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Abstract Background Increasing incidence of head and neck cancers (HNCs), driven by rising rates of oropharynx cancer (OPC), has been recorded around the world. This study examined trends in HNC and subsites (oral cavity, oropharynx, and larynx cancers) in Scotland focusing on assessing whether the sociodemographic profile has changed over the past 20 years. Methods Scottish Cancer Registry data (2001–2020) including European Age Standardised Rates of HNC and subsites were analysed in multivariate Poisson regression by age, sex, area-based socioeconomic status, and year of diagnosis (with interaction tests). Results Overall HNC and oral cavity cancer (OCC) incidence remained relatively stable. OPC incidence rates increased by 78%, while larynx cancer incidence declined by 27%. Over time, there were marginal shifts to a slightly older age profile for HNC (p = 0.001) and OCC (p = 0.001), but no changes in OPC (p = 0.86) and larynx cancer (p = 0.29). No shift in the sex profile of HNC was observed except for minor increases in female OCC rates (p = 0.001), and the socioeconomic distribution remained unchanged across all HNC subsites. Conclusions There have been no significant changes in the sociodemographic profile of HNC in Scotland over the last 20 years, despite the changing trends in HNCs with dramatically increasing incidence rates in OPC and reducing larynx cancer. This information can be used to target or stratify HNC prevention and control.

This article focuses on the thermal bridging issues associated with interface of parkade concrete suspended slab to base of wall. The study aims to determine the optimal length and thickness of insulation at the top and underside of the suspended slab to minimize heat loss. The thermal performance of wall to parkade suspended slab is investigated, for both wood frame and steel stud constructions. Various insulation configurations are proposed and evaluated, including different lengths and thicknesses of extruded polystyrene foam (XPS) and Fiberglass spray insulations. The thermal performance calculations are conducted using steady-state heat transfer analysis. A finite-element based software is utilized for the simulations. The study provides a detailed methodology for analyzing the thermal performance of building envelope details, considering different insulation configurations. The results of the simulations are presented as Thermal Resistance Values (R-Values) and Linear Thermal Resistance Values (PSI-Values), allowing for a comparison of the thermal efficiency of different insulation configurations. The results show that utilizing the optimal insulation configuration can lead to up to 80 % enhancement in the thermal efficiency of the assembly. The findings serve as a guideline and aim to assist building designers in improving the thermal performance of concrete suspended slabs.

Abstract Using a symmetry-preserving formulation of a vector $$\,\times \,$$ × vector contact interaction (SCI) and treating the proton as a quark + interacting-diquark bound state, whose structure is obtained by solving a Poincaré-covariant Faddeev equation, we provide a comprehensive, coherent set of predictions for unpolarised and polarised proton parton distribution functions (DFs): valence, glue, and four-flavour separated sea. The results enable many themes to be addressed, including: the asymmetry of antimatter in the proton; the neutron:proton structure function ratio; helicity retention in hard scattering processes; the charm quark momentum fraction; the sign and size of the polarised gluon DF; and the origin of the proton spin. In all cases where sound analyses of data are available, SCI predictions are semiquantitatively in agreement with the results. Those mismatches which exist are typically attributable to the momentum-independence of the underlying interaction. Judiciously interpreted, the SCI delivers a sound and insightful explanation of proton structure as expressed in DFs.

Summary: Pancreatic ductal adenocarcinoma (PDAC) exhibits an immunosuppressive tumor microenvironment (TME) contributing to its therapeutic resistance. Following our previous studies, we report that mast cells infiltrating the PDAC TME foster this immunosuppression and desmoplasia. Mast cell infiltration correlated with human PDAC progression, and genetic or pharmacological mast cell depletion reduced tumor growth and desmoplasia while enhancing survival in mouse PDAC models. Mechanistically, mast cell-derived IL-10 promoted PDAC progression. Strikingly, combining an agonistic anti-OX40 immunotherapy with mast cell blockade synergistically elicited durable anti-tumor immunity, marked by increased infiltration of CD8+ T effector cells expressing granzyme B and dramatic survival benefit unachievable with either approach alone. An OX40-associated gene signature correlated with improved survival in human PDAC, supporting therapeutic translation. Our findings establish mast cells as promoters of the suppressive PDAC TME and rational targets for combination immunotherapy. Targeting this mast cell-mediated resistance mechanism could overcome immunotherapy failure in PDAC.

ABSTRACT Marine pest introductions continue to occur and increase at accelerated rates, threatening the marine environment and blue economy. Environmental DNA (eDNA) is a tool for determining the presence of both indigenous and nonindigenous species, via the detection of genetic material that is shed into the local environment. Although eDNA approaches have gained widespread adoption in the last decade, fundamental knowledge gaps remain around factors that can influence the probability of detection, and how to optimize eDNA sampling in aquatic environments. Here, we partition eDNA research into four major research themes: eDNA concentration (shedding and decay), transport (advection and mixing), sampling design strategies, and the modeling of these dynamics. We review current developments and challenges in each theme with a focus on field sampling strategies and the use of biophysical models for understanding the movement of modeling eDNA in complex aquatic environments. We then introduce three modeling case studies from a large embayment where we (1) quantify the spatial and temporal variability of eDNA dispersion, (2) use biophysical models to inform a field sampling strategy, and (3) demonstrate a backtracking modeling technique to identify upstream DNA sources to an existing sample (monitoring) site. We conclude by identifying specific recommendations to help improve future eDNA studies. This work highlights how biophysical models can be applied to improve early detection and informing response and management decisions.

A reaction model for γ+p→J/ψ+p photoproduction, which exposes the cc¯ content of the photon in making the transition γ→cc¯+P→J/ψ and couples the intermediate cc¯ system to the proton's valence quarks via Pomeron (P) exchange, is used to deliver a description of available data, viz. both differential and total cross sections from near threshold, where data has newly been acquired, to invariant mass W≈300GeV. The study suggests that it is premature to link existing γ+p→J/ψ+p data with, for instance, in-proton gluon distributions, the quantum chromodynamics trace anomaly, or pentaquark production. Further developments in reaction theory and higher precision data are necessary before the validity of any such connections can be assessed.

The chief goal of the Blood Profiling Atlas in Cancer (BloodPAC) consortium is to promote collaborative efforts that support the development and implementation of liquid biopsy tests. Here, we report the results of a pilot study conducted by three BloodPAC members that aimed to demonstrate a multisite liquid biopsy testing framework using longitudinal blood specimens from 38 patients with metastatic breast cancer. Three laboratories receiving identical samples from two clinical sites each applied a different targeted sequencing platform to analyze mutations in cell-free DNA (cfDNA). The resulting mutational profiles reflected common breast cancer alterations, including clinically actionable mutations for 40% of hormone- receptor-positive patients. In 12 genes with shared target regions across sequencing panels, perfect inter-assay concordance was also observed for mutations detected above the lowest common assay limit of detection. Whole-genome copy number profiling of cfDNA and circulating tumor cells (CTCs) further revealed marked heterogeneity in copy number alterations and cfDNA tumor fractions across patients. Additionally, comparison of tumor fraction and CTC abundance demonstrated the complementary nature of cfDNA and CTC analyses. Overall, the framework described in this study may serve as a resource for future trials aiming to identify multimodal liquid biopsy biomarkers to guide clinical care.

