bluuebunny/crossref_metadata_2025_split huggingface dataset:
Visual search efficiency is modulated by symmetry type and texture regularity
Authors: Moreau Rachel , Alp Nihan , Clarke Alasdair DF , Freud Erez , Kohler Peter J. 
Published: June 2024

AbstractMore than a century of vision research has identified symmetry as a fundamental cue, which aids the visual system in making inferences about objects and surfaces in natural scenes. Most studies have focused on one type of symmetry, reflection, presented at a single image location. However, the visual system responds strongly to other types of symmetries, and to symmetries that are repeated across the image plane to form textures. Here we use a visual search paradigm with arrays of repeating lattices that contained either reflection or rotation symmetries but were otherwise matched. Participants were asked to report the presence of a target tile without symmetry. When lattices tile the plane without gaps, they form regular textures. We manipulated texture regularity by introducing jittered gaps between lattices. This paradigm lets us investigate the effect of symmetry type and texture regularity on visual search efficiency. Based on previous findings suggesting an advantage for reflection in visual processing, we hypothesized that search would be more efficient for reflection than rotation. We further hypothesized that regular textures would be processed more efficiently. We found independent effects of symmetry type and regularity on search efficiency that confirmed both hypotheses: visual search was more efficient for textures with reflection symmetry and more efficient for regular textures. This provides additional support for the perceptual advantage of reflection in the context of visual search and provides important new evidence in favor of visual mechanisms specialized for processing symmetries in regular textures.
Replicative senescence is ATM driven, reversible, and accelerated by hyperactivation of ATM at normoxia
Authors: Stuart Alexander , de Lange Titia 
Published: June 2024

AbstractProgrammed telomere shortening limits tumorigenesis through the induction of replicative senescence. Here we address three long-standing questions concerning senescence. First, we show that the ATM kinase is solely responsible for the induction of replicative senescence. Senescence was delayed by ATM inhibition (ATMi) or overexpression of TRF2, the shelterin subunit dedicated to ATM repression. In contrast, there was no evidence for ATR signaling contributing to replicative senescence even when ATMi was combined with ATR inhibition. Second, we show ATMi can induce apparently normal cell divisions in a subset of senescent cells, indicating that senescence can be reversed. Third, we show that the extended replicative life span at low (physiological) oxygen is due to diminished ATM activity. At low oxygen, cells show a decreased ATM response to dysfunctional telomeres and genome-wide DSBs compared to 20% oxygen. As this effect could be reversed by NAC, the attenuated response of ATM to critically short telomeres and the resulting extended life span at low oxygen is likely due to ROS-induced formation of cysteine disulfide-bridges that crosslink ATM dimers into a form that is not activated by DSBs. These findings show how primary human cells detect shortened telomeres and reveal the molecular mechanism underlying the telomere tumor suppressor pathway.
Reliability and criterion validity of a low-cost handgrip dynamometer: The Camry
Authors: Sánchez-Aranda Lucía , Fernández-Ortega Javier , Martín-Fuentes Isabel , Toval Ángel , Jurak Gregor , Ruiz Jonatan R , Csányi Tamás , Ortega Francisco B. 
Published: June 2024

