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Purpose: This study aims to examine predisposing anatomic factors and subsequent post-decompression functional outcomes among high-intensity athletes with thoracic outlet syndrome (TOS). Materials and Methods : A single-institution retrospective review was performed on a prospective database of patients with TOS from 2018 to 2023 who had undergone operative decompression for TOS. Demographics, TOS characteristics, predisposing anatomy, operative details, and postoperative outcomes were examined. The primary outcome was postoperative return to sport. Secondary outcomes included vascular patency. Results : A total of 13 patients who were engaged in high-demand athletic activity at the time of their diagnosis were included. Diagnoses included 8 (62%) patients with venous TOS, 4 (31%) patients with neurogenic TOS, and 1 (8%) patient with arterial TOS. Mixed vascular and neurogenic TOS was observed in 3 (23%) patients. The mean age of the cohort was 30 years. Abnormal scalene structure was observed in 12 (92%) patients, and abnormal bone structures were noted in 4 (27%) patients; 2 (15%) with cervical ribs and 3 (23%) patients with clavicular abnormalities. Prior ipsilateral upper extremity trauma was reported in 4 (27%) patients. Significant joint hypermobility was observed in 8 (62%) patients with a median Beighton score of 6. Supraclavicular cervical and/or first rib resection with scalenectomy was performed in all patients. One case of postoperative pneumothorax was treated non-operatively. Ten (77%) patients returned to sport. Duplex ultrasonography showed subclavian vein patency in all 8 patients with venous TOS and wide patency with no drop in perfusion indices in the patient with arterial TOS. Conclusion : Athletes with TOS who required operative intervention had a high incidence of musculoskeletal aberrations and joint hypermobility. Supraclavicular decompression was associated with a high success rate, with overall good functional outcomes and good likelihood of patients returning to preoperative high-intensity athletics.

In addition to tapping data from users’ behavioral surplus, by drawing on generative adversarial networks, data for artificial intelligence is now increasingly being generated through artificial intelligence. With this new method of producing data synthetically, the data economy is not only shifting from “data collection” to “data generation.” Synthetic data is also being employed to address some of the most pressing ethical concerns around artificial intelligence. It thereby comes with the sociotechnical imaginary that social problems can be cut out of artificial intelligence, separating training data from real persons. In response to this technical solutionism, this commentary aims to initiate a critical debate about synthetic data that goes beyond misuse scenarios such as the use of generative adversarial networks to create deep fakes or dark patterns. Instead, on a more general level, we seek to complicate the idea of “solving,” i.e., “closing” and thus “silencing” the ethico-political debates for which synthetic data is supposed to be a solution by showing how synthetic data itself is political. Drawing on the complex connections between recent uses of synthetic data and public debates about artificial intelligence, we therefore propose to consider and analyze synthetic data not only as a technical device but as a discursive one as well. To this end, we shed light on their relationship to three pillars that we see associated with them (a) algorithmic bias, (b) privacy, (c) platform economy.

Abstract Advancements in comprehending myelodysplastic neoplasms (MDS) have unfolded significantly in recent years, elucidating a myriad of cellular and molecular underpinnings integral to disease progression. While molecular inclusions into prognostic models have substantively advanced risk stratification, recent revelations have emphasized the pivotal role of immune dysregulation within the bone marrow milieu during MDS evolution. Nonetheless, immunotherapy for MDS has not experienced breakthroughs seen in other malignancies, partly attributable to the absence of an immune classification that could stratify patients toward optimally targeted immunotherapeutic approaches. A pivotal obstacle to establishing “immune classes” among MDS patients is the absence of validated accepted immune panels suitable for routine application in clinical laboratories. In response, we formed International Integrative Innovative Immunology for MDS (i4MDS), a consortium of multidisciplinary experts, and created the following recommendations for standardized methodologies to monitor immune responses in MDS. A central goal of i4MDS is the development of an immune score that could be incorporated into current clinical risk stratification models. This position paper first consolidates current knowledge on MDS immunology. Subsequently, in collaboration with clinical and laboratory specialists, we introduce flow cytometry panels and cytokine assays, meticulously devised for clinical laboratories, aiming to monitor the immune status of MDS patients, evaluating both immune fitness and identifying potential immune “risk factors.” By amalgamating this immunological characterization data and molecular data, we aim to enhance patient stratification, identify predictive markers for treatment responsiveness, and accelerate the development of systems immunology tools and innovative immunotherapies.

