bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deep learningversusgeometric morphometrics for archaeobotanical domestication study and subspecific identification
Authors: Bonhomme Vincent , Bouby Laurent , Claude Julien , Dham Camille , Gros-Balthazard Muriel , Ivorra Sarah , Jeanty Angèle , Pagnoux Clémence , Pastor Thierry , Terral Jean-Frédéric , Evin Allowen 
Published: September 2023

AbstractTaxonomical identification of archaeological fruit and seed is of prime importance for any archaeobotanical studies. We compared the relative performance of deep learning and geometric morphometrics at identifying pairs of plant taxa. We used their seeds and fruit stones that are the most abundant recovered organs in archaeobotanical assemblages, and whose morphological identification, chiefly between wild and domesticated types, allow to document their domestication and biogeographical history. We used existing modern datasets of four plant taxa (date palm, barley, olive and grapevine) corresponding to photographs of two orthogonal views of their seeds that were analysed separately to offer a larger spectrum of shape diversity. On these eight datasets, we compared the performance of a deep learning approach, here convolutional neural networks (CNN), to that of a geometric morphometric approach, here outline analyses using elliptical Fourier transforms (EFT). Sample sizes were at minimum eight hundred seeds in each class, which is quite small when training deep learning models but of typical magnitude for archaeobotanical studies. Our objectives were twofold: i) to test whether deep learning can beat geometric morphometrics in taxonomic identification and if so, ii) to test which minimal sample size is required. We ran simulations on the full datasets and also on subsets, starting from 50 images in each binary class. For CNN networks, we deliberately used a candid approach relying on pre-parameterised VGG16 network. For EFT, we used a state-of-the art morphometrical pipeline. The main difference rests in the data used by each model: CNN used bare photographs where EFT used (x, y) outline coordinates. This “pre-distilled” geometrical description of seed outlines is often the most time-consuming part of morphometric studies. Results show that CNN beats EFT in most cases, even for very small datasets. We finally discuss the potential of CNN for archaeobotany, why outline analyses and morphometrics have not yet said their last word by providing quantitative descriptions, and how bioarchaeological studies could embrace both approaches, used in a complementary way, to better assess and understand the past history of species.
Complete substitution with modified nucleotides suppresses the early interferon response and increases the potency of self-amplifying RNA
Authors: McGee Joshua E. , Kirsch Jack R. , Kenney Devin , Chavez Elizabeth , Shih Ting-Yu , Douam Florian , Wong Wilson W. , Grinstaff Mark W. 
Published: September 2023

ABSTRACTSelf-amplifying RNA (saRNA) will revolutionize vaccines andin situtherapeutics by enabling protein expression for longer duration at lower doses. However, a major barrier to saRNA efficacy is the potent early interferon response triggered upon cellular entry, resulting in saRNA degradation and translational inhibition. Substitution of mRNA with modified nucleotides (modNTPs), such as N1-methylpseudouridine (N1mΨ), reduce the interferon response and enhance expression levels. Multiple attempts to use modNTPs in saRNA have been unsuccessful, leading to the conclusion that modNTPs are incompatible with saRNA, thus hindering further development. Here, contrary to the common dogma in the field, we identify multiple modNTPs that when incorporated into saRNA at 100% substitution confer immune evasion and enhance expression potency. Transfection efficiency enhances by roughly an order of magnitude in difficult to transfect cell types compared to unmodified saRNA, and interferon production reduces by >8 fold compared to unmodified saRNA in human peripheral blood mononuclear cells (PBMCs). Furthermore, we demonstrate expression of viral antigensin vitroand observe significant protection against lethal challenge with a mouse-adapted SARS-CoV-2 strainin vivo. A modified saRNA vaccine, at 100-fold lower dose than a modified mRNA vaccine, results in a statistically improved performance to unmodified saRNA and statistically equivalent performance to modified mRNA. This discovery considerably broadens the potential scope of self-amplifying RNA, enabling entry into previously impossible cell types, as well as the potential to apply saRNA technology to non-vaccine modalities such as cell therapy and protein replacement.
Perspectives and Recommendations from Hospitalized Patients with Substance Use Disorders: A Qualitative Study
Authors: Balmuth Evan A. , Iyer Sonali , Scales David A. , Avery Jonathan 
Published: September 2023

