An international study presenting a federated learning AI platform for pediatric brain tumors.

While multiple factors impact disease, artificial intelligence (AI) studies in medicine often use small, non-diverse patient cohorts due to data sharing and privacy issues. Federated learning (FL) has emerged as a solution, enabling training across hospitals without direct data sharing. Here, we present FL-PedBrain, an FL platform for pediatric posterior fossa brain tumors, and evaluate its performance on a diverse, realistic, multi-center cohort. Pediatric brain tumors were targeted due to the scarcity of such datasets, even in tertiary care hospitals. Our platform orchestrates federated training for joint tumor classification and segmentation across 19 international sites. FL-PedBrain exhibits less than a 1.5% decrease in classification and a 3% reduction in segmentation performance compared to centralized data training. FL boosts segmentation performance by 20 to 30% on three external, out-of-network sites. Finally, we explore the sources of data heterogeneity and examine FL robustness in real-world scenarios with data imbalances.

Effectiveness of a guided digital self-help intervention to improve sleep and the biological clock in university students - Study protocol for a randomized controlled trial.

Background: Sleep problems occur in many university students which affects their mental health and daily functioning. Cognitive behavioural therapy for insomnia (CBT-I) has been proven effective in adults but research in university students, who struggle to maintain a 24-hour rhythm, is still limited. We hypothesize that a guided digital CBT-I intervention, enriched with components on the biological clock ('i-Sleep & BioClock') will be effective in reducing insomnia severity and improving mental health outcomes for students with sleep problems. Objectives: We aim to evaluate the effectiveness of a guided online sleep and biological clock self-help intervention in improving sleep, depression symptoms, anxiety symptoms, functioning, academic performance, and quality of life in university students at 6 weeks and 18 weeks. Methods: This is a two-arm parallel-group superiority randomized controlled trial, comparing a 5-week guided online 'i-Sleep & BioClock' intervention to online psychoeducation (PE). We aim to include 192 university students (Bachelor, Master, and PhD) with at least subthreshold insomnia (Insomnia Severity Index ≥10), aged ≥16, who can speak Dutch or English. We are excluding students with current risk for suicide or night shifts. The primary outcome is insomnia severity. Secondary outcomes include sleep estimates (sleep and light exposure diary), depression, anxiety, functioning, quality of life, and academic performance. The effectiveness of the intervention compared to online PE will be evaluated using linear mixed models. Discussion: The current study tests the effectiveness of an online self-help intervention for university students who suffer from sleep problems. This trial builds upon an open feasibility study and will provide evidence of an online guided self-help program for students. The findings of this study will determine the potential wider dissemination of the intervention to address the high need for available and accessible help for students experiencing insomnia. Trial registration: ClinicalTrials.Gov (NCT06023693), registered on August 3rd, 2023.

Integrated Strategies to Support Diabetes Technology in Pregnancy.

Managing diabetes in pregnancy can be overwhelming, with numerous dramatic physiologic changes taking place that require constant diligence and attention. Advances in diabetes technology have improved glycemic outcomes, well-being, and quality of life for people with type 1 diabetes of all ages. However, regulatory approval and access to diabetes technology in pregnancy has lagged behind these advancements, leaving many pregnant individuals without tools that could dramatically improve diabetes care before, during, and after gestation. Here, we review the benefits of continuous glucose monitors and automated insulin-delivery systems in pregnancy and highlight specific scientific and structural supports to help implement diabetes technology safely, effectively, and equitably in pregnancy.

Exploring Prognostic Implications of Race and Ethnicity in Patients With Peripheral Arterial Disease.

