Allele frequency dynamics under sex-biased demography and sex-specific inheritance in a pedigreed jay population.

Sex-biased demography, including sex-biased survival or migration, can alter allele frequency changes across the genome. In particular, we can expect different patterns of genetic variation on autosomes and sex chromosomes due to sex-specific differences in life histories, as well as differences in effective population size, transmission modes, and the strength and mode of selection. Here, we demonstrate the role that sex differences in life history played in shaping short-term evolutionary dynamics across the genome. We used a 25-year pedigree and genomic dataset from a long-studied population of Florida Scrub-Jays (Aphelocoma coerulescens) to directly characterize the relative roles of sex-biased demography and inheritance in shaping genome-wide allele frequency trajectories. We used gene dropping simulations to estimate individual genetic contributions to future generations and to model drift and immigration on the known pedigree. We quantified differential expected genetic contributions of males and females over time, showing the impact of sex-biased dispersal in a monogamous system. Due to female-biased dispersal, more autosomal variation is introduced by female immigrants. However, due to male-biased transmission, more Z variation is introduced by male immigrants. Finally, we partitioned the proportion of variance in allele frequency change through time due to male and female contributions. Overall, most allele frequency change is due to variance in survival and births. Males and females make similar contributions to autosomal allele frequency change, but males make higher contributions to allele frequency change on the Z chromosome. Our work shows the importance of understanding sex-specific demographic processes in characterizing genome-wide allele frequency change in wild populations.

Satisfaction with Teleophthalmology Services: Insights from Remote Areas of Taiwan.

During and after the COVID-19 pandemic, teleophthalmology provided access to eye care for rural populations. This study aimed to assess the efficacy of and satisfaction with an integrated real-time videoconferencing module. This project incorporated ophthalmic instruments and telecommunication devices and provided on-site consultations via videoconferencing. Both patients and healthcare providers completed satisfaction questionnaires. From May 2020 to May 2021, this project provided eye care services to 395 patients (aged 6-90 years). The most frequent eye condition was chronic conjunctivitis (n = 197), followed by senile cataract (n = 163), dry eye (n = 103), and refractive error (n = 95). Among them, 40 (10.1%) patients were referred to secondary or tertiary hospitals for further evaluation or treatment. In total, 181 recruited respondents provided good satisfaction scores in all dimensions, including quality of medical care (4.50 of 5.00), financial aspects of care (4.48), supportive attitude toward the project (4.47), quality of service (4.40), and quality of telecommunication (4.40). Women had a substantially more supportive attitude toward the project, and 25 healthcare providers provided low ratings in areas representing the quality of telecommunication (4.04) and user-friendliness of the instrument (4.00). This teleophthalmology system provided efficient and satisfactory eye care to participants in remote communities. However, better internet access and training in instrument use can reduce obstacles to the future implementation of the project.

Impacts of increasing isolation and environmental variation on Florida Scrub-Jay demography.

Isolation caused by anthropogenic habitat fragmentation and degradation can destabilize populations. Population demography is shaped by complex interactions among local vital rates, environmental fluctuations, and changing immigration rates. Empirical studies of these interactions are critical for testing theoretical expectations of how populations respond to isolation. We used a 34-year demographic and environmental dataset from a population of Florida Scrub-Jays ( Aphelocoma coerulescens ) that has experienced declining immigration to create mechanistic models linking environmental factors and variation in vital rates to population growth rates over time. We found that the population has remained stable despite declining immigration and increasing inbreeding, owing to a coinciding increase in breeder survival. We find evidence of density-dependent responses of immigration, breeder survival, and fecundity, indicating that interactions between vital rates and local density likely play a role in buffering the population against change. Our study elucidates the interactions between environment and demography that underlie population stability.

Addressing the Gap of Nutrition in Medical Education: Experiences and Expectations of Medical Students and Residents in France and the United States.