Abstract Intracranial aneurysms (IAs) are present in 2–6% of the global population and can be catastrophic upon rupture with a mortality rate of 30–50%. IAs are commonly detected through time-of-flight magnetic resonance angiography (TOF-MRA), however, this data is rarely available for research and training purposes. The provision of imaging resources such as TOF-MRA images is imperative to develop new strategies for IA detection, rupture prediction, and surgical training. To support efforts in addressing data availability bottlenecks, we provide an open-access TOF-MRA dataset comprising 63 patients, of which 24 underwent interval surveillance imaging by TOF-MRA. Patient scans were evaluated by a neuroradiologist, providing aneurysm and vessel segmentations, clinical annotations, 3D models, in addition to 3D Slicer software environments containing all this data for each patient. This dataset is the first to provide interval surveillance imaging for supporting the understanding of IA growth and stability. This dataset will support computational and experimental research into IA dynamics and assist surgical and radiology training in IA treatment.

Abstract Background Breast cancer (BC) is the most commonly diagnosed cancer and the leading cause of cancer death among women globally. Despite advances, there is considerable variation in clinical outcomes for patients with non-luminal A tumors, classified as difficult-to-treat breast cancers (DTBC). This study aims to delineate the proteogenomic landscape of DTBC tumors compared to luminal A (LumA) tumors. Methods We retrospectively collected a total of 117 untreated primary breast tumor specimens, focusing on DTBC subtypes. Breast tumors were processed by laser microdissection (LMD) to enrich tumor cells. DNA, RNA, and protein were simultaneously extracted from each tumor preparation, followed by whole genome sequencing, paired-end RNA sequencing, global proteomics and phosphoproteomics. Differential feature analysis, pathway analysis and survival analysis were performed to better understand DTBC and investigate biomarkers. Results We observed distinct variations in gene mutations, structural variations, and chromosomal alterations between DTBC and LumA breast tumors. DTBC tumors predominantly had more mutations in TP53, PLXNB3, Zinc finger genes, and fewer mutations in SDC2, CDH1, PIK3CA, SVIL, and PTEN. Notably, Cytoband 1q21, which contains numerous cell proliferation-related genes, was significantly amplified in the DTBC tumors. LMD successfully minimized stromal components and increased RNA–protein concordance, as evidenced by stromal score comparisons and proteomic analysis. Distinct DTBC and LumA-enriched clusters were observed by proteomic and phosphoproteomic clustering analysis, some with survival differences. Phosphoproteomics identified two distinct phosphoproteomic profiles for high relapse-risk and low relapse-risk basal-like tumors, involving several genes known to be associated with breast cancer oncogenesis and progression, including KIAA1522, DCK, FOXO3, MYO9B, ARID1A, EPRS, ZC3HAV1, and RBM14. Lastly, an integrated pathway analysis of multi-omics data highlighted a robust enrichment of proliferation pathways in DTBC tumors. Conclusions This study provides an integrated proteogenomic characterization of DTBC vs LumA with tumor cells enriched through laser microdissection. We identified many common features of DTBC tumors and the phosphopeptides that could serve as potential biomarkers for high/low relapse-risk basal-like BC and possibly guide treatment selections.

Australian blue mussels (Mytilus spp.) are an increasingly important sustainable product of the Australian aquaculture industry. Although important for commercial fisheries, aquaculture may have adverse environmental and ecological impacts. This study assessed the impact of standard hatchery-imposed selection practices on the genetic diversity of farmed blue mussels. Using microsatellite markers, relatedness and genetic structure analyses showed that hatchery-reared larvae have high levels of genetic diversity without a significant decline as they move through the hatchery rearing process. Selection and/or genetic drift does appear to be operating during the hatchery rearing process, however, evidenced by an increase in relatedness among larvae over time. Significant shifts in allele frequency as well as genetic clusters provides further evidence that selection is acting on larvae due to the selection practice applied at the hatchery. Comparison of the level of genetic diversity and genetic differentiation of adults from wild and farmed populations provided no evidence that farmed mussels have lower diversity, or that they are genetically swamping local natural populations. The data suggest that careful design and implementation of mussel breeding programs can maintain high genetic diversity among larvae that does not lead to genetic swamping of natural mussel populations in the surrounding area.

Abstract We performed a deep proteogenomic analysis of bulk tumor and laser microdissection enriched tumor cell populations from high-grade serous ovarian cancer (HGSOC) tissue specimens spanning a broad spectrum of purity. We identified patients with longer progression-free survival had increased immune-related signatures and validated proteins correlating with tumor-infiltrating lymphocytes in 65 tumors from an independent cohort of HGSOC patients, as well as with overall survival in an additional 126 HGSOC patient cohort. We identified that homologous recombination deficient (HRD) tumors are enriched in pathways associated with metabolism and oxidative phosphorylation that we validated in independent patient cohorts. We further identified that polycomb complex protein BMI-1 is elevated in HR proficient (HRP) tumors, that elevated BMI-1 correlates with poor overall survival in HRP but not HRD HGSOC patients, and that HRP HGSOC cells are uniquely sensitive to BMI-1 inhibition.

Background Task-sharing of spinal anaesthesia care by non-specialist graduate physicians, termed medical officers (MOs), is commonly practised in rural Indian healthcare facilities to mitigate workforce constraints. We sought to assess whether spinal anaesthesia failure rates of MOs were non-inferior to those of consultant anaesthesiologists (CA) following a standardised educational curriculum.Methods We performed a randomised, non-inferiority trial in three rural hospitals in Tamil Nadu and Chhattisgarh, India. Patients aged over 18 years with low perioperative risk (ASA I & II) were randomised to receive MO or CA care. Prior to the trial, MOs underwent task-based anaesthesia training, inclusive of remotely accessed lectures, simulation-based training and directly observed anaesthetic procedures and intraoperative care. The primary outcome measure was spinal anaesthesia failure with a non-inferiority margin of 5%. Secondary outcome measures consisted of incidence of perioperative and postoperative complications.Findings Between 12 July 2019 and 8 June 2020, a total of 422 patients undergoing surgical procedures amenable to spinal anaesthesia care were randomised to receive either MO (231, 54.7%) or CA care (191, 45.2%). Spinal anaesthesia failure rate for MOs (7, 3.0%) was non-inferior to those of CA (5, 2.6%); difference in success rate of 0.4% (95% CI=0.36–0.43%; p=0.80). Additionally, there were no statistically significant differences observed between the two groups for intraoperative or postoperative complications, or patients’ experience of pain during the procedure.Interpretation This study demonstrates that failure rates of spinal anaesthesia care provided by trained MOs are non-inferior to care provided by CAs in low-risk surgical patients. This may support policy measures that use task-sharing as a means of expanding anaesthesia care capacity in rural Indian hospitals.Trial registration number NCT04438811.

