bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incorporating photosynthetic acclimation improves stomatal optimisation models
Authors: Flo Victor , Joshi Jaideep , Sabot Manon , Sandoval David , Prentice Iain Colin 
Published: July 2023

AbstractStomatal opening in plant leaves is regulated through a balance of carbon and water exchange under different environmental conditions. Accurate estimation of stomatal regulation is crucial for understanding how plants respond to changing environmental conditions, particularly under climate change. A new generation of optimality-based modelling schemes determines instantaneous stomatal responses from a balance of trade-offs between carbon gains and hydraulic costs, but most such schemes do not account for biochemical acclimation in response to drought. Here, we compare the performance of seven instantaneous stomatal optimisation models with and without accounting for photosynthetic acclimation. Using experimental data from 38 plant species, we found that accounting for photosynthetic acclimation improves the prediction of carbon assimilation in a majority of the tested models. Non-stomatal mechanisms contributed significantly to the reduction of photosynthesis under drought conditions in all tested models. Drought effects on photosynthesis could not accurately be explained by the hydraulic impairment functions embedded in the stomatal models alone, indicating that photosynthetic acclimation must be considered to improve estimates of carbon assimilation during drought.Summary StatementAccounting for photosynthetic acclimation improves the predictions of carbon assimilation in all the stomatal optimization models evaluated. The influence of drought on photosynthesis cannot be fully explained by the hydraulic impairment function of the stomatal models alone.
Self-supervised Benchmarking for scRNAseq Clustering
Authors: Tyler Scott R , Schadt Eric E , Guccione Ernesto 
Published: July 2023

AbstractInterpretation of single cell RNAseq (scRNAseq) data are typically built upon clustering results and/or cell-cell topologies. However, the validation process is often exclusively left to bench biologists, which can take years and tens of thousands of dollars. Furthermore, a lack of objective ground-truth labels in complex biological datasets, has resulted in difficulties when benchmarking single cell analysis methods. Here, we address these gaps with count splitting, creating a cluster validation algorithm, accounting for Poisson sampling noise, and benchmark 120 pipelines using an independent test-set for ground-truth assessment, thus enabling the firstself-supervisedbenchmark. Anti-correlation-based feature selection paired with locally weighted Louvain modularity on the Euclidean distance of 50 principal-components with cluster-validation showed the best performance of all tested pipelines for scRNAseq clustering, yielding reproducible biologically meaningful populations. These new approaches enabled the discovery of a novel metabolic gene signature associated with hepatocellular carcinoma survival time.
Sex-Specific Effects of Anxiety on Cognition and Activity-Dependent Neural Networks: Insights from (Female) Mice and (Wo)Men
Authors: Hunsberger Holly C. , Lee Seonjoo , Jin Michelle , Lanio Marcos , Whye Alicia , Cha Jiook , Scarlata Miranda , Jayaseelan Keerthana , Denny Christine. A. 
Published: July 2023

ABSTRACTINTRODUCTIONNeuropsychiatric symptoms (NPS), such as depression and anxiety, are observed in 90% of Alzheimer’s disease (AD) patients, two-thirds of whom are women. NPS usually manifest long before AD onset creating a therapeutic opportunity. Here, we examined the impact of anxiety on AD progression and the underlying brain-wide neuronal mechanisms.METHODSTo gain mechanistic insight into how anxiety impacts AD progression, we performed a cross-sectional analysis on mood, cognition, and neural activity utilizing the ArcCreERT2x enhanced yellow fluorescent protein (eYFP) x APP/PS1 (AD) mice. The ADNI dataset was used to determine the impact of anxiety on AD progression in human subjects.RESULTSFemale AD mice exhibited anxiety-like behavior and cognitive decline at an earlier age than control (Ctrl) mice and male mice. Brain-wide analysis of c-Fos+revealed changes in regional correlations and overall network connectivity in AD mice. Sex-specific memory trace changes were observed; female AD mice exhibited impaired memory traces in dorsal CA3 (dCA3), while male AD mice exhibited impaired memory traces in the dorsal dentate gyrus (dDG). In the ADNI dataset, anxiety predicted transition to dementia. Female subjects positive for anxiety and amyloid transitioned more quickly to dementia than male subjects.CONCLUSIONSWhile future studies are needed to understand whether anxiety is a predictor, a neuropsychiatric biomarker, or a comorbid symptom that occurs during disease onset, these results suggest that AD network dysfunction is sexually dimorphic, and that personalized medicine may benefit male and female AD patients rather than a one size fits all approach.
A novel naïve Bayes approach to identifying grooming behaviors in the force-plate actometric platform
Authors: Anderson Collin J , Cadeddu Roberto , Anderson Daria Nesterovich , Huxford Job A , VanLuik Easton R , Odeh Karen , Pittenger Christopher , Pulst Stefan M , Bortolato Marco 
Published: July 2023

