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White adipose tissue (WAT) is essential for lipid storage and systemic energy homeostasis. Understanding adipocyte formation and stability is key to developing therapies for obesity and metabolic disorders. Through a high-throughput cDNA screen, we identified PATZ1, a POZ/BTB and AT-Hook Containing Zinc Finger 1 protein, as an important adipogenic transcription factor. PATZ1 is expressed in human and mouse adipocyte precursor cells (APCs) and adipocytes. In cellular models, PATZ1 promotes adipogenesis via protein-protein interactions and DNA binding. PATZ1 ablation in mouse adipocytes and APCs leads to a reduced APC pool, decreased fat mass, and hypertrophied adipocytes. ChIP-Seq and RNA-seq analyses show that PATZ1 supports adipogenesis by interacting with transcriptional machinery at the promoter regions of key early adipogenic factors. Mass-spec results show that PATZ1 associates with GTF2I, with GTF2I modulating PATZ1's function during differentiation. These findings underscore PATZ1's regulatory role in adipocyte differentiation and adiposity, offering insights into adipose tissue development. Adipogenesis is important for white adipose tissue function. Here the authors identify the transcription factor PATZ1 as a regulator of adipogenesis and adipocyte maintenance, and report that adipose-tissue specific loss of PATZ1 leads to reduced fat mass and larger adipocytes in mice. [ABSTRACT FROM AUTHOR]

The aim of this study was to explore the feasibility of a time-resolved reflectance imaging system employing a single photodetector to assess the activity of caries lesions that exploits the differential absorption of water at 1300 and 1950 nm. The time-resolved reflectivity of 10 active and 10 arrested lesions on the proximal surfaces and 5 active and 5 arrested lesions on the occlusal surfaces of extracted teeth were monitored simultaneously at 1300 and 1950 nm during forced air drying for 60 s. The presence of a highly mineralized surface zone measured with microcomputed tomography (microCT) was used to indicate lesion activity. Multiple kinetic parameters were extracted from the acquired short wavelength infrared (SWIR) intensity versus time dehydration curves and used to assess lesion activity. Differences in the reflectivity between curves acquired at 1300 and 1950 nm due to differential absorption of water provided improved discrimination between active and arrested lesions over the use of 1950 nm alone. This study demonstrates that it is feasible to use a device with a single photodetector operating at 1950 nm to collect dehydration curves for the assessment of lesion activity and that a system employing two SWIR wavelengths with differential water absorption can improve the performance of lesion activity assessment. [ABSTRACT FROM AUTHOR]

The sympathetic nervous system controls bodily functions including vascular tone, cardiac rhythm, and the "fight-or-flight response". Sympathetic chain ganglia develop in parallel with preganglionic motor nerves extending from the neural tube, raising the question of whether axon targeting contributes to sympathetic chain formation. Using nerve-selective genetic ablations and lineage tracing in mouse, we reveal that motor nerve-associated Schwann cell precursors (SCPs) contribute sympathetic neurons and satellite glia after the initial seeding of sympathetic ganglia by neural crest. Motor nerve ablation causes mispositioning of SCP-derived sympathoblasts as well as sympathetic chain hypoplasia and fragmentation. Sympathetic neurons in motor-ablated embryos project precociously and abnormally towards dorsal root ganglia, eventually resulting in fusion of sympathetic and sensory ganglia. Cell interaction analysis identifies semaphorins as potential motor nerve-derived signaling molecules regulating sympathoblast positioning and outgrowth. Overall, central innervation functions both as infrastructure and regulatory niche to ensure the integrity of peripheral ganglia morphogenesis. How tissues interact to help each other grow is a major question for biologists. Here, the authors show that motor innervation controls positioning of sympathetic progenitor cells to ensure correct shaping of ganglia in the peripheral nervous system. [ABSTRACT FROM AUTHOR]

This paper describes how students conceptualize real-life phenomena in which two or more quantities are covarying in an augmented reality environment. With this technology, real-world phenomena and virtual representations may be connected simultaneously. We aim to investigate how students connect elements of the two worlds when conceptualizing functional relationships. We relied on Zindel's conceptual facet model for functional relationships to achieve this goal, specifically focusing on the covariational approach. Three 11th-grade students participated in two real-life experiments (Galileo and Hooke's law experiments) at the heart of this study. The qualitative analysis of selected episodes revealed how students relate the two worlds and how covariational reasoning is reflected in such connections. The findings show that students frequently related elements of the real and virtual worlds while engaging in several forms of covariational reasoning. The theoretical contribution resulting from this study is expanding Zindel's model to address the conceptualization of families of functions indexed by a parameter. [ABSTRACT FROM AUTHOR]

Copyright of Canadian Journal of Anaesthesia / Journal Canadien d'Anesthésie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Early Warning Signals (EWS) have generated much excitement for their potential to anticipate transitions in various systems, ranging from climate change in ecology to disease staging in medicine. EWS hold particular promise for bifurcations, a transition mechanism in which a smooth, gradual change in a control parameter of the system results in a rapid change in system dynamics. The predominant reason to expect EWS is because many bifurcations are preceded by Critical Slowing Down (CSD): if assuming the system is subject to continuous, small, Gaussian noise, the system is slower to recover from perturbations closer to the transition. However, this focus on warning signs generated by stochasticity has overshadowed warning signs which may already be found in deterministic dynamics. This is especially true for higher-dimensional systems, where more complex attractors with intrinsic dynamics such as oscillations not only become possible—they are increasingly more likely. The present study focuses on univariate and multivariate EWS in deterministic dynamics to anticipate complex critical transitions, including the period-doubling cascade to chaos, chaos-chaos transitions, and the extinction of a chaotic attractor. In a four-dimensional continuous-time Lotka–Volterra model, EWS perform well for most bifurcations, even with lower data quality. The present study highlights three reasons why EWS may still work in the absence of CSD: changing attractor morphology (size, shape, and location in phase space), shifting power spectra (amplitude and frequency), and chaotic transitional characteristics (density across attractor). More complex attractors call for different warning detection methods to utilise warning signs already contained within purely deterministic dynamics. [ABSTRACT FROM AUTHOR]