Distinct pedagogical approaches within medical curricula in France and in the U.S. reflect a growing recognition of the importance of nutrition to address major public health challenges. However, recent generations of medical students have expressed mixed opinions regarding nutrition education. What pedagogical approach may improve nutrition education? Despite different medical systems, students from both France and the U.S. share similar concerns and expectations, that nutrition knowledge must be embedded in the curriculum and must be engaging. Hands-on, system-based, epistemological, and multidisciplinary approaches need better articulation to forge a robust medical curriculum. In the rapidly changing contexts of medicine and public awareness, social science research may facilitate recommendations for improved nutrition education.

Differential gene expression during floral transition in pineapple.

Pineapple (Ananas comosus var. comosus) and ornamental bromeliads are commercially induced to flower by treatment with ethylene or its analogs. The apex is transformed from a vegetative to a floral meristem and shows morphological changes in 8 to 10 days, with flowers developing 8 to 10 weeks later. During eight sampling stages ranging from 6 h to 8 days after treatment, 7961 genes were found to exhibit differential expression (DE) after the application of ethylene. In the first 3 days after treatment, there was little change in ethylene synthesis or in the early stages of the ethylene response. Subsequently, three ethylene response transcription factors (ERTF) were up-regulated and the potential gene targets were predicted to be the positive flowering regulator CONSTANS-like 3 (CO), a WUSCHEL gene, two APETALA1/FRUITFULL (AP1/FUL) genes, an epidermal patterning gene, and a jasmonic acid synthesis gene. We confirm that pineapple has lost the flowering repressor FLOWERING LOCUS C. At the initial stages, the SUPPRESSOR OF OVEREXPRESSION OF CONSTANS 1 (SOC1) was not significantly involved in this transition. Another WUSCHEL gene and a PHD homeobox transcription factor, though not apparent direct targets of ERTF, were up-regulated within a day of treatment, their predicted targets being the up-regulated CO, auxin response factors, SQUAMOSA, and histone H3 genes with suppression of abscisic acid response genes. The FLOWERING LOCUS T (FT), TERMINAL FLOWER (TFL), AGAMOUS-like APETELAR (AP2), and SEPETALA (SEP) increased rapidly within 2 to 3 days after ethylene treatment. Two FT genes were up-regulated at the apex and not at the leaf bases after treatment, suggesting that transport did not occur. These results indicated that the ethylene response in pineapple and possibly most bromeliads act directly to promote the vegetative to flower transition via APETALA1/FRUITFULL (AP1/FUL) and its interaction with SPL, FT, TFL, SEP, and AP2. A model based on AP2/ERTF DE and predicted DE target genes was developed to give focus to future research. The identified candidate genes are potential targets for genetic manipulation to determine their molecular role in flower transition.

Impact of oral/dental disease burden on postoperative infective complications: a prospective cohort study.

OBJECTIVES: This prospective cohort study aimed to assess the association between dental disease burden and postoperative infective complications (POICs) in patients undergoing major surgical procedures under general anaesthesia. METHODS: Pre-surgical dental assessment was undertaken on patients planned for major surgery. Demographic and surgical variables including putative risk factors for POICs and POIC status were documented. The univariable association between POIC status and each factor was examined. Those variables associated at P value ≤ 0.2 were candidates for inclusion in multiple logistic regression models. Backward stepwise variable selection was used to identify the independent predictors for POIC in the best fitting logistic regression model. The area under the receiver operating curve (AUC) was used to quantify the model's global classification performance. RESULTS: Among the 285 patients, 49 patients (17.2%) had POICs. The independent predictors for POIC were expected length of hospital stay (4-6 days; odds ratio [OR] = 4.80, 95% confidence internal [CI]: 1.30-17.70, P = 0.018, 7-9 days; OR = 5.42, 95% CI: 1.51-19.41, P = 0.009, ≥ 10 days; OR = 28.80, 95% CI: 4.12-201.18, P < 0.001), four or more decayed teeth (OR = 6.03, 95% CI: 2.28-15.94, P < 0.001) and visible tongue plaque (OR = 3.21, 95% CI: 1.54-6.70, P = 0.002). The AUC was 0.78 (95% CI: 0.71-0.85) indicating good discrimination. A simple screening tool for POIC was developed. CONCLUSIONS/CLINICAL RELEVANCE: In addition to systemic/surgical factors, this study identified clinically detected decayed teeth and visible tongue plaque as independent predictors for POICs. Preoperative dental assessment/care might be beneficial to assess risk for POICs and improve postoperative outcomes.