AbstractBackgroundSelf-grooming behavior in rodents serves as a valuable model for investigating stereotyped and perseverative responses. Most current grooming analyses primarily rely on video observation, which lacks standardization, efficiency, and quantitative information about force. To address these limitations, we developed an automated paradigm to analyze grooming using a force-plate actometer.New MethodGrooming behavior is quantified by calculating ratios of relevant movement power spectral bands. These ratios are then input into a naïve Bayes classifier, trained with manual video observations. To validate the effectiveness of this method, we applied it to the behavioral analysis of the early-life striatal cholinergic interneuron depletion (CIN-d) mouse, a model of tic pathophysiology recently developed in our laboratory, which exhibits prolonged grooming responses to acute stressors. Behavioral monitoring was simultaneously conducted on the force-place actometer and by video recording.ResultsThe naïve Bayes approach achieved 93.7% accurate classification and an area under the receiver operating characteristic curve of 0.894. We confirmed that male CIN-d mice displayed significantly longer grooming durations compared to controls. However, this elevation was not correlated with increases in grooming force. Notably, haloperidol, a benchmark therapy for tic disorders, reduced both grooming force and duration.Comparison with Existing MethodsIn contrast to observation-based approaches, our method affords rapid, unbiased, and automated assessment of grooming duration, frequency, and force.ConclusionsOur novel approach enables fast and accurate automated detection of grooming behaviors. This method holds promise for high-throughput assessments of grooming stereotypies in animal models of tic disorders and other psychiatric conditions.
Discovery of novel G-quadruplex stabilizing compounds from medicinal plant & Evaluates their cellular toxicity
Authors: Neha  , Ranjan Prashant , Das Parimal 
Published: July 2023

AbstractG-Quadruplexes (G4Q) are higher-order, four-stranded structures that can be formed by repeated guanine tracts in human genomes. In this study, we used a structure-based virtual screening of phytomolecules derived from medicinal plants in order to discover new natural DNA G4Q binders. The top 40 ligands were sorted out based on binding affinity values after completing a docking study on 314 phytomolecule samples with parallel and mixed hybrid structure. Further Thermal melting, circular dichroism, and fluorescence displacement experiment was used as a preliminary screening tool to determine the potential stabilizing properties of β-sitosterol-β-D-glucoside, and Glabrolide. The cytotoxicity experiments were conducted on HEK293T cells and found that both of the tested phyto molecules are non-toxic for up to 150 μM concentration. Based on their cytotoxic experiments at the suggested high concentration, these phyto molecules may potentially be employed as G-Quadruplex targets in future research or applications. These results suggest that the plant may be a “lead” in the future for the development of novel therapies for diseases.
Increasing adult-born neurons protects mice from epilepsy
Authors: Jain Swati , LaFrancois John J. , Gerencer Kasey , Botterill Justin J. , Kennedy Meghan , Criscuolo Chiara , Scharfman Helen E. 
Published: July 2023

