Dysregulated naive B cells and de novo autoreactivity in severe COVID-19.

Severe SARS-CoV-2 infection1 has been associated with highly inflammatory immune activation since the earliest days of the COVID-19 pandemic2-5. More recently, these responses have been associated with the emergence of self-reactive antibodies with pathologic potential6-10, although their origins and resolution have remained unclear11. Previously, we and others have identified extrafollicular B cell activation, a pathway associated with the formation of new autoreactive antibodies in chronic autoimmunity12,13, as a dominant feature of severe and critical COVID-19 (refs. 14-18). Here, using single-cell B cell repertoire analysis of patients with mild and severe disease, we identify the expansion of a naive-derived, low-mutation IgG1 population of antibody-secreting cells (ASCs) reflecting features of low selective pressure. These features correlate with progressive, broad, clinically relevant autoreactivity, particularly directed against nuclear antigens and carbamylated proteins, emerging 10-15 days after the onset of symptoms. Detailed analysis of the low-selection compartment shows a high frequency of clonotypes specific for both SARS-CoV-2 and autoantigens, including pathogenic autoantibodies against the glomerular basement membrane. We further identify the contraction of this pathway on recovery, re-establishment of tolerance standards and concomitant loss of acute-derived ASCs irrespective of antigen specificity. However, serological autoreactivity persists in a subset of patients with postacute sequelae, raising important questions as to the contribution of emerging autoreactivity to continuing symptomology on recovery. In summary, this study demonstrates the origins, breadth and resolution of autoreactivity in severe COVID-19, with implications for early intervention and the treatment of patients with post-COVID sequelae.

Dietary protein and amino acid intakes for mitigating sarcopenia in humans.

Adult humans generally experience a 0.5-1%/year loss in whole-body skeletal muscle mass and a reduction of muscle strength by 1.5-5%/year beginning at the age of 50 years. This results in sarcopenia (aging-related progressive losses of skeletal muscle mass and strength) that affects 10-16% of adults aged ≥ 60 years worldwide. Concentrations of some amino acids (AAs) such as branched-chain AAs, arginine, glutamine, glycine, and serine are reduced in the plasma of older than young adults likely due to insufficient protein intake, reduced protein digestibility, and increased AA catabolism by the portal-drained viscera. Acute, short-term, or long-term administration of some of these AAs or a mixture of proteinogenic AAs can enhance blood flow to skeletal muscle, activate the mechanistic target of rapamycin cell signaling pathway for the initiation of muscle protein synthesis, and modulate the metabolic activity of the muscle. In addition, some AA metabolites such as taurine, ß-alanine, carnosine, and creatine have similar physiological effects on improving muscle mass and function in older adults. Long-term adequate intakes of protein and the AA metabolites can aid in mitigating sarcopenia in elderly adults. Appropriate combinations of animal- and plant-sourced foods are most desirable to maintain proper dietary AA balance.

Functions and Metabolism of Amino Acids in the Hair and Skin of Dogs and Cats.

The hair and skin of domestic cats or dogs account for 2% and 12-24% of their body weight, respectively, depending on breed and age. These connective tissues contain protein as the major constituent and provide the first line of defense against external pathogens and toxins. Maintenance of the skin and hair in smooth and elastic states requires special nutritional support, particularly an adequate provision of amino acids (AAs). Keratin (rich in cysteine, serine and glycine) is the major protein both in the epidermis of the skin and in the hair. Filaggrin [rich in some AAs (e.g., serine, glutamate, glutamine, glycine, arginine, and histidine)] is another physiologically important protein in the epidermis of the skin. Collagen and elastin (rich in glycine and proline plus 4-hydroxyproline) are the predominant proteins in the dermis and hypodermis of the skin. Taurine and 4-hydroxyproline are abundant free AAs in the skin of dogs and cats, and 4-hydroxyproline is also an abundant free AA in their hair. The epidermis of the skin synthesizes melanin (the pigment in the skin and hair) from tyrosine and produces trans-urocanate from histidine. Qualitative requirements for proteinogenic AAs are similar between cats and dogs but not identical. Both animal species require the same AAs to nourish the hair and skin but the amounts differ. Other factors (e.g., breeds, coat color, and age) may affect the requirements of cats or dogs for nutrients. The development of a healthy coat, especially a black coat, as well as healthy skin critically depends on AAs [particularly arginine, glycine, histidine, proline, 4-hydroxyproline, and serine, sulfur AAs (methionine, cysteine, and taurine), phenylalanine, and tyrosine] and creatine. Although there are a myriad of studies on AA nutrition in cats and dogs, there is still much to learn about how each AA affects the growth, development and maintenance of the hair and skin. Animal-sourced foodstuffs (e.g., feather meal and poultry by-product meal) are excellent sources of the AAs that are crucial to maintain the normal structure and health of the skin and hair in dogs and cats.

