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In this work, we studied the free-carrier transport properties and space-charge formation/polarization in a CdZnTe bar-shaped radiation detector using the Laser-Induced Transient Current technique. We found out that a steady-state space charge ranging from 8 × 108 to 2.1 × 109 cm−3 is formed throughout the detector at about 0.5 s following biasing. The measured current waveforms were modeled by Monte Carlo simulations after taking into account the electric and weighting fields inside the detector and shielding box. Modeling of the unpolarized waveforms revealed an exceptionally high electron mobility-lifetime product μ e τ e ≥ 0.095 c m 2 V − 1 . The observed formation of positive space charge in the biased detector and linear scaling of the current waveform shapes on applied bias revealed that the detector polarization is attributed to carrier injection at the anode. Measurements in pulsed and DC bias in modified electrode geometry proved the surface-charge formation. [ABSTRACT FROM AUTHOR]

Background: Stakeholder engagement plays a vital role in driving advancements in product development. This imperative now extends to the healthcare domain, driven by the scarcity of healthcare professionals and the pressing demand for effective solutions. Through the application of design thinking and co-design methodologies, this study endeavours to promote comprehensive stakeholder involvement, creating streamlined processes and adaptable templates geared towards fostering innovative solutions for tele-emergency medicine. Methods: In this study design thinking and co-design methods are developed, adapted, and tested, to create effective tools and demonstrate their application. This is part of a process involving stakeholders and lead users to develop a telemedicine solution for emergency medical services. This research is descriptive in kind, offering a transparent and holistic portrayal of the co-design process. The rural region of Burgenland in Austria was chosen for this study, with the challenges of its weak infrastructure offering valuable insights. The tools were tested in co-design workshops, with the participants continuously observed by the research team. Results: Seventeen healthcare professionals, emergency medical technicians and academics participated in a co-design process to develop a telemedicine solution for emergency medical services. The results section presents practical co-creative healthcare innovation tools and templates that have been shown to facilitate the co-design process. Conclusions: The study developed and applied co-design elements for the creation of a prototype concept for telemedicine in emergency medicine and offers valuable insights for similar projects involving diverse stakeholders. It shows that structured co-design activities help all stakeholders to jointly create solutions that meet the overall needs. [ABSTRACT FROM AUTHOR]

Older age (≥ 65 years) is associated with impaired responses to influenza vaccination, leading to the preferential recommendation of MF59-adjuvanted (MF59Flu) or high-dose (HDFlu) influenza vaccines for this age group in the United States. Herein, we characterized transcriptomic profiles of CD4+ T cells isolated from 234 recipients (≥ 65 years) of either MF59Flu or HDFlu vaccine, prior to vaccination and 28 days thereafter. We identified 412 and 645 differentially expressed genes (DEGs) in CD4+ T cells of older adults after receiving MF59Flu and HDFlu, respectively. DEGs in CD4+ T cells of MF59Flu recipients were enriched in 14 KEGG pathways, all of which were downregulated. DEGs in CD4+ T cells of HDFlu recipients were enriched in 11 upregulated pathways and 20 downregulated pathways. CD4+ T cells in both vaccine groups shared 50 upregulated genes and 75 downregulated genes, all of which were enriched in 7 KEGG pathways. The remaining 287 and 520 DEGs were specifically associated with MF59Flu and HDFlu, respectively. Unexpectedly, none of these DEGs was significantly correlated with influenza A/H3N2-specific HAI titers, suggesting these DEGs at the individual level may have a limited role in protection against influenza. Our findings emphasize the need for further investigation into other factors influencing immunity against influenza in older adults. [ABSTRACT FROM AUTHOR]

From a game of darts to neurorehabilitation, the ability to explore and fine tune our movements is critical for success. Past work has shown that exploratory motor behaviour in response to reinforcement (reward) feedback is closely linked with the basal ganglia, while movement corrections in response to error feedback is commonly attributed to the cerebellum. While our past work has shown these processes are dissociable during adaptation, it is unknown how they uniquely impact exploratory behaviour. Moreover, converging neuroanatomical evidence shows direct and indirect connections between the basal ganglia and cerebellum, suggesting that there is an interaction between reinforcement-based and error-based neural processes. Here we examine the unique roles and interaction between reinforcement-based and error-based processes on sensorimotor exploration in a neurotypical population. We also recruited individuals with Parkinson's disease to gain mechanistic insight into the role of the basal ganglia and associated reinforcement pathways in sensorimotor exploration. Across three reaching experiments, participants were given either reinforcement feedback, error feedback, or simultaneously both reinforcement & error feedback during a sensorimotor task that encouraged exploration. Our reaching results, a re-analysis of a previous gait experiment, and our model suggests that in isolation, reinforcement-based and error-based processes respectively boost and suppress exploration. When acting in concert, we found that reinforcement-based and error-based processes interact by mutually opposing one another. Finally, we found that those with Parkinson's disease had decreased exploration when receiving reinforcement feedback, supporting the notion that compromised reinforcement-based processes reduces the ability to explore new motor actions. Understanding the unique and interacting roles of reinforcement-based and error-based processes may help to inform neurorehabilitation paradigms where it is important to discover new and successful motor actions. Author summary: Reinforcement-based and error-based processes play a pivotal role in regulating our movements. Converging neuroanatomical evidence show interconnected reinforcement-based and error-based neural circuits. Yet is unclear how reinforcement-based and error-based processes interact to influence sensorimotor behavior. In our past work we showed that reinforcement-based and error-based processes are dissociable. Building on this work, here we show that these process can also interact to influence trial-by-trial sensorimotor behaviour. [ABSTRACT FROM AUTHOR]