Sero-monitoring provides context to the epidemiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and changes in population immunity following vaccine introduction. Here, we describe results of a cross-sectional hospital-based study of anti-spike seroprevalence in New York City (NYC) from February 2020 to July 2022, and a follow-up period from August 2023 to October 2023. Samples from 55,092 individuals, spanning five epidemiological waves were analyzed. Prevalence ratios (PR) were obtained using Poisson regression. Anti-spike antibody levels increased gradually over the first two waves, with a sharp increase during the 3rd wave coinciding with SARS-CoV-2 vaccination in NYC resulting in seroprevalence levels >90% by July 2022. Our data provide insights into the dynamic changes in immunity occurring in a large and diverse metropolitan community faced with a new viral pathogen and reflects the patterns of antibody responses as the pandemic transitions into an endemic stage. Continued monitoring of population SARS-CoV-2 seroprevalence can reveal infection and vaccination patterns. Here, the authors report data from a prospective hospital-based sero-monitoring study in New York City from 2020–2023, including ~55,000 individuals. [ABSTRACT FROM AUTHOR]

Ecological Momentary Assessment (EMA) is a data collection approach utilizing smartphone applications or wearable devices to gather insights into daily life. EMA has advantages over traditional surveys, such as increasing ecological validity. However, especially prolonged data collection can burden participants by disrupting their everyday activities. Consequently, EMA studies can have comparably high rates of missing data and face problems of compliance. Giving participants access to their data via accessible feedback reports, as seen in citizen science initiatives, may increase participant motivation. Existing frameworks to generate such reports focus on single individuals in clinical settings and do not scale well to large datasets. Here, we introduce FRED (Feedback Reports on EMA Data) to tackle the challenge of providing personalized reports to many participants. FRED is an interactive online tool in which participants can explore their own personalized data reports. We showcase FRED using data from the WARN-D study, where 867 participants were queried for 85 consecutive days with four daily and one weekly survey, resulting in up to 352 observations per participant. FRED includes descriptive statistics, time-series visualizations, and network analyses on selected EMA variables. Participants can access the reports online as part of a Shiny app, developed via the R programming language. We make the code and infrastructure of FRED available in the hope that it will be useful for both research and clinical settings, given that it can be flexibly adapted to the needs of other projects with the goal of generating personalized data reports. [ABSTRACT FROM AUTHOR]

In this tribute to Jerald L. Ericksen, we present a multifaceted contribution that honors his exceptional legacy as a scientist, educator, and mentor. The contribution is divided into three sections, each providing a unique perspective on his life and work. Through these sections, we aim to preserve and celebrate Jerry's legacy, a legacy that extends far beyond his scholarly contributions and reverberates through the lives and careers of those he inspired and guided. [ABSTRACT FROM AUTHOR]

We consider the problem of producing a ruled Möbius band by subjecting an unstretchable, homogeneous, isotropic, elastic material surface material surface in a circular helicoidal reference configuration to a deformation that is isometric and chirality preserving. We find that such a Möbius band is completely determined by the unit binormal of the Frenet frame of its midline, which must be a geodesic and must have uniform torsion inversely proportional to the pitch of the helicoidal reference configuration. Granted that the energy density of the material surface depends quadratically on the mean curvature of its deformed configuration, we show that the total energy stored in producing a ruled Möbius band as described reduces, in closed form and without approximation, to an integral over the midline of the Möbius band. We formulate and numerically solve a constrained variational problem for finding relative minima of the dimensionally reduced bending energy and construct corresponding stable Möbius bands. The only input parameter entering our variational problem is the number ν of turns in a helicoidal reference configuration. We only find solutions if ν exceeds a certain threshold, which we compute to machine precision. Above that threshold, an interplay between the operative constraints leads to a multiplicity of coexisting stable solutions with n ≥ 3 half twists. For each n ≥ 3 , we construct an energetically optimal Möbius band which exhibits n -fold rotational symmetry. All other energy minima yield Möbius bands which lack symmetry. To our knowledge, this study contains the first examples of stable Möbius bands produced by isometrically deforming reference configurations that are not flat. [ABSTRACT FROM AUTHOR]

Electrosurgical and ultrasonic devices are used in surgical procedures for hemostatic sealing and bisection of vascular tissues. Previous benchtop studies alternatively demonstrated successful infrared laser sealing and cutting of blood vessels, in a sequential, two-step approach. This study describes a smaller, laparoscopic device compatible design, and simultaneous approach to sealing and bisection of vessels, with potential optical feedback. A 1470-nm infrared diode laser sealed and bisected 40 porcine renal arteries, ex vivo. A reciprocating, side-firing, optical fiber, housed in a transparent square quartz optical chamber (2.7 × 2.7 × 25 mm outer dimensions), delivered laser energy over an 11 mm scan length, with a range of incident powers (41–59 W) and treatment times (5–21 s). Vessel diameters ranged from 2.5 to 4.8 mm. Vessel burst pressure measurements were performed on each cut end (n = 80) with success indicated by pressures exceeding 360 mmHg. All vessel ends were successfully sealed and bisected (80/80). The highest incident power, 59 W, yielded short treatment times of 5–6 s. Peak temperatures on the external chamber surface reached 103 oC. Time to cool down to body temperature measured 37 s. Infrared lasers simultaneously seal and bisect blood vessels, with treatment times comparable to, and temperatures and cooling times lower than reported for conventional devices. Future work will focus on integrating the fiber and chamber into a standard 5-mm-outer-diameter laparoscopic device. Customization of fiber scan length to match vessel size may also reduce laser energy deposition, enabling lower peak temperatures, treatment times, and cooling times. [ABSTRACT FROM AUTHOR]