ABSTRACTBACKGROUNDIndividuals with substance use disorders (SUDs) are hospitalized in growing numbers. Stigma is pervasive among their hospital providers, and SUD management during medical admissions is often inadequate. However, little is known about how these patients perceive their care quality. In particular, few studies have explored their positive care perceptions or recommendations for improvement.OBJECTIVETo explore perspectives on positive aspects, negative aspects, and consequences of care, as well as recommendations for improvement among hospitalized patients with SUDs.DESIGN AND PARTICIPANTSWe conducted semi-structured, in-depth bedside interviews (n= 15) with patients who have been diagnosed with a SUD and were admitted to medical or surgical floors of an urban academic medical center.APPROACHInterviews explored patients’ hospital experiences and recommendations for improvement. The interviews were audio-recorded, transcribed verbatim, and imported into NVivo software. Two reviewers independently coded the transcripts using interpretative phenomenological analysis and inductive thematic analysis according to grounded theory, and recurring themes were identified from the data. Patients’ demographic and clinical data were analyzed with descriptive statistics.KEY RESULTSPerceived clinical and emotional proficiency were the most important components of positive experiences, whereas perceived bias and stigmatized attitudes, clinical improficiency, and inhumane treatment were characteristic of negative experiences. Such care components were most consequential for patients’ emotional wellbeing, trust, and care quality. Recommendations for improving care included specific suggestions for initiating and promoting continued recovery, educating, and partnering in compassionate care.CONCLUSIONSHospitalized patients with SUDs often experience lower quality and less compassionate care linked to pervasive stigma and poor outcomes. Our study highlights under-recognized perspectives from this patient population, including socioemotional consequences of care and recommendations grounded in lived experiences. By striving to advance our care in accordance with patients’ viewpoints, we can turn hospitalizations into opportunities for engagement and promoting recovery.
Prevalence of DSM-5 mild and major neurocognitive disorder in India: Results from the LASI-DAD
Authors: Gross Alden L. , Nichols Emma , Angrisani Marco , Ganguli Mary , Jin Haomiao , Khobragade Pranali , Langa Kenneth M. , Meijer Erik , Varghese Mathew , Dey AB , Lee Jinkook 
Published: September 2023

AbstractIntroductionIndia, with its rapidly aging population, faces an alarming burden of dementia. We implemented DSM-5 criteria in large-scale, nationally representative survey data in India to characterize the prevalence of mild and major Neurocognitive disorder.MethodsThe Longitudinal Aging Study in India’s Diagnostic Assessment of Dementia (LASI-DAD) (N=4,096) is a nationally representative cohort study in India including 36 Indian states and union territories using multistage area probability sampling methods. Using neuropsychological testing and informant reports, we defined DSM-5 mild and major neurocognitive disorder, reported its prevalence, and evaluated criterion and construct validity of the algorithm using clinician-adjudicated Clinical Dementia Ratings (CDR).ResultsThe prevalence of mild and major neurocognitive disorder, weighted to the population, is 17.6% and 7.2%. Demographic gradients with respect to age and education conform to hypothesized patterns. Among N=2390 participants with a clinician-adjudicated CDR, CDR ratings and DSM-5 classification agreed for N=2,139 (89.5%) participants.DiscussionThe prevalence of dementia in India is higher than previously recognized. These findings, coupled with a growing number of older adults in the coming decades in India, have important implications for society, public health, and families. We are aware of no previous Indian population-representative estimates of mild cognitive impairment, a group which will be increasingly important in coming years to identify for potential therapeutic treatment.
Mindfulness facets and psychological well-being among meditators: Serenity as a mediating process
Authors: Cheung Rebecca Y. M. , Wang Iris Yili , Lau Elsa Ngar-Sze 
Published: September 2023

