish-borne zoonotic disease caused by the liver fluke Amphimerus spp., has recently been reported as an emerging disease affecting an indigenous Ameridian group, the Chachi, living in Ecuador. The only method for diagnosing amphimeriasis was the microscopic detection of eggs from the parasite in patients' stool samples with very low sensitivity. Our group developed an ELISA technique for detection of anti-Amphimerus IgG in human sera and a molecular method based on LAMP technology (named LAMPhimerus) for specific and sensitive parasite DNA detection. The LAMPhimerus method showed to be much more sensitive than classical parasitological methods for amphimeriasis diagnosis using human stool samples for analysis. The objective of this work is to demonstrate the feasibility of using dried stool samples on filter paper as source of DNA in combination with the effectiveness of our previously designed LAMPhimerus assay for successfully Amphimerus sp. detection in clinical stool samples. A total of 102 untreated and undiluted stool samples collected from Chachi population were spread as thin layer onto common filter paper for easily transportation to our laboratory and stored at room temperature for one year until DNA extraction. When LAMPhimerus method was applied for Amphimerus sp. DNA detection, a higher number of positive results was detected (61/102; 59.80%) in comparison to parasitological methods (38/102; 37.25%), including 28/61 (45.90%) microscopy-confirmed Amphimerus sp. infections. The diagnostic parameters for the sensitivity and specificity werecalculated for our LAMPhimerus assay, which were 79.17% and 65.98%, respectively. We demonstrate, for the first time, that common filter paper is useful for easy collection and long-term storage of human stool samples for later DNA extraction and molecular analysis of human-parasitic trematode eggs. This simple, economic and easily handling method combined with the specific and sensible LAMPhimerus assay has the potential to beused as an effective molecular large-scale screening test for amphimeriasis-endemic areas. [ABSTRACT FROM AUTHOR]

Cooperation among kin is common in animal societies. Kin groups may form by individuals directly discriminating relatives based on kin recognition cues, or form passively through natal philopatry and limited dispersal. We describe the genetic landscape for a primitively eusocial wasp, Polistes dominula, and ask whether individuals choose cooperative partners that are nearby and/or that are genetic relatives. Firstly, we genotyped an entire sub-population of 1361 wasps and found genetic structuring on an extremely fine scale: the probability of finding genetic relatives decreases exponentially within just a few meters of an individual’s nest. At the same time, however, we found a lack of genetic structuring between natural nest aggregations within the population. Secondly, in a separate dataset where ~2000 wasps were genotyped, we show that wasps forced experimentally to make a new nest choice tended to choose new nests near to their original nests, and that these nests tended to contain some full sisters. However, a significant fraction of wasps chose nests that did not contain sisters, despite sisters being present in nearby nests. Although we cannot rule out a role for direct kin recognition or natal nest-mate recognition, our data suggest that kin groups may form via a philopatric rule-of-thumb, whereby wasps simply select groups and nesting sites that are nearby. The result is that most subordinate helpers obtain indirect fitness benefits by breeding cooperatively. [ABSTRACT FROM AUTHOR]

Swarm-founding wasps are endemic and common representatives of neotropical fauna and compose an interesting social tribe of vespids, presenting both complex social characteristics and uncommon traits for a eusocial group, such as the absence of castes with distinct morphology. The paper wasp Protonectarina sylveirae (Saussure) presents a broad distribution from Brazil, Argentina and Paraguay, occurring widespread in the Atlantic rainforest and arboreal Caatinga, being absent in the Amazon region. Given the peculiar distribution among swarm-founding wasps, an integrative approach to reconstruct the evolutionary history of P. sylveirae in a spatial-temporal framework was performed to investigate: the presence of genetic structure and its relationship with the geography, the evolution of distinct morphologic lineages and the possible historical event(s) in Neotropical region, which could explain the observed phylogeographic pattern. Individuals of P. sylveirae were obtained from populations of 16 areas throughout its distribution for DNA extraction and amplification of mitochondrial genes 12S, 16S and COI. Analysis of genetic diversity, construction of haplotype net, analysis of population structure and dating analysis of divergence time were performed. A morphometric analysis was also performed using 8 measures of the body of the adult (workers) to test if there are morphological distinction among populations. Thirty-five haplotypes were identified, most of them exclusively of a group and a high population structure was found. The possibility of genetic divergence because of isolation by distance was rejected. Morphological analysis pointed to a great uniformity in phenotypes, with only a small degree of differentiation between populations of south and the remaining. Divergence time analysis showed a Middle/Late Miocene origin, a period where an extensive marine ingression occurred in South America. Divergence of haplogroups began from the Plio/Pleistocene boundary and the last glacial maximum most likely modeled the current distribution of species, even though it was not the cause of genetic breaks. [ABSTRACT FROM AUTHOR]