Characteristics of the Digestive Tract of Dogs and Cats.

As for other mammals, the digestive system of dogs (facultative carnivores) and cats (obligate carnivores) includes the mouth, teeth, tongue, pharynx, esophagus, stomach, small intestine, large intestine, and accessory digestive organs (salivary glands, pancreas, liver, and gallbladder). These carnivores have a relatively shorter digestive tract but longer canine teeth, a tighter digitation of molars, and a greater stomach volume than omnivorous mammals such as humans and pigs. Both dogs and cats have no detectable or a very low activity of salivary α-amylase but dogs, unlike cats, possess a relatively high activity of pancreatic α-amylase. Thus, cats select low-starch foods but dogs can consume high-starch diets. In contrast to many mammals, the vitamin B12 (cobalamin)-binding intrinsic factor for the digestion and absorption of vitamin B12 is produced in: (a) dogs primarily by pancreatic ductal cells and to a lesser extent the gastric mucosa; and (b) cats exclusively by the pancreatic tissue. Amino acids (glutamate, glutamine, and aspartate) are the main metabolic fuels in enterocytes of the foregut. The primary function of the small intestine is to digest and absorb dietary nutrients, and its secondary function is to regulate the entry of dietary nutrients into the blood circulation, separate the external from the internal milieu, and perform immune surveillance. The major function of the large intestine is to ferment undigested food (particularly fiber and protein) and to absorb water, short-chain fatty acids (serving as major metabolic fuels for epithelial cells of the large intestine), as well as vitamins. The fermentation products, water, sloughed cells, digestive secretions, and microbes form feces and then pass into the rectum for excretion via the anal canal. The microflora influences colonic absorption and cell metabolism, as well as feces quality. The digestive tract is essential for the health, survival, growth, and development of dogs and cats.

Analysis of naloxone access and primary medication nonadherence in a community pharmacy setting.

BACKGROUND: Access to naloxone is a primary public health strategy to prevent opioid overdose death. Factors associated with primary medication nonadherence (PMN) to naloxone are underreported in the literature. OBJECTIVE: The objective of this study was to evaluate naloxone dispensing trends and PMN in a community pharmacy setting. METHODS: This retrospective analysis included patients of a community pharmacy chain in Maine and New Hampshire (57 and 29 pharmacy locations, respectively) for whom a claim for a naloxone prescription was billed between January 1, 2019, and July 31, 2020. RESULTS: A total of 2152 patients associated with 2606 naloxone claims were identified for analysis. A majority of the subjects were women (52.7%) and the mean age of all the subjects was 46.4 ± 16.0 years. Of the 2606 naloxone claims, 565 prescriptions were returned to stock and never dispensed to the patient for a PMN rate of 21.7%. Gender and age were not associated with naloxone PMN. Factors associated with naloxone PMN were urban location [x2(1) = 12.49, P = 0.0004], concomitant opioid analgesic [x2(1) = 4.56, P = 0.0328], and payment method [x2(4) = 251.07, P < 0.0001]. Regarding payment method, nonadherence was higher among cash (138 of 386, 35.8%) and private insurance (191 of 455, 42.0%) transactions whereas lower among Medicare (132 of 681, 19.4%) and Medicaid (89 of 899, 9.9%) transactions. Concomitant buprenorphine [x2(1) = 44.57, P < 0.0001] and the use of a naloxone standing order [x2(1) = 4.79, P = 0.0162] were associated with primary adherence to take-home naloxone. CONCLUSION: A notable portion of naloxone prescribed and filled in the community pharmacy setting was never obtained by the patient. Factors associated with PMN in this study included geographic location, use of a standing order, concomitant prescriptions for buprenorphine or opioid analgesic medications, and payment method. Underlying causes of PMN must be addressed (e.g., removing financial barriers and optimizing the use of standing orders) to increase naloxone access for persons at risk of opioid overdose.