Clubroot caused by the protist Plasmodiophora brassicae is a major disease affecting cultivated Brassicaceae. Using a combination of quantitative trait locus (QTL) fine mapping, CRISPR-Cas9 validation, and extensive analyses of DNA sequence and methylation patterns, we revealed that the two adjacent neighboring NLR (nucleotide-binding and leucine-rich repeat) genes AT5G47260 and AT5G47280 cooperate in controlling broad-spectrum quantitative partial resistance to the root pathogen P. brassicae in Arabidopsis and that they are epigenetically regulated. The variation in DNA methylation is not associated with any nucleotide variation or any transposable element presence/absence variants and is stably inherited. Variations in DNA methylation at the Pb-At5.2 QTL are widespread across Arabidopsis accessions and correlate negatively with variations in expression of the two genes. Our study demonstrates that natural, stable, and transgenerationally inherited epigenetic variations can play an important role in shaping resistance to plant pathogens by modulating the expression of immune receptors.

Abstract Metastability of many-body quantum states is rare and still poorly understood. An exceptional example is the low-temperature metallic state of the layered dichalcogenide 1T-TaS2 in which electronic order is frozen after external excitation. Here we visualize the microscopic dynamics of injected charges in the metastable state using a multiple-tip scanning tunnelling microscope. We observe non-thermal formation of a metastable network of dislocations interconnected by domain walls, that leads to macroscopic robustness of the state to external thermal perturbations, such as small applied currents. With higher currents, we observe annihilation of dislocations following topological rules, accompanied with a change of macroscopic electrical resistance. Modelling carrier injection into a Wigner crystal reveals the origin of formation of fractionalized, topologically entangled networks, which defines the spatial fabric through which single particle excitations propagate. The possibility of manipulating topological entanglement of such networks suggests the way forward in the search for elusive metastable states in quantum many body systems.

Abstract Theories with compact extra dimensions can exhibit a vacuum instability known as a bubble of nothing. These decay modes can be obstructed if the internal manifold is stabilized by fluxes, or if it carries Wilson lines for background gauge fields, or if the instanton is incompatible with the spin structure. In each of these cases the decay can proceed by adding dynamical charged membranes or gauge fields. We give a general, bottom-up procedure for constructing approximate bubble of nothing solutions in models with internal spheres stabilized by flux and study the influence of the brane tension on the tunneling exponent, finding two branches of solutions that merge at a minimal superextremal value of the tension. In the case of Wilson operators and incompatible fermions, the relevant bubble is shown to be the Euclidean Reissner-Nordstrom black hole, and the ordinary decay exponent is modified by 1/g 2 effects. We examine the Dirac operator on this background and comment on the relevance for models of supergravity with gauged R-symmetry.

Heliostat instance segmentation (HST-IS) is a crucial component of the heliostat tracking system at Heliogen’s Lancaster test facility. The system estimates the mirror normal of each heliostat by performing a nonlinear optimization-based fitting strategy using approximations of the non-shaded, non-blocked sunlit pixels on each heliostat, and the tracking system uses these estimates to improve performance. HST-IS is fundamentally challenging due to variability in lighting conditions and heliostat size relative to the capturing camera. Deep learning-based convolutional neural networks (CNN) have emerged in recent years by demonstrating noteworthy precision in tasks such as object recognition, detection, and segmentation. CNN-based methods offer a robust augmentation to HST-IS methods as they capture a context-less hierarchy of image features. In this study, we developed deep learning models to automatically segment heliostat instances from elevated images taken from the field. We study various image parameters and architectural customizations to optimize for scalability, robustness, and accuracy in our predictions. We perform robust evaluations of our best model to quantify gaps between model development and real-world deployment and provide evidence for utility in the field.

Accessory liver lobes are rare. We present the rare case of torsion of an accessory liver lobe in a neonate.