Simple Summary: Much research has been conducted on the causes of childhood cancer, but many areas of uncertainty remain. We conducted a detailed search of recent studies investigating the causes of childhood cancer. Our findings, based on publications from 2014 to 2021, are summarized by topic in three separate papers: factors acting during childhood (Paper 1), factors relating to the parents and pregnancy (Paper 2), and factors relating to the environment (Paper 3). In this first paper, we summarize convincing evidence from studies that show increased childhood cancer risk associated with genetic cancer predisposition, birth defects, prior cancer, medical ionizing radiation, organ transplantation and exposure to cancer-causing viruses, and a reduced risk associated with some childhood vaccinations. Other factors discussed in this paper include the impact of the child's diet, allergies, medications, and body mass index. This review of factors associated with childhood cancer may help evidence-based efforts to reduce cancer in our pediatric populations. Purpose: To review the childhood risk factors for pediatric cancer (diagnosis before age 20). Methods: We conducted literature searches using Ovid Medline and Scopus to find primary research studies, review articles, and meta-analyses published from 2014 to 3 March 2021. Results: Strong evidence indicates that an array of genetic and epigenetic phenomena, structural birth defects, and chromosomal anomalies are associated with an increased risk of various childhood cancers. Increased risk is also associated with prior cancer, likely due to previous treatment agents and therapeutic ionizing radiation. Convincing evidence supports associations between several pediatric cancers and ionizing radiation, immunosuppression, and carcinogenic virus infection both in healthy children and in association with immune suppression following organ transplantation. Breastfeeding and a childhood diet rich in fruits and vegetables appears to reduce the risk of pediatric leukemia but the evidence is less strong. Childhood vaccination against carcinogenic viruses is associated with a lower risk of several cancers; there is less strong evidence that other childhood vaccinations more broadly may also lower risk. Ultraviolet (UV) radiation is associated with increased melanoma risk, although most melanomas following childhood UV exposure occur later, in adulthood. Evidence is weak or conflicting for the role of body mass index, other childhood infections, allergies, and certain treatments, including immunomodulator medications and human growth therapy. [ABSTRACT FROM AUTHOR]

Purpose: Advances in germline genetics, and related therapeutic opportunities, present new opportunities and challenges in prostate cancer. The Prostate Cancer Clinical Trials Consortium Germline Genetics Working Group was established to address genetic testing for men with prostate cancer, especially those with advanced disease undergoing testing for treatment-related objectives and clinical trials. Methods: The Prostate Cancer Clinical Trials Consortium Germline Genetics Working Group met monthly to discuss the current state of genetic testing of men with prostate cancer for therapeutic or clinical trial purposes. We assessed current institutional practices, developed a framework to address unique challenges in this population, and identified areas of future research. Results: Genetic testing practices in men with prostate cancer vary across institutions; however, there were several areas of agreement. The group recognized the clinical benefits of expanding germline genetic testing, beyond cancer risk assessment, for the goal of treatment selection or clinical trial eligibility determination. Genetic testing for treatment selection should ensure patients receive appropriate pretest education and consent and occur under auspices of a research study whenever feasible. Providers offering genetic testing should be able to interpret results and recommend post-test genetic counseling for patients. When performing tumor (somatic) genomic profiling, providers should discuss the potential for uncovering germline mutations and recommend appropriate genetic counseling. In addition, family members may benefit from cascade testing and early cancer screening and prevention strategies. Conclusion: As germline genetic testing is incorporated into practice, further development is needed in establishing prompt testing for time-sensitive treatment decisions, integrating cascade testing for family, ensuring equitable access to testing, and elucidating the role of less-characterized germline DNA damage repair genes, individual gene-level biologic consequences, and treatment response prediction in advanced disease. [ABSTRACT FROM AUTHOR]

Objectives:Schizophrenia is a severe psychiatric disease affecting about 1% of the general population. The relative contribution of genetic factors has been estimated to be up to 80%. The mode of inheritance is complex, non-Mendelian, and in most cases involving the combined action of large numbers of genes. Methods:This review summarises recent efforts to identify genetic variants associated with schizophrenia detected, e.g., through genome-wide association studies, studies on copy-number variants or next-generation sequencing. Results:A large, new body of evidence on genetics of schizophrenia has accumulated over recent years. Many new robustly associated genetic loci have been detected. Furthermore, there is consensus that at least a dozen microdeletions and microduplications contribute to the disease. Genetic overlap between schizophrenia, other psychiatric disorders, and neurodevelopmental syndromes raised new questions regarding the current classification of psychiatric and neurodevelopmental diseases. Conclusions:Future studies will address especially the functional characterisation of genetic variants. This will hopefully open the doors to our understanding of the pathophysiology of schizophrenia and other related diseases. Complementary, integrated systems biology approaches to genomics, transcriptomics, proteomics and metabolomics may also play crucial roles in enabling a precision medicine approach to the treatment of individual patients. [ABSTRACT FROM PUBLISHER]

Genetic relatedness figures heavily in contemporary ethical debates on egg freezing, although the arguments lack empirical‐based evidence. Rather than adding another theoretical view on the moral relevance of genetic connections, this paper instead proposes an empirically grounded perspective based on two independent qualitative interview‐based studies conducted in Belgium and France. Three themes emerge from our empirical data: (1) prioritizing family building; (2) centering the gestational experience of motherhood; and (3) identifying the complexities and limitations of adoption. These themes suggest that the relationship between egg freezing, genetics, biological motherhood, and adoption is highly complex and less straightforward than what is often assumed in the egg freezing debate. Our study provides more detailed insights into women's ambivalent experiences regarding those reproductive options. We discuss the ethical implications of our empirical findings and hold that pursuing genetic desire is not necessarily the main moral reason why women freeze their eggs. [ABSTRACT FROM AUTHOR]