ABSTRACTBackgroundHandgrip strength has been related with multiple health outcomes, including all-cause mortality and morbidity. Handgrip testing is a highly valid and reliable method, included in evidence-based fitness test batteries from preschool to older ages. Previously, Jamar and TKK dynamometers have shown good reliability and validity against known weights. However, the cost of these dynamometers is the major limitation for implementing handgrip strength testing in certain countries and settings, as well as at large scale. Recently, a ten times cheaper model (Camry Dynamometer) has been used in fitness surveillance systems, though its reliability and validity, compared to known weights and other well-validated dynamometers, remains unknown. Therefore, the aims of the current study were to test to examine test-retest reliability, inter-model reliability (comparing a Camry dynamometer with 3000 uses versus a new Camry dynamometer), and inter-instrument reliability (Camry versus TKK dynamometer) of Camry dynamometer, using calibrated known weights.MethodsA digital TKK 5401 dynamometer and two Camry EH101, a new and an “old” (3000 uses), dynamometers were used. Intra-instrument and inter-instrument reliability, and criterion related validity were assessed comparing the measures of the dynamometers with calibrated weights using the Bland and Altman’s method.ResultsIntra-instrument (retest minus test) reliability was very high (systematic error for test-retest reliability: New Camry = 0.01±0.49kg; Old Camry = -0.10±0.49kg; TKK = 0.14±0.77kg). The comparison between instruments showed small mean differences between Camry dynamometers and TKK (New Camry VS TKK: 0.84±0.79kg; Old Camry VS TKK: 0.88 ±0.85kg). The systematic error between New and Old Camry dynamometers was 0.03±0.57kg. Criterion-related validity showed smaller magnitude systematic errors in the Camry than TKK instruments (New Camry: -0.21±0.35kg; Old Camry: -0.18±0.79kg; TKK: -1.07±0.75kg).ConclusionsOur results support that Camry dynamometer has an excellent reliability and validity and is therefore a more affordable alternative for handgrip strength assessment. Our results also indicate a good durability of these devices, and that calibration is not necessary, even after several thousands of uses.
The association between age and high-intensity treatment in traumatic brain injury patients: a CENTER-TBI study
Authors: van Veen Ernest , Kompanje Erwin J. O. , van der Jagt Mathieu , Mikolić Ana , Citerio Giuseppe , Stocchetti Nino , Gommers Diederik , Menon David K. , Maas Andrew I. R. , Lingsma Hester F. ,   the CENTER-TBI investigators and participants
Published: June 2024

ABSTRACTIntroductionOlder age is associated with worse outcome after traumatic brain injury (TBI). Whether this association is entirely driven by frailty, or clinicians’ reluctance to give specific treatments to older patients is unclear. Therefore, we aimed to confirm the association between age and worse outcome, and to assess the association between age and received high-intensity treatment (HIT).MethodsWe included TBI patients aged 16 and older from the CENTER-TBI study. The association between age and HIT, and between age and outcome (the Glasgow Outcome Scale Extended (GOSE) at 6 months), was analyzed using multivariable ordinal and logistic regression respectively. In the overall cohort, HIT was defined as receiving emergency intracranial surgery, or ICU admission. In the subset of patients admitted to the ICU, HIT was defined as receiving metabolic suppression, intensive hypocapnia, hypothermia below 35 °C, decompressive craniectomy, or intracranial surgery not scheduled on admission. We adjusted for pre-injury health, injury severity (Glasgow Coma Scale (GCS) motor score and pupillary reactivity at baseline; major extracranial injury (MEI); Marshall CT classification), and in the subset of ICU patients for the median ICP before receiving any HIT.ResultsIn total, 4349 patients were included. Of these, 1999 patients (46%) were admitted to the ICU. The median age was 51 years. Every ten-year increase in age for patients over 65, was associated with worse outcome (OR = 0.6, CI = 0.5 – 0.7, OR in the subset of ICU patients = 0.5, CI = 0.3 – 0.5). Furthermore, every ten-year increase in age for patients over 65 was associated with a lower likelihood of receiving emergency intracranial surgery (OR = 0.4, CI = 0.3 – 0.6), and ICU admission (OR = 0.6, CI = 0.5 – 0.8). Similarly, in the subset of ICU patients, every ten-year increase in age for patients over 65, was associated with a lower likelihood of receiving neuromuscular blockade (OR = 0.6, CI = 0.4 – 0.9), intensive hypocapnia (OR = 0.2, CI = 0.1 – 0.9), decompressive craniectomy (OR = 0.4, CI = 0.2 – 0.8), and intracranial surgery (OR = 0.5, CI = 0.3 – 0.8).ConclusionOlder patients have poorer outcome, and were less likely to receive high-intensity treatments, independent of patient and injury characteristics. Clinicians should not withhold high-intensity treatments solely based on older age. Educating clinicians about this delicate topic, and performing further comparative effectiveness research focusing on older patients may improve diagnosis, treatments, and understanding of TBI outcomes in this group.
Improving postsurgical fall detection for older Americans using LLM-driven analysis of clinical narratives
Authors: Pillai Malvika , Blumke Terri L , Studnia Joachim , Wang Yuqing , Veigulis Zachary P , Ware Anna D , Hoover Peter J , Carroll Ian R , Humphreys Keith , Osborne Thomas F , Asch Steven M. , Hernandez-Boussard Tina , Curtin Catherine M 
Published: June 2024