Using a symmetry-preserving truncation of the quantum field equations describing hadron properties, parameter-free predictions are delivered for pion and kaon elastic electromagnetic form factors, FP=π,K, thereby unifying them with kindred results for nucleon elastic electromagnetic form factors. Regarding positive-charge states, the analysis stresses that the presence of scaling violations in QCD entails that Q2FP(Q2) should exhibit a single maximum on Q2>0. Locating such a maximum is both necessary and sufficient to establish the existence of scaling violations. The study predicts that, for charged π, K mesons, the Q2FP(Q2) maximum lies in the neighbourhood Q2≃5 GeV2. Foreseeable experiments will test these predictions and, providing their Q2 reach meets expectations, potentially also provide details on the momentum dependence of meson form factor scaling violation.

Abstract Objective We estimate annual hospital expenditures to achieve high emergency department (ED) pediatric readiness (HPR), that is, weighted Pediatric Readiness Score (wPRS) ≥ 88 (0–100 scale) across EDs with different pediatric volumes of children, overall and after accounting for current levels of readiness. Methods We calculated the annual hospital costs of HPR based on two components: (1) ED pediatric equipment and supplies and (2) labor costs required for a Pediatric Emergency Care Coordinator (PECC) to perform pediatric readiness tasks. Data sources to generate labor cost estimates included: 2021 national salary information from U.S. Bureau of Labor Statistics, detailed patient and readiness data from 983 EDs in 11 states, the 2021 National Pediatric Readiness Project assessment; a national PECC survey; and a regional PECC survey. Data sources for equipment and supply costs included: purchasing costs from seven healthcare organizations and equipment usage per ED pediatric volume. We excluded costs of day‐to‐day ED operations (ie, direct clinical care and routine ED supplies). Results The total annual hospital costs for HPR ranged from $77,712 (95% CI 54,719–100,694) for low volume EDs to $279,134 (95% CI 196,487–362,179) for very high volume EDs; equipment costs accounted for 0.9–5.0% of expenses. The total annual cost‐per‐patient ranged from $3/child (95% CI 2–4/child) to $222/child (95% CI 156–288/child). After accounting for current readiness levels, the cost to reach HPR ranged from $23,775 among low volume EDs to $145,521 among high volume EDs, with costs per patient of $4/child to $48/child. Conclusions Annual hospital costs for HPR are modest, particularly when considered per child.

Abstract We aimed to determine the relative contribution of hypercapnia and hypoxia to the bradycardic response to apneas. We hypothesized that apneas with hypercapnia would cause greater bradycardia than normoxia, similar to the response seen with hypoxia, and that apneas with hypercapnic hypoxia would induce greater bradycardia than hypoxia or hypercapnia alone. Twenty‐six healthy participants (12 females; 23 ± 2 years; BMI 24 ± 3 kg/m2) underwent three gas challenges: hypercapnia (+5 torr end tidal partial pressure of CO2 [PETCO2]), hypoxia (50 torr end tidal partial pressure of O2 [PETO2]), and hypercapnic hypoxia (combined hypercapnia and hypoxia), with each condition interspersed with normocapnic normoxia. Heart rate and rhythm, blood pressure, PETCO2, PETO2, and oxygen saturation were measured continuously. Hypercapnic hypoxic apneas induced larger bradycardia (−19 ± 16 bpm) than normocapnic normoxic apneas (−11 ± 15 bpm; p = 0.002), but had a comparable response to hypoxic (−19 ± 15 bpm; p = 0.999) and hypercapnic apneas (−14 ± 14 bpm; p = 0.059). Hypercapnic apneas were not different from normocapnic normoxic apneas (p = 0.134). After removal of the normocapnic normoxic heart rate response, the change in heart rate during hypercapnic hypoxia (−11 ± 16 bpm) was similar to the summed change during hypercapnia+hypoxia (−9 ± 10 bpm; p = 0.485). Only hypoxia contributed to this bradycardic response. Under apneic conditions, the cardiac response is driven by hypoxia.

Abstract There has recently been an explosion of studies implicating the human microbiome in playing a critical role in many disease and wellness states. The etiology of abnormal semen analysis (SA) parameters is not identified in 30% of cases; investigations involving the semen microbiome may bridge this gap. Here, we explore the relationship between the semen microbiome and alterations of sperm parameters. We recruited men presenting for fertility evaluation or vasectomy consultation with proven biological paternity. SA and next generation sequencing was performed. Differential abundance testing using Analysis of composition of Microbiota with Bias Correction (ANCOM-BC) was performed along with canonical correlational analysis for microbial community profiling. Men with abnormal (N = 27) sperm motility showed a higher abundance of Lactobacillus iners compared to those with normal (N = 46) sperm motility (mean proportion 9.4% versus 2.6%, p = 0.046). This relationship persisted on canonical correlational analysis (r = 0.392, p = 0.011). Men with abnormal sperm concentration (N = 20) showed a higher abundance of Pseudomonas stutzeri (2.1% versus 1.0%, p = 0.024) and Pseudomonas fluorescens (0.9% versus 0.7%, p = 0.010), but a lower abundance of Pseudomonas putida (0.5% versus 0.8%, p = 0.020), compared to those with normal sperm concentration (N = 53). Major limitations are related to study design (cross-sectional, observational). Our results suggest that a small group of microorganisms may play a critical role in observed perturbations of SA parameters. Some of these microbes, most notably Lactobacillus iners, have been described extensively within other, fertility-related, contexts, whereas for others, this is the first report where they have potentially been implicated. Advances in our understanding of the semen microbiome may contribute to potentially new therapeutic avenues for correcting impairments in sperm parameters and improving male fertility.

The incidence of breast implant illness (BII) and BII-related explant procedures has not decreased with current surgical and treatment techniques. It is speculated the main underlying cause of BII complications is the result of chronic, sub-clinical infections residing on and around the implant. The infection, and subsequent biofilm, produce antagonistic compounds that drive chronic inflammation and immune responses. In this study, the microbial communities in over 600 consecutive samples of infected explant capsules and tissues were identified via next-generation sequencing to identify any commonality between samples. The majority of the bacteria identified were Gram-positive, with Cutibacterium acnes and Staphylococcus epidermidis being the dominant organisms. No correlation between sample richness and implant filling was found. However, there was a significant correlation between sample richness and patient age. Due to the complex nature, breast augmentation failures may be better addressed from a holistic approach than one of limited scope.

Abstract Gamete traits can vary widely among species, populations and individuals, influencing fertilisation dynamics and overall reproductive fitness. Sexual selection can play an important role in determining the evolution of gamete traits with local environmental conditions determining the strength and direction of sexual selection. Here, we test for signatures of post‐mating selection on gamete traits in relation to population density, and possible interactive effects of population density and sperm concentration on sperm motility and fertilisation rates among natural populations of mussels. Our study shows that males from high‐density populations produce smaller sperm compared with males from low‐density populations, but we detected no effect of population density on egg size. Our results also reveal that females from low‐density populations tended to exhibit lower fertilisation rates across a range of sperm concentrations, although this became less important as sperm concentration increased. Variances in fertilisation success were higher for females than males and the effect of gamete compatibility between males and females increases as sperm concentrations increase. These results suggest that local population density can influence gamete traits and fertilisation dynamics but also highlight the importance of phenotypic plasticity in governing sperm–egg interactions in a highly dynamic selective environment.