Simple Summary: The incidence of gastric cancer (GC) is increasing. Many people receive an advanced diagnosis of GC. Furthermore, a large number of patients are surgically inoperable and are unresponsive to preoperative chemotherapy. Patients with GC do not currently have an immunotherapy option. Our study's objective was to provide insight into extracellular vesicles (EVs) and GC. EVs in GC can be studied, as this article explains. EVs screening, which is available for all patients, is an option for combatting GC. Extracellular vesicles, or EVs, are membrane-bound nanocompartments produced by tumor cells. EVs carry proteins and nucleic acids from host cells to target cells, where they can transfer lipids, proteomes, and genetic material to change the function of target cells. EVs serve as reservoirs for mobile cellular signals. The collection of EVs using less invasive processes has piqued the interest of many researchers. Exosomes carry substances that can suppress the immune system. If the results of exosome screening are negative, immunotherapy will be beneficial for GC patients. In this study, we provide an update on EVs and GC based on ongoing review papers and clinical trials. [ABSTRACT FROM AUTHOR]

In light of the post-genomic era, epigenetics brings about an opportunity to better understand how the molecular machinery works and is led by a complex dynamic set of mechanisms, often intricate and complementary in many aspects. In particular, epigenetics links developmental biology and genetics, as well as many other areas of knowledge. The present work highlights substantial scopes and relevant discoveries related to the development of the term from its first notions. To our understanding, the concept of epigenetics needs to be revisited, as it is one of the most relevant and multifaceted terms in human knowledge. To redirect future novel experimental or theoretical efforts, it is crucial to compile all significant issues that could impact human and ecological benefit in the most precise and accurate manner. In this paper, the reader can find one of the widest compilations of the landmarks and epistemic considerations of the knowledge of epigenetics across the history of biology from the earliest epigenetic formulation to genetic determinism until the present. In the present work, we link the current body of knowledge and earlier pre-genomic concepts in order to propose a new definition of epigenetics that is faithful to its regulatory nature. [ABSTRACT FROM AUTHOR]

Introduction: There is growing interest in identifying genetic predispositions to dental caries using non-invasive tools. Dermatoglyphics, examining dermal ridge patterns on the hands and feet, is linked to genetic foundations. Galton’s theory asserts fingerprint constancy. In dentistry, dermatoglyphics gains attention for its correlation with students pathologies. This study evaluates the association of dental caries in students with dermatoglyphics. Materials and Methods: The research at the Department of Oral and Maxillofacial Pathology, Dharmsinh Desai University, involved 50 subjects (28 females and 22 males) with normal fingerprints. Ethical clearance was obtained from the institute’s Ethics Committee. Fingerprints were recorded using the conventional method, employing ink, paper, roller, glass slab and sponging pad. The prints were examined, classified and analysed through the Cummins method, categorising them into whorls, loops and arches. The dental caries were assessed through the decayed, missing and filled teeth (DMFT) scores of the participants. The DMFT score was tested for association and difference according to the type of fingerprint pattern. Results: Females commonly exhibit loop patterns, while males show an equal distribution between loops and whorls. The connection between fingerprint patterns and DMFT scores is notable. A Chi-square test for left-side patterns (Chi-square = 27.74, P = 0.002) reveals a strong association, linking specific patterns to distinct DMFT scores. Similarly, for right-side patterns (Chi-square = 11.349, P = 0.045), there is significance, emphasising the relationship between fingerprint types and dental caries. Conclusion: The study examined the connection between fingerprint patterns and dental caries in children, discovering a positive correlation. Specific patterns such as arch, loop and whorl were linked to caries presence or absence, suggesting their potential as an early detection tool, although accuracy might vary based on genetic factors. [ABSTRACT FROM AUTHOR]

Deep Brain Stimulation (DBS) is an effective treatment option for patients with dopaminergic complications of Parkinson's disease (PD) and drug-refractory PD tremor. However, DBS and its indications can be challenging, and they are not often debated in the medical community. Through a critical narrative review, the objective of this paper is to improve the comprehension of DBS indications and help to solve the puzzle that this process can be. Proper patient selection is the first step for a good surgical outcome. In this review, then, relevant considerations are discussed, involving PD genes, PD phenotypes, indications of early stages, non-motor symptoms, neuroimaging predictors, comorbidities, and age. Individualized approaches are encouraged, including clinical and radiological factors. Social support during the whole follow-up and expectations alignment are necessary through this process and are also debated. [ABSTRACT FROM AUTHOR]

Epigenetics in the form of DNA methylation and other processes is an established property of genotypes and a focus of empirical research. Yet, there remain fundamental gaps in the evolutionary theory of epigenetics. To support a comprehensive understanding of epigenetics, this paper investigates theoretically the combined effects of deleterious mutation and epimutation with and without inbreeding. Both spontaneous epimutation and paramutation are considered to cover a broader range of epigenetic phenomena. We find that inbreeding generally reduces the amount of segregating deleterious genetic and epigenetic variation at equilibrium, although interestingly inbreeding can also increase the amount of deleterious genetic or epigenetic variation. Furthermore, we also demonstrate that epimutation indirectly can cause increased or decreased deleterious genetic variation at equilibrium relative to classic expectations, which is particularly evident when paramutation is occurring. With the addition of deleterious epimutation, there may be significantly increased purging of deleterious variation in more inbred populations and a significantly increased amount of segregating deleterious variation in more outbred populations, with notable exceptions. [ABSTRACT FROM AUTHOR]