ABSTRACTNeurogenesis occurs in the adult brain in the hippocampal dentate gyrus, an area that contains neurons which are vulnerable to insults and injury, such as severe seizures. Previous studies showed that increasing adult neurogenesis reduced neuronal damage after these seizures. Because the damage typically is followed by chronic life-long seizures (epilepsy), we asked if increasing adult-born neurons would prevent epilepsy. Adult-born neurons were selectively increased by deleting the pro-apoptotic geneBaxfrom Nestin-expressing progenitors. Tamoxifen was administered at 6 weeks of age to conditionally deleteBaxin Nestin-CreERT2Baxfl/flmice. Six weeks after tamoxifen administration, severe seizures (status epilepticus; SE) were induced by injection of the convulsant pilocarpine. After mice developed epilepsy, seizure frequency was quantified for 3 weeks. Mice with increased adult-born neurons exhibited fewer chronic seizures. Postictal depression was reduced also. These results were primarily in female mice, possibly because they were the more affected byBaxdeletion than males, consistent with sex differences inBax. The female mice with enhanced adult-born neurons also showed less neuronal loss of hilar mossy cells and hilar somatostatin-expressing neurons than wild type females or males, which is notable because these two hilar cell types are implicated in epileptogenesis. The results suggest that selectiveBaxdeletion to increase adult-born neurons can reduce experimental epilepsy, and the effect shows a striking sex difference. The results are surprising in light of past studies showing that suppressing adult-born neurons can also reduce chronic seizures.
Integrating Community-Based Health Information System with a Patient-Centered Medical Home to Improve Care of Patients with Hypertension: A Longitudinal Observational Study Protocol
Authors: Khan Unab I. , Shah Sabeen , Viswanathan Shankar , Qureshi Asra , Noornabi Yasmeen , Niaz Mahnoor , Wylie-Rosett Judith 
Published: July 2023

AbstractIntroductionVertical health delivery models in Pakistan focus on providing episodic, disease-based care. Health care for middle-class communities is largely through a fee-for-service model that ignores preventive care. The growing burden of cardiovascular illnesses requires restructuring of primary health care system allowing well-coordinated efforts between patients and providers. We propose a model of care that integrates a Patient-Centered Medical Home (PCMH) with a Community-Based Health Information System (CBHIS) for bidirectional communication at the patient and community level. This protocol describes the integration and evaluation of the PCMH-CBHIS infrastructure using hypertension (HTN) as a model.MethodsThis is a population-based, observational, longitudinal study in an urban setting in Pakistan. Through convenience sampling, participants will be enrolled in CBHIS and followed longitudinally over two years for HTN outcomes. A mixed-methods approach will be used to evaluate the process of integrating PCMH with CBHIS. This will involve building partnerships with the community through formal and informal meetings, focus group discussions, and a household health assessment survey. Community members identified with HTN will be linked to PCMH for disease management and skills to improve self-management. A customized electronic medical record system will be developed to link community-level data with family and patient-level data to track changes in disease burden. The RE-AIM evaluation framework will be used to monitor community and individual-level metrics to guide implementation assessment, the potential for generalization, and the effectiveness of the PCMH in improving health outcomes.Ethics and dissemination planEthical clearance was obtained from Ethics Review Committee at Aga Khan University (2022-6723-20985). We plan to present the findings from this research at conferences and publish them in peer-reviewed journals. Additionally, we intend to leverage findings from this research to obtain funds focusing on chronic disease care in similar settings.Article SummaryStrengths and limitations of this studyThe study integrates a comprehensive health assessment survey to assess the disease burden at the community level to guide the prioritization of health services and prevention efforts at the health facility.A mixed methods approach will be used to measure the effectiveness of hypertension management through the proposed model of care.The development of a customized electronic medical record system will allow aligning clinic- and community-based activities.Community members may migrate from the catchment area, limiting the longitudinal assessment of hypertension management.With a patient-driven model, we cannot predict how many community participants would choose the health facility for ongoing care.
Declining use of clean cooking fuels & food security in 2022: Downstream impact of the Russian-Ukrainian war in a Kenyan informal urban settlement
Authors: Shupler Matthew , Mwitari James , O’Keefe Mark , Lorenzetti Federico , Nabukwangwa Willah , Gohole Arthur , Perros Tash , Nix Emily , Puzzolo Elisa , Pope Daniel , Osiolo Helen Hoka 
Published: July 2023