Purpose: Childhood cancer survivors (CCS) have an increased risk of developing late chronic diseases, which can be influenced by the cancer type and its treatment. These chronic diseases can be severe and disabling, typically emerging years to decades after treatment. These deficits negatively impact quality of life, intelligence quotient, and memory. This study investigated how much the cancer type and treatment could affect the neurological hospitalisations in the French Childhood Cancer Survivors Study (FCCSS). Methods: We included 5579 childhood cancer survivors (CCS), diagnosed with solid tumours or lymphoma between 1945 and 2000, treated before 2001 and below the age of 21 years at initial treatment. The follow-up period was from 2006 to 2018. Hospitalisation data were obtained by linkage with the National Health Data System. We calculated the relative hospitalisation rate (RHRs) and absolute excess rate (AERs). Multivariable analyses were conducted using a Generalized Linear Model (GLM) with a Poisson distribution to estimate the association between neurological hospitalisation and patient characteristics. The expected number of hospitalisations served as an offset to compare the risk for FCCSS survivors with that of the reference population. Risk estimates were reported as relative risk (RR) with 95% confidence intervals. Results: The hospitalisation rate for CCS was 114.2 per 10,000 person-years (PY), compared to 48.4 in the reference population. The highest hospitalisation rates were observed for epilepsy (AER = 27.1 per 10000 PY, 95%CI: 23.5–31.2 and RHR = 5.1, 95%CI 4.4–5.7). In multivariable analyses, central nervous system (CNS) tumours survivors had the highest relative risk (RR) of hospitalisation (RR = 9.4, 95%CI: 6.7–13.1) followed by neuroblastoma survivors (RR = 2.5, 95%CI: 1.7–3.7). In the whole population, survivors who received radiation to the head and neck had a significantly higher risk of hospitalisation (RR = 3.9, 95%CI: 3.3–4.7) compared to those who did not receive radiotherapy. Conclusions: Head and neck irradiation was identified as a strong risk factor for hospitalisation. This underlines the importance of implementing specific neurologic surveillance programs for at-risk individuals. [ABSTRACT FROM AUTHOR]

Unmyelinated C-fibers constitute the vast majority of axons in peripheral nerves and play key roles in homeostasis and signaling pain. However, little is known about their ion channel expression, which controls their firing properties. Also, because of their small diameters (~ 1 μm), it has not been possible to characterize their membrane properties using voltage clamp. We developed a novel library of isoform-specific ion channel models to serve as the basis functions of our C-fiber models. We then developed a particle swarm optimization (PSO) framework that used the isoform-specific ion channel models to reverse engineer C-fiber membrane properties from measured autonomic and cutaneous C-fiber conduction responses. Our C-fiber models reproduced experimental conduction velocity, chronaxie, action potential duration, intracellular threshold, and paired pulse recovery cycle. The models also matched experimental activity-dependent slowing, a property not included in model optimization. We found that simple conduction responses, characterizing the action potential, were controlled by similar membrane properties in both the autonomic and cutaneous C-fiber models, but complicated conduction response, characterizing the afterpotenials, were controlled by differential membrane properties. The unmyelinated C-fiber models constitute important tools to study autonomic signaling, assess the mechanisms of pain, and design bioelectronic devices. Additionally, the novel reverse engineering approach can be applied to generate models of other neurons where voltage clamp data are not available. Author summary: Computational models of axons play an important role in studying neural signaling and developing therapeutic electrical stimulation devices. While robust models of large myelinated axons exist, models of unmyelinated C-fibers do not adequately reproduce experimental conduction responses. C-fibers constitute the vast majority of axons in peripheral nerves and play key roles in homeostasis and signaling pain, but because of their small diameters (~ 1 μm), it has not been possible to characterize their membrane properties using voltage clamp. We used particle swarm optimization and a novel library of isoform-specific ion channel models to reverse engineer C-fiber membrane properties from measured autonomic and cutaneous C-fiber conduction responses. Our C-fiber models reproduced experimental conduction velocity, chronaxie, action potential duration, intracellular threshold, paired pulse recovery cycle, and activity dependent slowing. The models constitute important tools to study autonomic signaling, assess the mechanisms of pain, and design bioelectronic devices. Additionally, the novel reverse engineering approach can be applied to generate models of other neurons where voltage clamp data are not available. [ABSTRACT FROM AUTHOR]

Several small genetic association studies have been conducted for atypical femur fracture (AFF) without replication of results. We assessed previously implicated and novel genes associated with AFFs in a larger set of unrelated AFF cases using whole exome sequencing (WES). We performed gene-based association analysis on 139 European AFF cases and 196 controls matched for bisphosphonate use. We tested all rare, protein-altering variants using both candidate gene and hypothesis-free approaches. In the latter, genes suggestively associated with AFFs (uncorrected p-values <.01) were investigated in a Swedish whole-genome sequencing replication study and assessed in 46 non-European cases. In the candidate gene analysis, PLOD2 showed a suggestive signal. The hypothesis-free approach revealed 10 tentative associations, with XRN2, SORD, and PLOD2 being the most likely candidates for AFF. XRN2 and PLOD2 showed consistent direction of effect estimates in the replication analysis, albeit not statistically significant. Three SNPs associated with SORD expression according to the GTEx portal were in linkage disequilibrium (R2 ≥ 0.2) with an SNP previously reported in a genome-wide association study of AFF. The prevalence of carriers of variants for both PLOD2 and SORD was higher in Asian versus European cases. While we did not identify genes enriched for damaging variants, we found suggestive evidence of a role for XRN2, PLOD2, and SORD, which requires further investigation. Our findings indicate that genetic factors responsible for AFFs are not widely shared among AFF cases. The study provides a stepping-stone for future larger genetic studies of AFF. Lay Summary: We investigated the genetic factors contributing to atypical femur fractures (AFF), which are rare and unusual fractures in the thigh bone. These fractures are related to the use of bisphosphonates (BP), which are prescribed to prevent fractures caused by osteoporosis. Previous studies suggested potential genetic links, but their findings were not confirmed in larger groups. To address this, we analyzed genetic data from 139 European individuals with AFF and 196 individuals without AFF, all of whom used BP, using a genetic technique called whole exome sequencing. Our results suggested three genes—XRN2, SORD, and PLOD2—might be linked to AFF, although the evidence was not conclusive. Importantly, our findings suggest that AFF may be caused by different genes in different individuals. A much larger sample size is now needed to fully understand the genetic architecture of AFF. These findings may guide future research into the genetic causes of AFF. [ABSTRACT FROM AUTHOR]