The experience of adopted college/university students and young adults, and their unique challenges in understanding the development of their personal identities, is an important topic for research and clinical practice with adopted people. This paper examines college and university students' understanding of how their life experiences of being born Asian but being raised in a non-Asian adoptive family have influenced their personal racial identity formation and how this may have affected their choices of study and career. In addition to subjects' responses to a questionnaire, participants completed five peer-reviewed scales that revealed information about how they perceive their racial identities and their efforts to distinguish genetics from environmental influences on their personal identities. This article reports on the key findings that have significance for psychotherapists treating these students. [ABSTRACT FROM AUTHOR]

Introduction: International Orthopaedics was founded in 1977. Within the 40 volumes and 247 issues since its launch, 5462 scientific articles have been published. This article identifies, analyses and categorises the best cited articles published by the journal to date.Methods: We searched Elsevier Scopus database for citations of all papers published in International Orthopaedics since its foundation. Source title was selected, and the journal's title was introduced in the search engine. The identified articles were sorted based on their total number of received citations, forming a descending list from 1 to 100. Total citations and self-citations of all co-authors were recorded. Year of publication, number of co-authors, number of pages, country and institution of origin and study type were identified.Results: The best 100 papers and their citations correspond approximately to 2% of all the journal's publications. Total citations ranged from 62 to 272; 26 papers had >100 citations, of which self-citations accounted for <4%. Mean authorship number per paper was four and mean page number 6.5. United States, Japan and Germany ranked the top three countries of origin. The most common study type was case series, and most common topics were adult reconstruction, sports medicine and trauma.Conclusions: This article identifies topics, authors and institutions that contributed with their high-quality work in the journal's development over time. International Orthopaedics remains faithful to its authors and readers by publishing topical, well-written articles in excellent English. [ABSTRACT FROM AUTHOR]

In May 2015, my mother was diagnosed with stage IV pancreatic cancer and passed away three months later at the age of 78. Two years later, my older brother, only 53 at the time, was also diagnosed with pancreatic cancer. He passed away 15 months later. With this news, we engaged in the genetic retelling of family histories and connections, drawing genealogical maps on pieces of paper that reminded me of teaching Anthro 101 and starkly reimagined which relatives 'mattered' in our lives. As an anthropologist interested in subject formation and spatiality informed by a Foucauldian analytic, I have been propelled into exploring what it means to become 'high risk' (as a biologically related daughter and sister), subject to new regimes of surveillance and self‐management espoused by the field of precision medicine. This paper addresses this experience and thus contributes to questions of subject formation within the already‐existing truth‐making practices of genetic probability and personalized risk management. [ABSTRACT FROM AUTHOR]

Background: Sleep problems are regularly reported in people with intellectual disabilities. Recent years have seen a substantial increase in studies comparing sleep in people with intellectual disabilities to control participants, with an increase in the use of validated, objective measures. Emerging patterns of differences in sleep time and sleep quality warrant pooled investigation. Methods: A systematic search was conducted across three databases (Ovid Embase, PsycInfo and Medline) and returned all papers comparing sleep in people with intellectual disabilities to a control group, published since the last meta‐analysis on the topic. A quality framework was employed to rate the risk of bias across studies. Separate meta‐analyses of sleep duration and sleep quality were conducted. Subgrouping compared findings for those studies with participants with genetic syndromes or neurodevelopmental conditions and those with heterogeneous intellectual disability. Results: Thirteen new papers were identified and combined with those from the previous meta‐analysis to provide 34 papers in total. Quality of studies was generally rated highly, though sampling provided risk of bias and adaptive functioning was rarely measured. People with intellectual disability associated with genetic syndromes or neurodevelopmental conditions sleep for shorter time periods (standardised mean difference =.26) and experience worse sleep quality (standardised mean difference =.68) than their peers. People with intellectual disability of heterogeneous origin show no difference in sleep time but have poorer sleep quality. There was some evidence that age moderated these effects. Conclusions: People with intellectual disability have poorer sleep than those without. Subtle patterns suggest that aetiology of intellectual disability moderates the topography of these difficulties, with further work needed to differentiate common and distinct mechanisms across groups. [ABSTRACT FROM AUTHOR]

The article offers information on the genetics papers. Topics include male genetic landscape of China, a set of almost 38,000 Y-STR sequences, Y-STR stands for Y-chromosomal short tandem repeat polymorphism, bits of repetitive DNA often used in forensic investigations, Springer Nature, launched an investigation, consent problems in China and the potential for abuse of the data, the Charité University Hospital in Berlin fired for hosting the genetic database used in several papers.