Abstract In August 2022, a novel henipavirus (HNV) named Langya virus (LayV) was isolated from patients with severe pneumonic disease in China. This virus is closely related to Mòjiāng virus (MojV), and both are divergent from the bat-borne HNV members, Nipah (NiV) and Hendra (HeV) viruses. The spillover of LayV is the first instance of a HNV zoonosis to humans outside of NiV and HeV, highlighting the continuing threat this genus poses to human health. In this work, we determine the prefusion structures of MojV and LayV F proteins via cryogenic electron microscopy to 2.66 and 3.37 Å, respectively. We show that despite sequence divergence from NiV, the F proteins adopt an overall similar structure but are antigenically distinct as they do not react to known antibodies or sera. Glycoproteomic analysis revealed that while LayV F is less glycosylated than NiV F, it contains a glycan that shields a site of vulnerability previously identified for NiV. These findings explain the distinct antigenic profile of LayV and MojV F, despite the extent to which they are otherwise structurally similar to NiV. Our results carry implications for broad-spectrum HNV vaccines and therapeutics, and indicate an antigenic, yet not structural, divergence from prototypical HNVs.

Mutations in GBA1, encoding the lysosomal acid β-glucosidase (GCase), cause neuronopathic Gaucher disease (nGD) and promote Parkinson disease (PD). The mutations on GBA1 include deletion and missense mutations that are pathological and lead to GCase deficiency in Gaucher disease. Both nGD and PD lack disease-modifying treatments and are critical unmet medical needs. In this study, we evaluated a cell therapy treatment using mouse iPSC-derived neural precursor cells (NPCs) engineered to overexpress GCase (termed hGBA1-NPCs). The hGBA1-NPCs secreted GCase that was taken up by adjacent mouse Gba−/− neurons and improved GCase activity, reduced GCase substrate accumulation, and improved mitochondrial function. Short-term in vivo effects were evaluated in 9H/PS-NA mice, an nGD mouse model exhibiting neuropathology and α-synuclein aggregation, the typical PD phenotypes. Intravenously administrated hGBA1-NPCs were engrafted throughout the brain and differentiated into neural lineages. GCase activity was increased in various brain regions of treated 9H/PS-NA mice. Compared with vehicle, hGBA1-NPC-transplanted mice showed ∼50% reduction of α-synuclein aggregates in the substantia nigra, significant reduction of neuroinflammation and neurodegeneration in the regions of NPC migration, and increased expression of neurotrophic factors that support neural cell function. Together, these results support the therapeutic benefit of intravenous delivery of iPSC-derived NPCs overexpressing GCase in mitigating nGD and PD phenotypes and establish the feasibility of combined cell and gene therapy for GBA1-associated PD.

Apicomplexan parasites exhibit tremendous diversity in much of their fundamental cell biology, but study of these organisms using light microscopy is often hindered by their small size. Ultrastructural expansion microscopy (U-ExM) is a microscopy preparation method that physically expands the sample by ~4.5×. Here, we apply U-ExM to the human malaria parasite Plasmodium falciparum during the asexual blood stage of its lifecycle to understand how this parasite is organized in three dimensions. Using a combination of dye-conjugated reagents and immunostaining, we have cataloged 13 different P. falciparum structures or organelles across the intraerythrocytic development of this parasite and made multiple observations about fundamental parasite cell biology. We describe that the outer centriolar plaque and its associated proteins anchor the nucleus to the parasite plasma membrane during mitosis. Furthermore, the rhoptries, Golgi, basal complex, and inner membrane complex, which form around this anchoring site while nuclei are still dividing, are concurrently segregated and maintain an association to the outer centriolar plaque until the start of segmentation. We also show that the mitochondrion and apicoplast undergo sequential fission events while maintaining an association with the outer centriolar plaque during cytokinesis. Collectively, this study represents the most detailed ultrastructural analysis of P. falciparum during its intraerythrocytic development to date and sheds light on multiple poorly understood aspects of its organelle biogenesis and fundamental cell biology.

Summary: Myelin sheath in the central nervous system (CNS) is essential for efficient action potential conduction. Microglia, the macrophages in the CNS, are suggested to regulate myelin development. However, the specific involvement of microglia in initial myelination is yet to be elucidated. Here, first, by culturing neural stem cells, we demonstrated that myelin sheath formation only occurred in the presence of a microglia-conditioned medium. Furthermore, the absence of C1q, a microglia-derived factor, resulted in myelination failure in the neural stem cell culture. Additionally, adding native human C1q protein was sufficient to induce myelination in vitro. Finally, in the C1q conditional knockout mouse model (C1qaFL/FL: Cx3cr1CreER), C1q deficiency prior to the onset of myelination led to reduced myelin thickness and elevated g-ratio during initial myelination. This study uncovers the pivotal role of microglia-derived C1q in developmental myelination and could potentially pave the way for new therapeutic strategies for treating demyelinating diseases.