Neuromodulation using high frequency (>1 kHz) electric stimulation (HFS) enables preferential activation or inhibition of individual neural types, offering the possibility of more effective treatments across a broad spectrum of neurological diseases. To improve effectiveness, it is important to better understand the mechanisms governing activation and inhibition with HFS so that selectivity can be optimized. In this study, we measure the membrane potential (Vm) and spiking responses of ON and OFF α-sustained retinal ganglion cells (RGCs) to a wide range of stimulus frequencies (100–2500 Hz) and amplitudes (10–100 µA). Our findings indicate that HFS induces shifts in Vm, with both the strength and polarity of the shifts dependent on the stimulus conditions. Spiking responses in each cell directly correlate with the shifts in Vm, where strong depolarization leads to spiking suppression. Comparisons between the two cell types reveal that ON cells are more depolarized by a given amplitude of HFS than OFF cells—this sensitivity difference enables the selective targeting. Computational modeling indicates that ion-channel dynamics largely account for the shifts in Vm, suggesting that a better understanding of the differences in ion-channel properties across cell types may improve the selectivity and ultimately, enhance HFS-based neurostimulation strategies. Whole-cell recordings of retinal ganglion cells responses to high-frequency stimulation (HFS) revealed that membrane depolarization mediates both inhibition and preferential activation. The results indicate that understanding ion-channel dynamics is crucial for improving HFS-based stimulation. [ABSTRACT FROM AUTHOR]

Abstract Vacuolar protein sorting 41 (VPS41) is as part of the Homotypic fusion and Protein Sorting (HOPS) complex required for lysosomal fusion events and, independent of HOPS, for regulated secretion. Here, we report three patients with compound heterozygous mutations in VPS41 (VPS41S285P and VPS41R662*; VPS41c.1423‐2A>G and VPS41R662*) displaying neurodegeneration with ataxia and dystonia. Cellular consequences were investigated in patient fibroblasts and VPS41‐depleted HeLa cells. All mutants prevented formation of a functional HOPS complex, causing delayed lysosomal delivery of endocytic and autophagic cargo. By contrast, VPS41S285P enabled regulated secretion. Strikingly, loss of VPS41 function caused a cytosolic redistribution of mTORC1, continuous nuclear localization of Transcription Factor E3 (TFE3), enhanced levels of LC3II, and a reduced autophagic response to nutrient starvation. Phosphorylation of mTORC1 substrates S6K1 and 4EBP1 was not affected. In a C. elegans model of Parkinson’s disease, co‐expression of VPS41S285P/VPS41R662* abolished the neuroprotective function of VPS41 against α‐synuclein aggregates. We conclude that the VPS41 variants specifically abrogate HOPS function, which interferes with the TFEB/TFE3 axis of mTORC1 signaling, and cause a neurodegenerative disease.

Background: Severe COVID-19, with the need in supplemental oxygen and hospitalization, leads to major burden on patients and healthcare systems. As a result, safe and effective ambulatory treatment strategies for severe COVID-19 are of urgent need. In this systematic review, we aimed to evaluate interventions to transition care to the ambulatory setting for patients with active severe COVID-19 that required supplemental oxygen. Methods: We searched Medline, Scopus, Web of Science, and DOAJ databases to identify articles with original data published until the 1st of April 2023. Characteristics and outcomes of interventions to transition care to home management were reviewed. Given the heterogeneous settings and outcomes studied, a meta-analysis was not performed. Results: Of the 235 studies identified, 11 observational studies, with 2645 patients, were included. The interventions were initiated from the emergency department, observation units or inpatient units, and included continuous home telemonitoring (n = 8), mobile applications (n = 2), and patient-initiated medical contact (n = 3). Included patients had an overall short length of hospital stay, high readmission rates, and positive patients' feedback. There was a lack of prospective controlled data and cost-effectiveness analyses. Conclusion: Our findings highlight the potential in treating severe COVID-19 at the ambulatory setting and the lack of high-quality data in this field. Dedicated medical teams, adjusted monitoring methods, improving clinical trajectory, and correct inclusion settings are needed for safe and effective transition of care. [ABSTRACT FROM AUTHOR]

Nanoscale heterostructure design can control laser-induced heat dissipation and strain propagation, as well as their efficiency for driving magnetization precession. Here, we incorporate MgO layers into the experimental platform of metallic Pt-Cu-Ni heterostructures to block the propagation of hot electrons. We show via ultrafast x-ray diffraction the capability of our platform to control the spatio-temporal shape of the transient heat and strain. Time-resolved magneto-optical Kerr experiments with systematic tuning of the magnetization precession frequency showcase control of the magnetization dynamics in the Ni layer. Our experimental analysis highlights the role of quasi-static strain as a driver of precession when the magnetic material is rapidly heated via electrons. The effective magnetic field change originating from demagnetization partially compensates the change induced by quasi-static strain. The strain pulses can be shaped via the nanoscale heterostructure design to efficiently drive the precession, paving the way for opto-magneto-acoustic devices with low heat energy deposited in the magnetic layer. Nanoscale heterostructure design can control laser-induced heat dissipation and strain propagation as well as their efficiency for driving magnetization precession. The authors present a platform that incorporates MgO layers into metallic Pt-Cu-Ni heterostructures, in order to clarify how controlled transient strain and heat tailor magnetization dynamics. [ABSTRACT FROM AUTHOR]

The development of craniofacial skeletal structures is fascinatingly complex and elucidation of the underlying mechanisms will not only provide novel scientific insights, but also help develop more effective clinical approaches to the treatment and/or prevention of the numerous congenital craniofacial malformations. To this end, we performed a genome-wide analysis of RNA transcription from non-coding regulatory elements by CAGE-sequencing of the facial mesenchyme of human embryos and cross-checked the active enhancers thus identified against genes, identified by GWAS for the normal range human facial appearance. Among the identified active cis-enhancers, several belonged to the components of the PI3/AKT/mTORC1/autophagy pathway. To assess the functional role of this pathway, we manipulated it both genetically and pharmacologically in mice and zebrafish. These experiments revealed that mTORC1 signaling modulates craniofacial shaping at the stage of skeletal mesenchymal condensations, with subsequent fine-tuning during clonal intercalation. This ability of mTORC1 pathway to modulate facial shaping, along with its evolutionary conservation and ability to sense external stimuli, in particular dietary amino acids, indicate that the mTORC1 pathway may play a role in facial phenotypic plasticity. Indeed, the level of protein in the diet of pregnant female mice influenced the activity of mTORC1 in fetal craniofacial structures and altered the size of skeletogenic clones, thus exerting an impact on the local geometry and craniofacial shaping. Overall, our findings indicate that the mTORC1 signaling pathway is involved in the effect of environmental conditions on the shaping of craniofacial structures. Children's faces resemble their parents to various degrees. Here they show that the maternal diet affects the facial appearances of newborns and that inherited and adaptive mechanisms sculpturing facial bones are linked via dietary protein levels and the mTOR signaling pathway. [ABSTRACT FROM AUTHOR]