Spatially and temporally accurate termination of axon outgrowth, a process called axon termination, is required for efficient, precise nervous system construction and wiring. The mechanosensory neurons that sense low-threshold mechanical stimulation or gentle touch have proven exceptionally valuable for studying axon termination over the past 40 years. In this Review, we discuss progress made in deciphering the molecular and genetic mechanisms that govern axon termination in touch receptor neurons. Findings across model organisms, including Caenorhabditis elegans, Drosophila, zebrafish and mice, have revealed that complex signaling is required for termination with conserved principles and players beginning to surface. A key emerging theme is that axon termination is mediated by complex signaling networks that include ubiquitin ligase signaling hubs, kinase cascades, transcription factors, guidance/adhesion receptors and growth factors. Here, we begin a discussion about how these signaling networks could represent termination codes that trigger cessation of axon outgrowth in different species and types of mechanosensory neurons. [ABSTRACT FROM AUTHOR]

Purpose: Determine if the SPIKES method was associated with less distress and more compassion than current modes of delivering negative pregnancy test results to patients undergoing in vitro fertilization. Methods: Twenty-seven nurses from two centers were randomized to use the modified SPIKES script or continue their standard of care; 136 patients with a negative hCG following embryo transfer were included. SPIKES nurses received 1 h of training by a study psychologist; nurses in the control group were instructed to deliver the news as done previously. Patients who underwent embryo transfer and received a call by a participating nurse with a negative test result received an email invitation on the following day. Results: Control patients reported significantly less distress than SPIKES patients; 33% of SPIKES patients reported that they had felt "extremely sad," compared to 15.2% of the control patients (p = 0.01). Perceived compassion did not differ between the groups (all p ≥ 0.22). Conclusion: Patients who received a negative pregnancy test result from the nurses who received a brief training and a script on how to deliver bad news via the modified SPIKES protocol reported significantly more distress than patients receiving negative results from nurses utilizing their standard of care. It is unclear whether a modified SPIKES method to deliver negative pregnancy test results will benefit patients undergoing in vitro fertilization. Trial registration: Clinical trials.gov NCT04917445. [ABSTRACT FROM AUTHOR]

Whereas hackathons are widespread within and outside academia and have been argued to be a valid pedagogical method for teaching interdisciplinarity, no detailed frameworks or methods are available for conceptualizing and organizing educational hackathons, i.e., hackathons dedicated to best achieving pedagogic objectives. This paper is dedicated to introducing EDUCational Hackathons for learning how to solve Interdisciplinary Challenges (EDUCHIC) through: (1) defining the fundamental principles for framing an activity as an EDUCHIC, integrating principles from pedagogical methods, hackathon organization, and interdisciplinarity processes; (2) describing general properties that EDUCHIC possess as a consequence of the interaction of the fundamental principles; (3) developing operational guidelines for streamlining the practical organization of EDUCHIC, including an exhaustive end‐to‐end process covering all the steps for organizing EDUCHIC and practical frames for carrying the key decisions to be made in this process; and (4) a demonstration of these guidelines through illustrating their application for organizing a concrete EDUCHIC. [ABSTRACT FROM AUTHOR]

Diffusion-weighted imaging (DWI) is the primary method to investigate macro- and microstructure of neural white matter in vivo. DWI can be used to identify and characterize individual-specific white matter bundles, enabling precise analyses on hypothesis-driven connections in the brain and bridging the relationships between brain structure, function, and behavior. However, cortical endpoints of bundles may span larger areas than what a researcher is interested in, challenging presumptions that bundles are specifically tied to certain brain functions. Functional MRI (fMRI) can be integrated to further refine bundles such that they are restricted to functionally-defined cortical regions. Analyzing properties of these Functional Sub-Bundles (FSuB) increases precision and interpretability of results when studying neural connections supporting specific tasks. Several parameters of DWI and fMRI analyses, ranging from data acquisition to processing, can impact the efficacy of integrating functional and diffusion MRI. Here, we discuss the applications of the FSuB approach, suggest best practices for acquiring and processing neuroimaging data towards this end, and introduce the FSuB-Extractor, a flexible open-source software for creating FSuBs. We demonstrate our processing code and the FSuB-Extractor on an openly-available dataset, the Natural Scenes Dataset. [ABSTRACT FROM AUTHOR]

Vestibular problems are frequent reasons for primary care consultations. However, there is considerable uncertainty about the prevalence and cost of vestibular disorders. Despite ambiguous effectiveness data, the histamine analogue betahistine is widely and almost exclusively used for treatment of vertigo. Prescription of betahistine can, therefore, be used as a proxy estimate for prevalence. We used openly available claims data from the French health insurance data warehouse, defining annual prevalence of vestibular disease as the number of people who received at least one betahistine prescription that year. Dosage and pack size of each prescribed formulation were extracted to calculate the sum of betahistine in mg and the Defined Daily Dose (DDD) for age and sex strata and in total. To estimate the relative impact of one landmark trial, the BEMED study, we compared prescriptions from the years 2014/2015 to prescriptions in 2019/2022. A total of 735,121 (2014), 694,705 (2015), 614,431 (2019), and 562,476 (2022) persons filled in a prescription of betahistine. Patients were predominantly older and female. Average amount dispensed per year and per person increased from 4422.54 mg during the pre-BEMED period to 4736.90 mg during the post-BEMED period. DDD decreased from 130 Mio per year in 2014/2015 to 116 Mio per year in 2019/2022. Total costs for betahistine decreased by 42% from 21,615,037 Euro in 2014 to 12,894,249 Euro in 2022. Vestibular disease is frequent in France and has a relevant impact on population health. Despite conflicting clinical evidence, betahistine continues to be prescribed widely in medical practice. [ABSTRACT FROM AUTHOR]