Papillary fibroelastoma (PFE) is a rare, often benign, tumor originating typically in the endocardium and valves, with a preference for the left side of the heart. Although PFEs can appear asymptomatic, in the setting of embolization, they can lead to stroke, acute limb ischemia, and/or mesenteric ischemia. Rarely, PFEs can originate from the pulmonary valve, with the potential for embolic showering into the pulmonary artery, leading to potential right-sided heart outflow obstruction. Treatment has been open surgery in most cases, although treatment of right-sided heart masses with extracorporeal circulatory support extraction systems have been described. Recently, large bore suction thrombectomy devices have become available, typically used for cases of venous thromboembolism. In the present report, we describe a case of a symptomatic infected PFE treated by percutaneous suction thrombectomy using the Inari FlowTriever system (Inari Medical).

Antecedentes: la escala de sentido de capacidad, originalmente validada en universitarios franceses (Drouin & Costalat-Founeau, 2020), mide la representación subjetiva de las personas sobre sus capacidades y percepciones respecto a lo que otros piensan de ellas. El objetivo de este estudio es adaptar la escala para universitarios de Lima, Perú y analizar sus propiedades psicométricas. Método: 516 estudiantes de una universidad privada completaron el cuestionario. Se empleó análisis factorial y correlaciones para precisar evidencias de validez. Se utilizó el alfa de Cronbach y omega de McDonald para evaluar la fiabilidad. Resultados: contrariamente a la estructura original de 2 factores, nuestros resultados sugirieron una solución de factor único que explicó el 52% de la varianza; los ítems tenían cargas elevadas. Se confirmó el modelo mediante un ajuste óptimo (χ2 = 362.84; df = 35; p < .001; CFI = .99; TLI = .98; SRMR = .06; RMSEA = .10). Se encontró una correlación positiva moderada con afecto positivo y florecimiento, así como una correlación negativa moderada con afecto negativo. No hubo diferencias significativas por sexo, nivel o tipo de carrera. Conclusiones: la nueva versión de la escala muestra evidencias de validez y confiabilidad adecuada (α = .88) en estudiantes de una universidad privada de Lima, Perú.

BackgroundPolymorphous low-grade neuroepithelial tumor of the young (PLNTY) is a recently described entity that can mimic high-grade glioma (HGG) in histologic and molecular features; however, factors predicting aggressive behavior in these tumors are unclear.MethodsWe present an indolent neuroepithelial neoplasm in a 59-year-old female with imaging initially suggestive of HGG, and a series of adult patients with HGG harboring FGFR3-TACC3 fusions are also presented for comparison.ResultsPathology in the case patient revealed low-grade cytomorphology, microcalcifications, unusual neovascularization, and a low proliferation index. The lesion was diffusely CD34+ and harbored an FGFR3-TACC3 fusion and TERT promoter mutation. A diagnosis of PLNTY was therefore favored and the patient was observed with no progression at 15-month follow-up. In patients with HGG with FGFR3-TACC3 fusions, molecular findings included IDH-wildtype status, absence of 1p19q codeletion, CDKN2A loss, TERT promoter mutations and lack of MGMT promoter methylation. These patients demonstrated a median 15-month overall survival and a 6-month progression-free survival.ConclusionPLNTY is a rare low-grade entity that can display characteristics of HGG, particularly in adults. Presence of FGFR3-TACC3 fusions and other high-grade features should raise concern for a more malignant precursor lesion when a diagnosis of PLNTY is considered.