We developed 10 polymorphic microsatellite loci for the Japanese paper wasp Polistes rothneyi using the magnetic particle method. Eight of the 10 loci tested were highly polymorphic, having four to eight alleles in P. rothneyi with an expected heterozygosity of 0.60–0.75. They also appeared to be applicable to other related species such as Polistes jokahamae. These loci can be used to study parameters concerning genetic relatedness such as worker reproduction and kin structure. [ABSTRACT FROM AUTHOR]

Objectives: Schizophrenia is a group of severe psychiatric disorders with high heritability but only low odds ratios of risk genes. Despite progress in the identification of pathophysiological processes, valid biomarkers of the disease are still lacking. Methods: This comprehensive review summarises recent efforts to identify genetic underpinnings, clinical and cognitive endophenotypes and symptom dimensions of schizophrenia and presents findings from neuroimaging studies with structural, functional and spectroscopy magnetic resonance imaging and positron emission tomography. The potential of findings to be biomarkers of schizophrenia is discussed. Results: Recent findings have not resulted in clear biomarkers for schizophrenia. However, we identified several biomarkers that are potential candidates for future research. Among them, copy number variations and links between genetic polymorphisms derived from genome-wide analysis studies, clinical or cognitive phenotypes, multimodal neuroimaging findings including positron emission tomography and magnetic resonance imaging, and the application of multivariate pattern analyses are promising. Conclusions: Future studies should address the effects of treatment and stage of the disease more precisely and apply combinations of biomarker candidates. Although biomarkers for schizophrenia await validation, knowledge on candidate genomic and neuroimaging biomarkers is growing rapidly and research on this topic has the potential to identify psychiatric endophenotypes and in the future increase insight on individual treatment response in schizophrenia. [ABSTRACT FROM AUTHOR]

Endocrine disrupting compounds (EDCs) are chemicals that negatively impact endocrine system function, with effluent from paper mills one example of this class of chemicals. In Florida, female Eastern mosquitofish (Gambusia holbrooki) have been observed with male secondary sexual characteristics at three paper mill-impacted sites, indicative of EDC exposure, and are still found at one site on the Fenholloway River. The potential impacts that paper mill effluent exposure has on the G. holbrooki endocrine system and the stream ecosystem are unknown. The objective of this study was to use gene expression analysis to determine if exposure to an androgen receptor agonist was occurring and to couple this analysis with in vitro assays to evaluate the presence of androgen and progesterone receptor active chemicals in the Fenholloway River. Focused gene expression analyses of masculinized G. holbrooki from downstream of the Fenholloway River paper mill were indicative of androgen exposure, while genes related to reproduction indicated potential progesterone exposure. Hepatic microarray analysis revealed an increase in the expression of metabolic genes in Fenholloway River fish, with similarities in genes and biological processes compared to G. holbrooki exposed to androgens. Water samples collected downstream of the paper mill and at a reference site indicated that progesterone and androgen receptor active chemicals were present at both sites, which corroborates previous chemical analyses. Results indicate that G. holbrooki downstream of the Fenholloway River paper mill are impacted by a mixture of both androgens and progesterones. This research provides data on the mechanisms of how paper mill effluents in Florida are acting as endocrine disruptors. [ABSTRACT FROM AUTHOR]

Introduction: This paper explores the potential influence of a single nucleotide variant in the ANK-2 gene on COVID-19 myocarditis-related ventricular tachycardia. Case Description: A 53-year-old female with a history of Crohn's disease and asthma developed COVID-19. Shortly after infection, she experienced symptoms of chest pressure, palpitations, and shortness of breath, leading to the eventual diagnosis of myocarditis complicated by recurrent ventricular tachycardia. Treatment with mechanistically driven anti-arrhythmic therapy and beta-blockers suppressed this highly symptomatic ventricular tachycardia. Genetic testing to further risk stratify and influence long term care identified a single nucleotide variant in the ANK-2 gene, which is known to be associated with arrhythmic risk. Discussion: This case study highlights the use of rationally selected anti-arrhythmic therapy, mexiletine, in the management of ventricular tachycardia associated with COVID-19 myocarditis and the presence of a single nucleotide variant in ANK-2, raising the possibility of its contribution to VT susceptibility and severity. Our patient demonstrated significant improvement with administered therapeutics, including the resolution of myocarditis and ventricular tachycardia. The normalization of the QT interval during the resolution phase further supports the potential influence of the genetic variant in ANK-2 on potassium channel activity. [ABSTRACT FROM AUTHOR]

Objective: Few studies have been conducted on the association between gut microbes and gastric ulcers. This paper aims to investigate the causal relationship between gut flora and gastric ulcer development using a two-sample Mendelian randomization method. Methods: Relevant single nucleotide polymorphisms were screened as instrumental genetic variables (SNPs) from the genetic variation database of the gut microbiota (MiBioGen), and the weighted median estimator of random effects (WME), inverse variance weighting (IVW) and MR-Egger regression three Mendelian randomization methods were used to study the causal association between gut microbes and gastric ulcer development. Results and Discussion: Family Lachnospiraceae, genus Eubacterium ventriosum group, genus Olsenella were risk factors for gastric ulcer, while genus Butyrivibrio, genus Odoribacter, genus Sutterella had a suggestive protective effect on gastric ulcer, but the mechanism of intestinal flora and gastric ulcer needs to be further verified, but this study still provides some theoretical basis for future studies between gastric ulcer and intestinal flora. Conclusions: In this study, a potentially positive and negative causal relationship between intestinal flora and the gastric ulcer was derived by a two-sample Mendelian analysis, from which it was known that the family Lachnospiraceae, genus Eubacterium ventricose group, genus Olsenella are risk factors for gastric ulcer. In contrast, the genus Butyrivibrio, genus Odoribacter, and genus Sutterella had suggestive protective effects against gastric ulcers. [ABSTRACT FROM AUTHOR]