INTRODUCTION: Significant health inequalities in major adverse limb events exist. Ethnically minoritized groups are more prone to have a major adverse event following peripheral vascular interventions. This systematic review and meta-analysis aimed to describe the postoperative implications of racial and ethnic status on clinical outcomes following vascular interventions for claudication and chronic limb-threatening ischemia. METHODS: Searches were conducted across seven databases from inception to June 2021 and were updated in October 2022 to identify studies reporting claudication or chronic limb-threatening ischemia in patients who underwent open, endovascular, or hybrid procedures. Studies with documented racial and ethnic status and associated clinical outcomes were selected. Extracted data included demographic and clinical characteristics, vascular interventions, and measured outcomes associated with race or ethnicity. Meta-analyses were performed using random-effect models to report pooled odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: Seventeen studies evaluating the impact of Black versus White patients undergoing amputation as a primary intervention were combined in a meta-analysis, revealing that Black patients had a higher incidence of amputations as a primary intervention than White patients (OR: 1.91, 95% CI: 1.61-2.27). Another meta-analysis demonstrated that Black patients had significantly higher rates of amputation after revascularization (OR: 1.56, 95% CI: 1.28-1.89). Furthermore, multiple trends were demonstrated in the secondary outcomes evaluated. CONCLUSIONS: Our findings suggest that Black patients undergo primary major amputation at a significantly higher rate than White patients, with similar trends seen among Hispanic and First Nations patients. Black patients are also significantly more likely to be subjected to amputation following attempts at revascularization when compared to White patients.

Elucidating the Subcellular Localization of GLRaV-3 Proteins Encoded by the Unique Gene Block in N. benthamiana Suggests Implications on Plant Host Suppression.

Grapevine leafroll-associated virus 3 (GLRaV-3) is a formidable threat to the stability of the global grape and wine industries. It is the primary etiological agent of grapevine leafroll disease (GLD) and significantly impairs vine health, fruit quality, and yield. GLRaV-3 is a member of the genus Ampelovirus, Closteroviridae family. Viral genes within the 3' proximal unique gene blocks (UGB) remain highly variable and poorly understood. The UGBs of Closteroviridae viruses include diverse open reading frames (ORFs) that have been shown to contribute to viral functions such as the suppression of the host RNA silencing defense response and systemic viral spread. This study investigates the role of GLRaV-3 ORF8, ORF9, and ORF10, which encode the proteins p21, p20A, and p20B, respectively. These genes represent largely unexplored facets of the GLRaV-3 genome. Here, we visualize the subcellular localization of wildtype and mutagenized GLRaV-3 ORFs 8, 9, and 10, transiently expressed in Nicotiana benthamiana. Our results indicate that p21 localizes to the cytosol, p20A associates with microtubules, and p20B is trafficked into the nucleus to carry out the suppression of host RNA silencing. The findings presented herein provide a foundation for future research aimed at the characterization of the functions of these ORFs. In the long run, it would also facilitate the development of innovative strategies to understand GLRaV-3, mitigate its spread, and impacts on grapevines and the global wine industry.

Impact of Iron Intake and Reserves on Cognitive Function in Young University Students.

Iron is a key nutrient for cognitive function. During periods of high academic demand, brain and cognitive activity increase, potentially affecting iron intake and reserves. The present study aimed to investigate the impact of iron levels on cognitive function in a university sample, considering the influence of gender. A cross-sectional study was conducted with 132 university students (18-29 years) from the University of Castilla-La Mancha (Spain). A dietary record was formed through a questionnaire to analyze iron consumption, and blood and anthropometric parameters were measured. The Wechsler Adult Intelligence Scale-IV was used to determine the Intelligence Quotient (IQ), as well as the Verbal Comprehension Index (VCI), Working Memory Index (WMI), Processing Speed Index (PSI), and Perceptual Reasoning Index (PRI), to assess cognitive abilities. Among women, the prevalence of iron deficiency (ID) and iron deficiency anemia (IDA) was 21% and 4.2%, respectively. No ID or IDA was found in men. The impact of iron intake on IQ and cognitive abilities was mainly associated with the female population, where a positive association between iron intake, serum ferritin, and total IQ was revealed. In conclusion, low iron intake is related to poorer intellectual ability, suggesting that an iron-rich diet is necessary to maintain the academic level of university students.

Exploring the impact of maternal early life adversity on interoceptive sensibility in pregnancy: implications for prenatal depression.