The role of climate change and niche shifts in divergent range dynamics of a sister-species pair.

Species ranges are set by limitations in factors including climate tolerances, habitat use, and dispersal abilities. Understanding the factors governing species range dynamics remains a challenge that is ever more important in our rapidly changing world. Species ranges can shift if environmental changes affect available habitat, or if the niche or habitat connectivity of a species changes. We tested how changes in habitat availability, niche, or habitat connectivity could contribute to divergent range dynamics in a sister-species pair. The great-tailed grackle (Quiscalus mexicanus) has expanded its range northward from Texas to Nebraska in the past 40 years, while its closest relative, the boattailed grackle (Quiscalus major), has remained tied to the coasts of the Atlantic Ocean and the Gulf of Mexico as well as the interior of Florida. We created species distribution and connectivity models trained on citizen science data from 1970-1979 and 2010-2019 to determine how the availability of habitat, the types of habitat occupied, and range-wide connectivity have changed for both species. We found that the two species occupy distinct habitats and that the great-tailed grackle has shifted to occupy a larger breadth of urban, arid environments farther from natural water sources. Meanwhile, the boattailed grackle has remained limited to warm, wet, coastal environments. We found no evidence that changes in habitat connectivity affected the ranges of either species. Overall, our results suggest that the great-tailed grackle has shifted its realized niche as part of its rapid range expansion, while the range dynamics of the boat-tailed grackle may be shaped more by climate change. The expansion in habitats occupied by the great-tailed grackle is consistent with observations that species with high behavioral flexibility can rapidly expand their geographic range by using human-altered habitat. This investigation identifies how opposite responses to anthropogenic change could drive divergent range dynamics, elucidating the factors that have and will continue to shape species ranges.

Increased genetic diversity and immigration after West Nile virus emergence in American crows: No evidence for a genetic bottleneck.

Infectious diseases can cause steep declines in wildlife populations, leading to changes in genetic diversity that may affect the susceptibility of individuals to infection and the overall resilience of populations to pathogen outbreaks. Here, we examine evidence for a genetic bottleneck in a population of American crows (Corvus brachyrhynchos) before and after the emergence of West Nile virus (WNV). More than 50% of marked birds in this population were lost over the 2-year period of the epizootic, representing a 10-fold increase in adult mortality. Using analyses of single-nucleotide polymorphisms (SNPs) and microsatellite markers, we tested for evidence of a genetic bottleneck and compared levels of inbreeding and immigration in the pre- and post-WNV populations. Counter to expectations, genetic diversity (allelic diversity and the number of new alleles) increased after WNV emergence. This was likely due to increases in immigration, as the estimated membership coefficients were lower in the post-WNV population. Simultaneously, however, the frequency of inbreeding appeared to increase: Mean inbreeding coefficients were higher among SNP markers, and heterozygosity-heterozygosity correlations were stronger among microsatellite markers, in the post-WNV population. These results indicate that loss of genetic diversity at the population level is not an inevitable consequence of a population decline, particularly in the presence of gene flow. The changes observed in post-WNV crows could have very different implications for their response to future pathogen risks, potentially making the population as a whole more resilient to a changing pathogen community, while increasing the frequency of inbred individuals with elevated susceptibility to disease.

Gene therapy for cross-correction of somatic organs and the CNS in mucopolysaccharidosis II in rodents and non-human primates.