SUMMARY: Phytohormones are essential signaling molecules regulating various processes in growth, development, and stress responses. Genetic and molecular studies, especially using Arabidopsis thaliana (Arabidopsis), have discovered many important players involved in hormone perception, signal transduction, transport, and metabolism. Phytohormone signaling pathways are extensively interconnected with other endogenous and environmental stimuli. However, our knowledge of the huge and complex molecular network governed by a hormone remains limited. Here we report a global overview of downstream events of an abscisic acid (ABA) receptor, REGULATORY COMPONENTS OF ABA RECEPTOR (RCAR) 6 (also known as PYRABACTIN RESISTANCE 1 [PYR1]‐LIKE [PYL] 12), by integrating phosphoproteomic, proteomic and metabolite profiles. Our data suggest that the RCAR6 overexpression constitutively decreases the protein levels of its coreceptors, namely clade A protein phosphatases of type 2C, and activates sucrose non‐fermenting‐1 (SNF1)‐related protein kinase 1 (SnRK1) and SnRK2, the central regulators of energy and ABA signaling pathways. Furthermore, several enzymes in sugar metabolism were differentially phosphorylated and expressed in the RCAR6 line, and the metabolite profile revealed altered accumulations of several organic acids and amino acids. These results indicate that energy‐ and water‐saving mechanisms mediated by the SnRK1 and SnRK2 kinases, respectively, are under the control of the ABA receptor‐coreceptor complexes. Significance Statement: Phosphoproteomic, proteomic, and metabolite profiles of the Arabidopsis overexpressing an abscisic acid (ABA) receptor were integrated, providing a global overview of the complex network governed by a hormone. The overproduction of an ABA receptor caused the decreased protein levels of its coreceptor phosphatases, activating the central regulatory kinases of energy and stress signaling. [ABSTRACT FROM AUTHOR]

Advancing the mechanistic understanding of absence epilepsy is crucial for developing new therapeutics, especially for patients unresponsive to current treatments. Utilizing a recently developed mouse model of absence epilepsy carrying the BK gain-of-function channelopathy D434G, here we report that attenuating the burst firing of midline thalamus (MLT) neurons effectively prevents absence seizures. We found that enhanced BK channel activity in the BK-D434G MLT neurons promotes synchronized bursting during the ictal phase of absence seizures. Modulating MLT neurons through pharmacological reagents, optogenetic stimulation, or deep brain stimulation effectively attenuates burst firing, leading to reduced absence seizure frequency and increased vigilance. Additionally, enhancing vigilance by amphetamine, a stimulant medication, or physical perturbation also effectively suppresses MLT bursting and prevents absence seizures. These findings suggest that the MLT is a promising target for clinical interventions. Our diverse approaches offer valuable insights for developing next generation therapeutics to treat absence epilepsy. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Recruitment challenges in people with and without Down syndrome (DS) can delay research progress and risk sample bias. This study identified and quantified differences in research attitudes across populations of research enrollment decision‐makers for individuals with and without DS. METHODS: We performed analyses using data from two registries: the University of California, Irvine Consent‐to‐Contact (C2C) Registry and DS‐Connect. The former represented a sample of non‐DS decision‐makers (N = 4818), while for the latter, we excluded individuals with DS, leaving a population of DS family decision‐makers (N = 976). We assessed scores on the Research Attitudes Questionnaire (RAQ) between DS and non‐DS decision‐makers. We compared total RAQ scores using linear regression and assessed item‐level RAQ differences using proportional odds regression. RESULTS: Mean total RAQ scores were not statistically different between decision‐makers in the two registries, after adjusting for age, sex, race and ethnicity, education, and the coronavirus disease 2019 (COVID‐19) time frame (Est. Diff = 0.11, 95% confidence interval [CI]: ‐0.22, 0.43; p = 0.531). However, in a pre‐specified analysis, we did find evidence of differential attitudes on item‐level RAQ scores. Specifically, decision‐makers for participants with DS had increased odds of a more favorable response to the question of responsibility to help others (DS vs. non‐DS: odds ratio [OR] = 1.26, 95% CI: 1.08, 1.48) and decreased odds of a more favorable response to the question regarding the belief that medical research would find cures for major diseases during their lifetime (DS vs. non‐DS: OR = 0.77, 95% CI: 0.66, 0.90). DISCUSSION: Our findings provide insights for researchers to develop strategies for recruiting individuals with and without DS into clinical research. The observed item‐level differences warrant further investigation to instruct precise recruitment strategies. Highlights: Research attitudes between decision‐makers for individuals with Down syndrome (DS) and decision‐makers without DS were observed to be similar on average.Item‐level differences in research attitudes were observed to differ for DS and non‐DS decision‐makers.These results can help facilitate precise recruitment strategies for populations with DS. [ABSTRACT FROM AUTHOR]

This document, published in Acta Neuropathologica Communications, discusses the identification of a subtype of diffuse midline glioma (DMG) called H3K27/MAPKinase co-altered. The study analyzes a cohort of 182 pediatric and adult cases of DMG, H3K27-altered and identifies 30 tumors with a loss of ATRX expression. The authors provide clinical, histopathological, and molecular data on these tumors and suggest that the loss of ATRX expression may be a potential diagnostic tool for identifying DMG, H3K27/MAPK co-altered. The study highlights the distinct features of this subtype and emphasizes the importance of integrating clinical, radiological, histopathological, and molecular results for an accurate diagnosis. [Extracted from the article]