ABSTRACTEnergy market turmoil due to the Russian-Ukrainian war increased global fuel/food prices. While risks to energy and food security have been suggested, little research has documented impacts for the most vulnerable. During September-October 2022, surveys were administered to 701 households using pay-as-you-go liquefied petroleum gas (PAYG LPG) for clean cooking in an informal settlement in Nairobi, Kenya. Paired t-tests compared PAYG LPG consumption/payment behaviors before (July-October 2021) and during a >15% inflationary food price period (July-October 2022). Three-quarters (74%; %; n=520) of all households and 94% of food insecure households (n=393; 54% of sample) changed their dietary behavior (changed foods cooked, skipped more meals, and/or reduced PAYG LPG consumption) in 2022. Between July-October 2021 and 2022, PAYG LPG prices increased by 16% (214 Kenyan Shilling (KSh)/kg ($1.53USD/kg) to 249 KSh/kg ($1.78USD/kg) and households reduced their monthly PAYG LPG expenditure by 79% (856 KSh ($6.07USD) to 184 KSh ($1.31USD)). Although 97% of participants continued using PAYG LPG in July-October 2022, average consumption declined by two-thirds (0.82 to 0.27 kg/capita/month; difference(paired-t):-0.28 95%CI:[-0.36,-0.21]). Higher food and LPG prices in 2022 led to substantial declines in food security and LPG consumption in an informal urban settlement, highlighting increased obstacles to achieving the Sustainable Development Goals.Highlights67% reduction (0.82 to 0.27 kg/capita/month) in mean PAYG LPG use between 2021 and 202297% of homes continued using LPG but monthly fuel expenditure decreased 79% between 2021- 202256% of households were food insecure94% of food insecure homes changed foods cooked, skipped meals or reduced LPG use in 2022One of first studies linking rising food prices with declines in clean energy consumptionSynopsisUsing smart meter data, this study illustrates that LPG consumption for cooking dropped by two-thirds and food insecurity increased in an informal urban settlement due to higher food costs in 2022.
Single-dose effectiveness of mpox vaccine in Quebec, Canada: test-negative design with and without adjustment for self-reported exposure risk
Authors: Brousseau Nicholas , Carazo Sara , Febriani Yossi , Padet Lauriane , Hegg-Deloye Sandrine , Cadieux Geneviève , Bergeron Geneviève , Fafard Judith , Charest Hugues , Lambert Gilles , Talbot Denis , Longtin Jean , Dumont-Blais Alexandre , Bastien Steve , Dalpé Virginie , Minot Pierre-Henri , De Serres Gaston , Skowronski Danuta M. 
Published: July 2023

AbstractIntroductionDuring the 2022 mpox outbreak, the province of Quebec, Canada prioritized first doses for pre-exposure vaccination of people at high mpox risk, delaying second doses due to limited supply. We estimated single-dose mpox vaccine effectiveness (VE) adjusting for virus exposure risk based only on surrogate indicators available within administrative databases (e.g. clinical record of sexually transmitted infections), or supplemented by self-reported risk factor information (e.g. sexual contacts).MethodsWe conducted a test-negative case-control study between June 19 and September 24, 2022. Information from administrative databases was supplemented by a questionnaire collecting self-reported risk factors specific to the three-week period before testing. Two study populations were assessed: all within the administrative databases (All-Admin) and the subset completing the questionnaire (Sub-Quest). Logistic regression models were adjusted for age, calendar-time and exposure-risk, the latter based on administrative indicators only (All-Admin and Sub-Quest populations) or supplemented by questionnaire information (Sub-Quest population).ResultsThere were 532 All-Admin participants, of which 199 (37%) belonged to Sub-Quest. With exposure-risk adjustment based only on administrative indicators, single-dose mpox VE among All-Admin and Sub-Quest populations was similar at 35% (95%CI:-2-59) and 30% (95%CI:-38-64), respectively. With adjustment supplemented by questionnaire information, Sub-Quest VE increased to 65% (95%CI:1-87). Protection against severe outcomes was higher (VE=82%; 95%CI:-50-98) but with overlapping confidence intervals.ConclusionsOne vaccine dose reduced mpox risk by about two-thirds when adjustment incorporated self-reported risk factors, but by only one-third when adjustment relied solely upon administrative indicators. Inadequate adjustment for exposure risk may substantially under-estimate mpox VE.
Modeling the Therapeutic Process of Patients with Cocaine Use Disorders: The Texas Christian University Process Model as a Guidance to Predict Readmission
Authors: Dacosta-Sánchez Daniel , Fernández-Calderón Fermín , Díaz-Batanero Carmen , Mancheño-Velasco Cinta , Lozano Óscar M. 
Published: July 2023