Integration of Experiments across Diverse Environments Identifies the Genetic Determinants of Variation in Sorghum bicolor Seed Element Composition.

Seedling establishment and seed nutritional quality require the sequestration of sufficient element nutrients. The identification of genes and alleles that modify element content in the grains of cereals, including sorghum (Sorghum bicolor), is fundamental to developing breeding and selection methods aimed at increasing bioavailable element content and improving crop growth. We have developed a high-throughput work flow for the simultaneous measurement of multiple elements in sorghum seeds. We measured seed element levels in the genotyped Sorghum Association Panel, representing all major cultivated sorghum races from diverse geographic and climatic regions, and mapped alleles contributing to seed element variation across three environments by genome-wide association. We observed significant phenotypic and genetic correlation between several elements across multiple years and diverse environments. The power of combining high-precision measurements with genome-wide association was demonstrated by implementing rank transformation and a multilocus mixed model to map alleles controlling 20 element traits, identifying 255 loci affecting the sorghum seed ionome. Sequence similarity to genes characterized in previous studies identified likely causative genes for the accumulation of zinc, manganese, nickel, calcium, and cadmium in sorghum seeds. In addition to strong candidates for these five elements, we provide a list of candidate loci for several other elements. Our approach enabled the identification of single-nucleotide polymorphisms in strong linkage disequilibrium with causative polymorphisms that can be evaluated in targeted selection strategies for plant breeding and improvement.

Locomotor and energetic consequences of behavioral thermoregulation in the sanguivorous leech Hirudo verbana.

Medicinal leeches (Hirudo verbana) thermoregulate with respect to their sanguivorous feeding behavior. Immediate postprandial preferences are for warmer than their initial acclimation temperature (Ta, 21°C, Petersen et al. 2011), while unfed leeches have a lower preferred temperature (Tpref, 12.5°C). This may reduce energy expenditure and defer starvation if feeding opportunities are limited. Energetic benefits may have an associated cost if low temperatures reduce mobility and the ability to locate further hosts. These costs could be limited if mobility is unimpaired at low temperatures, or if acclimation can restore locomotor performance to the levels at Ta. The transition from Ta to the unfed Tpref significantly reduced speed and propulsive cycle frequency during swimming, and extension and retraction rates during crawling. Aerobic metabolic rate was also reduced from 0.20±0.03Wkg-1 at Ta to 0.10±0.03Wkg-1 at Tpref. The Q10 values of 1.7-2.9 for energetic and swimming parameters indicate a substantial temperature effect, although part of the decline in swimming performance can be attributed to temperature-related changes in water viscosity. 6 weeks at Ta resulted in no detectable acclimation in locomotor performance or aerobic metabolism. The energetic savings associated with a lower Tpref in unfed leeches effectively doubled the estimated time until depletion of energy reserves. Given that some mobility is still retained at Tpref, and that acclimation is in itself costly, the energetic benefits of selecting cooler temperatures between feedings may outweigh the costs associated with reduced locomotor performance.

Transcriptome sequencing identifies SPL7-regulated copper acquisition genes FRO4/FRO5 and the copper dependence of iron homeostasis in Arabidopsis.