Background: Multiple sclerosis (MS) is a clinically and biologically heterogenous disease with currently unpredictable progression and relapse. After the development and success of neurofilament as a cerebrospinal fluid (CSF) biomarker, there is reinvigorated interest in identifying other markers of or contributors to disease. The objective of this study is to probe the predictive potential of a panel of brain-enriched proteins on MS disease progression and subtype. Methods: This study includes 40 individuals with MS and 14 headache controls. The MS cohort consists of 20 relapsing remitting (RR) and 20 primary progressive (PP) patients. The CSF of all individuals was analyzed for 63 brain enriched proteins using a method of liquid-chromatography tandem mass spectrometry. Wilcoxon rank sum test, Kruskal-Wallis one-way ANOVA, logistic regression, and Pearson correlation were used to refine the list of candidates by comparing relative protein concentrations as well as relation to known imaging and molecular biomarkers. Results: We report 30 proteins with some relevance to disease, clinical subtype, or severity. Strikingly, we observed widespread protein depletion in the disease CSF as compared to control. We identified numerous markers of relapsing disease, including KLK6 (kallikrein 6, OR = 0.367, p < 0.05), which may be driven by active disease as defined by MRI enhancing lesions. Other oligodendrocyte-enriched proteins also appeared at reduced levels in relapsing disease, namely CNDP1 (carnosine dipeptidase 1), LINGO1 (leucine rich repeat and Immunoglobin-like domain-containing protein 1), MAG (myelin associated glycoprotein), and MOG (myelin oligodendrocyte glycoprotein). Finally, we identified three proteins—CNDP1, APLP1 (amyloid beta precursor like protein 1), and OLFM1 (olfactomedin 1)—that were statistically different in relapsing vs. progressive disease raising the potential for use as an early biomarker to discriminate clinical subtype. Conclusions: We illustrate the utility of targeted mass spectrometry in generating potential targets for future biomarker studies and highlight reductions in brain-enriched proteins as markers of the relapsing remitting disease stage. [ABSTRACT FROM AUTHOR]

Hertwig's rule states that cells divide along their longest axis, usually driven by forces acting on the mitotic spindle. Here, we show that in contrast to this rule, microtubule-based pulling forces in early Caenorhabditis elegans embryos align the spindle with the short axis of the cell. We combine theory with experiments to reveal that in order to correct this misalignment, inward forces generated by the constricting cytokinetic ring rotate the entire cell until the spindle is aligned with the cell's long axis. Experiments with slightly compressed mouse zygotes indicate that this cytokinetic ring-driven mechanism of ensuring Hertwig's rule is general for cells capable of rotating inside a confining shell, a scenario that applies to early cell divisions of many systems. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to develop a high-resolution whole-brain multiparametric quantitative MRI approach for simultaneous mapping of myelin-water fraction (MWF), T1, T2, and proton-density (PD), all within a clinically feasible scan time. Methods: We developed 3D visualization of short transverse relaxation time component (ViSTa)-MRF, which combined ViSTa technique with MR fingerprinting (MRF), to achieve high-fidelity whole-brain MWF and T1/T2/PD mapping on a clinical 3T scanner. To achieve fast acquisition and memory-efficient reconstruction, the ViSTa-MRF sequence leverages an optimized 3D tiny-golden-angle-shuffling spiral-projection acquisition and joint spatial-temporal subspace reconstruction with optimized preconditioning algorithm. With the proposed ViSTa-MRF approach, high-fidelity direct MWF mapping was achieved without a need for multicompartment fitting that could introduce bias and/or noise from additional assumptions or priors. Results: The in vivo results demonstrate the effectiveness of the proposed acquisition and reconstruction framework to provide fast multi-parametric mapping with high SNR and good quality. The in vivo results of 1mm- and 0.66 mm-isotropic resolution datasets indicate that the MWF values measured by the proposed method are consistent with standard ViSTa results that are 30× slower with lower SNR. Furthermore, we applied the proposed method to enable 5-min whole-brain 1 mm-iso assessment of MWF and T1/T2/PD mappings for infant brain development and for post-mortem brain samples. Conclusions: In this work, we have developed a 3D ViSTa-MRF technique that enables the acquisition of whole-brain MWF, quantitative T1, T2, and PD maps at 1 and 0.66mm isotropic resolution in 5 and 15min, respectively. This advancement allows for quantitative investigations of myelination changes in the brain. [ABSTRACT FROM AUTHOR]

Objective: Despite recent attention to cognitive impairment in essential tremor, few studies examine rates of conversion to diagnoses of mild cognitive impairment and dementia. Development of dementia in essential tremor is associated with loss of functional ability and a doubling of mortality rate. This prospective, longitudinal study comprehensively reports the prevalence and incidence of, and the annual rates of conversion to, mild cognitive impairment and dementia in an essential tremor cohort. Methods: Patients underwent detailed cognitive assessments and were assigned diagnoses of normal cognition, mild cognitive impairment, or dementia. There were 222 patients at baseline (mean age = 79.3 ± 9.7 years), and 177 patients participated in follow‐up evaluations at 18, 36, 54, and 72 months (mean years of observation = 5.1 ± 1.7). Data were compared to those of historical controls and Parkinson disease patients. Results: The cumulative prevalence of dementia and average annual conversion rate of mild cognitive impairment to dementia were 18.5% and 12.2%, nearly three times higher than rates in the general population, and approximately one half the magnitude of those reported for Parkinson disease patients. The cumulative prevalence of mild cognitive impairment (26.6%) was almost double that of the general population, but less than that in Parkinson disease populations. Interpretation: We present the most complete exposition of the longitudinal trajectory of cognitive impairment in an essential tremor cohort yet presented. The prevalence of and conversion rates to dementia in essential tremor fall between those associated with the natural course of aging and the more pronounced rates observed in Parkinson disease. ANN NEUROL 2024;95:1193–1204 [ABSTRACT FROM AUTHOR]