ABSTRACTPostsurgical falls have significant patient and societal implications but remain challenging to identify and track. Detecting postsurgical falls is crucial to improve patient care for older adults and reduce healthcare costs. Large language models (LLMs) offer a promising solution for reliable and automated fall detection using unstructured data in clinical notes. We tested several LLM prompting approaches to postsurgical fall detection in two different healthcare systems with three open-source LLMs. The Mixtral-8×7B zero-shot had the best performance at Stanford Health Care (PPV = 0.81, recall = 0.67) and the Veterans Health Administration (PPV = 0.93, recall = 0.94). These results demonstrate that LLMs can detect falls with little to no guidance and lay groundwork for applications of LLMs in fall prediction and prevention across many different settings.
Efficient blockLASSO for Polygenic Scores with Applications to All of Us and UK Biobank
Authors: Raben Timothy G. , Lello Louis , Widen Erik , Hsu Stephen D.H. 
Published: June 2024

AbstractWe develop a “block” LASSO (blockLASSO) method for training polygenic scores (PGS) and demonstrate its use in All of Us (AoU) and the UK Biobank (UKB). BlockLASSO utilizes the approximate block diagonal structure (due to chromosomal partition of the genome) of linkage disequilibrium (LD). LASSO optimization is performed chromosome by chromosome, which reduces computational complexity by orders of magnitude. The resulting predictors for each chromosome are combined using simple re-weighting techniques. We demonstrate that blockLASSO is generally as effective for training PGS as (global) LASSO and other approaches. This is shown for 11 different phenotypes, in two different biobanks, and across 5 different ancestry groups (African, American, East Asian, European, and South Asian). The block approach works for a wide variety of pheno-types. In the past, it has been shown that some phenotypes are more/less polygenic than others. Using sparse algorithms, an accurate PGS can be trained for type 1 diabetes (T1D) using 100 single nucleotide variants (SNVs). On the other extreme, a PGS for body mass index (BMI) would need more than 10k SNVs. blockLasso produces similar PGS for phenotypes while training with just a fraction of the variants per block. For example, within AoU (using only genetic information) block PGS for T1D (1,500 cases/113,297 controls) reaches an AUC of 0.63±0.02and for BMI (102,949 samples) a correlation of 0.21±0.01. This is compared to a traditional global LASSO approach which finds for T1D an AUC 0.65±0.03and BMI a correlation 0.19±0.03. Similar results are shown for a total of 11 phenotypes in both AoU and the UKB and applied to all 5 ancestry groups as defined via an Admixture analysis. In all cases the contribution from common covariates – age, sex assigned at birth, and principal components – are removed before training. This new block approach is more computationally efficient and scalable than global machine learning approaches. Genetic matrices are typically stored as memory mapped instances, but loading a million SNVs for a million participants can require 8TB of memory. Running a LASSO algorithm requires holding in memory at least two matrices this size. This requirement is so large that even large high performance computing clusters cannot perform these calculations. To circumvent this issue, most current analyses use subsets: e.g., taking a representative sample of participants and filtering SNVs via pruning and thresholding. High-end LASSO training uses ∼ 500 GB of memory (e.g., ∼ 400k samples and ∼ 50k SNVs) and takes 12-24 hours to complete. In contrast, the block approach typically uses ∼ 200× (2 orders of magnitude) less memory and runs in ∼ 500× less time.
Identifying real-time surveillance indicators that can be used to estimate COVID-19 hospital admissions
Authors: Grover Elise N. , Hill Andrew , Kasarskis Irina M. , Wu Emma J. , Alden Nisha , Cronquist Alicia B. , Weisbeck Kirsten , Herlihy Rachel , Carlton Elizabeth J. 
Published: June 2024