The transition metal copper (Cu) is essential for all living organisms but is toxic when present in excess. To identify Cu deficiency responses comprehensively, we conducted genome-wide sequencing-based transcript profiling of Arabidopsis thaliana wild-type plants and of a mutant defective in the gene encoding SQUAMOSA PROMOTER BINDING PROTEIN-LIKE7 (SPL7), which acts as a transcriptional regulator of Cu deficiency responses. In response to Cu deficiency, FERRIC REDUCTASE OXIDASE5 (FRO5) and FRO4 transcript levels increased strongly, in an SPL7-dependent manner. Biochemical assays and confocal imaging of a Cu-specific fluorophore showed that high-affinity root Cu uptake requires prior FRO5/FRO4-dependent Cu(II)-specific reduction to Cu(I) and SPL7 function. Plant iron (Fe) deficiency markers were activated in Cu-deficient media, in which reduced growth of the spl7 mutant was partially rescued by Fe supplementation. Cultivation in Cu-deficient media caused a defect in root-to-shoot Fe translocation, which was exacerbated in spl7 and associated with a lack of ferroxidase activity. This is consistent with a possible role for a multicopper oxidase in Arabidopsis Fe homeostasis, as previously described in yeast, humans, and green algae. These insights into root Cu uptake and the interaction between Cu and Fe homeostasis will advance plant nutrition, crop breeding, and biogeochemical research.

TGF-ß-induced activation of mTOR complex 2 drives epithelial-mesenchymal transition and cell invasion.

In cancer progression, carcinoma cells gain invasive behavior through a loss of epithelial characteristics and acquisition of mesenchymal properties, a process that can lead to epithelial-mesenchymal transition (EMT). TGF-ß is a potent inducer of EMT, and increased TGF-ß signaling in cancer cells is thought to drive cancer-associated EMT. Here, we examine the physiological requirement for mTOR complex 2 (mTORC2) in cells undergoing EMT. TGF-ß rapidly induces mTORC2 kinase activity in cells undergoing EMT, and controls epithelial cell progression through EMT. By regulating EMT-associated cytoskeletal changes and gene expression, mTORC2 is required for cell migration and invasion. Furthermore, inactivation of mTORC2 prevents cancer cell dissemination in vivo. Our results suggest that the mTORC2 pathway is an essential downstream branch of TGF-ß signaling, and represents a responsive target to inhibit EMT and prevent cancer cell invasion and metastasis.

Loss of immune cell identity with age inferred from large atlases of single cell transcriptomes.

By analyzing two large atlases of almost 4 million cells, we show that immune-senescence involves a gradual loss of cellular identity, reflecting increased cellular heterogeneity, for effector, and cytotoxic immune cells. The effects are largely similar in both males and females and were robustly reproduced in two atlases, one assembled from 35 diverse studies including 678 adults, the other the OneK1K study of 982 adults. Since the mean transcriptional differences among cell-types remain constant across age deciles, there is little evidence for the alternative mechanism of convergence of cell-type identity. Key pathways promoting activation and stemness are down-regulated in aged T cells, while CD8 TEM and CD4 CTLs exhibited elevated inflammatory, and cytotoxicity in older individuals. Elevated inflammatory signaling pathways, such as MAPK and TNF-alpha signaling via NF-kB, also occur across all aged immune cells, particularly amongst effector immune cells. This finding of lost transcriptional identity with age carries several implications, spanning from a fundamental biological understanding of aging mechanisms to clinical perspectives on the efficacy of immunomodulation in elderly people.

Nutritional Composition of Post-Catastrophic Foods.