Attention-deficit/hyperactivity disorder (ADHD) is a rapidly globalizing medical category, and there is a need to attend to the on the-ground processes through which laypeople deploy the ADHD label in different local contexts. Based on in-depth interviews with Israeli mothers of children with ADHD, this article explores how mothers, as lay actors in the social field of diagnosis, interpreted the origins and meanings of their child's 'troubles'. The temporal perspective on mothers' meaning-making processes revealed a progression of four common phases through which mothers revisited their understanding of ADHD, and recast their own responsibilities and moral roles. We found that mothers' self-understanding was crucially impacted by the invisibility of the disability and the fact that diagnosis did not fully relieve them from blame for their children's stigmatizing behavior. While not all mothers accepted the validity of the diagnosis, participating in the medicalization of their child's condition allowed them to reach similar pragmatic and narrative goals. We discuss the cultural and institutional features of the Israeli ADHD landscape that shape mothers' narratives of their children, and their relations with expertise. We point to a culturally unique framing of children with ADHD in Israel as those characterized by emotional vulnerability and risk of social exclusion. [ABSTRACT FROM AUTHOR]

The purpose is to investigate the natural course and long-term prognosis of postpartum depression (PPD). In this retrospective longitudinal cohort study, mothers diagnosed as either suffering from PPD or without PPD were reassessed 5–8 years thereafter by a semi-structured interview and their charts were reviewed for past psychiatric illness prior to the index (initial) episode and for new-onset episodes in the following years. Present psychiatric state was also evaluated by interview and questionnaires. Sixty-five mothers with and 35 without past PPD underwent the full assessment. A total of 66.2% of mothers with past PPD had any axis I psychopathology before their index PPD episode, compared with only 8.6% in the non-PPD group (p < 0.001, φ =.55). Furthermore, 37.2% of the females who had a history of PPD and experienced subsequent childbirths during the follow-up years, developed at least one new episode of PPD. Throughout the 5 years subsequent to the index PPD episode, 42.5% of the PPD group compared with only 3.7% for the non-PPD group developed a new episode of depression (p < 0.001). Lastly, reported psychopathology was higher and functional level was significantly worse in the PPD group at the time of reassessment. Females who develop an episode of PPD show a high degree of subsequent psychopathology and unfavorable prognosis. Clinicians treating females for PPD should consider a longer treatment continuation phase in an effort to prevent further psychopathology and a closer follow-up program. [ABSTRACT FROM AUTHOR]

This document is a foreword for a volume of the Journal of Elasticity dedicated to the memory of Jerald LaVerne Ericksen. Ericksen made significant contributions to the field of mechanics of materials, particularly in the study of nonlinear material behavior. His research influenced various areas of continuum mechanics, including rheology, elasticity, viscoelasticity, and thermomechanics. The foreword also highlights Ericksen's personal qualities, such as his kindness, simplicity, and dedication to education. The volume includes portraits, essays, and research papers that showcase Ericksen's impact and legacy. The document concludes with acknowledgments and a note from the publishers. [Extracted from the article]

Over the past decade, stereotactically placed electrodes have become the gold standard for deep brain recording and stimulation for a wide variety of neurological and psychiatric diseases. Current electrodes, however, are limited in their spatial resolution and ability to record from small populations of neurons, let alone individual neurons. Here, we report on an innovative, customizable, monolithically integrated human-grade flexible depth electrode capable of recording from up to 128 channels and able to record at a depth of 10 cm in brain tissue. This thin, stylet-guided depth electrode is capable of recording local field potentials and single unit neuronal activity (action potentials), validated across species. This device represents an advance in manufacturing and design approaches which extends the capabilities of a mainstay technology in clinical neurology. Electrodes available for deep brain recording and stimulation have a number of limitations. Here the authors describe a thin-film depth electrode that may offer improved spatial and temporal resolution for recording brain activity. [ABSTRACT FROM AUTHOR]

Currently, we find ourselves in a paradigm in which we believe that accepting climate change data will lead to a kind of automatic action toward the preservation of our environment. I have argued elsewhere (Fried 2020) that this lack of civic action on climate data is significant when placed in the historical, military context of the technologies that collect this data––Earth remote sensing technologies. However, I have not yet discussed the phenomenological or moral implications of this context, which are deeply interconnected. In this paper, I assert that Earth remote sensing technologies can, if we are not careful, lead us to a kind of environmental deskilling. This assertion comes in four parts. First, the military context of Earth remote sensing technologies––which collect important data on climate change––acts as a kind of stability, as defined by Don Ihde and others. Second, I invoke Sir Patrick Heelan to argue that the theoretical underpinnings of Earth systems science do not translate from military to environmental praxes as we imagine they do. Third, Hannah Arendt makes the case that a state's trust in simplifying narratives like that of climate data, meant to create "islands" of certainty in an uncertain world, can be self-defeating. That is to say, they can silence public action. I extend these arguments through Vallor's analysis of moral deskilling, in which she points out that an overemphasis on autonomous data collection––and trust in a kind of automated decision-making on that data––can deskill us from important questions relevant to our collective flourishing. In all of these examples, the lines between environmental and military research are blurry. [ABSTRACT FROM AUTHOR]

Motivated by a question of Defant and Propp (Electron J Combin 27:Article P3.51, 2020) regarding the connection between the degrees of noninvertibility of functions and those of their iterates, we address the combinatorial optimization problem of minimizing the sum of squares over partitions of n with a nonnegative rank. Denoting the sequence of the minima by (m n) n ∈ N , we prove that m n = Θ n 4 / 3 . Consequently, we improve by a factor of 2 the lower bound provided by Defant and Propp for iterates of order two. [ABSTRACT FROM AUTHOR]