ABSTRACTSkin microbiome can be altered in patients with atopic dermatitis (AD). An understanding of the changes from healthy to atopic skin can help develop new targets for treatment by identifying microbial and molecular biomarkers. This study investigates the skin microbiome and metabolome of healthy adult subjects and lesion (ADL) and non-lesion (ADNL) of AD patients by 16S rRNA gene sequencing and mass spectrometry, respectively. Samples from AD patients showed alterations in the diversity and composition of the skin microbiome, with ADL skin having the greatest divergence. Staphylococcus species, especially S. aureus, were significantly increased in AD patients. Metabolomic profiles were also different between the groups. Dipeptide derivatives are more abundant in ADL, which may be related to skin inflammation. Co-occurrence network analysis of the microbiome and metabolomics data revealed higher co-occurrence of metabolites and bacteria in healthy ADNL compared to ADL. S. aureus co-occurred with dipeptide derivatives in ADL, while phytosphingosine-derived compounds showed co-occurrences with commensal bacteria, for example, Paracoccus sp., Pseudomonas sp., Prevotella bivia, Lactobacillus iners, Anaerococcus sp., Micrococcus sp., Corynebacterium ureicelerivorans, Corynebacterium massiliense, Streptococcus thermophilus, and Roseomonas mucosa, in healthy and ADNL groups. Therefore, these findings provide valuable insights into how AD affects the human skin metabolome and microbiome.IMPORTANCEThis study provides valuable insight into changes in the skin microbiome and associated metabolomic profiles in an adult population with mild to moderate atopic dermatitis. It also identifies new therapeutic targets that may be useful for developing personalized treatments for individuals with atopic dermatitis based on their unique skin microbiome and metabolic profiles.

Background Moyamoya is a rare arteriopathy affecting the intracranial circulation with a risk of stroke in the pediatric population. High‐volume centers provide improved outcomes after surgical revascularization compared with low‐volume centers. However, private insurers are often reluctant to approve care out‐of‐network. We hypothesized that rare diseases that can be treated in a single procedure, such as revascularization for moyamoya, can yield improved clinical outcomes with substantial cost savings to insurance companies when approved for care at high‐volume centers of excellence. Methods Longitudinal deidentified data of pediatric patients undergoing surgical revascularization for moyamoya from January 2018 to December 2020 (N = 125) were obtained from national commercial insurers by an independent third‐party analytics core. Patients were selected according to International Classification of Diseases, Tenth Revision (ICD‐10) diagnosis and procedure codes. For a 9‐month episode, clinical and cost outcome metrics were compared across centers, with patients from the highest volume center designated as the primary cohort. Results Patients in the primary cohort were on average younger at time of surgery, with greater medical comorbidities, yet exhibited decreased postoperative complications and fewer unplanned readmissions. The primary cohort had an overall 42% lower expense compared with patients treated at other single institution health systems ($89 000 versus $153 000). The primary cohort minimized out‐of‐network costs with implementation of a partnership care model, using local resources for preoperative workup in 68% of episodes, compared with only 8% of episodes at a comparator high‐volume center. Conclusion Implementation of a partnership model takes advantages of the surgical resources of a high‐volume center while maximizing local resource use for preoperative and postoperative care. Referral to high‐volume centers for pediatric moyamoya revascularization provides both improved outcomes for the patients and substantial cost savings for the insurers. These data suggest the development of high‐volume centers of excellence for select conditions requiring neurosurgical treatment confer benefit to both patients and insurers, even in cases of out‐of‐network care.

Exploiting an evolution scheme for parton distribution functions (DFs) that is all-orders exact, contemporary lattice-QCD (lQCD) results for low-order Mellin moments of the pion valence quark DF are shown to be mutually consistent. The analysis introduces a means by which key odd moments can be obtained from the even moments in circumstances where only the latter are available. Combining these elements, one arrives at parameter-free lQCD-based predictions for the pointwise behaviour of pion valence, glue, and sea DFs, with sound uncertainty estimates. The behaviour of the pion DFs at large light-front momentum fraction, x≳0.85, is found to be consistent with QCD expectations and continuum analyses of pion structure functions, i.e., damping like (1−x)βparton, with βvalence≈2.4, βglue≈3.6, βsea≈4.6. It may be possible to test these predictions using data from forthcoming experiments.

Abstract The metastasis-invasion cascade describes the series of steps required for a cancer cell to successfully spread from its primary tumor and ultimately grow within a secondary organ. Despite metastasis being a dynamic, multistep process, most omics studies to date have focused on comparing primary tumors to the metastatic deposits that define end-stage disease. This static approach means we lack information about the genomic and epigenomic changes that occur during the majority of tumor progression. One particularly understudied phase of tumor progression is metastatic colonization, during which cells must adapt to the new microenvironment of the secondary organ. Through temporal profiling of chromatin accessibility and gene expression in vivo, we identify dynamic changes in the epigenome that occur as osteosarcoma tumors form and grow within the lung microenvironment. Furthermore, we show through paired in vivo and in vitro CRISPR drop-out screens and pharmacological validation that the upstream transcription factors represent a class of metastasis-specific dependency genes. While current models depict lung colonization as a discrete step within the metastatic cascade, our study shows it is a defined trajectory through multiple epigenetic states, revealing new therapeutic opportunities undetectable with standard approaches.

Abstract Background Military individuals, retirees, and their families have free care or minimal out‐of‐pocket costs in the US military health system (MHS). In contrast, out‐of‐pocket costs in the US general population vary substantially. This study compared cancer patients with various insurance types in the general population to those in the MHS in cancer stage at diagnosis. Methods Patients were identified from the US Department of Defense's (DoD) Automated Central Tumor Registry (ACTUR) and the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program. Tumor stage at diagnosis of breast, prostate, lung, and colon cancers during 2007–2013 was compared between ACTUR and SEER insurance categories of “insured,” “insured‐no specifics,” “any Medicaid,” and “uninsured,” A multivariable logistic regression analysis estimated the odds ratio (OR) of late stage (Stages III and IV) versus early stage (Stages I and II) cancers comparing SEER insurance status to ACTUR. Results There were 18,440 eligible patients identified from ACTUR and 831,959 patients identified from SEER. For all cancer types, patients in the SEER‐insured/no specifics, Medicaid, and uninsured groups had significantly greater likelihood of late stage diagnosis compared to ACTUR patients. The adjusted ORs were greatest among uninsured and Medicaid patients. The SEER‐insured group also had a significantly higher odds of advanced stage disease than ACTUR patients for prostate cancer and lung cancer. Conclusion Patients in the MHS with universal access to healthcare were diagnosed at an earlier stage than those in the general population. This difference was most evident compared to Medicaid and uninsured groups.