In addition to current challenges in food production arising from climate change, soil salinization, drought, flooding, and human-caused disruption, abrupt sunlight reduction scenarios (ASRS), e.g., a nuclear winter, supervolcano eruption, or large asteroid or comet strike, are catastrophes that would severely disrupt the global food supply and decimate normal agricultural practices. In such global catastrophes, teragrams of particulate matter, such as aerosols of soot, dust, and sulfates, would be injected into the stratosphere and block sunlight for multiple years. The reduction of incident sunlight would cause a decrease in temperature and precipitation and major shifts to climate patterns leading to devastating reductions in agricultural production of traditional food crops. To survive a catastrophic ASRS or endure current and future disasters and famines, humans might need to rely on post-catastrophic foods, or those that could be foraged, grown, or produced under the new climate conditions to supplement reduced availability of traditional foods. These foods have sometimes been referred to as emergency, alternate, or resilient foods in the literature. While there is a growing body of work that summarizes potential post-catastrophic foods and their nutritional profiles based on existing data in the literature, this article documents a list of protocols to experimentally determine fundamental nutritional properties of post-catastrophic foods that can be used to assess the relative contributions of those foods to a balanced human diet that meets established nutritional requirements while avoiding toxic levels of nutrients. © 2024 The Author(s). Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Total digestible glucans Basic Protocol 2: Apparent protein digestibility Basic Protocol 3: Vitamins B1, B3, B9, C, and D2 by HPLC Basic Protocol 4: Total antioxidant activity (DPPH-scavenging activity) Basic Protocol 5: Total phenolic compounds (Folin-Ciocalteu reagent method) Basic Protocol 6: Mineral content by ICP-OES.

Radiation and anti-PD-L1 synergize by stimulating a stem-like T cell population in the tumor-draining lymph node.

Radiotherapy (RT) and anti-PD-L1 synergize to enhance local and distant (abscopal) tumor control. However, clinical results in humans have been variable. With the goal of improving clinical outcomes, we investigated the underlying synergistic mechanism focusing on a CD8+ PD-1+ Tcf-1+ stem-like T cell subset in the tumor-draining lymph node (TdLN). Using murine melanoma models, we found that RT + anti-PD-L1 induces a novel differentiation program in the TdLN stem-like population which leads to their expansion and differentiation into effector cells within the tumor. Our data indicate that optimal synergy between RT + anti-PD-L1 is dependent on the TdLN stem-like T cell population as either blockade of TdLN egress or specific stem-like T cell depletion reduced tumor control. Together, these data demonstrate a multistep stimulation of stem-like T cells following combination therapy which is initiated in the TdLN and completed in the tumor.

Zinc biofortification through seed nutri-priming using alternative zinc sources and concentration levels in pea and sunflower microgreens.

Micronutrient deficiencies caused by malnutrition and hidden hunger are a growing concern worldwide, exacerbated by climate change, COVID-19, and conflicts. A potentially sustainable way to mitigate such challenges is the production of nutrient-dense crops through agronomic biofortification techniques. Among several potential target crops, microgreens are considered suitable for mineral biofortification because of their short growth cycle, high content of nutrients, and low level of anti-nutritional factors. A study was conducted to evaluate the potential of zinc (Zn) biofortification of pea and sunflower microgreens via seed nutri-priming, examining the effect of different Zn sources (Zn sulfate, Zn-EDTA, and Zn oxide nanoparticles) and concentrations (0, 25, 50, 100, and 200 ppm) on microgreen yield components; mineral content; phytochemical constituents such as total chlorophyll, carotenoids, flavonoids, anthocyanin, and total phenolic compounds; antioxidant activity; and antinutrient factors like phytic acid. Treatments were arranged in a completely randomized factorial block design with three replications. Seed soaked in a 200 ppm ZnSO4 solution resulted in higher Zn accumulation in both peas (126.1%) and sunflower microgreens (229.8%). However, an antagonistic effect on the accumulation of other micronutrients (Fe, Mn, and Cu) was seen only in pea microgreens. Even at high concentrations, seed soaking in Zn-EDTA did not effectively accumulate Zn in both microgreens' species. ZnO increased the chlorophyll, total phenols, and antioxidant activities compared to Zn-EDTA. Seed soaking in ZnSO4 and ZnO solutions at higher concentrations resulted in a lower phytic acid/Zn molar ratio, suggesting the higher bioaccessibility of the biofortified Zn in both pea and sunflower microgreens. These results suggest that seed nutrient priming is feasible for enriching pea and sunflower microgreens with Zn. The most effective Zn source was ZnSO4, followed by ZnO. The optimal concentration of Zn fertilizer solution should be selected based on fertilizer source, target species, and desired Zn-enrichment level.