Purpose: Venoarterial extracorporeal membrane oxygenation (V-A ECMO) can be used to support severely ill patients with cardiogenic shock. While age is commonly used in patient selection, little is known regarding its association with outcomes in this population. We sought to evaluate the association between increasing age and outcomes following V-A ECMO. Methods: We used individual-level patient data from 440 centers in the international Extracorporeal Life Support Organization registry. We included all adult patients receiving V-A ECMO from 2017 to 2019. The primary outcome was hospital mortality. Secondary outcomes included a composite of complications following initiation of V-A ECMO. We conducted Bayesian analyses of the relationship between increasing age and outcomes of interest. Results: We included 15,172 patients receiving V-A ECMO. Of these, 8172 (53.9%) died in hospital. For the analysis conducted using weakly informed priors, and as compared to the reference category of age 18–29, the age bracket of 30–39 (odds ratio [OR] 0.94, 95% credible interval [CrI] 0.79–1.10) was not associated with hospital mortality, but age brackets 40–49 (odds ratio [OR] 1.26, 95% CrI: 1.08–1.47), 50–59 (OR 1.78, 95% CrI: 1.55–2.06), 60–69 (OR 2.24, 95% CrI: 1.94–2.59), 70–79 (OR 2.90, 95% CrI: 2.49–3.39) and ≥ 80 (OR 4.02, 95% CrI: 3.13–5.20) were independently associated with increasing hospital mortality. Similar results were found in the analysis conducted with an informative prior, as well as between increasing age and post-ECMO complications. Conclusions: Among patients receiving V-A ECMO for cardiogenic shock, increasing age is strongly associated with increasing odds of death and complications, and this association emerges as early as 40 years of age. [ABSTRACT FROM AUTHOR]

Personalized medicine has revolutionized approaches to treatment in the field of lung cancer by enabling therapies to be specific to each patient. However, physicians encounter an immense number of challenges in providing the optimal treatment regimen for the individual given the sheer complexity of clinical aspects such as tumor molecular profile, tumor microenvironment, expected adverse events, acquired or inherent resistance mechanisms, the development of brain metastases, the limited availability of biomarkers and the choice of combination therapy. The integration of innovative next-generation technologies such as deep learning—a subset of machine learning—and radiomics has the potential to transform the field by supporting clinical decision making in cancer treatment and the delivery of precision therapies while integrating numerous clinical considerations. In this review, we present a brief explanation of the available technologies, the benefits of using these technologies in predicting immunotherapy response in lung cancer, and the expected future challenges in the context of precision medicine. [ABSTRACT FROM AUTHOR]

Theta burst stimulation (TBS) is a form of repetitive transcranial magnetic stimulation designed to induce changes of cortical excitability that outlast the period of TBS application. In this study, we explored the effects of continuous TBS (cTBS) and intermittent TBS (iTBS) versus sham TBS stimulation, applied to the left primary motor cortex, on modulation of resting state electroencephalography (rsEEG) power. We first conducted hypothesis-driven region-of-interest (ROI) analyses examining changes in alpha (8–12 Hz) and beta (13–21 Hz) bands over the left and right motor cortex. Additionally, we performed data-driven whole-brain analyses across a wide range of frequencies (1–50 Hz) and all electrodes. Finally, we assessed the reliability of TBS effects across two sessions approximately 1 month apart. None of the protocols produced significant group-level effects in the ROI. Whole-brain analysis revealed that cTBS significantly enhanced relative power between 19 and 43 Hz over multiple sites in both hemispheres. However, these results were not reliable across visits. There were no significant differences between EEG modulation by active and sham TBS protocols. Between-visit reliability of TBS-induced neuromodulatory effects was generally low-to-moderate. We discuss confounding factors and potential approaches for improving the reliability of TBS-induced rsEEG modulation. [ABSTRACT FROM AUTHOR]

Θ-Hilbertianity and its strengthening, strong Θ-Hilbertianity, are two generalizations of Hilbertianity inspired by Jarden's definition of p-Hilbertianity and strong p-Hilbertianity. Jarden has asked whether the two notions defined by him are actually the same. We address this question in its more general version of Θ-Hilbertianity and show that for PRC, and, in particular, for PAC fields, p-Hilbertianity and strong p-Hilbertianity coincide. [ABSTRACT FROM AUTHOR]

Medical follow-up of symptomatic patients after acute Coronavirus Disease 2019 (COVID-19) results in major burdens on patients and healthcare systems. The value of serological markers as part of this follow-up remains undetermined. We aimed to evaluate the clinical implications of serological markers for follow-up of acute COVID-19. For this purpose, we conducted an observational cohort study of patients 3 months after acute COVID-19. Participants visited a respiratory-clinic between October 2020 and March 2021, and completed pulmonary function tests (PFTs), serological tests, symptom-related questionnaires, and chest CT scans. Overall, 275 patients were included at a median of 82 days (IQR 64–111) post infection. 162 (59%) patients had diffusing capacity for carbon monoxide corrected for hemoglobin (DLCOc) below 80%, and 69 (25%) had bilateral chest abnormalities on CT scan. In multivariate analysis, anti-S levels were an independent predictor for DLCOc (β = − 0.14, p = 0.036). Anti-S levels were also associated with severe COVID-19 and older age, and correlated with anti-nucleocapsid (r = 0.30, p < 0.001) and antibodies to receptor binding domain (RBD, r = 0.37, p < 0.001). Other serological variables were not associated with clinical outcomes. In conclusion, symptomatic patients 3-months after COVID-19 had high respiratory symptomatic burden, in which anti-S levels were significantly associated with previous severe COVID-19 and DLCOc. [ABSTRACT FROM AUTHOR]

Dilational materials, for which the angles between pairs of material fibers are preserved under deformations, are an important class of metamaterials. Although these materials are typically made by assembling discrete elemental building blocks in repeating patterns, continuum mechanics provides a powerful tool for exploring their macroscopic properties and response. We present an analysis of the constraint, the constitutive relation, and the equilibrium equations for homogeneous and isotropic dilational elastic material surfaces. We also describe the possibility of penalizing deviations from local area preservation to yield a framework for approximating isometric deformations of unstretchable elastic material surfaces. [ABSTRACT FROM AUTHOR]