AbstractNumerous approaches have been used to track COVID-19 trends, from wastewater surveillance to laboratory reporting of diagnostic test results. However, questions remain about how best to focus surveillance efforts during and after public health emergencies. Using an archive of SARS-CoV-2 surveillance data, we reconstructed seven real-time surveillance indicators and assessed their performance as predictors of 7-day moving average COVID-19 hospital admissions in Colorado from October 2020 to March 2024. Models were constructed using neural network models and Ordinary Least Squares regression. We found that hospital census data, emergency-department based syndromic surveillance, and daily COVID-19 hospital admissions were the best indicators of COVID-19 hospital demand in Colorado during the public health emergency (PHE) (October 2020 – May 2023) and after (May 2023 – March 2024). The removal of wastewater from our multi-indicator models resulted in a decrease in model performance, indicating that wastewater provides important and unique information. By contrast, capacity to predict COVID-19 hospital admissions was not meaningfully reduced when sentinel test positivity, statewide test positivity, and/or case report data were dropped from our prediction models during and after the PHE. These findings underscore the importance of hospital-based reporting for monitoring COVID-19 hospital admissions, and, conversely, suggest that case reporting and percent positivity are not essential to monitoring COVID-19 hospitalizations in Colorado.
Atrial fibrillation, venous thromboembolism, and risk of pulmonary hypertension: A Swedish Nationwide Register Study
Authors: Hjalmarsson Clara , Lindgren Martin , Bergh Niklas , Hornestam Björn , Smith J. Gustav , Adiels Martin , Rosengren Annika 
Published: June 2024

AbstractBackgroundAtrial fibrillation (AF) is a recognized risk factor for systemic arterial- and venous thromboembolism (VTE), including pulmonary embolism (PE), and may thereby contribute to the development of chronic thrombo-embolic pulmonary hypertension (PH). AF may also play a direct role in the development of post-capillary PH. We aimed to investigate the association between AF - with or without incident VTE - and the occurrence of PH.MethodsA total of 521 988 patients diagnosed with AF between 1987–2013, without a previous diagnosis of VTE or PH, were identified from the Swedish National Patient Register (NPR) and matched for age, sex, and county with 1 017 277 population controls without AF, VTE or PH.ResultsThe mean age of the AF patients was 71.1 (SD ±10.1) years and 42.8 % were women. During a median follow-up period of 11 (IQR 5.1,17) years, 4 454 (0.9%) AF patients and 1 855 (0.2%) controls were diagnosed with PH, HR 4.7 (4.4-5.0). The AF group had a significantly higher comorbidity burden at baseline, with a mean CHA2DS2-VASc of 2.9 compared to 2.1 in controls. In the absence of intercurrent VTE, the HR of PH was 4.2 (3.9-4.5) among AF patients compared to controls. Intercurrent VTE increased the HR of PH a further 1.9-fold (1.7-2.1) and 3.5 (3.1-4.0), among AF patients and controls, respectively. The HR for PH in AF patients with incident VTE was 8.1 (7.3-9.1).ConclusionAF was associated with a markedly increased risk of developing incident PH, and this risk was further increased by incident VTE.
Working memory affects motor, but not perceptual timing
Authors: Farajzadeh MohammadAmin , Sanayei Mehdi 
Published: June 2024

AbstractWhether different timing tasks utilize the same brain processes is still debated. To address this question, we investigated how working memory affects two different timing tasks: time reproduction and time discrimination. We found that delay intervals led to an overestimation in the reproduction task but did not introduce any bias in the perception of time in the discrimination task. Delay intervals affected the perception of time when subjects had to actively reproduce the perceived interval, but not when subjects were merely recalling the content of working memory. In subsequent Bayesian modeling, we showed that in the reproduction task, subjects updated their measurement of the stimulus on the current trial (likelihood) based on the delay interval, rather than changes in the motor system or updating priors based on the delay interval. Our findings suggest that the brain processes involved in time reproduction and discrimination are not completely overlapping, and that delay intervals in working memory tasks lead to changes in updating the likelihood. This robustness in prior and updates in likelihood provides both stability and sensitivity in the perception of time.
Function and firing of theStreptomyces coelicolorcontractile injection system requires the membrane protein CisA
Authors: Casu Bastien , Sallmen Joseph W. , Haas Peter E. , Chandra Govind , Afanasyev Pavel , Xu Jingwei , Schlimpert Susan , Pilhofer Martin 
Published: June 2024