Mucopolysaccharidosis II (MPS II) is a rare lysosomal storage disease characterized by deficient activity of iduronate-2-sulfatase (I2S), leading to pathological accumulation of glycosaminoglycans (GAGs) in tissues. We used iduronate-2-sulfatase knockout (Ids KO) mice to investigate if liver-directed recombinant adeno-associated virus vectors (rAAV8-LSP-hIDSco) encoding human I2S (hI2S) could cross-correct I2S deficiency in Ids KO mouse tissues, and we then assessed the translation of mouse data to non-human primates (NHPs). Treated mice showed sustained hepatic hI2S production, accompanied by normalized GAG levels in somatic tissues (including critical tissues such as heart and lung), indicating systemic cross-correction from liver-secreted hI2S. Brain GAG levels in Ids KO mice were lowered but not normalized; higher doses were required to see improvements in brain histology and neurobehavioral testing. rAAV8-LSP-hIDSco administration in NHPs resulted in sustained hepatic hI2S production and therapeutic hI2S levels in cross-corrected somatic tissues but no hI2S exposure in the central nervous system, perhaps owing to lower levels of liver transduction in NHPs than in mice. Overall, we demonstrate the ability of rAAV8-LSP-hIDSco to cross-correct I2S deficiency in mouse somatic tissues and highlight the importance of showing translatability of gene therapy data from rodents to NHPs, which is critical for supporting translation to clinical development.

The Pain Clinic for Older People.

OBJECTIVE: Multidisciplinary pain clinics have an established role in the management of persistent pain, but there is little evidence to support this approach in an older population. This study describes the characteristics and pain outcomes of patients attending a pain clinic designed exclusively for older people. METHODS: A retrospective audit was performed of outcomes of the Pain Clinic for Older People (PCOP) in 2015-2019. Response to treatment was determined by change in Brief Pain Inventory (BPI) scores at initial attendance and after a treatment program. Clinically meaningful improvement was defined by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) consensus criteria of ≥30% improvement in average pain and one-point improvement in pain interference. Results were compared with the national benchmark collated by the electronic Persistent Pain Outcomes Collaboration (ePPOC), which reports the combined results from 67 participating Australian and New Zealand pain services. RESULTS: Patients attending the PCOP had a mean age of 80.5 years and had high rates of frailty (84%), cognitive impairment (30%), and multimorbidity. Significant reductions in BPI average pain and BPI pain interference scores were achieved. Clinically meaningful improvement in BPI average pain was achieved in 63% of patients attending the PCOP who were 65-74 years of age and in 46% of patients who were ≥75 years of age, which met the national benchmark set by ePPOC of 40% for both age groups. Clinically meaningful improvement in BPI pain interference was achieved in 69% of those attending the PCOP who were 65-74 years of age and in 66% of those who were ≥75 years of age, comparable to the ePPOC benchmark of 71% and 65% for the respective age groups. CONCLUSION: PCOP clients achieved significant and meaningful improvements in their pain outcomes that satisfied the national benchmark. Advanced age, cognitive impairment, frailty and multimorbidity should not be regarded as barriers to benefit from a pain clinic specifically designed for older people.

Ecological niche contributes to the persistence of the Western x Glaucous-winged Gull hybrid zone.

Hybrid zones occur in nature when populations with limited reproductive barriers overlap in space. Many hybrid zones persist over time, and different models have been proposed to explain how selection can maintain hybrid zone stability. More empirical studies are needed to elucidate the role of ecological adaptation in maintaining stable hybrid zones. Here, we investigated the role of exogenous factors in maintaining a hybrid zone between western gulls (Larus occidentalis) and glaucous-winged gulls (L. glaucescens). We used ecological niche models (ENMs) and niche similarity tests to quantify and examine the ecological niches of western gulls, glaucous-winged gulls, and their hybrids. We found evidence of niche divergence between all three groups. Our results best support the bounded superiority model, providing further evidence that exogenous selection favoring hybrids may be an important factor in maintaining this stable hybrid zone.