Our ability to recall memories of personal experiences is an essential part of daily life. These episodic memories often involve movement through space and thus require continuous encoding of one's position relative to the surrounding environment. The medial temporal lobe (MTL) is thought to be critically involved, based on studies in freely moving rodents and stationary humans. However, it remains unclear if and how the MTL represents both space and memory especially during physical navigation, given challenges associated with deep brain recordings in humans during movement. We recorded intracranial electroencephalographic (iEEG) activity while participants completed an ambulatory spatial memory task within an immersive virtual reality environment. MTL theta activity was modulated by successful memory retrieval or spatial positions within the environment, depending on dynamically changing behavioral goals. Altogether, these results demonstrate how human MTL oscillations can represent both memory and space in a temporally flexible manner during freely moving navigation. Here the authors show in freely moving human participants that deep brain oscillations in the medial temporal lobe flexibly encode both memory and spatial information, depending on the current cognitive task demands. [ABSTRACT FROM AUTHOR]

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Neurosurgeons are in a unique position to shed light on the neural basis for consciousness, not only by their clinical care of patients with compromised states of consciousness, but also by employing neurostimulation and neuronal recordings through intracranial electrodes in awake surgical patients, as well as during stages of sleep and anethesia. In this review, we discuss several aspects of consciousness, i.e., perception, memory, and willed actions, studied by electrical stimulation and single neuron recordings in the human brain. We demonstrate how specific neuronal activity underlie the emergence of concepts, memories, and intentions in human consciousness. We discuss the representation of specific conscious content by temporal lobe neurons and present the discovery of "concept cells" and the encoding and retrieval of memories by neurons in the medial temporal lobe. We review prefrontal and parietal neuronal activation that precedes conscious intentions to act. Taken together with other studies in the field, these findings suggest that specific conscious experience may arise from stochastic fluctuations of neuronal activity, reaching a dynamic threshold. Advances in brain recording and stimulation technology coupled with the rapid rise in artificial intelligence are likely to increase the amount and analysis capabilities of data obtained from the human brain, thereby improving the decoding of conscious and preconscious states and open new horizons for modulation of human cognitive functions such as memory and volition. [ABSTRACT FROM AUTHOR]

Aims: We investigated the implementation of new guidelines in ST-segment elevation myocardial infarction (STEMI) patients in a large real-world patient population in the metropolitan area of Berlin (Germany) over a 20-year period. Methods: From January 2000 to December 2019, a total of 25 792 patients were admitted with STEMI to one of the 34 member hospitals of the Berlin-Brandenburg Myocardial Infarction Registry (B2HIR) and were stratified for sex and age < 75 and ≥ 75 years. Results: The median age of women was 72 years (IQR 61–81) compared to 61 years in men (IQR 51–71). PCI treatment as a standard of care was implemented in men earlier than in women across all age groups. It took two years from the 2017 class IA ESC STEMI guideline recommendation to prefer the radial access route rather than femoral until > 60% of patients were treated accordingly. In 2019, less than 60% of elderly women were treated via a radial access. While the majority of patients < 75 years already received ticagrelor or prasugrel as antiplatelet agent in the year of the class IA ESC STEMI guideline recommendation in 2012, men ≥ 75 years lagged two years and women ≥ 75 three years behind. Amongst the elderly, in-hospital mortality was 22.6% (737) for women and 17.3% (523) for men (p < 0.001). In patients < 75 years fatal outcome was less likely with 7.2% (305) in women and 5.8% (833) in men (p < 0.001). After adjustment for confounding variables, female sex was an independent predictor of in-hospital mortality in patients ≥ 75 years (OR 1.37, 95% CI 1.12–1.68, p = 0.002), but not in patients < 75 years (p = 0.076). Conclusion: In-hospital mortality differs considerably by age and sex and remains highest in elderly patients and in particular in elderly females. In these patient groups, guideline recommended therapies were implemented with a significant delay. [ABSTRACT FROM AUTHOR]

Purpose: We investigated predictors of limitations in work performance, odds of drop out of work, and odds of receiving disability pension in sarcoma patients. Methods: We measured clinical and sociodemographic data in adult sarcoma patients and recorded if the patients received a (1) disability pension at baseline or (2) had dropped out of work 1 year after initial assessment. (3) Work limitations were assessed using the Work-limitations questionnaire (WLQ©). We analyzed exploratively. Results: (1) Amongst 364 analyzed patients, odds to receive a disability pension were higher in patients with abdominal tumors, older patients, high grade patients and with increasing time since diagnosis. (2) Of 356 patients employed at baseline, 21% (n = 76) had dropped out of work after 1 year. The odds of dropping out of work were higher in bone sarcoma patients and in patients who received additive radiotherapy ± systemic therapy compared with patients who received surgery alone. Odds of dropping out of work were less amongst self-employed patients and dropped with increasing time since diagnosis. (3) Work limitations were higher in woman and increased with age. Patients with bone and fibrous sarcomas were more affected than liposarcoma patients. Patients with abdominal tumors reported highest restrictions. Sarcoma treatment in the last 6 months increased work limitations. Conclusion: Work limitations, drop out of work and dependence on a disability pension occurs frequently in patients with sarcoma adding to the burden of this condition. We were able to identify vulnerable groups in both the socioeconomic and disease categories. [ABSTRACT FROM AUTHOR]