Summary: Background: We previously demonstrated the safety and immunogenicity of an MF59-adjuvanted COVID-19 vaccine based on the SARS-CoV-2 spike glycoprotein stabilised in a pre-fusion conformation by a molecular clamp using HIV-1 glycoprotein 41 sequences. Here, we describe 12-month results in adults aged 18–55 years and ≥56 years. Methods: Phase 1, double-blind, placebo-controlled trial conducted in Australia (July 2020–December 2021; ClinicalTrials.gov NCT04495933; active, not recruiting). Healthy adults (Part 1: 18–55 years; Part 2: ≥56 years) received two doses of placebo, 5 μg, 15 μg, or 45 μg vaccine, or one 45 μg dose of vaccine followed by placebo (Part 1 only), 28 days apart (n = 216; 24 per group). Safety, humoral immunogenicity (including against virus variants), and cellular immunogenicity were assessed to day 394 (12 months after second dose). Effects of subsequent COVID-19 vaccination on humoral responses were examined. Findings: All two-dose vaccine regimens were well tolerated and elicited strong antigen-specific and neutralising humoral responses, and CD4+ T-cell responses, by day 43 in younger and older adults, although cellular responses were lower in older adults. Humoral responses waned by day 209 but were boosted in those receiving authorised vaccines. Neutralising activity against Delta and Omicron variants was present but lower than against the Wuhan strain. Cross-reactivity in HIV diagnostic tests declined over time but remained detectable in most participants. Interpretation: The SARS-CoV-2 molecular clamp vaccine is well tolerated and evokes robust immune responses in adults of all ages. Although the HIV glycoprotein 41-based molecular clamp is not being progressed, the clamp concept represents a viable platform for vaccine development. Funding: This study was funded by the Coalition for Epidemic Preparedness Innovations, the National Health and Medical Research Council of Australia, and the Queensland Government.

This paper addresses the need for retrofit approaches that simultaneously improve heat integration through heat exchangers and heat pumps considering process restrictions and an economic analysis framework. For this purpose, the Heat Pump Bridge Analysis method is extended to include the targeting of economic break-even points for heat pumping and the investigation of different modelling levels. For evaluation purposes, the case study of an electroplating process is used where retrofit safety-relevant process restrictions must be considered. The results include two heat recovery systems with one or two heat exchangers according to this grey box approach. The concept with only one heat recovery exchanger fulfils the economic requirements for full supply by heat recovery and heat pumps with an electricity-to-reference price ratio of 1.8 compared to the concept with two heat recovery exchangers or the white box approach, which ignores the process restrictions.

Rationale & Objective: Patients with chronic kidney disease (CKD) have dysfunctional high-density lipoprotein (HDL) particles that lack cardioprotective properties; altered lipid composition may be associated with these changes. To investigate HDL lipids as potential cardiovascular risk factors in CKD, we tested the associations of HDL ceramides, sphingomyelins, and phosphatidylcholines with mortality. Study Design: We leveraged data from a longitudinal prospective cohort of participants with CKD. Setting & Participants: We included participants aged greater than 21 years with CKD, excluding those on maintenance dialysis or with prior kidney transplant. Exposure: HDL particles were isolated using density gradient ultracentrifugation. We quantified the relative abundance of HDL ceramides, sphingomyelins, and phosphatidylcholines via liquid chromatography tandem mass spectrometry (LC-MS/MS). Outcomes: Our primary outcome was all-cause mortality. Analytical Approach: We tested associations using Cox regressions adjusted for demographics, comorbid conditions, laboratory values, medication use, and highly correlated lipids with opposed effects, controlling for multiple comparisons with false discovery rates (FDR). Results: There were 168 deaths over a median follow-up of 6.12 years (interquartile range, 3.71-9.32). After adjustment, relative abundance of HDL ceramides (HR, 1.22 per standard deviation; 95% CI, 1.06-1.39), sphingomyelins with long fatty acids (HR, 1.44; 95% CI, 1.05-1.98), and saturated and monounsaturated phosphatidylcholines (HR, 1.22; 95% CI, 1.06-1.41) were significantly associated with increased risk of all-cause mortality (FDR

Abstract High-fidelity and rapid readout of a qubit state is key to quantum computing and communication, and it is a prerequisite for quantum error correction. We present a readout scheme for superconducting qubits that combines two microwave techniques: applying a shelving technique to the qubit that reduces the contribution of decay error during readout, and a two-tone excitation of the readout resonator to distinguish among qubit populations in higher energy levels. Using a machine-learning algorithm to post-process the two-tone measurement results further improves the qubit-state assignment fidelity. We perform single-shot frequency-multiplexed qubit readout, with a 140 ns readout time, and demonstrate 99.5% assignment fidelity for two-state readout and 96.9% for three-state readout–without using a quantum-limited amplifier.