The delivery of genetic services in developing countries is faced with significant challenges, despite medical and technological advances globally. The Philippines, being an archipelago, faces even more challenges, with significant disparities in access to healthcare, and tertiary medical centers and specialists being concentrated in the major cities. The utilization of different networks for the integration of genetic services in the existing public health delivery system has been valuable. Using the well-established network of the national newborn screening program, genetic services have been successfully integrated into the delivery of healthcare, even at the grassroot level. Equitable access to healthcare, including genetic services, was highlighted and supported by the enactment of the Rare Disease Law in 2016. The support of the academe to assure the sustainability of services was evident in the establishment of a genetic counseling program to augment the work of a handful of clinical geneticists. Professional societies and support groups have been instrumental in identifying genetic conditions to be prioritized and lobbying for increased public awareness, leading to national programs and policies. This paper primarily discusses the value of networks in the delivery of genetic services, specifically newborn screening, programs for rare diseases, birth defects, and genetic counseling. [ABSTRACT FROM AUTHOR]

• Advantages and challenges of a dedicated patient registry for people with CFTR-RD. • The CFTR-RD risk for infants with a CRMS/CFSPID designation. • Peculiarities of genetic counseling in people and families with CFTR-RD. • Identification of barriers to disseminate, implement and monitor CFTR-RD management. • Feasibility of clinical trials in people with CFTR-RD. After three publications defining an updated guidance on the diagnostic criteria for people with cystic fibrosis transmembrane conductance regulator (CFTR)-related disorders (pwCFTR-RDs), establishing its relationship to CFTR-dysfunction and describing the individual disorders, this fourth and last paper in the series addresses some critical challenges facing health care providers and pwCFTR-RD. Topics included are: 1) benefits and obstacles to collect data from pwCFTR-RD are discussed, together with the opportunity to integrate them into established CF-registries; 2) the potential of infants designated CRMS/CFSPID to develop a CFTR-RD and how to communicate this information; 3) a description of the challenges in genetic counseling, with particular regard to phenotypic variability, unknown long-term evolution, CFTR testing and pregnancy termination 4) a proposal for the assessment of potential barriers to the implementation and dissemination of the produced documents to health care professionals involved in the care of pwCFTR-RD and a process to monitor the implementation of the CFTR-RD recommendations; 5) clinical trials investigating the efficacy of CFTR modulators in CFTR-RD and how endpoints and outcomes might be adapted to the heterogeneity of these disorders. [ABSTRACT FROM AUTHOR]

Objectives: Cytogenetic abnormalities are predictors of poor prognosis in multiple myeloma (MM). This paper aims to build and validate a multiparametric conventional and functional whole-body MRI-based prediction model for cytogenetic risk classification in newly diagnosed MM. Methods: Patients with newly diagnosed MM who underwent multiparametric conventional whole-body MRI, spinal dynamic contrast-enhanced (DCE-)MRI, spinal diffusion-weighted MRI (DWI) and had genetic analysis were retrospectively included (2011–2020/Ghent University Hospital/Belgium). Patients were stratified into standard versus intermediate/high cytogenetic risk groups. After segmentation, 303 MRI features were extracted. Univariate and model-based methods were evaluated for feature and model selection. Testing was performed using receiver operating characteristic (ROC) and precision-recall curves. Models comparing the performance for genetic risk classification of the entire MRI protocol and of all MRI sequences separately were evaluated, including all features. Four final models, including only the top three most predictive features, were evaluated. Results: Thirty-one patients were enrolled (mean age 66 ± 7 years, 15 men, 13 intermediate-/high-risk genetics). None of the univariate models and none of the models with all features included achieved good performance. The best performing model with only the three most predictive features and including all MRI sequences reached a ROC-area-under-the-curve of 0.80 and precision-recall-area-under-the-curve of 0.79. The highest statistical performance was reached when all three MRI sequences were combined (conventional whole-body MRI + DCE-MRI + DWI). Conventional MRI always outperformed the other sequences. DCE-MRI always outperformed DWI, except for specificity. Conclusions: A multiparametric MRI-based model has a better performance in the noninvasive prediction of high-risk cytogenetics in newly diagnosed MM than conventional MRI alone. Critical relevance statement: An elaborate multiparametric MRI-based model performs better than conventional MRI alone for the noninvasive prediction of high-risk cytogenetics in newly diagnosed multiple myeloma; this opens opportunities to assess genetic heterogeneity thus overcoming sampling bias. Key points: • Standard genetic techniques in multiple myeloma patients suffer from sampling bias due to tumoral heterogeneity. • Multiparametric MRI noninvasively predicts genetic risk in multiple myeloma. • Combined conventional anatomical MRI, DCE-MRI, and DWI had the highest statistical performance to predict genetic risk. • Conventional MRI alone always outperformed DCE-MRI and DWI separately to predict genetic risk. DCE-MRI alone always outperformed DWI separately, except for the parameter specificity to predict genetic risk. • This multiparametric MRI-based genetic risk prediction model opens opportunities to noninvasively assess genetic heterogeneity thereby overcoming sampling bias in predicting genetic risk in multiple myeloma. [ABSTRACT FROM AUTHOR]