Lipomatosis of peripheral nerves (LPN, also known as fibrolipomatous or lipofibromatous hamartoma of peripheral nerves) is a very rare, benign, intraneural, tumorous lesion that predominantly involves the median nerve but may rarely affect any peripheral nerve. Recently, PIK3CA mutations have been reported in macrodactyly, a rare condition related to LPN, and in other localized lipomatous overgrowth syndromes. In this retrospective study, we report 6 cases of FPN involving the median nerve (4 of them identified among 570 patients with carpal tunnel syndrome who underwent surgical decompression at our center from 2012 to 2022 and two seen in consultation by one of the authors). All cases were diagnosed via biopsy or resection supplemented by MRI. Patients were 4 males and 2 females aged 23 to 60 years (mean 38 years). One patient with bilateral lesions had in addition extensive angiomatosis of the paravertebral region. Histological examination showed an abnormal amount of mature fatty tissue containing disordered fibrous bands, entrapping normal-looking nerve fibers with prominent perineurial and endoneurial fibrosis. Genetic analysis using snapshot assay constructed to detect hotspots mutations in PIK3CA revealed similar PIK3CA mutations (p.H1047R; c.3140A>G) in 5/6 cases (83.3%). Our study represents a further contribution to the literature on LPN and highlights the diagnostic value of PIK3CA mutation testing as surrogate tool in equivocal cases and in those lesions without associated macrodactyly, especially as the biopsy findings of this lesion are essentially nonspecific. [ABSTRACT FROM AUTHOR]

Administration of long-acting injectable suspensions is an increasingly common approach to increasing patient compliance and improving therapeutic efficacy through less frequent dosing. While several long-acting suspensions have recently been marketed, parameters modulating drug absorption from suspension-based formulations are not well understood. Further, methods for predicting clinical pharmacokinetic data from preclinical studies are not well established. Together, these limitations hamper compound selection, formulation design and formulation selection through heavy reliance on iterative optimization in preclinical and clinical studies. This article identifies key parameters influencing absorption from suspension-based formulations through compilation and analysis of preclinical and clinical pharmacokinetic data of seven compounds marketed as suspensions; achievable margins for predicting the clinical dose and input rate from preclinical studies as a function of the preclinical species, the clinical injection location and the intended therapeutic duration were also established. [ABSTRACT FROM AUTHOR]

Introduction: Nephrotoxin exposure is significantly associated with acute kidney injury (AKI) development. A standardized list of nephrotoxic medications to surveil and their perceived nephrotoxic potential (NxP) does not exist for non-critically ill patients. Objective: This study generated consensus on the nephrotoxic effect of 195 medications used in the non-intensive care setting. Methods: Potentially nephrotoxic medications were identified through a comprehensive literature search, and 29 participants with nephrology or pharmacist expertise were identified. The primary outcome was NxP by consensus. Participants rated each drug on a scale of 0–3 (not nephrotoxic to definite nephrotoxicity). Group consensus was met if ≥ 75% of responses were one single rating or a combination of two consecutive ratings. If ≥ 50% of responses indicated "unknown" or not used in the non-intensive care setting, the medication was removed for consideration. Medications not meeting consensus for a given round were included in the subsequent round(s). Results: A total of 191 medications were identified in the literature, with 4 medications added after the first round from participants' recommendations. NxP index rating consensus after three rounds was: 14 (7.2%) no NxP in almost all situations (rating 0); 62 (31.8%) unlikely/possibly nephrotoxic (rating 0.5); 21 (10.8%) possibly nephrotoxic (rating 1); 49 (25.1%) possibly/probably nephrotoxic (rating 1.5); 2 (1.0%) probably nephrotoxic (rating 2); 8 (4.1%) probably/definite nephrotoxic (rating 2.5); 0 (0.0%) definitely nephrotoxic (rating 3); and 39 (20.0%) medications were removed from consideration. Conclusions: NxP index rating provides clinical consensus on perceived nephrotoxic medications in the non-intensive care setting and homogeneity for future clinical evaluations and research. [ABSTRACT FROM AUTHOR]

Given access to a single long trajectory generated by an unknown irreducible Markov chain M, we simulate an α -lazy version of M which is ergodic. This enables us to generalize recent results on estimation and identity testing, that were stated for ergodic Markov chains, in a way that allows fully empirical inference. In particular, our approach shows that the pseudo spectral gap introduced by Paulin (Electron J Probab 20:32, 2015) and defined for ergodic Markov chains may be given a meaning already in the case of irreducible but possibly periodic Markov chains. [ABSTRACT FROM AUTHOR]

Background: Guillain–Barré syndrome (GBS) often carries a favorable prognosis. Of adult patients with GBS, 10–30% require mechanical ventilation during the acute phase of the disease. After the acute phase, the focus shifts to restoration of motor strength, ambulation, and neurological function, with variable speed and degree of recovery. The objective of these guidelines is to provide recommendations on the reliability of select clinical predictors that serve as the basis of neuroprognostication and provide guidance to clinicians counseling adult patients with GBS and/or their surrogates. Methods: A narrative systematic review was completed using Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. Candidate predictors, including clinical variables and prediction models, were selected based on clinical relevance and presence of appropriate body of evidence. The Population/Intervention/Comparator/Outcome/Time frame/Setting (PICOTS) question was framed as follows: "When counseling patients or surrogates of critically ill patients with Guillain–Barré syndrome, should [predictor, with time of assessment if appropriate] be considered a reliable predictor of [outcome, with time frame of assessment]?" Additional full-text screening criteria were used to exclude small and lower quality studies. Following construction of an evidence profile and summary of findings, recommendations were based on four GRADE criteria: quality of evidence, balance of desirable and undesirable consequences, values and preferences, and resource use. In addition, good practice recommendations addressed essential principles of neuroprognostication that could not be framed in PICOTS format. Results: Eight candidate clinical variables and six prediction models were selected. A total of 45 articles met our eligibility criteria to guide recommendations. We recommend bulbar weakness (the degree of motor weakness at disease nadir) and the Erasmus GBS Respiratory Insufficiency Score as moderately reliable for prediction of the need for mechanical ventilation. The Erasmus GBS Outcome Score (EGOS) and modified EGOS were identified as moderately reliable predictors of independent ambulation at 3 months and beyond. Good practice recommendations include consideration of both acute and recovery phases of the disease during prognostication, discussion of the possible need for mechanical ventilation and enteral nutrition during counseling, and consideration of the complete clinical condition as opposed to a single variable during prognostication. Conclusions: These guidelines provide recommendations on the reliability of predictors of the need for mechanical ventilation, poor functional outcome, and independent ambulation following GBS in the context of counseling patients and/or surrogates and suggest broad principles of neuroprognostication. Few predictors were considered moderately reliable based on the available body of evidence, and higher quality data are needed. [ABSTRACT FROM AUTHOR]