PURPOSE: Pregnancy is a sensitive period of development in adult life characterized by massive changes in physical, emotional, and cognitive function. Such changes may be adaptive, e.g., facilitating adjustment to physical demands, but they may also reflect or contribute to risks inherent to this stage of life, e.g., prenatal depression. One cognitive ability that may undergo change during pregnancy and contribute to mental wellness is interoception - the ability to perceive, integrate, and model sensory information originating from the body. Strong interoceptive abilities are associated with lower rates of depression in non-pregnant adult populations, and interoception is generally weaker in individuals at higher risk for depression, for example, exposure to early life adversity (ELA). In the present online, cross-sectional study, we investigated whether interoception in pregnant women differed based on histories of ELA, in ways that increased their relative risk for prenatal depression symptoms. METHODS: The pregnant individuals were in the second trimester of their first pregnancy and were compared to a group of nulliparous, non-parenting women. RESULTS: Previous exposure to ELA significantly moderated pregnancy-related differences in self-reported interoception (interoceptive sensibility). A further moderated-mediation analysis revealed that the extent to which interoceptive sensibility buffered against depressive symptoms was conditional on ELA exposure, suggesting more ELA is associated with lower interoceptive sensibility during pregnancy, which increased prenatal depression risk. CONCLUSIONS: Together this work suggests that levels of interoception during pregnancy are sensitive to previous adversity exposure. It also suggests that interoceptive-focused interventions for preventing/treating prenatal depressive symptoms in high-risk women may be worth exploring.

Femtosecond Core-Level Spectroscopy Reveals Involvement of Triplet States in the Gas-Phase Photodissociation of Fe(CO)5.

Excitation of iron pentacarbonyl [Fe(CO)5], a prototypical photocatalyst, at 266 nm causes the sequential loss of two CO ligands in the gas phase, creating catalytically active, unsaturated iron carbonyls. Despite numerous studies, major aspects of its ultrafast photochemistry remain unresolved because the early excited-state dynamics have so far eluded spectroscopic observation. This has led to the long-held assumption that ultrafast dissociation of gas-phase Fe(CO)5 proceeds exclusively on the singlet manifold. Herein, we present a combined experimental-theoretical study employing ultrafast extreme ultraviolet transient absorption spectroscopy near the Fe M2,3-edge, which features spectral evolution on 100 fs and 3 ps time scales, alongside high-level electronic structure theory, which enables characterization of the molecular geometries and electronic states involved in the ultrafast photodissociation of Fe(CO)5. We assign the 100 fs evolution to spectroscopic signatures associated with intertwined structural and electronic dynamics on the singlet metal-centered states during the first CO loss and the 3 ps evolution to the competing dissociation of Fe(CO)4 along the lowest singlet and triplet surfaces to form Fe(CO)3. Calculations of transient spectra in both singlet and triplet states as well as spin-orbit coupling constants along key structural pathways provide evidence for intersystem crossing to the triplet ground state of Fe(CO)4. Thus, our work presents the first spectroscopic detection of transient excited states during ultrafast photodissociation of gas-phase Fe(CO)5 and challenges the long-standing assumption that triplet states do not play a role in the ultrafast dynamics.

A worldwide study of white matter microstructural alterations in people living with Parkinson's disease.