Background: Next-generation sequencing (NGS) methods for microbial profiling have increased sensitivity to detect urinary pathogens. Objective: To determine whether NGS microbial profiling can be used to guide antibiotic prophylaxis and reduce infection compared with the standard of care. Design, setting, and participants: A prospective randomized controlled clinical trial of patients undergoing urologic stone interventions at an academic health center from December 2019 to January 2022 was conducted. Urine was collected at the preoperative visit for standard culture and intervention NGS diagnostics. Evaluable patients were culture negative, met 2-wk follow-up, and did not cancel surgery. Of 240 individuals (control = 121, intervention = 119), 83 control and 74 intervention patients were evaluable. Intervention: Microbial findings (paired quantitative polymerase chain reaction and NGS) were sent to an infectious disease pharmacist to recommend prophylactic antimicrobial regimen. Outcome measurements and statistical analysis: The primary outcome was postoperative urinary infection within the follow-up period (Fisher’s exact test). The primary outcome was analyzed by modified intent-to-treat (mITT) and per-protocol analyses. Secondary endpoints considered included positive culture concordance, antibiotic use, and adverse events. Additional post hoc analyses investigated factors contributing to infection (univariate logistic regression). Results and limitations: The intervention significantly reduced postsurgical urinary infection risk by 7.1% (–0.73%, 15%) compared with the standard of care in the mITT analysis (1.4% vs 8.4%, p = 0.045) or by 8.5% (0.88%, 16%) compared with the per-protocol analysis (0% vs 8.5%, p = 0.032). NGS-guided treatment altered the distribution of antibiotics used (p = 0.025), and antibiotics poorly matched with NGS findings were associated with increased infection odds (odds ratio [OR] = 5.9, p = 0.046). Women were at greater odds to develop infection (OR = 10, p = 0.03) and possessed differentiated microbial profiles (p

Abstract The progression from conception through to the postpartum period represents an extraordinary period of physiological adaptation in the mother to support the growth and development of the fetus. Healthy, normotensive human pregnancies are associated with striking increases in both plasma volume and sympathetic nerve activity, yet normal or reduced blood pressure; it represents a unique period of apparent healthy sympathetic hyperactivity. However, how this normal blood pressure is achieved in the face of sympathoexcitation, and the mechanisms responsible for this increased activity are unclear. Importantly, sympathetic activation has been implicated in hypertensive pregnancy disorders – the leading causes of maternal–fetal morbidity and mortality in the developed world. An understudied link between pregnancy and the development of maternal hypertension may lie in the sympathetic nervous system regulation of blood pressure. This brief review presents the latest data on sympathoexcitation in both healthy and hypertensive pregnancies, and concurrent adaptations along the neurovascular cascade.

Abstract Background Sweet syndrome (SS), also known as acute febrile neutrophilic dermatosis, is an immunologic syndrome characterized by widespread neutrophilic infiltration. Histiocytoid Sweet syndrome (H-SS) is a histopathologic variant of SS. While SS most commonly occurs in adults, this case report discusses an infant patient who presented with H-SS. Case presentation Through a multidisciplinary approach, this patient was also found to have very early onset inflammatory bowel disease (VEO-IBD) and Mevalonate kinase-associated disease (MKAD). While prior case studies have characterized an association between VEO-IBD and MKAD, there is no literature describing the association of all three diagnoses this case: H-SS, VEO-IBD and MKAD. Initiation of canakinumab in this patient resulted in successful control of the disease. Conclusions This case highlights the importance of a multidisciplinary approach to rare diagnoses, and collaboration during cases with significant diagnostic uncertainty.

The stellarator is a type of fusion energy device that—if properly designed—could provide clean, safe, and abundant energy to the grid. To generate this energy, a stellarator must keep a hot mixture of charged particles (known as a plasma) sufficiently confined by using a fully shaped magnetic field. If this is achieved, the heat from fusion reactions within the plasma can be harvested as energy. We present a novel method for designing reactor-relevant stellarator magnetic fields, which combine several key physical properties. These include plasma stability, excellent confinement of the fast-moving particles generated by fusion reactions, and reduction of the turbulence that is known to limit the performance of the most advanced stellarator experiment in the world, Wendelstein 7-X.

Abstract Background Protein biomarkers of cancer progression and response to therapy are increasingly important for improving personalized medicine. Advanced quantitative pathology platforms enable measurement of protein expression in tissues at the single-cell level. However, this rich quantitative cell-by-cell biomarker information is most often not exploited. Instead, it is reduced to a single mean across the cells of interest or converted into a simple proportion of binary biomarker-positive or -negative cells. Results We investigated the utility of retaining all quantitative information at the single-cell level by considering the values of the quantile function (inverse of the cumulative distribution function) estimated from a sample of cell signal intensity levels in a tumor tissue. An algorithm was developed for selecting optimal cutoffs for dichotomizing cell signal intensity distribution quantiles as predictors of continuous, categorical or survival outcomes. The proposed algorithm was used to select optimal quantile biomarkers of breast cancer progression based on cancer cells’ cell signal intensity levels of nuclear protein Ki-67, Proliferating cell nuclear antigen, Programmed cell death 1 ligand 2, and Progesterone receptor. The performance of the resulting optimal quantile biomarkers was validated and compared to the standard cancer compartment mean signal intensity markers using an independent external validation cohort. For Ki-67, the optimal quantile biomarker was also compared to established biomarkers based on percentages of Ki67-positive cells. For proteins significantly associated with PFS in the external validation cohort, the optimal quantile biomarkers yielded either larger or similar effect size (hazard ratio for progression-free survival) as compared to cancer compartment mean signal intensity biomarkers. Conclusion The optimal quantile protein biomarkers yield generally improved prognostic value as compared to the standard protein expression markers. The proposed methodology has a broad application to single-cell data from genomics, transcriptomics, proteomics, or metabolomics studies at the single cell level.

Recent work suggests that inwardly propagating internal gravity waves (IGWs) within a star can be fully converted to outward magnetic waves if they encounter a sufficiently strong magnetic field. The resulting magnetic waves dissipate as they propagate outward to regions with lower Alfvén velocity. While tidal forcing is known to excite IGWs, this conversion and subsequent damping of magnetic waves have not been explored as a tidal dissipation mechanism. In particular, stars with sufficiently strong magnetic fields could fully dissipate tidally excited waves, yielding the same tidal evolution as the previously studied “traveling wave regime.” Here, we evaluate the viability of this mechanism using stellar models of stars with convective cores (F-type stars in the mass range of 1.2–1.6 M _⊙ ), which were previously thought to be weakly tidally dissipative (due to the absence of nonlinear gravity-wave breaking). The criterion for wave conversion to operate is evaluated for each stellar mass using the properties of each star’s interior along with estimates of the magnetic field produced by a convective core dynamo under the assumption of equipartition between kinetic (convective) and magnetic energies. Our main result is that this previously unexplored source of efficient tidal dissipation can operate in stars within this mass range for significant fractions of their lifetimes. This tidal dissipation mechanism appears to be consistent with the observed inspiral of WASP-12b and more generally could play an important role in the orbital evolution of hot Jupiters—and to lower-mass ultra-short-period planets—orbiting F-type stars.

Abstract Forest protection and afforestation have been identified as a means to partially offset anthropogenic CO2 emissions. Yet, increasingly frequent observations of drought‐induced tree mortality are reported. Here, we applied a risk analysis framework for global drought‐induced forest mortality by examining extreme reductions in greenness and water content of forest canopies during past mortality events as well as growth recovery of surviving individual trees following stand‐scale mortality events. We defined a drought‐induced mortality risk index (DMR) that explains 80% of documented tree mortality. Rising CO2 alleviated the increase of DMR with short‐term drought, however, the observed DMR increases with long‐term drought no matter whether considering plant responses to CO2. DMR in sites where tree mortality has been observed significantly increased since the 1980s. More than that, drought exposure threatened 0.28 billion hectares of forested areas. Our framework highlights how climate change‐induced drought, especially hotter‐droughts, threatens the sustainability of global forests.