Background: Among cardiac arrest survivors, about half remain comatose 72 h following return of spontaneous circulation (ROSC). Prognostication of poor neurological outcome in this population may result in withdrawal of life-sustaining therapy and death. The objective of this article is to provide recommendations on the reliability of select clinical predictors that serve as the basis of neuroprognostication and provide guidance to clinicians counseling surrogates of comatose cardiac arrest survivors. Methods: A narrative systematic review was completed using Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. Candidate predictors, which included clinical variables and prediction models, were selected based on clinical relevance and the presence of an appropriate body of evidence. The Population, Intervention, Comparator, Outcome, Timing, Setting (PICOTS) question was framed as follows: "When counseling surrogates of comatose adult survivors of cardiac arrest, should [predictor, with time of assessment if appropriate] be considered a reliable predictor of poor functional outcome assessed at 3 months or later?" Additional full-text screening criteria were used to exclude small and lower-quality studies. Following construction of the evidence profile and summary of findings, recommendations were based on four GRADE criteria: quality of evidence, balance of desirable and undesirable consequences, values and preferences, and resource use. In addition, good practice recommendations addressed essential principles of neuroprognostication that could not be framed in PICOTS format. Results: Eleven candidate clinical variables and three prediction models were selected based on clinical relevance and the presence of an appropriate body of literature. A total of 72 articles met our eligibility criteria to guide recommendations. Good practice recommendations include waiting 72 h following ROSC/rewarming prior to neuroprognostication, avoiding sedation or other confounders, the use of multimodal assessment, and an extended period of observation for awakening in patients with an indeterminate prognosis, if consistent with goals of care. The bilateral absence of pupillary light response > 72 h from ROSC and the bilateral absence of N20 response on somatosensory evoked potential testing were identified as reliable predictors. Computed tomography or magnetic resonance imaging of the brain > 48 h from ROSC and electroencephalography > 72 h from ROSC were identified as moderately reliable predictors. Conclusions: These guidelines provide recommendations on the reliability of predictors of poor outcome in the context of counseling surrogates of comatose survivors of cardiac arrest and suggest broad principles of neuroprognostication. Few predictors were considered reliable or moderately reliable based on the available body of evidence. [ABSTRACT FROM AUTHOR]

Change-point detection in dynamic networks is a challenging task which is particularly due to the complex nature of temporal graphs. Existing approaches are based on the extraction of a network's information by the reduction to a model or to a single metric. Whereas the former one requires restrictive assumptions and has limited applicability for real-world social networks, the latter one may suffer from a huge information loss. We demonstrate that an extension to a well-balanced multivariate approach that uses multiple metrics jointly to cover the relevant network information can overcome both issues, since it is applicable to arbitrary network shapes and promises to strongly mitigate the information loss. In this context, we give guidelines on the crucial questions of how to properly choose a suitable multivariate metric set together with the choice of a meaningful parametric or nonparametric control chart and show that an improper application may easily lead to unsatisfying results. Furthermore, we identify a solution that achieves reasonable performances in flexible circumstances in order to give a reliably applicable approach for various types of social networks and application fields. Our findings are supported by the use of extensive simulation studies, and its applicability is demonstrated on two real-world data sets from economics and social sciences. [ABSTRACT FROM AUTHOR]

Purpose: We examined how migration background is associated with awareness and usage of psycho-oncology services. Methods: Oncologists in community-based practices and outpatient clinics asked their patients and their relatives to complete a questionnaire. Migrants were purposely over-sampled. The questionnaire was provided in Arabic, English, Farsi, French, German, Hindi, Kurdish, Pashto, Russian, Somali, Turkish, Urdu, and Vietnamese. Results: From 9 collaborators, 177 participants were enrolled (130 with and 47 without migration background). The existence of outpatient cancer counselling centres was known to 38% of the participants without and 32% with migration background, self-help groups to 32 vs. 12%, and psychotherapy to 43 vs. 25%. Respondents from the Near and Middle East were less likely to know about psychotherapy (odds ratio (OR) 0.1, p = 0.01); those from the Commonwealth of the Independent States or former Yugoslavia were less often informed about self-help groups (OR 0.1, p = 0.06). Migrants retrieved information less frequently from the internet than non-migrants (10 vs. 25%). At least one service had been used by 27% of migrants and 42% of non-migrants (OR 0.5, p = 0.06). After adjusting for gender, age, education, and patient-relative status, there was no evidence for an association between migration background and service use. Conclusions: Migrants should be better informed about psychotherapy and self-help groups, in particular the ones coming from the Near or Middle East and the Commonwealth of the Independent States or former Yugoslavia. The under-use of psychosocial services can largely be explained by confounding factors. Therefore, these factors must always be taken into account when analysing the use of psychosocial services in the aforementioned populations. [ABSTRACT FROM AUTHOR]

One of the bottlenecks to building semiconductor chips is the increasing cost required to develop chemical plasma processes that form the transistors and memory storage cells1,2. These processes are still developed manually using highly trained engineers searching for a combination of tool parameters that produces an acceptable result on the silicon wafer3. The challenge for computer algorithms is the availability of limited experimental data owing to the high cost of acquisition, making it difficult to form a predictive model with accuracy to the atomic scale. Here we study Bayesian optimization algorithms to investigate how artificial intelligence (AI) might decrease the cost of developing complex semiconductor chip processes. In particular, we create a controlled virtual process game to systematically benchmark the performance of humans and computers for the design of a semiconductor fabrication process. We find that human engineers excel in the early stages of development, whereas the algorithms are far more cost-efficient near the tight tolerances of the target. Furthermore, we show that a strategy using both human designers with high expertise and algorithms in a human first–computer last strategy can reduce the cost-to-target by half compared with only human designers. Finally, we highlight cultural challenges in partnering humans with computers that need to be addressed when introducing artificial intelligence in developing semiconductor processes.A virtual process game to benchmark the performance of humans and computers for the fabrication of semiconductors leads to a strategy combining human expert design with optimization algorithms to improve semiconductor process development. [ABSTRACT FROM AUTHOR]