Testicular cancer is a common cancer among reproductive age men, with the necessary treatment options having varying impacts on fertility and sexual function. Treatment begins with orchiectomy and is often followed by a combination of chemotherapy, radiation, and/or retroperitoneal lymph node dissection, which have different effects on spermatogenesis, gonadotropin levels, and ejaculation. Alkylating agents such as cisplatin are commonly used for testicular cancer and are amongst the most spermatotoxic chemotherapeutic agents. Radiation poses gonadotoxic effects despite gonadal shielding due to a scatter effect. Suprahilar and bilateral retroperitoneal lymph node dissections can cause ejaculatory dysfunction. Options to preserve fertility vary by pubertal status. While the standard recommendation for post pubertal patients is cryopreservation, prepubertal patients rely on experimental protocols for cryopreservation of germ cells with stem cell capabilities, with the hope that these cells will one day be stimulated to produce sperm. These topics are reviewed to give insight into current literature around fertility in testicular cancer survivorship and determine best possible practices in fertility preservation among patients.

Abstract The coronavirus disease 2019 (COVID-19) has developed into a pandemic. Data-driven techniques can be used to inform and guide public health decision- and policy-makers. In generalizing the spread of a virus over a large area, such as a province, it must be assumed that the transmission occurs as a stochastic process. It is therefore very difficult for policy and decision makers to understand and visualize the location specific dynamics of the virus on a more granular level. A primary concern is exposing local virus hot-spots, in order to inform and implement non-pharmaceutical interventions. A hot-spot is defined as an area experiencing exponential growth relative to the generalised growth of the pandemic. This paper uses the first and second waves of the COVID-19 epidemic in Gauteng Province, South Africa, as a case study. The study aims provide a data-driven methodology and comprehensive case study to expose location specific virus dynamics within a given area. The methodology uses an unsupervised Gaussian Mixture model to cluster cases at a desired granularity. This is combined with an epidemiological analysis to quantify each cluster’s severity, progression and whether it can be defined as a hot-spot.

Abstract While Machine Learning (ML) models have been increasingly applied to a range of histopathology tasks, there has been little emphasis on characterizing these models and contrasting them with human experts. We present a detailed empirical analysis comparing expert neuropathologists and ML models at predicting IDH mutation status in H&E-stained histology slides of infiltrating gliomas, both independently and synergistically. We find that errors made by neuropathologists and ML models trained using the TCGA dataset are distinct, representing modest agreement between predictions (human-vs.-human κ = 0.656; human-vs.-ML model κ = 0.598). While no ML model surpassed human performance on an independent institutional test dataset (human AUC = 0.901, max ML AUC = 0.881), a hybrid model aggregating human and ML predictions demonstrates predictive performance comparable to the consensus of two expert neuropathologists (hybrid classifier AUC = 0.921 vs. two-neuropathologist consensus AUC = 0.920). We also show that models trained at different levels of magnification exhibit different types of errors, supporting the value of aggregation across spatial scales in the ML approach. Finally, we present a detailed interpretation of our multi-scale ML ensemble model which reveals that predictions are driven by human-identifiable features at the patch-level.

Abstract In this work we present a new class of N $$ \mathcal{N} $$ = 1 supersymmetric confining gauge theories, with strikingly simple infrared theories that descend from intricate interconnected networks of product gauge groups. A diagram of the gauge groups and the charged matter content of the ultraviolet theory has the structure of a triangular lattice, with SU(N) or SU(3N) gauge groups at each of the vertices, connected by bifundamental chiral superfields. This structure admits a U(1) R conserving superpotential with marginal (trilinear) operators. With the introduction of this superpotential, the SU(3N) and SU(N) gauge groups confine: in the far infrared limit of the supersymmetric theory, the relevant degrees of freedom are gauge invariant “mesons” and “baryons.” In this paper we show how the properties of the infrared degrees of freedom depend on the topology and shape of the moose/quiver “lattice” of the original gauge theory. Between the local structure of the moose lattice at higher energies, and the boundary dependence that emerges in the infrared, the 4d moose lattice theory reproduces features of a 6d spacetime with two compact dimensions. We investigate various deformations of the theory, and propose some phenomenological applications for BSM models.