At least 200 billion black soldier fly (Hermetia illucens) larvae (BSFL) are reared each year as food and feed, and the insect farming industry is projected to grow rapidly. Despite interest by consumers, producers, and legislators, no empirical evidence exists to guide producers in practicing humane – or instantaneous – slaughter for these novel mini-livestock. BSFL may be slaughtered via freezing, boiling, grinding, or other methods; however standard operating procedures (SOPs) and equipment design may affect the likelihood of instantaneous death using these methods. We tested how larval body size and particle size plate hole diameter affect the likelihood of instantaneous death for black soldier fly larvae that are slaughtered using a standard meat grinder. Larval body size did not affect the likelihood of instantaneous death for larvae that are 106–175 mg in mass. However, particle size plate hole diameter had a significant effect on the likelihood of instantaneous death, with only 54% of larvae experiencing an instant death when using the largest particle size plate (12-mm hole diameter) compared to 84% using the smallest particle size plate (2.55 mm). However, a higher percentage of instantaneous death (up to 99%) could be achieved by reducing the proportion of larvae that become stuck in the machine. We conclude by outlining specific recommendations to support producers in achieving a 99% instantaneous death rate through specific SOPs to be used with similarly designed machines. We also develop a protocol for producers that wish to test their own grinding SOPs.

A novel meroterpenoid cabagranin D was isolated with related neolignans cabagranins A–C from the leaves of Piper cabagranum (Costa Rica). Cabagranins A–C represent the first examples of 3,3′-neolignans isolated from the plant genus Piper, and the meroterpenoid cabagranin D displays an unprecedented Diels–Alder conjugate of an unsubstituted phenylpropenone and α-phellandrene. Details of the full structural elucidation of these compounds and a discussion of their potential biosynthetic relationships are presented.

Abstract Recent mass loss from ice sheets and ice shelves is now persistent and prolonged enough that it impacts downstream oceanographic conditions. To demonstrate this, we use an ensemble of coupled GISS‐E2.1‐G simulations forced with historical estimates of anomalous freshwater, in addition to other climate forcings, from 1990 through 2019. There are detectable differences in zonal‐mean sea surface temperatures (SST) and sea ice in the Southern Ocean, and in regional sea level around Antarctica and in the western North Atlantic. These impacts mostly improve the model's representation of historical changes, including reversing the forced trends in Antarctic sea ice. The changes in SST may have implications for estimates of the SST pattern effect on climate sensitivity and for cloud feedbacks. We conclude that the changes are sufficiently large that model groups should strive to include more accurate estimates of these drivers in all‐forcing historical simulations in future coupled model intercomparisons.

While the direct effects of COVID-19 caused widespread global suffering and death, the indirect impacts—via public health preventative measures and a reduction in health and social care services—were also devastating for many. More recently, it has also become increasingly apparent that such measures have had disproportionate effects, exacerbating existing health inequalities. For caregivers of individuals with chronic illness, the effects have been marked and particularly so for informal caregivers of individuals with complex neurodegenerative conditions such as Parkinson’s. Nine informal caregivers (all partners: three men and six women) of individuals with Parkinson’s in England took part in individual semi-structured interviews on two occasions (December 2021/January 2022 and May 2022). The interviews focused on their experiences of supporting their partner, their own challenges, and how these evolved and changed post-lockdown. Interpretative phenomenological analysis was used to inform the methodology and analysis. Four themes were identified: (i) lockdown-induced revolution and evolution of the relationship dynamic with partner; (ii) fighting to be seen, heard, and understood in healthcare encounters; (iii) making sense of, and adapting to, risk in a time of COVID-19; and (iv) managing isolation and need for support during and after lockdown. The negative effects from both the lockdowns and the depletion of usual health and support services were apparent for all participants. Existing vulnerabilities from being a carer of an individual with complex needs were also exacerbated. As caregivers worked hard to mitigate these effects for their partners as much as possible, the long-term impact of such intense psychological and practical effort was often considerable. Ultimately, a simple restoration of pre-lockdown support levels may be insufficient to facilitate a successful return to optimal levels of support and wellbeing.

Abstract Environmental DNA (eDNA)‐based methods are increasingly used by government agencies to detect pests and threatened species, and for broader biodiversity monitoring. Given rapid technological advances and a growing number of commercial service providers, there is a need to standardize methods for quality assurance and to maintain confidence in eDNA‐based results. Here, we introduce two documents to provide best‐practice guidelines for Australian and New Zealand eDNA researchers and end‐users (available from https://sednasociety.com/publications): the Environmental DNA protocol development guide for biomonitoring provides minimum standard considerations for eDNA and environmental RNA projects across the complete workflow, from ethical considerations and experimental design to interpreting and communicating results. The Environmental DNA test validation guidelines outline key steps to be used in assay development and validation for species‐specific testing and metabarcoding. Both guidelines were developed as an initiative of the Australian Government Department of Agriculture, Fisheries and Forestry and led by the Southern eDNA Society in a collaborative process including multiple consultation rounds with eDNA experts, end‐users, and stakeholders to adapt the guidelines to Australian and New Zealand needs. The aim of these guidelines is not to be prescriptive, but to set minimum standards to support a consistent and best‐practice approach to eDNA testing. We anticipate that the guidelines will be reviewed and regularly updated as required. Our aspiration is that these best‐practice guidelines will ensure environmental managers are provided with robust scientific evidence to support decision‐making.

Understanding the strong interaction dynamics that govern the emergence of hadron mass (EHM) represents a challenging open problem in the Standard Model. In this paper we describe new opportunities for gaining insight into EHM from results on nucleon resonance (N*) electroexcitation amplitudes (i.e., γvpN* electrocouplings) in the mass range up to 1.8 GeV for virtual photon four-momentum squared (i.e., photon virtualities Q2) up to 7.5 GeV2 available from exclusive meson electroproduction data acquired during the 6-GeV era of experiments at Jefferson Laboratory (JLab). These results, combined with achievements in the use of continuum Schwinger function methods (CSMs), offer new opportunities for charting the momentum dependence of the dressed quark mass from results on the Q2-evolution of the γvpN* electrocouplings. This mass function is one of the three pillars of EHM and its behavior expresses influences of the other two, viz. the running gluon mass and momentum-dependent effective charge. A successful description of the Δ(1232)3/2+ and N(1440)1/2+ electrocouplings has been achieved using CSMs with, in both cases, common momentum-dependent mass functions for the dressed quarks, for the gluons, and the same momentum-dependent strong coupling. The properties of these functions have been inferred from nonperturbative studies of QCD and confirmed, e.g., in the description of nucleon and pion elastic electromagnetic form factors. Parameter-free CSM predictions for the electrocouplings of the Δ(1600)3/2+ became available in 2019. The experimental results obtained in the first half of 2022 have confirmed the CSM predictions. We also discuss prospects for these studies during the 12-GeV era at JLab using the CLAS12 detector, with experiments that are currently in progress, and canvass the physics motivation for continued studies in this area with a possible increase of the JLab electron beam energy up to 22 GeV. Such an upgrade would finally enable mapping of the dressed quark mass over the full range of distances (i.e., quark momenta) where the dominant part of hadron mass and N* structure emerge in the transition from the strongly coupled to perturbative QCD regimes.