During the corona pandemic, youths were confronted with substantial challenges and in urgent need of information on how to prevent mental health problems. This experimental pre-post-follow-up study examined the efficacy and reception of an innovative website (www.corona-und-du.info) containing evidence-based information for youths on how to overcome psychological distress during the pandemic. 34 youths aged 11–18 years were presented domains of the website in the laboratory. Standardized questionnaires were applied to assess changes in knowledge, the reception of the website, and changes in behavioral intention to seek psychological help. For all content domains, we found a significant knowledge gain with large effect sizes from pre to post, and from pre to follow-up. The reception of the website was very positive, and participants indicated increased intention to seek psychological support when needed. The results constitute an important basis for future attempts to promote mental health information in youths in times of crisis. [ABSTRACT FROM AUTHOR]

Background: Neither radiological phenotypic characteristics nor reconstruction CT scan has been used to study the early anatomical disruption of the cranial bone in children with the so-called idiopathic type of West syndrome. Material and Methods: The basic diagnostic measures and the classical antiepileptic treatments were applied to these children in accordance with the conventional protocol of investigations and treatment for children with West syndrome. Boys from three unrelated families were given the diagnosis of the idiopathic type of West syndrome, aged 7, 10 and 12 years old. Parents underwent extensive clinical examinations. Three parents (age range of 28–41 year) were included in this study. All children showed a history of intellectual disabilities, cryptogenic epileptic spasms and fragmented hypsarrhythmia. These children and their parents were referred to our orthopedic departments because of variable skeletal deformities. Variable forms of skeletal deformities were the motive for the families to seek orthopedic advice. A constellation of flat foot, torticollis and early-onset osteoarthritis were observed by the family doctor. Apparently, and from the first clinical session in our practice, we felt that all these children are manifesting variable forms of abnormal craniofacial contour. Thereby, we immediately performed detailed cranial radiological phenotypic characterization of every affected child, as well as the siblings and parents, and all were enrolled in this study. All affected children underwent whole-exome sequence analysis. Results: The craniofacial phenotype of all children revealed apparent developmental anatomical disruption of the cranial bones. Palpation of the skull bones showed unusual palpable bony ridges along different sutural locations. A 7-year-old child showed abnormal bulging over the sagittal suture, associated with bilateral bony ridges over the squamosal sutures. AP skull radiograph of a 7-year-old boy with West syndrome showed facial asymmetry with early closure of the metopic suture, and other sutures seemed ill-defined. A 3D reconstruction CT scan of the skull showed early closure of the metopic suture. Another 3D reconstruction CT scan of the skull while the patient was in flexion showed early closure of the squamosal sutures, pressing the brain contents upward, causing the development of a prominent bulge at the top of the mid-sagittal suture. A reformatted 3D reconstruction CT scan confirmed the bilateral closure of the squamosal suture. Examination of the parents revealed a similar skull radiographic abnormality in his mother. A 3D reformatted frontal cranial CT of a 35-year-old mother showed early closure of the metopic and sagittal sutures, causing a mid-sagittal bony bulge. A 10-year-old boy showed an extremely narrow frontal area, facial asymmetry and a well palpable ridge over the lambdoid sutures. A 3D axial reconstruction CT scan of a 10-year-old boy with West syndrome illustrated the asymmetry of the posterior cranial bones along the lambdoid sutures. Interestingly, his 28-year-old mother has been a client at the department of spine surgery since she was 14 years old. A 3D reconstruction CT scan of the mother showed a noticeable bony ridge extending from the metopic suture upwards to involve the sagittal suture (red arrow heads). The black arrow shows a well demarcated bony ridge over the squamosal suture. A 3D reconstruction CT scan of the skull and spine showed the thick bony ridge of the metopic and the anterior sagittal as well as bilateral involvement of the squamosal, causing apparent anterior narrowing of the craniofacial contour. Note the lumbar scoliosis. A 12-year-old boy showed brachycephaly. A lateral skull radiograph of a 12-year-old boy with West syndrome showed premature sutural fusion, begetting an abnormal growth pattern, resulting in cranial deformity. The nature of the deformity depends on which sutures are involved, the time of onset and the sequence in which individual sutures fuse. In this child, brachycephalic secondary to craniosynostosis, which occurred because of bilateral early ossification of the coronal sutures, led to bi-coronal craniosynostosis. Thickened frontal bones and an ossified interclinoid ligament of the sella turcica were encountered. The lateral skull radiograph of a 38-year-old mother with a history of poor schooling achievements showed a very similar cranial contour of brachycephaly, thickening of the frontal bones and massive ossification of the clinoid ligament of the sella turcica. Maternal history revealed a history of multiple spontaneous miscarriages in the first trimester of more than five times. Investigating his parents revealed a brachycephalic mother with borderline intelligence. We affirm that the pattern of inheritance in the three boys was compatible with the X-linked recessive pattern of inheritance. Whole-exome sequencing showed non-definite phenotype/genotype correlation. Conclusions: The aim of this study was sixfold: firstly, to refute the common usage of the term idiopathic; secondly, we feel that it could be possible that West syndrome is a symptom complex rather than a separate diagnostic entity; thirdly, to further detect the genetic carrier, we explored the connection between the cranial bones in children with West syndrome with what has been clinically observed in their parents; fourthly, the early life anatomical disruptions of the cranial bones among these children seem to be heterogeneous; fifthly, it shows that the progressive deceleration in the development of this group of children is highly connected to the progressive closure of the cranial sutures; sixthly, we affirm that our findings are novel. [ABSTRACT FROM AUTHOR]