AbstractGuided by the theoretical processes of mindfulness and psychological well-being, this study examined serenity as a mediator between mindfulness facets and psychological well-being, as indexed by depressive symptoms and life satisfaction. Participants were 133 mindfulness practitioners who took part in a 3-day transnational meditation event in Hong Kong. Upon informed consent, participants completed a self-report questionnaire. The findings from structural equation modeling showed that serenity mediated the relation between two facets of mindfulness, including describing and nonreacting to inner experience, and life satisfaction. Serenity also mediated the relation between the mindfulness facet of describing and depressive symptoms. Direct associations were indicated between two mindfulness facets, including observing and nonjudging of inner experience, and depressive symptoms. Taken together, the findings revealed mindfulness facets as major correlates of serenity and psychological outcomes among Chinese meditation practitioners. To foster psychological well-being, researchers, educators, and practitioners should pay attention to role of serenity, describing, and nonreacting to inner experience in mental health.
WITHDRAWN: Exposure to Ambient Particulate Matter during Pregnancy: Implications for Infant Telomere Length
Authors: Ahlers Nina E. , Lin Jue , Weiss Sandra J. 
Published: September 2023

Withdrawal StatementThis manuscript has been withdrawn by the authors as it was submitted and made public without the full consent of all the authors. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.The authors have an approved version for citation that is peer reviewed. Ahlers, N.E.; Lin, J.; Weiss, S.J. Exposure to Ambient Particulate Matter during Pregnancy: Implications for Infant Telomere Length. Air 2024, 2, 24-37.https://doi.org/10.3390/air2010002
Sex-specific differences in physiological parameters related to SARS-CoV-2 infections among a national cohort (COVI-GAPP study)
Authors: Grossmann Kirsten , Risch Martin , Markovic Andjela , Aeschbacher Stefanie , Weideli Ornella C , Velez Laura , Kovac Marc , Pereira Fiona , Wohlwend Nadia , Risch Corina , Hillmann Dorothea , Lung Thomas , Renz Harald , Twerenbold Raphael , Rothenbühler Martina , Leibovitz Daniel , Kovacevic Vladimir , Klaver Paul , Brakenhoff Timo B , Franks Billy , Mitratza Marianna , Downward George S , Dowling Ariel , Montes Santiago , Veen Duco , Grobbee Diederick E , Cronin Maureen , Conen David , Goodale Brianna M , Risch Lorenz 
Published: September 2023

AbstractConsidering sex as a biological variable in modern digital health solutions, we investigated sex-specific differences in the trajectory of four physiological parameters across a COVID-19 infection.A wearable medical device measured breathing rate, heart rate, heart rate variability, and wrist skin temperature in 1163 participants (mean age = 44.1 years, standard deviation [SD]=5.6; 667 [57%] females). Participants reported daily symptoms and confounders in a complementary app. A machine learning algorithm retrospectively ingested daily biophysical parameters to detect COVID-19 infections. COVID-19 serology samples were collected from all participants at baseline and follow-up. We analysed potential sex-specific differences in physiology and antibody titres using multilevel modelling and t-tests.Over 1.5 million hours of physiological data were recorded. During the symptomatic period of infection, men demonstrated larger increases in skin temperature, breathing rate and heart rate as well as larger decreases in heart rate variability than women. The COVID-19 infection detection algorithm performed similarly well for men and women.Our study belongs to the first research to provide evidence for differential physiological responses to COVID-19 between females and males, highlighting the potential of wearable technology to inform future precision medicine approaches.This work has received support from the Princely House of the Principality of Liechtenstein, the government of the Principality of Liechtenstein, the Hanela Foundation in Switzerland, and the Innovative Medicines Initiative (IMI) 2 Joint Undertaking under grant agreement No 101005177. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA.
Neural correlates of visual object recognition in rats
Authors: Rhee Juliana Y. , Echavarría César , Soucy Ed , Greenwood Joel , Masís Javier A. , Cox David D. 
Published: September 2023