Background: With efforts underway globally to scale up access to surgical care for the billions who lack it, understanding the impact of climate change on surgical care delivery is critical for clinicians and policymakers. We aimed to assess the current state of knowledge regarding the impact of climate change on the Lancet Commission on Global Surgery Bellwether Procedures: laparotomy, caesarean delivery and treatment of an open fracture. Methods: Adhering to PRISMA guidelines, we performed a systematic review of PubMed, Embase, CINAHL and Web of Science. We included studies that incorporated at least one of each of our two sets of search terms: (1) a specific Bellwether Procedure or its directly related pathophysiology, and (2) a climate change pressure (e.g. extreme heat, major storm, etc.). We excluded studies published before January 1, 2000; in languages outside coauthors’ fluency; and those without primary data (e.g. meta-analyses). Two co-authors screened each abstract and then the qualifying full articles for inclusion and data extraction. Our study is registered in PROSPERO (#CRD42021271933). Results: We initially identified 4,618 references, narrowed to 32 for final analysis. Most studies (n = 18, 56.3%) were conducted in high income countries. Only one study was conducted in Africa; none were conducted in South America or the Western Pacific. Caesarean section was the most studied procedure (n = 20, 54.1%) and major storms were the most studied climate change pressure (n = 14, 37.8%). Conclusion: Overall, the impact of climate change on surgery is understudied. Major specific content gaps include laparotomy procedures; long-term climate pressures (e.g. heat, air pollution); geographic regions in South America, the Western Pacific and Africa; and low income country contexts. Though the existing body of literature is small, current trends can inform future research and policy initiatives in global surgery.

IntroductionThe ability to scale anticipatory postural adjustments (APAs) according to the predicted size of the upcoming movement is reduced with aging. While age-related changes in central set may be one reason for this effect, an individual’s emotional state might also contribute to changes in anticipatory postural control. Therefore, the purpose of this study was to determine whether an altered emotional state, as elicited through postural threat, alters the scaling of APAs during a handle pull movement in young and older adults. It was hypothesized that the presence of postural threat would lead to more homogenous APAs (i.e., less scaling of APAs) across a range of pulling forces.MethodsYoung (n = 23) and older adults (n = 16) stood on top of a force plate that was mounted to a motorized platform. From this position, participants performed a series of handle pull trials without (no threat) or with (threat) the possibility of receiving a postural perturbation in the form of an unpredictable surface translation. Handle pulls were performed at force levels between 50 and 90% of maximum force. For each trial, the magnitude and timing of the APA were quantified from center of pressure (COP) recordings as well as electromyographic (EMG) activity of the soleus and medial gastrocnemius. The scaling of APAs with respect to force exertion was then determined through regression analyses and by comparing APAs during pulls of lower versus higher force.Results and discussionAs evidenced by their smaller slope of the regression line between various dependent measures (i.e., COP velocity, soleus EMG onset latency, and soleus EMG amplitude) and the pulled forces, older adults demonstrated less scaling of APAs than the young. However, increases in arousal, anxiety and fear of falling due to postural threat, only minimally altered the scaling of APAs. Regardless of age, the slope of the regressions for none of the measures were affected by threat while only the soleus and medial gastrocnemius EMG onsets demonstrated significant force × threat interaction effects. These results suggest that the decreased ability to scale APAs with aging is unlikely to be due to changes in emotional state.

The thickness of current sheets is extremely important, especially as it relates to the onset of fast magnetic reconnection. Onset determines how much magnetic free energy can build up in a field before it is explosively released. This has implications for many phenomena on the Sun and throughout the Universe, including the heating of the solar corona. Significant effort has been devoted to the question of whether equilibrium current sheets in realistic geometries have finite or zero thickness. Using a simple force balance analysis, we show why current sheets without a guide field (2D) and with a guide field that is invariant in the guide field direction (2.5D) cannot be in equilibrium if they have both finite thickness and finite length. We then estimate the conditions under which the tension of a curved line-tied guide field can facilitate equilibrium in 3D sheets that are finite in all dimensions. Finally, we argue that some quasi-statically evolving current sheets undergoing slow stressing—e.g., when the coronal magnetic field is subjected to photospheric boundary driving—may reach a critical shear, at which point they lose equilibrium, spontaneously collapse, and reconnect. The critical shear is generally consistent with the heating requirements of solar active regions.

Visible matter is characterised by a single mass scale; namely, the proton mass. The proton’s existence and structure are supposed to be described by quantum chromodynamics (QCD); yet, absent Higgs boson couplings, chromodynamics is scale-invariant. Thus, if the Standard Model is truly a part of the theory of Nature, then the proton mass is an emergent feature of QCD; and emergent hadron mass (EHM) must provide the basic link between theory and observation. Nonperturbative tools are necessary if such connections are to be made; and in this context, we sketch recent progress in the application of continuum Schwinger function methods to an array of related problems in hadron and particle physics. Special emphasis is given to the three pillars of EHM—namely, the running gluon mass, process-independent effective charge, and running quark mass; their role in stabilising QCD; and their measurable expressions in a diverse array of observables.

Abstract Background Cancer risk assessment models are used to support prevention and early detection. However, few models have been developed for head and neck cancer (HNC). Methods A rapid review of Embase and MEDLINE identified n = 3045 articles. Following dual screening, n = 14 studies were included. Quality appraisal using the PROBAST (risk of bias) instrument was conducted, and a narrative synthesis was performed to identify the best performing models in terms of risk factors and designs. Results Six of the 14 models were assessed as “high” quality. Of these, three had high predictive performance achieving area under curve values over 0.8 (0.87–0.89). The common features of these models were their inclusion of predictors carefully tailored to the target population/anatomical subsite and development with external validation. Conclusions Some existing models do possess the potential to identify and stratify those at risk of HNC but there is scope for improvement.

Abstract Using a symmetry-preserving regularisation of a vector $$\times $$ × vector contact interaction (SCI), we complete a systematic treatment of twelve semileptonic transitions with vector meson final states: $$D\rightarrow \rho $$ D → ρ , $$D_{(s)}\rightarrow K^*$$ D ( s ) → K ∗ , $$D_s\rightarrow \phi $$ D s → ϕ , $$B\rightarrow \rho $$ B → ρ , $$B_s\rightarrow K^*$$ B s → K ∗ , $$B_{(s)}\rightarrow D_{(s)}^*$$ B ( s ) → D ( s ) ∗ , $$B_c \rightarrow B_{(s)}^*, J/\psi , D^*$$ B c → B ( s ) ∗ , J / ψ , D ∗ ; and thereby finalise a unified analysis of semileptonic decays of heavy + heavy and heavy + light pseudoscalar mesons to both pseudoscalar and vector meson final states. The analysis is marked by algebraic simplicity, few parameters, and the ability to consistently describe systems from Nambu-Goldstone modes to heavy + heavy mesons. Regarding the behaviour of the transition form factors, the SCI results compare well wherever sound experimental or independent theory analyses are available; hence, the SCI branching fraction predictions should be a reasonable guide. Considering the ratios $$R(D_{(s)}^{(*)})$$ R ( D ( s ) ( ∗ ) ) , $$R(J/\psi )$$ R ( J / ψ ) , $$R(\eta _c)$$ R ( η c ) , whose values are key tests of lepton universality in weak interactions, the SCI values agree with Standard Model predictions. The $$B_{(s)}\rightarrow D_{(s)}^*$$ B ( s ) → D ( s ) ∗ transitions are used to predict the precursor functions that evolve into the universal Isgur–Wise function in the heavy-quark limit, with results that conform with those from other sources where such are available. The study also exposes effects on the transition form factors that flow from interference between emergent hadron mass from the strong interaction and Higgs boson couplings via current-quark masses, including flavour symmetry violation.