Background: Microtia is a congenital ear malformation that can occur as isolated microtia or as part of a syndrome. The etiology is currently poorly understood, although there is strong evidence that genetics has a role in the occurrence of microtia. This systematic review aimed to determine the genes involved and the abnormalities in microtia patients' head and neck regions. Methods: We used seven search engines to search all known literature on the genetic and phenotypic variables associated with the development or outcome of microtia. The identified publications were screened and selected based on inclusion and exclusion criteria and assessed for methodological quality using the Joanna Briggs Institute (JBI) critical appraisal tools. We found 40 papers in this systematic review with phenotypic data in microtia involving 1459 patients and 30 articles containing genetic data involved in microtia. Result: The most common accompanying phenotype of all microtia patients was external ear canal atresia, while the most common head and neck abnormalities were the auricular, mental, and oral regions. The most common syndrome found was craniofacial microsomia syndrome. In the syndromic microtia group, the most common genes were TCOF1 (43.75%), SIX2 (4.69%), and HSPA9 (4.69%), while in the non-syndromic microtia group, the most frequently found gene was GSC exon 2 (25%), FANCB (16.67%), HOXA2 (8.33%), GSC exon 3 (8.33%), MARS1 (8.33%), and CDT1 (8.33%). Conclusions: Our systematic review shows some genes involved in the microtia development, including TCOF1, SIX2, HSPA9, GSC exon 2, FANCB, HOXA2, GSC exon 3, MARS1, and CDT1 genes. We also reveal a genotype-phenotype association in microtia. In addition, further studies with more complete and comprehensive data are needed, including patients with complete data on syndromes, phenotypes, and genotypes. [ABSTRACT FROM AUTHOR]

Parkinson's disease is the world's fastest growing brain disorder, and exposure to environmental toxicants is the principal reason. In this paper, we consider alternative, but unsatisfactory, explanations for its rise, including improved diagnostic skills, aging populations, and genetic causes. We then detail three environmental toxicants that are likely among the main causes of Parkinson's disease— certain pesticides, the solvent trichloroethylene, and air pollution. All three environmental toxicants are ubiquitous, many affect mitochondrial functioning, and all can access humans via various routes, including inhalation and ingestion. We reach the hopeful conclusion that most of Parkinson's disease is thus preventable and that we can help to create a world where Parkinson's disease is increasingly rare. [ABSTRACT FROM AUTHOR]

Simple Summary: There are three subfamilies of human PDZ-LIM family proteins with a total of 10 protein molecules, and PDZ-LIM family proteins serve as a class of scaffolding proteins that assume the function of signal transduction. In this paper, we describe the signature structural domains and major regulatory signals of PDZ-LIM family proteins and provide an overview and discussion of their functions in various tumors and major diseases, aiming to provide directions for future disease (mainly tumor) prevention and drug development. PDZ-LIM family proteins (PDLIMs) are a kind of scaffolding proteins that contain PDZ and LIM interaction domains. As protein–protein interacting molecules, PDZ and LIM domains function as scaffolds to bind to a variety of proteins. The PDLIMs are composed of evolutionarily conserved proteins found throughout different species. They can participate in cell signal transduction by mediating the interaction of signal molecules. They are involved in many important physiological processes, such as cell differentiation, proliferation, migration, and the maintenance of cellular structural integrity. Studies have shown that dysregulation of the PDLIMs leads to tumor formation and development. In this paper, we review and integrate the current knowledge on PDLIMs. The structure and function of the PDZ and LIM structural domains and the role of the PDLIMs in tumor development are described. [ABSTRACT FROM AUTHOR]

Internationally, there is considerable inconsistency in the recognition and regulation of children's genetic connections outside the family. In the context of gamete and embryo donation, challenges for regulation seem endless. In this paper, I review some of the paths that have been taken to manage children' being closely genetically related to people outside their families. I do so against the background of recognising the importance of children's interests as moral status holders. I look at recent qualitative research involving donor‐conceived people and borrow their own words to make sense of a purported interest to know (of) their close genetic ties. I also review ways in which gamete donation may have facilitated new kinds of kinship, which are at the same time genetic and chosen. In short, in this paper, I explore what meaning there could be in genetic connections that is not about parenthood. Further, I argue that the focus on parenthood in previous work in this area may be detrimental to appreciating some of the goods that can be derived from close genetic connections. [ABSTRACT FROM AUTHOR]