The progression of Parkinson's disease (PD) is associated with microstructural alterations in neural pathways, contributing to both motor and cognitive decline. However, conflicting findings have emerged due to the use of heterogeneous methods in small studies. Here we performed a large diffusion MRI study in PD, integrating data from 17 cohorts worldwide, to identify stage-specific profiles of white matter differences. Diffusion-weighted MRI data from 1654 participants diagnosed with PD (age: 20-89 years; 33% female) and 885 controls (age: 19-84 years; 47% female) were analyzed using the ENIGMA-DTI protocol to evaluate white matter microstructure. Skeletonized maps of fractional anisotropy (FA) and mean diffusivity (MD) were compared across Hoehn and Yahr (HY) disease groups and controls to reveal the profile of white matter alterations at different stages. We found an enhanced, more widespread pattern of microstructural alterations with each stage of PD, with eventually lower FA and higher MD in almost all regions of interest: Cohen's d effect sizes reached d = -1.01 for FA differences in the fornix at PD HY Stage 4/5. The early PD signature in HY stage 1 included higher FA and lower MD across the entire white matter skeleton, in a direction opposite to that typical of other neurodegenerative diseases. FA and MD were associated with motor and non-motor clinical dysfunction. While overridden by degenerative changes in the later stages of PD, early PD is associated with paradoxically higher FA and lower MD in PD, consistent with early compensatory changes associated with the disorder.

Phosphorylation patterns in the AT1R C-terminal tail specify distinct downstream signaling pathways.

Different ligands stabilize specific conformations of the angiotensin II type 1 receptor (AT1R) that direct distinct signaling cascades mediated by heterotrimeric G proteins or ß-arrestin. These different active conformations are thought to engage distinct intracellular transducers because of differential phosphorylation patterns in the receptor C-terminal tail (the "barcode" hypothesis). Here, we identified the AT1R barcodes for the endogenous agonist AngII, which stimulates both G protein activation and ß-arrestin recruitment, and for a synthetic biased agonist that only stimulates ß-arrestin recruitment. The endogenous and ß-arrestin-biased agonists induced two different ensembles of phosphorylation sites along the C-terminal tail. The phosphorylation of eight serine and threonine residues in the proximal and middle portions of the tail was required for full ß-arrestin functionality, whereas phosphorylation of the serine and threonine residues in the distal portion of the tail had little influence on ß-arrestin function. Similarly, molecular dynamics simulations showed that the proximal and middle clusters of phosphorylated residues were critical for stable ß-arrestin-receptor interactions. These findings demonstrate that ligands that stabilize different receptor conformations induce different phosphorylation clusters in the C-terminal tail as barcodes to evoke distinct receptor-transducer engagement, receptor trafficking, and signaling.

When and how perceived control buffers against cognitive declines: A moderated mediation analysis.

Although perceived control is a well-established predictor of cognitive aging, less is known about how and under what developmental circumstances these beliefs about personal influence may protect against cognitive declines. Our study examined light physical activity (LPA) as an unexplored mechanism that may link changes in two facets of perceived control (personal mastery, perceived constraints) to longitudinal trajectories of cognitive functioning. We also examined whether mediated pathways were moderated by age (i.e., differed across the adult lifespan). We analyzed two-wave, 9-year data from the national Midlife in the United States Study (n = 2,456; Mage = 56 years, range = 30-84; 56% female) using autoregressive mediation and moderated mediation models. Mediation models showed that changes in personal mastery and perceived constraints predicted episodic memory and executive functioning via self-reported change in LPA. Only the mediated effects of constraints remained significant in a model that included both mastery and constraints as predictors. Moderated mediation models showed that, for episodic memory, the mediated pathways were strongest in old age and emerged only for constraints: For older but not younger adults, declines in constraints were associated with less decline in episodic memory, as mediated by increases in LPA. Results were consistent in sensitivity analyses that controlled for levels and change in moderate-to-vigorous physical activity. Findings inform lifespan theories of control and provide initial evidence that change in a largely overlooked health behavior (LPA) may underlie the link between perceived constraints and cognitive functioning, with this pathway becoming more pronounced in late life. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Development of a family-level intervention for families with transgender and/or nonbinary youth: Lessons and recommendations.