AbstractBackgroundPatients readmitted for Cocaine Use Disorders are, along with Opiates Use Disorder, one of the group of patients with highest demand of treatment in specialized centers of addiction and with greater therapeutic failure.ObjectiveOur aim is to apply the Texas Christian University Process Model to modeling the relationships between patient’s attributes at intake of treatment, treatment progress indicators and outcomes, including treatment success and readmissions.MethodA retrospective observational design was used with 10,298 Cocaine Use Disorder patients. Electronic health records were used for statistical analysis of the data. Randomized subsample 1 (n= 5,150) was used for exploratory analysis and subsample 2 (n = 5,148) to modeling variables relations.ResultsPatients attributes at intake have limited relevance in explaining the treatment progress indicators and outcomes. Time on treatment and patient’s adherence are relevant to explain treatment success. Readmissions are mainly explained by time in treatment and therapeutic success. Been referred to addiction centers by health of services also appear to be relevant.Discussion and conclusionOur study reflects that the therapeutic process is important in order to have and adequate therapeutic adherence and to stay longer in treatment. Patients with a successful treatment and longer stay in treatment are less likely to have future readmissions. Through this study we highlight, therefore, the value of an adequate therapeutic adherence to obtain successful short- and medium-term results. This would make the treatment of these patients more efficient, and alleviate suffering for the patients and their families.
Tetracycline transactivator overexpression in keratinocytes triggers a TRPV1 primary sensory neuron-dependent neuropathic itch
Authors: Crowther Andrew J. , Kashem Sakeen W. , Jewell Madison E. , Chang Henry Le , Casillas Mariela Rosa , Midavaine Élora , Rodriguez Sian , Braz Joao M. , Kania Artur , Basbaum Allan I. 
Published: July 2023

AbstractMouse models that combine tetracycline-controlled gene expression systems and conditional genetic activation can tightly regulate transgene expression in discrete cell types and tissues. However, the commonly used Tet-Off variant, tetracycline transactivator (tTA), when overexpressed and fully active, can lead to developmental lethality, disease, or more subtle behavioral phenotypes. Here we describe a profound itch phenotype in mice expressing a genetically encoded tTA that is conditionally activated within the Phox2a lineage. Phox2a; tTA mice develop intense, localized scratching and regional skin lesions that can be controlled by the tTA inhibitor, doxycycline. As gabapentin, but not morphine, relieved the scratching, we consider this phenotype to result from chronic neuropathic itch, not pain. In contrast to the Phox2a lineage, mice with tTA activated within the Phox2b lineage, which has many similar areas of recombination within the nervous system, did not recapitulate the scratching phenotype. In Phox2a-Cre mice, but not Phox2b-Cre, intense Cre-dependent reporter expression was found in skin keratinocytes which formed the area at which skin lesions developed. Most interestingly, repeated topical application of the DREADD agonist, CNO, which chronically induced Gisignaling in Phox2a-keratinocytes, completely reversed the localized scratching and skin lesions. Furthermore, ablation of TRPV1-expressing, primary afferent neurons reduced the scratching with a time course comparable to that produced by Gi-DREADD inhibition. These temporal properties suggest that the neuropathic itch condition arises not only from localized keratinocyte activation of peripheral nerves but also from a persistent, gabapentin-sensitive state of central sensitization.