Background. Traditional detection of Leishmania from ulcers involves collection of invasive specimens that cause discomfort, require technical expertise, and carry risks of invasive procedures. We compared traditional diagnostic methods with a molecular noninvasive filter paper-based method for the diagnosis of cutaneous leishmaniasis. Methods. Consecutive patients presenting to the Leishmania Clinic at Hospital Nacional Cayetano Heredia were enrolled. Polymerase chain reaction (PCR) was performed on lesion scrapings, aspirates, and filter paper impressions. The reference standard was any 2 of 5 tests positive: smear, aspirate culture, invasive-specimen PCR (scrapings and aspirates), filter paper PCR, and leishmanin skin test. Outcome measures were sensitivity and specificity. Leishmania speciation was performed by PCR--restriction fragment length polymorphism (RFLP) of positive specimens. Results. Forty-five patients with 66 lesions were enrolled. Of 52 lesions diagnosed as cutaneous leishmaniasis, 50 were positive by PCR of invasive specimens versus 48 by PCR of filter papers (P = .930). Sensitivity and specificity of PCR on invasively obtained specimens were 94.2% (95% confidence interval [CI], 87.9%-100%) and 92.9% (95% CI, 79.4%-100%). Sensitivity and specificity of filter paper PCR were 92.3% (95% CI, 85.1%-99.5%) and 100%. Culture, smear, and leishmanin skin test all had inferior sensitivities, compared with PCR of invasive or noninvasive specimens (P < .001). Of 50 specimens positive by PCR, 19 had sufficient DNA for PCR-RFLP analysis. Conclusions. Filter paper PCR constitutes a sensitive and specific alternative to traditional diagnostic assays. This novel, rapid, well-tolerated method has the potential for widespread use in the field and in pediatric populations where traditional specimen collection is most difficult to perform, and can potentially be used for rapid species identification. [ABSTRACT FROM AUTHOR]

Abstract: There is an explosion in the numbers of nurse authors exploring new and exciting opportunities to understand genomic medicine because of international success on The Human Genome Project. Objectives: The primary purpose of this paper is to spotlight and to promote collaborative interdisciplinary and international nursing research within genetics and genomics. Design: Review of the literature. Data sources: Research in nursing pertaining to genetics and genomics, policy statements, and opinion papers. Review methods: Synthesis of the literature in four areas: genetic nursing research, genomic medicine, barriers to international collaboration, and elements that foster international collaboration. Results: Genetics and genomic medicine have implications for virtually all diseases in all health care settings in developed and still developing nations. Research in nursing, genetics and genomics is scarce. There is a gap in nursing literature about how to address barriers to foster international collaboration. Conclusions: The authors who have engaged in international collaboration offer a tentative road map for establishing and assessing the progress of research collaboration. New funding mechanisms to support international nursing research in this area are needed. [Copyright &y& Elsevier]

In January 2003 the Norwegian Parliament passed the Biobanks Act, regulating biobank research in Norway. There have been strong differences of opinion both in the process of making the law as well as in its first years of implementation. The main controversy relates to what kind of informed consent should be required for biobank research. Central to the controversy over current interpretations of the Biobanks Act is the informed consent given by the donors to the biobank of the Nord-Trøndelag Health Study (HUNT), and whether the consent given ‘was worth the paper it was written on’. This article traces the history behind the informed consent procedure of the blood samples in the largest research biobank in Norway, the HUNT biobank. Second, findings from a focus group study with biobank participants are presented. Third, a philosophical analysis is made of the concept of informed consent in light of the findings from the focus-group study as well as the history behind the HUNT biobank. Findings from the focus-group study show that the consenters base their participation on trust in the researchers and the regulation of research in Norwegian society, rather than on specific information on the research in question. The history behind the HUNT biobank fosters trust. The story provides a strong case for not limiting the debate to legalistic and formalistic ethics but also including a research ethics that says that process and trust matter. Otherwise no informed consent in medical research is worth the paper it is written on. [ABSTRACT FROM AUTHOR]

Avery's et al.'s 1944 paper provides the first direct evidence of DNA having gene-like properties and marks the beginning of a new phase in early molecular genetics (with a strong focus on chemistry and DNA). The study of its reception shows that on the whole, Avery's results were immediately appreciated and motivated new research on transformation, the chemical nature of DNA's biological specificity and bacteria genetics. It shows, too, that initial problems of transferring transformation to other systems and prominent criticism of its results nurtured skepticism. Avery's experiment was downplayed and neglected particularly by many of those scientists who worked in the new fields of biochemical and biophysical genetics, genetic phage, and TMV research. This was not due to the fact that the implications of the paper could not be connected to generally accepted knowledge. Contrary to a widespread belief, the assumed uniformity of DNA as opposed to proteins was not used as an argument against the validity of Avery's et al.'s finding. The indifference rather reflected, among other things, the disciplinary gap between the chemically oriented microbiologists and the old and new geneticists who remained committed to genetic and physical methods (in particular x-ray studies) and clung to the assumption that proteins were the sole carriers of biological specificity. The responses to Avery's et al.'s paper show how different research interests in the areas between microbiology, genetics, and biochemistry interacted with the prejudices, dogmas, individual farsightedness or short-sightedness, and scientific authority during a pivotal period of early molecular biology. [ABSTRACT FROM AUTHOR]

The classical theory of descent with modification by means of natural selection had no mother, but did have two English fathers, Charles Darwin (1809-1882) and Alfred Russel Wallace (1823-1913). In 1858, the Linnean Society of London published two contributions of these naturalists and acknowledged both authors as the proponents of a novel hypothesis on the driving force of organismic evolution. In the present report the most important sections of the Darwin-Wallace papers are summarized. This close reading of both publications reveals six striking differences in emphasis: Darwin and Wallace did not propose identical ideas. The species definitions of both authors are described and the further development of the concept of natural selection in wild populations is reviewed. It is shown that the contributions of A.R. Wallace, who died 90 years ago, are more significant than usually acknowledged. I conclude that natural selection's lesser known co-discoverer should be regarded as one of the most important pioneers of evolutionary biology, whose original contributions are underestimated by most contemporary scientists. [ABSTRACT FROM AUTHOR]