IntroductionAlthough pre/pro/postbiotics have become more prevalent in dermatologic and cosmetic fields, the mode of action when topically applied is largely unknown. A multi-omic approach was applied to decipher the impact of the skincare products with pre/postbiotics on skin microbiome and metabolome.MethodsSubjects with dry skin applied a body wash and body lotion with or without pre/postbiotics for 6 weeks. Skin hydration was measured at baseline, 3 and 6 weeks. Skin swabs were collected for 16S rRNA gene sequencing, metagenomics and metabolomics analysis.ResultsSkin hydration significantly increased in both groups. The prebiotic group significantly reduced opportunistic pathogens, e.g., Pseudomonas stutzeri and Sphingomonas anadarae, and increased the commensals, e.g., Staphylococcus equorum, Streptococcus mitis, Halomonas desiderata. Bacterial sugar degradation pathways were enriched in the prebiotic group, while fatty acid biosynthesis pathways were reduced in control. The changes on skin metabolome profiles by the products were more prominent. The prebiotic group performed greater modulation on many clinically-relevant metabolites compared to control. Correlation analysis showed H. desiderata and S. mitis positively correlated with skin hydration, P. stutzeri and S. anadarae negatively correlated with the metabolites that are positively associated with skin hydration improvement.ConclusionThis holistic study supported a hypothesis that the pre/postbiotics increased skin hydration through the modulation of skin microbiome, metabolic pathways and metabolome.

Severe congenital neutropenia caused by jagunal homolog 1 (JAGN1) mutation is a rare condition resulting from maturation arrest secondary to endoplasmic reticulum stress response from impaired neutrophil protein glycosylation. Here, we report a case of a 4-year-old boy who presented with a history of recurrent infections and manifestations, including recurrent intracranial hemorrhage. A review of similar cases reported in the literature indicates that a bleeding diathesis has not been previously described in these patients. We hypothesize that this newly described association of bleeding complications in this patient with JAGN1 mutation is secondary to defective glycosylation in the normal functioning of platelets or clotting factors. Recurrent infections with intracranial hemorrhage, new focal neurologic defects, or altered mental status in a child should warrant a suspicion for this immunodeficiency for the prompt initiation of treatment and prophylaxis for life-threatening infections or trauma.

Original article: https://doi.org/10.17159/sajs.2022/13844 An error appears in the key (but not the data points) in Figure 3: the square symbol representing Sourveld should be depicted in orange, while the circle symbol representing Sweetveld should be depicted in green.

IntroductionPostural threat elicits modifications to standing balance. However, the underlying neural mechanism(s) responsible remain unclear. Shifts in attention focus including directing more attention to balance when threatened may contribute to the balance changes. Sample entropy, a measure of postural sway regularity with lower values reflecting less automatic and more conscious control of balance, may support attention to balance as a mechanism to explain threat-induced balance changes. The main objectives were to investigate the effects of postural threat on sample entropy, and the relationships between threat-induced changes in physiological arousal, perceived anxiety, attention focus, sample entropy, and traditional balance measures. A secondary objective was to explore if biological sex influenced these relationships.MethodsHealthy young adults (63 females, 42 males) stood quietly on a force plate without (No Threat) and with (Threat) the expectation of receiving a postural perturbation (i.e., forward/backward support surface translation). Mean electrodermal activity and anterior–posterior centre of pressure (COP) sample entropy, mean position, root mean square, mean power frequency, and power within low (0–0.05 Hz), medium (0.5–1.8 Hz), and high-frequency (1.8–5 Hz) components were calculated for each trial. Perceived anxiety and attention focus to balance, task objectives, threat-related stimuli, self-regulatory strategies, and task-irrelevant information were rated after each trial.Results and DiscussionSignificant threat effects were observed for all measures, except low-frequency sway. Participants were more physiologically aroused, more anxious, and directed more attention to balance, task objectives, threat-related stimuli, and self-regulatory strategies, and less to task-irrelevant information in the Threat compared to No Threat condition. Participants also increased sample entropy, leaned further forward, and increased the amplitude and frequency of COP displacements, including medium and high-frequency sway, when threatened. Males and females responded in the same way when threatened, except males had significantly larger threat-induced increases in attention to balance and high-frequency sway. A combination of sex and threat-induced changes in physiological arousal, perceived anxiety, and attention focus accounted for threat-induced changes in specific traditional balance measures, but not sample entropy. Increased sample entropy when threatened may reflect a shift to more automatic control. Directing more conscious control to balance when threatened may act to constrain these threat-induced automatic changes to balance.

Abstract Launched in May 2012 as part of the New Therapeutic Uses program, the National Center for Advancing Translational Sciences (NCATS)’ National Institutes of Health (NIH)‐Industry Partnerships initiative fostered collaboration between pharmaceutical companies and the biomedical research community to advance therapeutic development. Over the 10‐year life of the initiative, the industry partners included: AstraZeneca; AbbVie (formerly Abbott); Bristol‐Myers Squibb; Eli Lilly and Company; GlaxoSmithKline; Janssen Pharmaceutical Research & Development, L.L.C.; Pfizer; Sanofi; and Mereo (out licensed assets). The initiative provided researchers at academic medical centers with a rare opportunity to propose clinical trials to test ideas for new therapeutic uses for a selection of clinic‐ready and often previously proprietary experimental pharmaceutical assets that were provided by industry partners. Here, we describe the process by which collaborations between pharmaceutical companies with viable experimental assets and academic researchers with ideas for new uses of those assets were established; and how NCATS/NIH funding supported not only phase I and II clinical trials as well as any nonclinical studies needed before testing in a new patient population, it also provided an opportunity for testing innovative outcome measures for proof‐of‐concept trials. Although the program did not demonstrate improved success rates for phase II clinical trials, this collaboration model leverages the strengths of each party and with a focus toward evaluating an innovative outcome measure, could be used to reduce patient burden and trial costs, and improve patient engagement.

Biodiversity and ecosystem functions are deteriorating worldwide, and there is an urgent need to reverse these declines and set ecosystems on a path to recovery. Effective monitoring, including a fit for purpose indicator framework, is essential to track progress towards targets but, as yet there is no universal framework that delivers timely data on biodiversity and ecosystem change. Ecosystem integrity is a unifying concept that refers to the capacity of an ecosystem to be resilient to natural or anthropogenic perturbations, and to maintain characteristic species composition, structure, functioning and self-organisation over time within a natural range of variability. Using a case study which can be generalised to international contexts, we implement and test a new global standard for the assessment, monitoring and ranking of ecosystem integrity of active sand dunes in Aotearoa New Zealand.