Plants exposed to incidences of excessive temperatures activate heat-stress responses to cope with the physiological challenge and stimulate long-term acclimation1,2. The mechanism that senses cellular temperature for inducing thermotolerance is still unclear3. Here we show that TWA1 is a temperature-sensing transcriptional co-regulator that is needed for basal and acquired thermotolerance in Arabidopsis thaliana. At elevated temperatures, TWA1 changes its conformation and allows physical interaction with JASMONATE-ASSOCIATED MYC-LIKE (JAM) transcription factors and TOPLESS (TPL) and TOPLESS-RELATED (TPR) proteins for repressor complex assembly. TWA1 is a predicted intrinsically disordered protein that has a key thermosensory role functioning through an amino-terminal highly variable region. At elevated temperatures, TWA1 accumulates in nuclear subdomains, and physical interactions with JAM2 and TPL appear to be restricted to these nuclear subdomains. The transcriptional upregulation of the heat shock transcription factor A2 (HSFA2) and heat shock proteins depended on TWA1, and TWA1 orthologues provided different temperature thresholds, consistent with the sensor function in early signalling of heat stress. The identification of the plant thermosensors offers a molecular tool for adjusting thermal acclimation responses of crops by breeding and biotechnology, and a sensitive temperature switch for thermogenetics.TWA1 is a temperature-sensing transcriptional co-regulator that is needed for basal and acquired thermotolerance in Arabidopsis thaliana. [ABSTRACT FROM AUTHOR]

A better understanding of the materials' fundamental physical processes is necessary to push hybrid perovskite photovoltaic devices towards their theoretical limits. The role of the perovskite grain boundaries is essential to optimise the system thoroughly. The influence of the perovskite grain size and crystal orientation on physical properties and their resulting photovoltaic performance is examined. We develop a novel, straightforward synthesis approach that yields crystals of a similar size but allows the tuning of their orientation to either the (200) or (002) facet alignment parallel to the substrate by manipulating dimethyl sulfoxide (DMSO) and tetrahydrothiophene-1-oxide (THTO) ratios. This decouples crystal orientation from grain size, allowing the study of charge carrier mobility, found to be improved with larger grain sizes, highlighting the importance of minimising crystal disorder to achieve efficient devices. However, devices incorporating crystals with the (200) facet exhibit an s-shape in the current density–voltage curve when standard scan rates are used, which typically signals an energetic interfacial barrier. Using the drift-diffusion simulations, we attribute this to slower-moving ions (mobility of 0.37 × 10−10 cm2 V−1 s−1) in combination with a lower density of mobile ions. This counterintuitive result highlights that reducing ion migration does not necessarily minimise hysteresis. [ABSTRACT FROM AUTHOR]

Background: The choice of a hospital should be based on individual need and accessibility. For maternity hospitals, this includes known or expected risk factors, the geographic accessibility and level of care provided by the hospital. This study aims to identify factors influencing hospital choice with the aim to analyze if and how many deliveries are conducted in a risk-appropriate and accessible setting in Bavaria, Germany. Methods: This is a cross-sectional secondary data analysis based on all first births in Bavaria (2015-18) provided by the Bavarian Quality Assurance Institute for Medical Care. Information on the mother and on the hospital were included. The Bavarian Index of Multiple Deprivation 2010 was used to account for area-level socioeconomic differences. Multiple logistic regression models were used to estimate the strength of association of the predicting factors and to adjust for confounding. Results: We included 195,087 births. Distances to perinatal centers were longer than to other hospitals (16 km vs. 12 km). 10% of women with documented risk pregnancies did not deliver in a perinatal center. Regressions showed that higher age (OR 1.03; 1.02–1.03 95%-CI) and risk pregnancy (OR 1.44; 1.41–1.47 95%-CI) were associated with choosing a perinatal center. The distances travelled show high regional variation with a strong urban-rural divide. Conclusion: In a health system with free choice of hospitals, many women chose a hospital close to home and/or according to their risks. However, this is not the case for 10% of mothers, a group that would benefit from more coordinated care. [ABSTRACT FROM AUTHOR]

Bark beetle outbreaks damage forests and kill trees worldwide, but many aspects of their dynamics remain unexplained. Our aim was to identify predictors for individual tree deaths within the small (0.7 km2) Plešné Lake catchment in the Šumava National Park in southwestern Czechia. Within this area, >60,000 trees were geo-referenced and categorized from ten aerial images (20 cm spatial resolution) between 2000 and 2015. For each year for which aerial images were available, we calculated tree densities of different categories and diameters. Tree height was evaluated by means of LiDAR in two terrestrial campaigns (2010 and 2011). A machine learning technique was then used to evaluate the most important variables. The resulting relationships were largely nonlinear and differed among years; however, individual trait tree height proved to be the most influential variable in each year. Higher trees were more likely to have died during either the undisturbed phase (2000 and 2003), the disturbed phase (2005–2011), or the recovery phase (2013). Our results indicate that salvage logging may not be the most effective measure for protecting trees in small catchments. [ABSTRACT FROM AUTHOR]