AbstractBacterial contractile injection systems (CIS) are phage tail-like macromolecular complexes that mediate cell-cell interactions by injecting effector proteins into target cells. CIS fromStreptomyces coelicolor(CISSc) are localized in the cytoplasm. Under stress, they induce cell death and impact the bacteria’s life cycle. It remains unknown whether CISScrequire accessory proteins to directly interact with the cytoplasmic membrane and function.Here, we characterize the putative membrane adaptor CisA, a conserved factor inCISgene clusters acrossStreptomycesspecies. We show by cryo-electron tomography imaging andin vivoassays that CISSccontraction and function depend on CisA. Using single-particle cryo-electron microscopy, we provide an atomic model of the extended CISScapparatus; however, CisA is not part of the complex. Instead, our findings show that CisA is a membrane protein with a cytoplasmic N-terminus predicted to interact with CISSccomponents, thereby providing a possible mechanism for mediating CISScrecruitment to the membrane and subsequent firing.Our work shows that CIS function in multicellular bacteria is distinct from Type 6 Secretion Systems and extracellular CIS, and possibly evolved due to the role CISScplay in regulated cell death.
Central tendency and serial dependence in vestibular path integration
Authors: Willemsen Sophie C.M.J. , Oostwoud Wijdenes Leonie , van Beers Robert J. , Koppen Mathieu , Medendorp W. Pieter 
Published: June 2024

AbstractPath integration, the process of updating one’s position using successive self-motion signals, has previously been studied using visual distance reproduction tasks in which optic flow patterns provide information about traveled distance. These studies have reported that reproduced distances show two types of systematic biases: central tendency and serial dependence. In the present study, we investigated whether these biases are also present in vestibular path integration. Participants were seated on a linear motion platform and performed a distance reproduction task in total darkness. The platform first passively moved the participant a pre-defined stimulus distance which they then actively reproduced by steering the platform back the same distance. Stimulus distances were sampled from short- and long-distance probability distributions and presented in either a randomized order or in separate blocks to study the effect of presentation context. Similar to the effects observed in visual path integration, we found that reproduced distances showed an overall positive central tendency effect as well as a positive, attractive serial dependence effect. Furthermore, reproduction behavior was affected by presentation context. These results were mostly consistent with predictions of a Bayesian Kalman-filter model, originally proposed for visual path integration.New & NoteworthyDistance reproduction tasks based on visual information about the traveled distance have shown that reproductions are biased by central tendency and serial dependence effects. Here, we show that distance reproductions based on vestibular signals show similar biases and that the reproductions are affected by the presentation order of the stimulus distances.
Engineering a probioticBacillus subtilisfor acetaldehyde removal: Ahaglocus integration to robustly express acetaldehyde dehydrogenase
Authors: Hassan-Casarez Chandler , Ryan Valerie , Shuster Bentley , Oliver John W. K. , Abbott Zachary D. 
Published: June 2024

AbstractWe have identified solutions to key challenges in probiotic design to create a commercially viable strain for the removal of the intestinal toxin acetaldehyde. Here we report engineering of a σD-dependent flagellin expression locus, hag, as a stable location for robust enzyme production. We demonstrate constitutive gene expression in relevant conditions driven by the endogenous hag promoter following a deletion of the gene encoding a post-translational regulator of σD, FlgM, and a point mutation to abrogate the binding of the translational inhibitor CsrA. Reporter constructs demonstrate hag locus activity after germination and show a steady increase in heterologous expression throughout outgrowth and resumption of vegetative growth. To test the chassis as a spore-based probiotic solution we identified the physiologically relevant pathway of ethanol metabolism and the buildup of gut-derived acetaldehyde after alcohol consumption. Herein, we describe the integration of a robustly expressed Cupriavidus necator aldehyde dehydrogenase, AcoD, under a flagellin protein promoter at the hag locus and report the rapid reduction of acetaldehyde levels after germination in gut simulated conditions.