SummaryInvariant object recognition—the ability to recognize objects across size, rotation, or context—is fundamental for making sense of a dynamic visual world. Although initially believed to be unique to primates due to its complexity, emerging evidence suggests rodents, too, can recognize objects across a range of identity-preserving transformations. Here, we describe a comprehensive pipeline for investigating visual behavior in rats, from high-throughput training to cellular resolution imaging in awake, head-fixed animals. Using this suite of tools, we demonstrate that rats excel in visual object recognition and explore potential neural pathways which may support this capacity. We leverage our optical approach to systematically profile multiple visual areas with responses to a range of stimulus types recorded in the same neurons. Primary and higher-order areas of rat visual cortex exhibit a hierarchical organization consistent with a role in visual object recognition. However, marked deviations from the functional organization of primate visual cortex suggest species-specific differences in the neural circuits underlying visual object recognition. This work reinforces the notion that rats possess sophisticated visual abilities and offers the technical foundation for their use as a powerful model to link neuronal responses to perception and behavior.
Mechanical regulation of cell fate transitions underlying colorectal cancer metastasis formation
Authors: van der Net Mirjam C , Vliem Marjolein J , Kemp Lars JS , Perez-Gonzalez Carlos , Strating Esther A , Krotenberg-Garcia Ana , Houtekamer Ronja M , van den Anker Karen B , Monster Jooske L , Snippert Hugo JG , Khalil Antoine A , van Rheenen Jacco , Suijkerbuijk Saskia JE , Kranenburg Onno , Matic Vignjevic Danijela , Gloerich Martijn 
Published: September 2023

AbstractColorectal cancer (CRC) cells exhibit high plasticity and transition between different cellular states during the development of metastasis. Lgr5-expressing cancer stem cells fuel the growth of the primary tumor and metastasis, yet disseminated tumor cells arriving at the metastatic site are devoid of Lgr5 expression. It is currently unknown how CRC cell fate transitions are regulated during the metastatic process and how tumor cells give rise to metastatic lesions despite being Lgr5neg. Here, we show that the reprogramming of disseminating CRC cells is driven by mechanical interactions with the Collagen I-rich interstitial matrix. Collagen I-induced pulling forces are sensed by integrins and mechanosensitive calcium channels, which together direct the transition of CRC cells into a fetal-like state. The fetal-like state is maintained after reaching the blood circulation and promotes metastasis-initiation of disseminated CRC cells in the liver. Our findings indicate a key contribution of mechanical signals in controlling cell fate transitions that underlie the metastatic potential of CRC, involving an interplay between different mechanosensitive mechanisms.
NDH complex-mediated cyclic electron flow in bundle sheath cells enables C4photosynthesis
Authors: Ermakova Maria , Woodford Russell , Fitzpatrick Duncan , Zwahlen Soraya M. , Farquhar Graham , von Caemmerer Susanne , Furbank Robert T. 
Published: September 2023

AbstractThe superior productivity of C4plants is achieved via a metabolic C4cycle which acts as a CO2pump across mesophyll and bundle sheath (BS) cells and requires an additional input of energy in the form of ATP. Chloroplast NADH dehydrogenase-like complex (NDH) increases ATP production in C3plants by operating cyclic electron flow (CEF) around Photosystem I (PSI), and its importance for C4photosynthesis has been proposed from evolutionary and reverse genetics studies. We used the gene-edited C4speciesSetaria viridiswith nullndhOalleles lacking NDH to study a contribution of the complex to the cell-level electron transport. Our results indicate that NDH is the primary PSI electron acceptor mediating the majority of CEF in BS cells whilst the contribution of the complex to CEF in mesophyll cells is minimal. Moreover, the reduced leaf CO2assimilation rate and growth of plants lacking the complex cannot be rescued by supplying additional CO2, indicating that NDH is essential for generating ATP required for CO2fixation by the C3cycle. Hereby we resolve a cell-level mechanism for the contribution of NDH to supporting high CO2assimilation rates in C4photosynthesis.
Mitochondrial genome analyses uncover intriguing population structure across the invasive trajectory of an iconic invader
Authors: Cheung K , Amos TG , Shine R , DeVore JL , Ducatez S , Edwards RJ , Rollins LA 
Published: September 2023