Valley Fever (VF), caused by fungi in the genus Coccidioides, is a prevalent disease in southwestern and western parts of the United States that affects both humans and animals, such as dogs. Although the immune responses to infection with Coccidioides spp. are not fully characterized, antibody-detection assays are used in conjunction with clinical presentation and radiologic findings to aid in the diagnosis of VF. These assays often use Complement Fixation (CF) and Tube Precipitin (TP) antigens as the main targets of IgG and IgM reactivity, respectively. Our group previously reported evidence of over 800 genes expressed at the protein level in C. posadasii. However, antibody reactivity to the majority of these proteins has never been explored. Using a new, high-throughput screening technology, the Nucleic Acid Programmable Protein Array (NAPPA), we screened serum specimens from dogs against 708 of these previously identified proteins for IgG reactivity. Serum from three separate groups of dogs was analyzed and revealed a small panel of proteins to be further characterized for immuno-reactivity. In addition to CF/CTS1 antigen, sera from most infected dogs showed antibody reactivity to endo-1,3-betaglucanase, peroxisomal matrix protein, and another novel reactive protein, CPSG_05795. These antigens may provide additional targets to aid in antibody-based diagnostics. [ABSTRACT FROM AUTHOR]

Aim: This retrospective cohort study aimed to assess the utility of maternal C‐reactive protein (CRP) and leukocyte levels in predicting neonatal sepsis after preterm premature rupture of membranes (pPROM). Methods: We conducted a retrospective cohort study (2009–2021), encompassing preterm infants born ≤29 + 6 weeks of gestation following pPROM. The primary outcome was early‐onset neonatal sepsis within the initial 72 h of life. Results: We analysed data from 706 patients with a median gestational age at pPROM of 25.1 weeks and a median gestational age at birth of 26.4 weeks. Overall survival rate was 86.1%, with 65.7% survival without severe morbidities. These rates were significantly worse in preterm infants with sepsis. Maternal CRP and leukocyte levels correlated significantly with neonatal infection markers and sepsis. However, their predictive values, correlation coefficients, and area under the curve values were generally low. Using maternal CRP ≥2 mg/dL to predict neonatal sepsis yielded a positive predictive value of 18.5%, negative predictive value of 91.5%, AUC of 0.589, 45.5% sensitivity, and 74.5% specificity. Conclusion: Maternal CRP and leukocyte levels were ineffective as a tool for predicting early‐onset neonatal sepsis following early pPROM. Consequently, these biomarkers lack the reliability required for clinical decision‐making in this context. [ABSTRACT FROM AUTHOR]

Essential in halting the COVID-19 pandemic caused by SARS-CoV-2, it is crucial to have stable, effective, and easy-to-manufacture vaccines. We developed a potential vaccine using a tobacco mosaic virus (TMV) epitope display model presenting peptides derived from the SARS-CoV-2 spike protein. The TMV-epitope fusions in laboratory tests demonstrated binding to the SARS-CoV-2 polyclonal antibodies. The fusion constructs maintained critical epitopes of the SARS-CoV-2 spike protein, and two in particular spanned regions of the receptor-binding domain that have mutated in the more recent SARS-CoV-2 variants. This would allow for the rapid modification of vaccines in response to changes in circulating variants. The TMV-peptide fusion constructs also remained stable for over 28 days when stored at temperatures between −20 and 37 °C, an ideal property when targeting developing countries. Immunogenicity studies conducted on BALB/c mice elicited robust antibody responses against SARS-CoV-2. A strong IFNγ response was also observed in immunized mice. Three of the six TMV-peptide fusion constructs produced virus-neutralizing titers, as measured with a pseudovirus neutralization assay. These TMV-peptide fusion constructs can be combined to make a multivalent vaccine that could be adapted to meet changing virus variants. These findings demonstrate the development of a stable COVID-19 vaccine candidate by combining SARS-CoV-2 spike protein-derived peptides presented on the surface of a TMV nanoparticle. [ABSTRACT FROM AUTHOR]

For 49 years, the right to abortion was taken for granted—inhaled by every girl, every woman—by all people assigned female at birth in the United States. This right no longer exists. In 2022, with the Dobbs v. Jackson decision, the Supreme Court removed federal protection for the legal right to abortion and therefore women's agency over their bodies. This paper will contextualize abortion as part of a continuum that encompasses gender, motherhood and the meaning of reproduction and reproductive rights as sociocultural and intrapsychic phenomena. The expectation that mature female-bodied people are child-desiring women persists and is not conceptualized as optional. It is the original choice women do not have. The next choice women no longer have, if they become pregnant, is whether or not to continue a pregnancy. The Dobbs decision means the cultural reinstatement of female de-sexualization, along with the suffocating and silencing of agency—a negation of women's voices, desire, power and subjectivity—a recipe for psychological destabilization. Personal and clinical material will illustrate these points. [ABSTRACT FROM AUTHOR]

Objective: The anterior loop, the mandibular incisive canal, and the lingual symphyseal foramen are important structures in the anterior mandible. The purpose of this study was to assess the prevalence of these structures using CBCT. Method and materials: A total of 170 projections were analyzed in different sectional planes. The study analyzed the prevalence and extension of the anterior loop and the prevalence of both the mandibular incisive canal and the lingual symphyseal foramen by using the GALAXIS software by Sirona. Results: In 98.2 % (n = 167) a lingual symphyseal foramen was detected. An anterior loop was present in 31.2% (n = 53) with statistically significant higher detection rate in younger patients (P = .001). The median length was 1.26 mm (range 0.53-3.70 mm). No statistically significant differences regarding patient side or sex were found in either case. In 72.4% (n = 123) a mandibular incisive canal was detected. There was a statistically significant dependence of the mandibular incisive canal on patient sex (P = .007): female patients had a mandibular incisive canal significantly more often than male patients. Among male patients a significant difference of the mandibular incisive canal regarding the mandibular side (P = .031) was found; it was significantly less frequent on the right than on the left side. Conclusion: Anterior loop, mandibular incisive canal, and lingual symphyseal foramen are often present. Furthermore, the anatomical, neurovascular variability in the interforaminal area of the mandible emphasizes the importance of 3D imaging like CBCT in preoperative assessment, and confirms that a general safe zone should not solely be relied upon when performing surgery in this region. [ABSTRACT FROM AUTHOR]