Abstract Since the introduction of integrated histological and molecular diagnoses by the 2016 World Health Organization (WHO) Classification of Tumors of the Nervous System, an increasing number of molecular markers have been found to have prognostic significance in infiltrating gliomas, many of which have now become incorporated as diagnostic criteria in the 2021 WHO Classification. This has increased the applicability of targeted-next generation sequencing in the diagnostic work-up of neuropathology specimens and in addition, raises the question of whether targeted sequencing can, in practice, reliably replace older, more traditional diagnostic methods such as immunohistochemistry and fluorescence in-situ hybridization. Here, we demonstrate that the Oncomine Cancer Gene Mutation Panel v2 assay targeted-next generation sequencing panel for solid tumors is not only superior to IHC in detecting mutation in IDH1/2 and TP53 but can also predict 1p/19q co-deletion with high sensitivity and specificity relative to fluorescence in-situ hybridization by looking at average copy number of genes sequenced on 1p, 1q, 19p, and 19q. Along with detecting the same molecular data obtained from older methods, targeted-next generation sequencing with an RNA sequencing component provides additional information regarding the presence of RNA based alterations that have diagnostic significance and possible therapeutic implications. From this work, we advocate for expanded use of targeted-next generation sequencing over more traditional methods for the detection of important molecular alterations as a part of the standard diagnostic work up for CNS neoplasms.

Abstract There is growing policy interest in identifying contexts that cultivate self-regulation. Doing so often entails comparing groups of individuals (e.g., from different schools). We show that self-report questionnaires—the most prevalent modality for assessing self-regulation—are prone to reference bias, defined as systematic error arising from differences in the implicit standards by which individuals evaluate behavior. In three studies, adolescents (N = 229,685) whose peers performed better academically rated themselves lower in self-regulation and held higher standards for self-regulation. This effect was not observed for task measures of self-regulation and led to paradoxical predictions of college persistence 6 years later. These findings suggest that standards for self-regulation vary by social group, limiting the policy applications of self-report questionnaires.

Introduction: The scope of primary care increasingly encompasses patient behavioral health problems, manifest typically through depression screening and treatment. Although substance use is highly comorbid with depression, it is not commonly identified and addressed in the primary care context. This study aimed to examine the association between the likelihood of substance use disorder and increased depression severity, both cross-sectionally and longitudinally, among a sample of 2409 patients from 41 geographically dispersed and diverse primary care clinics across the US. Methods: This is secondary analysis of data obtained from a multi-site parent study of integrated behavioral health in primary care, among patients with both chronic medical and behavioral health conditions. Patient reported outcome surveys were gathered from patients at 3 time points. The primary care practices were blind to which of their patients completed surveys. Included were standardized measures of depression severity (Patient Health Questionnaire—9) [PHQ-9] and substance use disorder likelihood (Global Appraisal of Individual Needs—Short Screener [GSS]). Results: Four percent of the study population screened positive for substance use disorder. PHQ-9 scores indicated depression among 43% of all patients. There was a significant association between the likelihood of substance use disorder and depression initially, at a 9-month follow-up, and over time. These associations remained significant after adjusting for age, gender, race, ethnicity, education, income, and other patient and contextual characteristics. Conclusions: The findings suggest that substance use disorder is associated with depression severity cross-sectionally and over time. Primary care clinics and health systems might consider implementing substance use screening in addition to the more common screening strategies for depression. Especially for patients with severe depression or those who do not respond to frontline depression treatments, the undermining presence of a substance use disorder should be explored.

Lot feeding of cattle has gained momentum in recent years to improve efficiency in meeting market demands for high quality protein. Concurrently, societal concern for the welfare of animals raised in intensive farming systems has increased. Thus, the reporting of animal health and welfare measures is a key goal for the Australian cattle lot-fed industry. Although feedlots vary in location, climate, capacity, cattle genotype, and feeding programs, many welfare concerns are applicable across the industry. Despite this, no recognised standardised animal welfare assessment protocol exists for the Australian lot-fed industry. This study aimed to identify relevant measures to develop an assessment protocol, by identifying key welfare issues and their relevant measures, considering the validity, reliability, and practicality of each when applied to the feedlot context. An advisory model was derived after reviewing the relevant literature and five international protocols for the assessment of beef cattle (Welfare Quality®, AssureWel, US Beef Quality Assurance assessment tool, Canadian Feedlot Animal Care Assessment program, and an Australian Live Export industry protocol), followed by stakeholder consultation. A total of 109 measures were evaluated, with 99 environmental-, management-, resource- and animal-based measures being proposed. Piloting of the protocol on commercial feedlots will enable further refinement and validation, to provide an evidence-based, practical protocol to facilitate standardised monitoring of cattle welfare. Such a protocol could promote continued advances in animal welfare at a feedlot level and support a sustainable industry by addressing societal concerns.