Differential expression and regulation of iron-regulated metal transporters in Arabidopsis halleri and Arabidopsis thaliana--the role in zinc tolerance.

To avoid zinc (Zn) toxicity, plants have developed a Zn homeostasis mechanism to cope with Zn excess in the surrounding soil. In this report, we uncovered the difference of a cross-homeostasis system between iron (Fe) and Zn in dealing with Zn excess in the Zn hyperaccumulator Arabidopsis halleri ssp. gemmifera and nonhyperaccumulator Arabidopsis thaliana. Arabidopsis halleri shows low expression of the Fe acquisition and deficiency response-related genes IRT1 and IRT2 compared with A. thaliana. In A. thaliana, lowering the expression of IRT1 and IRT2 through the addition of excess Fe to the medium increases Zn tolerance. Excess Zn induces significant Fe deficiency in A. thaliana and reduces Fe accumulation in shoots. By contrast, the accumulation of Fe in shoots of A. halleri was stable under various Zn treatments. Root ferric chelate reductase (FRO) activity and expression of FIT are low in A. halleri compared with A. thaliana. Overexpressing a ZIP family member IRT3 in irt1-1, rescues the Fe-deficient phenotype. A fine-tuned Fe homeostasis mechanism in A. halleri maintains optimum Fe level by Zn-regulated ZIP transporters and prevents high Zn uptake through Fe-regulated metal transporters, and in part be responsible for Zn tolerance.

Chloroplast Fe(III) chelate reductase activity is essential for seedling viability under iron limiting conditions.

Photosynthesis, heme biosynthesis, and Fe-S cluster assembly all take place in the chloroplast, and all require iron. Reduction of iron via a membrane-bound Fe(III) chelate reductase is required before iron transport across membranes in a variety of systems, but to date there has been no definitive genetic proof that chloroplasts have such a reduction system. Here we report that one of the eight members of the Arabidopsis ferric reductase oxidase (FRO) family, FRO7, localizes to the chloroplast. Chloroplasts prepared from fro7 loss-of-function mutants have 75% less Fe(III) chelate reductase activity and contain 33% less iron per microgram of chlorophyll than wild-type chloroplasts. This decreased iron content is presumably responsible for the observed defects in photosynthetic electron transport. When germinated in alkaline soil, fro7 seedlings show severe chlorosis and die without setting seed unless watered with high levels of soluble iron. Overall, our results provide molecular evidence that FRO7 plays a role in chloroplast iron acquisition and is required for efficient photosynthesis in young seedlings and for survival under iron-limiting conditions.

Time to pump iron: iron-deficiency-signaling mechanisms of higher plants.

Iron is an essential nutrient for plants, yet it often limits plant growth. On the contrary, overaccumulation of iron within plant cells leads to oxidative stress. As a consequence, iron-uptake systems are carefully regulated to ensure that iron homeostasis is maintained. In response to iron limitation, plants induce expression of sets of activities that function at the root-soil interface to solubilize iron and subsequently transfer it across the plasma membrane of root cells. Recent advances have revealed key players in the signaling pathways that function to induce these iron-uptake responses. Transcription factors belonging to the basic helix-loop-helix, ABI3/VP1(B3), and NAC families appear to function either directly or indirectly in the upregulation of iron deficiency responses.

Alteration of iron responsive gene expression in Arabidopsis glutaredoxin S17 loss of function plants with or without iron stress.