Acute Orbital Apex Syndrome Caused by Idiopathic Sclerosing Orbital Inflammation.

Idiopathic sclerosing orbital inflammation (ISOI) is a distinct entity among other orbital diseases. It is characterized by marked fibrosis and inflammatory cell infiltration that can damage orbital structures. Clinical manifestations were variable, including ocular and periocular redness, proptosis, and pain. Ocular motor restrictions and optic nerve dysfunction might occur in severe cases. We herein report a patient of ISOI who presented with total ophthalmoplegia and acute vision loss. His symptoms were relieved mainly as his vision improved to 20/25 after receiving corticosteroid and immunosuppressant therapies. Therefore, ISOI should be one of the deferential diagnoses when we encounter cases with acute orbital apex syndrome. With prompt evaluation and in-time treatment, a favorable outcome is possible.

Taking quantitative genomics into the wild.

We organized this special issue to highlight new work and review recent advances at the cutting edge of 'wild quantitative genomics'. In this editorial, we will present some history of wild quantitative genetic and genomic studies, before discussing the main themes in the papers published in this special issue and highlighting the future outlook of this dynamic field.

Taro raphide-associated proteins: Allergens and crystal growth.

Calcium oxalate raphide crystals are found in bundles in intravacuolar membrane chambers of specialized idioblasts cells of most plant families. Aroid raphides are proposed to cause acridity in crops such as taro (Colocasia esculenta (L.) Schott). Acridity is irritation that causes itchiness and pain when raw/insufficiently cooked tissues are eaten. Since raphides do not always cause acridity and since acridity can be inactivated by cooking and/or protease treatment, it is possible that a toxin or allergen-like compound is associated with the crystals. Using two-dimensional (2D) gel electrophoresis and mass spectrometry (MS) peptide sequencing of selected peptides from purified raphides and taro apex transcriptome sequencing, we showed the presence on the raphides of peptides normally associated with mitochrondria (ATP synthase), chloroplasts (chaperonin ~60 kDa), cytoplasm (actin, profilin), and vacuole (V-type ATPase) that indicates a multistage biocrystallation process ending with possible invagination of the tonoplast and addition of mucilage that may be derived from the Golgi. Actin might play a crucial role in the generation of the needle-like raphides. One of the five raphide profilins genes was highly expressed in the apex and had a 17-amino acid insert that significantly increased that profilin's antigenic epitope peak. A second profilin had a 2-amino acid insert and also had a greater B-cell epitope prediction. Taro profilins showed 83% to 92% similarity to known characterized profilins. Further, commercial allergen test strips for hazelnuts, where profilin is a secondary allergen, have potential for screening in a taro germplasm to reduce acridity and during food processing to avoid overcooking.

A transformer-Based neural language model that synthesizes brain activation maps from free-form text queries.

Neuroimaging studies are often limited by the number of subjects and cognitive processes that can be feasibly interrogated. However, a rapidly growing number of neuroscientific studies have collectively accumulated an extensive wealth of results. Digesting this growing literature and obtaining novel insights remains to be a major challenge, since existing meta-analytic tools are constrained to keyword queries. In this paper, we present Text2Brain, an easy to use tool for synthesizing brain activation maps from open-ended text queries. Text2Brain was built on a transformer-based neural network language model and a coordinate-based meta-analysis of neuroimaging studies. Text2Brain combines a transformer-based text encoder and a 3D image generator, and was trained on variable-length text snippets and their corresponding activation maps sampled from 13,000 published studies. In our experiments, we demonstrate that Text2Brain can synthesize meaningful neural activation patterns from various free-form textual descriptions. Text2Brain is available at https://braininterpreter.com as a web-based tool for efficiently searching through the vast neuroimaging literature and generating new hypotheses.

Acute Vision Loss as the Initial Manifestation of Granulomatosis with Polyangiitis Involving the Orbital Apex.