AbstractInvasive species offer insights into rapid adaptations in novel environments. The iconic cane toad (Rhinella marina) is an excellent model for studying rapid adaptation during invasion. Previous research using the mitochondrial NADH dehydrogenase 3 (ND3) gene in the Hawai’ian and Australian invasive populations found a single haplotype, indicating an extreme genetic bottleneck following introduction. Nuclear genetic diversity also exhibited reductions across the genome in these two populations. Here, we investigated the mitochondrial genome diversity of cane toads across this invasion trajectory. We created the first reference mitochondrial genome of the cane toad with long-read sequencing and constructed a phylogeny of Anura full mitochondrial genomes. We used transcriptomic data of 125 individuals from the native (French Guiana) and introduced (Hawai’i and Australia) ranges to construct nearly-complete mitochondrial genomes for population genomics analyses. As expected, the cane toad belongs to family Bufonidae, distinct from genusBufo. In agreement with previous investigations of these populations, we identified genetic bottlenecks in both Hawai’ian and Australian introduced populations, alongside evidence of population expansion in the invasive ranges. Although mitochondrial genetic diversity in introduced populations was reduced, our results revealed that it had been underestimated: we identified 45 mitochondrial haplotypes in Hawai’ian and Australian samples, none of which were found in the native range. Additionally, we identified two distinct groups of haplotypes from the native range, separated by a minimum of 110 base pairs (0.6%). These findings enhance our understanding of Anura phylogenetics and how invasion has shaped the genetic landscape of this species.
PERK modulation, with GSK2606414, Sephin1 or salubrinal, failed to produce therapeutic benefits in the SOD1G93A mouse model of ALS
Authors: Vieira Fernando G. , Tassinari Valerie R. , Kidd Joshua D. , Moreno Andrew , Thompson Kenneth , Perrin Steven , Gill Alan , Hatzipetros Theo 
Published: September 2023

AbstractAmyotrophic lateral sclerosis (ALS) has been linked to overactivity of the protein kinase RNA-like ER kinase (PERK) branch of the unfolded protein response (UPR) pathway, both in ALS patients and mouse models. However, attempts to pharmacologically modulate PERK for therapeutic benefit have yielded inconsistent and often conflicting results. This study sought to address these discrepancies by comprehensively evaluating three commonly used PERK modulators (GSK2606414, salubrinal, and Sephin1) in the same experimental models, with the goal of assessing the viability of targeting the PERK pathway as a therapeutic strategy for ALS. To achieve this goal, a tunicamycin-challenge assay was developed using wild-type mice to monitor changes in liver UPR gene expression in response to PERK pathway modulation. Subsequently, multiple dosing regimens of each PERK modulator were tested in standardized, well-powered, gender-matched, and litter-matched survival efficacy studies using the SOD1G93A mouse model of ALS. The alpha-2-adrenergic receptor agonist clonidine was also tested to elucidate the results obtained from the Sephin1, and of the previously reported guanabenz studies, by comparing the effects of presence or absence of α-2 agonism. The results revealed that targeting PERK may not be an ideal approach for ALS treatment. Inhibiting PERK with GSK2606414 or activating it with salubrinal did not confer therapeutic benefits. While Sephin1 showed some promising therapeutic effects, it appears that these outcomes were mediated through PERK-independent mechanisms. Clonidine also produced some favorable therapeutic effects, which were unexpected and not linked to the UPR. In conclusion, this study highlights the challenges of pharmacologically targeting PERK for therapeutic purposes in the SOD1G93A mouse model and suggests that exploring other targets within, and outside, the UPR may be more promising avenues for ALS treatment.