Iron (Fe) is a mineral nutrient and a metal cofactor essential for plants. Iron limitation can have detrimental effects on plant growth and development, while excess iron inside plant cells leads to oxidative damage. As a result, plants have evolved complex regulatory networks to respond to fluctuations in cellular iron concentrations. The mechanisms that regulate these responses however, are not fully understood. Heterologous expression of an Arabidopsis thaliana monothiol glutaredoxin S17 (GRXS17) suppresses the over-accumulation of iron in the Saccharomyces cerevisiae Grx3/Grx4 mutant and disruption of GRXS17 causes plant sensitivity to exogenous oxidants and iron deficiency stress. GRXS17 may act as an important regulator in the plant's ability to respond to iron deficiency stress and maintain redox homeostasis. Here, we extend this investigation by analyzing iron-responsive gene expression of the Fer-like iron deficiency-induced transcription factor (FIT) network (FIT, IRT1, FRO1, and FRO2) and the bHLH transcription factor POPEYE (PYE) network (PYE, ZIF1, FRO3, NAS4, and BTS) in GRXS17 KO plants and wildtype controls grown under iron sufficiency and deficiency conditions. Our findings suggest that GRXS17 is required for tolerance to iron deficiency, and plays a negative regulatory role under conditions of iron sufficiency.

Species-Specific Duplication Event Associated with Elevated Levels of Nonstructural Carbohydrates in Sorghum bicolor.

Simple sugars are the essential foundation to plant life, and thus, their production, utilization, and storage are highly regulated processes with many complex genetic controls. Despite their importance, many of the genetic and biochemical mechanisms remain unknown or uncharacterized. Sorghum, a highly productive, diverse C4 grass important for both industrial and subsistence agricultural systems, has considerable phenotypic diversity in the accumulation of nonstructural sugars in the stem. We use this crop species to examine the genetic controls of high levels of sugar accumulation, identify genetic mechanisms for the accumulation of nonstructural sugars, and link carbon allocation with iron transport. We identify a species-specific tandem duplication event controlling sugar accumulation using genome-wide association analysis, characterize multiple allelic variants causing increased sugar content, and provide further evidence of a putative neofunctionalization event conferring adaptability in Sorghum bicolor Comparative genomics indicate that this event is unique to sorghum which may further elucidate evolutionary mechanisms for adaptation and divergence within the Poaceae. Furthermore, the identification and characterization of this event was only possible with the continued advancement and improvement of the reference genome. The characterization of this region and the process in which it was discovered serve as a reminder that any reference genome is imperfect and is in need of continual improvement.

The Mount Sinai Patient-Centered Preoperative Criteria Meant to Optimize Outcomes Are Less of a Barrier to Care Than WPATH SOC 7 Criteria Before Transgender-Specific Surgery.

Objectives: With expanding coverage of gender-affirming care in the United States, many insurers default to the World Professional Association for Transgender Health (WPATH) Standards of Care 7 (SOC 7) to establish eligibility requirements for surgery coverage. Informed by bariatric and transplant surgery evaluation models, the Mount Sinai Center for Transgender Medicine and Surgery (CTMS) developed patient-centered criteria to assess readiness for surgery, focusing on concerns that could impair recovery. To make recommendations for the next version of the WPATH SOC, SOC 8, we compared Mount Sinai patient-centered surgical readiness criteria with the WPATH SOC 7 criteria. Methods: Data were extracted from a deidentified data set developed as part the quality dashboard for CTMS. The data set included all patients seeking vaginoplasty who were evaluated by a single mental health provider, from July 2016 through August 2018, and who completed the full CTMS assessment. The number of patients eligible for surgery based on the Mount Sinai CTMS criteria was compared with the number of patients eligible for surgery according to WPATH SOC 7 criteria. Results: Of 139 patients identified, 63 (45%) were ready for surgery immediately based on the Mount Sinai patient-centered model. By contrast, only 21 (15%) out of the 139 met criteria for surgery based on WPATH SOC 7. Fifty patients (40%) were ready for surgery as per Mount Sinai patient-centered readiness review but not WPATH criteria. Conclusion: An assessment designed to better prepare patients for surgery may also result in fewer barriers to care than existing criteria used by insurance companies in the United States.