Family support plays an important role in promoting resilience and health among transgender and/or nonbinary youth (TNBY), but family members often experience barriers to supporting their TNBY, including minority-adjacent stress stemming from exposure to structural stigma and antitransgender legislation. TNBY and their families need effective family-level interventions developed using community-based participatory research (CBPR), which integrates community members (e.g., TNBY, family members, service providers for families with TNBY) into the intervention development process to ensure the resulting intervention is relevant and useful. Informed by findings from the Trans Teen and Family Narratives Project, we used CBPR to develop the Trans Teen and Family Narratives Conversation Toolkit, a family-level intervention designed to educate families about TNBY and facilitate conversations about gender. The toolkit was developed across 1.5 years (June 2019 to January 2021) using four integrated phases: (1) content development: digital storytelling workshop with TNBY; (2) content review: digital storyteller interviews and user focus groups; (3) content development: study team content synthesis and website development; and (4) content review: website review by TNBY, family members, and mental health providers, and intervention refinement. This article outlines the intervention development process, describes strategies employed to navigate challenges encountered along the way, and shares key learnings to inform future CBPR intervention development efforts. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

The quantitative and qualitative analysis of dye in fentanyl tablets via ultraviolet-visible spectroscopy-A forensic approach.

In the United States, illicit fentanyl is often trafficked as blue tablets mimicking the legitimate M-30 oxycodone tablet produced by Mallinckrodt. The analysis of dyes extracted from seized fentanyl tablets could provide a useful tool for law enforcement to establish linkages between cases and could prove useful for attributing a seizure to a given trafficking organization. Fentanyl tablet seizures associated with a particular drug trafficking organization (DTO), either through investigative or intelligence information, were used as the sample set for this study. The blue dye from the tablets was isolated by solid phase extraction and then qualitatively and quantitatively analyzed via ultraviolet-visible spectroscopy. This research revealed that the illicit tableting facilities use a different dye than several known pharmaceutical companies. The concentration of dye in individual tablets within a seizure proved to be very minimal, and the small sample size made it difficult to draw linkages from case to case. Analysis of the dyes could not effectively differentiate between the drug trafficking organizations in the tested population due to each DTO using the same dye; however, it is important to note that the dye found was consistent between illicit tablets.

High prevalence of dysfunctional uterine bleeding in candidates for metabolic/bariatric surgery: increased endometrial cancer risk?

BACKGROUND: Endometrial cancer (EC) is the strongest obesity-associated malignancy and the fastest-growing cancer in young women. Early identification of EC and other endometrial pathology (malignant and nonmalignant) in women with severe obesity may improve treatment options and uterine preservation. Screening for endometrial pathology using abnormal or postmenopausal uterine bleeding (APUB) as a surrogate in women pursuing metabolic/bariatric surgery may be clinically beneficial, but data supporting this effort are limited. OBJECTIVE: To develop and institute a screening program for APUB as a surrogate for endometrial pathology in bariatric surgery candidates. SETTING: Two, academic metabolic/bariatric surgery programs in Louisiana, United States. METHODS: The Modified SAMANTA is a 10-item questionnaire that was implemented to identify patients with APUB, specifically combining tools designed to identify anovulatory/postmenopausal and heavy menstrual bleeding. Demographic (age, race), body mass index, and questionnaire data were analyzed with respect to positive screening using data from March 2021 through May 2023. RESULTS: Of 1371 eligible women presenting for surgical evaluation, 664 (48.4%) positive screens were identified and referred for gynecologic evaluation to rule out endometrial hyperplasia/cancer or other endometrial pathology. The likelihood of positive screening for APUB was associated with increasing BMI (P = .001) and Black/African American race (P = .003), as well as increasing SAMANTA score (P < .001). In contrast, risk of positive screening was negatively associated with increasing age (P < .001). CONCLUSIONS: Women presenting for metabolic/bariatric surgery have a high prevalence of APUB and, given this dysfunctional bleeding and concurrent obesity, are at greater risk for underlying EC. Potential risk factors for APUB, given their associations with screening positive, include increased body mass index, younger age, and Black/African American race. Standardized screening with appropriate gynecologic referral should be a routine part of the overall evaluation for women with severe obesity.

Microvascular Disease and Early Diabetes Onset Are Associated with Deficits in Femoral Neck Bone Density and Structure Among Older Adults with Longstanding Type 1 Diabetes.