Granulomatosis with polyangiitis (GPA) is a systemic autoimmune disease consisting of necrotizing granulomatosis of the respiratory tract, necrotizing vasculitis, and necrotizing glomerulonephritis. It is under the category of ANCA-associated vasculitis, which involves small vessels. The nose, sinus, and ear were the most affected sites besides lung and kidney in localized form. They might precede other disease manifestations before progressing to the systemic form. Our patient presented with an intractable headache, followed by acute vision loss. His symptoms deteriorated regardless of antibiotic treatment for paranasal sinusitis. The sequential CT/MRI images showed the inflammatory raid of the orbital apex and cavernous sinus within days. The sinus biopsy and elevated PR3-anti-neutrophil cytoplasmic antibody led us to the diagnosis of GPA. Fortunately, the patient's vision improved gradually after steroid and immunosuppressant treatment.

Apocrine Hidrocystoma with IgG4 Plasma Cell Infiltration Presenting as Recurrent Chalazion: A Case Report.

Apocrine hidrocystomas are benign cystic tumors resulting from apocrine sweat glands' proliferation. They typically present as solitary, slow-growing nodules at the head and neck, especially in the periorbital cutaneous region. We present a case of periorbital apocrine hidrocystoma in a 22-year-old woman that was treated as chalazion previously. Besides the hallmark histopathological findings of apocrine hidrocystoma, IgG4 plasma cell infiltration of the cystic wall was also found. The ratio of IgG4-to-IgG-positive plasma cells was high, whereas serum IgG4 was within the standard limit. This is, to date, the only probable IgG4-related ophthalmic disease associated with apocrine hidrocystoma.

Periocular Infection of Mycobacterium avium Complex in a Patient with Interferon-γ Autoantibodies: A Case Report.

The neutralizing anti-interferon-γ autoantibody (nAIGA)-associated immunodeficiency is an emerging entity frequently associated with the nontuberculosis mycobacterium (NTM) infection and other opportunistic infections. We present a female patient with a mysterious periocular Mycobacterium avium complex (MAC) infection, accompanied by sequential opportunistic infections including Salmollelosis and herpes zoster infection. Her condition stabilized after long-term antimycobacterial treatment. Nevertheless, neutralizing anti-interferon-γ autoantibody was found in her serum, which was compatible with the scenario of adult-onset immunodeficiency.

Dynamics of reduced genetic diversity in increasingly fragmented populations of Florida scrub jays,Aphelocoma coerulescens.

Understanding the genomic consequences of population decline is important for predicting species' vulnerability to intensifying global change. Empirical information about genomic changes in populations in the early stages of decline, especially for those still experiencing immigration, remains scarce. We used 7834 autosomal SNPs and demographic data for 288 Florida scrub jays (Aphelocoma coerulescens; FSJ) sampled in 2000 and 2008 to compare levels of genetic diversity, inbreeding, relatedness, and lengths of runs of homozygosity (ROH) between two subpopulations within dispersal distance of one another but have experienced contrasting demographic trajectories. At Archbold Biological Station (ABS), the FSJ population has been stable because of consistent habitat protection and management, while at nearby Placid Lakes Estates (PLE), the population declined precipitously due to suburban development. By the onset of our sampling in 2000, birds in PLE were already less heterozygous, more inbred, and on average more related than birds in ABS. No significant changes occurred in heterozygosity or inbreeding across the 8-year sampling interval, but average relatedness among individuals decreased in PLE, thus by 2008 average relatedness did not differ between sites. PLE harbored a similar proportion of short ROH but a greater proportion of long ROH than ABS, suggesting one continuous population of shared demographic history in the past, which is now experiencing more recent inbreeding. These results broadly uphold the predictions of simple population genetic models based on inferred effective population sizes and rates of immigration. Our study highlights how, in just a few generations, formerly continuous populations can diverge in heterozygosity and levels of inbreeding with severe local population decline despite ongoing gene flow.