Adults with type 1 diabetes (T1D) have increased hip fracture risk, yet no studies have assessed volumetric bone density or structure at the hip in older adults with T1D. Here, we used previously collected 3D CT scans of the proximal femur from older adults with longstanding T1D and non-diabetic controls to identify bone deficits that may contribute to hip fracture in T1D. In this retrospective cohort study, we identified 101 adults with T1D and 181 age-, sex- and race-matched non-diabetic controls (CON) who received abdominal or pelvis CT exams from 2010-2020. Among adults with T1D, 33 (33%) had mild-to-moderate nephropathy, 61 (60%) had neuropathy and 71 (70%) had retinopathy. Within the whole cohort, adults with T1D tended to have lower FN density, though differences did not reach statistical significance. The subset of the T1D group who were diagnosed before age 15 had lower total bone mineral content (-14%, TtBMC), cortical BMC (-19.5%, CtBMC) and smaller Ct cross-sectional area (-12.6, CtCSA) than their matched controls (P<.05 for all). Individuals with T1D who were diagnosed at a later age did not differ from controls in any bone outcome (P>.21). Furthermore, adults with T1D and nephropathy had lower FN aBMD (-10.6%), TtBMC (-17%), CtBMC (-24%) and smaller CtCSA (-15.4%) compared to matched controls (P<.05 for all). Adults with T1D and neuropathy had cortical bone deficits (8.4-12%, P<.04). In summary, among older adults with T1D, those who were diagnosed before age of 15 yrs, those with nephropathy, and those with neuropathy had unfavorable bone outcomes at the FN that may contribute to high hip fracture risk among patients with T1D. These novel observations highlight the longstanding detrimental impact of T1D when present during bone accrual and skeletal fragility as an additional complication of microvascular disease in individuals with T1D.

Older adults with type 1 diabetes (T1D) are at higher risk for hip fractures, but the reasons for this are unclear. In this study, we analyzed existing clinical CT scans of the hip from older adults with longstanding T1D and those without diabetes. While overall bone density differences were not significant, older adults with T1D who were diagnosed before age 15 or had complications like nephropathy or neuropathy showed worse bone outcomes at the femoral neck. These findings suggest that early-onset T1D and related complications contribute to increased hip fracture risk.

A feasibility study assessing knowledge, vaccine hesitancy, and completion rates of free HPV vaccination in low-income uninsured adults.

Background: Human Papillomavirus (HPV) vaccination rates remain low in the U.S., particularly among minorities and low-income, uninsured patients. We report preliminary data on a pilot study program providing education and free HPV vaccination at a clinic serving low-income uninsured adults. Methods: From October 2020 through October 2022, we assessed HPV vaccination knowledge, awareness, and prevalence of hesitancy towards receiving the vaccine among low-income uninsured patients age 18-45. The Parents Attitudes about Childhood Vaccines (PACV) survey was modified and used to evaluate vaccine hesitancy. An educational video on HPV was shown to patients declining vaccination. Results: 43 patients were enrolled. 69.8% had heard of the HPV vaccine and 85.7% were non-hesitant based on PACV scores of 0-49. Black participants had a statistically significant higher PACV score (more hesitant) than White participants. Familiarity with the HPV vaccine correlated with lower PACV scores. Only 27% completed all three HPV vaccine doses. Discussion: The availability of an education program together with free HPV vaccination are not sufficient to achieve adequate vaccination rates in low-income, uninsured adults. Innovative, culturally sensitive education and supportive interventions, in addition to access to free HPV vaccination, are warranted in order to improve vaccination rates in this underserved population.

Paternal behavior in captive fat-tailed dwarf lemurs (Cheirogaleus medius) is preserved under socially relevant conditions.

Fat-tailed dwarf lemurs (Cheirogaleus medius), primates endemic to Madagascar, are obligate hibernators that form stable, lifelong pairs in the wild. Given the temporal constraints imposed by seasonal hibernation, infant dwarf lemurs must grow, develop, and wean within the first two months of life. Maternal as well as paternal infant care, observed in the wild, has been deemed critical for infant survival. Given the importance of fathers' involvement in early infant care, we expect this behavior to persist even under captive conditions. At the Duke Lemur Center, in Durham NC, we observed two families of fat-tailed dwarf lemurs and focused on the behavior of adult males within the first two months of the infants' lives. We report evidence of paternal involvement, including babysitting, co-feeding, grooming, accompanying, and leading infants, consistent with observations from the wild. As expected, paternal babysitting decreased as infants gained independence, while co-feeding increased. Supplemental anecdotes, video recorded by observers, also highlight clear cases of involvement by both parents, and even older siblings, in safeguarding and socializing new infants. We argue that maintaining captive fat-tailed dwarf lemur populations under socially and ecologically relevant conditions facilitates the full expression of physiological and behavioral repertoires. Most importantly, it also allows dwarf lemurs to realize their species' potential and become robust proxies of their wild kin.

Adam19 Deficiency Impacts Pulmonary Function: Human GWAS Follow-up in a Mouse Knockout Model.

PURPOSE: Over 550 loci have been associated with human pulmonary function in genome-wide association studies (GWAS); however, the causal role of most remains uncertain. Single nucleotide polymorphisms in a disintegrin and metalloprotease domain 19 (ADAM19) are consistently related to pulmonary function in GWAS. Thus, we used a mouse model to investigate the causal link between Adam19 and pulmonary function. METHODS: We created an Adam19 knockout (KO) mouse model and validated the gene targeting using RNA-Seq and RT-qPCR. Mouse body composition was assessed using dual-energy X-ray absorptiometry. Mouse lung function was measured using flexiVent. RESULTS: Contrary to prior publications, the KO was not neonatal lethal. KO mice had lower body weight and shorter tibial length than wild-type (WT) mice. Their body composition revealed lower soft weight, fat weight, and bone mineral content. Adam19 KO had decreased baseline respiratory system elastance, minute work of breathing, tissue damping, tissue elastance, and forced expiratory flow at 50% forced vital capacity but higher FEV0.1 and FVC. Adam19 KO had attenuated tissue damping and tissue elastance in response to methacholine following LPS exposure. Adam19 KO also exhibited attenuated neutrophil extravasation into the airway after LPS administration compared to WT. RNA-Seq analysis of KO and WT lungs identified several differentially expressed genes (Cd300lg, Kpna2, and Pttg1) implicated in lung biology and pathogenesis. Gene set enrichment analysis identified negative enrichment for TNF pathways. CONCLUSION: Our murine findings support a causal role of ADAM19, implicated in human GWAS, in regulating pulmonary function.

Genomic and functional determinants of host spectrum in Group B Streptococcus.

Group B Streptococcus (GBS) is a major human and animal pathogen that threatens public health and food security. Spill-over and spill-back between host species is possible due to adaptation and amplification of GBS in new niches but the evolutionary and functional mechanisms underpinning those phenomena are poorly known. Based on analysis of 1,254 curated genomes from all major GBS host species and six continents, we found that the global GBS population comprises host-generalist, host-adapted and host-restricted sublineages, which are found across host groups, preferentially within one host group, or exclusively within one host group, respectively, and show distinct levels of recombination. Strikingly, the association of GBS genomes with the three major host groups (humans, cattle, fish) is driven by a single accessory gene cluster per host, regardless of sublineage or the breadth of host spectrum. Moreover, those gene clusters are shared with other streptococcal species occupying the same niche and are functionally relevant for host tropism. Our findings demonstrate (1) the heterogeneity of genome plasticity within a bacterial species of public health importance, enabling the identification of high-risk clones; (2) the contribution of inter-species gene transmission to the evolution of GBS; and (3) the importance of considering the role of animal hosts, and the accessory gene pool associated with their microbiota, in the evolution of multi-host bacterial pathogens. Collectively, these phenomena may explain the adaptation and clonal expansion of GBS in animal reservoirs and the risk of spill-over and spill-back between animals and humans.