bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-Term Forecasting of a Motor Outcome Following Rehabilitation in Chronic Stroke via a Hierarchical Bayesian Model of Motor Learning
Authors: Schweighofer Nicolas , Ye Dongze , Luo Haipeng , D’Argenio David Z. , Winstein Carolee 
Published: October 2022

AbstractBackgroundGiven the heterogeneity of stroke, it is important to determine the best course of motor therapy for each patient, i.e., to personalize rehabilitation based on predictions of long-term outcomes. Here, we propose a Hierarchical Bayesian dynamical (i.e., state-space) model of motor learning to forecast long-term changes in a motor outcome due to rehabilitation in the chronic phase post-stroke.MethodsThe model incorporates the effects of clinician-supervised training, self-training, and forgetting. In addition, to improve forecasting early in rehabilitation, when data are sparse or unavailable, we use a hierarchical Bayesian structure, which incorporates prior information from similar patients. We use this dynamical model to re-analyze Motor Activity Log (MAL) data of participants with chronic stroke included in two clinical trials: 1) the DOSE trial, in which participants were assigned to a 0, 15, 30, or 60-hour dose condition (data of 40 participants analyzed), and 2) the EXCITE trial, in which participants were assigned a 60-hour dose, in either an immediate or a delayed condition (95 participants analyzed).ResultsFor both datasets, the dynamical model accounts well for individual trajectory in the MAL during and outside of training and better fits the data than other simpler models without the effects of either supervised training, self-training or forgetting or (static) regression models. We then show how the model can be used to forecast the MAL of new participants up to 8 months ahead and how the hierarchical structure improves the accuracy of the predictions early in training when data are sparse. Finally, we verify that this model, despite its simplicity, can reproduce previous findings of the DOSE trial on the efficiency, efficacy, and retention of motor therapy.ConclusionIn future work, such forecasting models can be simulated for different stages of recovery, dosages, and training schedules to optimize rehabilitation for each person.
An integrated compositional approach to investigating the full effect of dietary intake on health
Authors: Corrêa Leite Maria Léa 
Published: October 2022

AbstractNutritional epidemiology studies aim to investigate the impact of diet on disease risk, and their findings inform subsequent dietary recommendations. The issue of whether foods or nutrients should be the unit of exposure in such studies is a topic of debate. However, although nutrient-based analyses can elucidate biological mechanisms, they are technically problematic; furthermore, although foods have been considered the most suitable unit of dietary exposure because “we eat food, not nutrients” and the findings of food-based analyses can be easily translated into dietary advice, there is a greater risk of confounding and/or reverse causation because food selection and consumption are closely related to socio-economic and behavioural factors. This note describes an integrated approach that combines the positive aspects of nutrient-and food-based analyses. Individual dietary exposure is characterised by its overall macro-and micronutrient compositions and, in line with the compositional nature of dietary data, methods based on log-ratio transformations of nutrient compositions are used in diet/outcome association analyses that provide fully adjusted isocaloric estimates of the impact of specific nutrient balances on health outcomes. These estimates can then be combined with the nutrient compositions of selected foods to produce outcome-related scores which, as they are defined regardless of a subject’s food selection/consumption, are not subject to confounding or reverse causation, and therefore have important implications for public health professionals. Data coming from an Italian population-based study were used to illustrate the approach in the context of diet/serum uric acid relationships, and some resulting new insights were briefly discussed.
Efficacy of Linear Regression Modelling of SARS-CoV-2 cases based on local wastewater surveillance
Authors: Lehmann Martin , Geissler Michael , Hahn Waldemar , Gebler Richard , Helm Björn , Dumke Roger , Dalpke Alexander , Wolfien Markus 
Published: October 2022

AbstractIn the ongoing SARS-CoV-2 pandemic, there is a need for new strategies for surveillance and identification of arising infection waves. Reported cases of new infections based on individual testing are soon deemed inaccurate due to ever changing regulations and limited testing capacity. Wastewater based epidemiology is one promising solution that can be broadly applied with low efforts in comparison to current large-scale testing of individuals. Here, we are combining local wastewater data from the city of Dresden (Germany) along with reported cases and vaccination data from a central database (Robert-Koch-Institute) with virus variant information to investigate the correlation of virus concentrations in the wastewater and reported SARS-CoV-2 cases. In particular, we compared Linear Regression and Machine Learning (ML) models, which are both revealing an existing correlation of virus particles in wastewater and reported cases. Our findings demonstrate that the different virus variants of concern (Alpha, Delta, BA.1, and BA.2) contribute differently over time and parameters vary between variants, as well. By comparing the Linear Regression and ML-based models, we observed that ML can achieve a good fit for training data, but Linear Regression is a more robust tool, especially for new virus variants. We hereby conclude that deriving the rate of new infections from local wastewater by applying Linear Regression may be a robust approximation of tracing the state of the pandemic for practitioners and policy makers alike.
Meeting the 2030 End TB goals in the wake of COVID-19: a modelling study of countries in the USAID TB portfolio
Authors: Arinaminpathy Nimalan , Mukadi Ya Diul , Bloom Amy , Vincent Cheri , Ahmedov Sevim 
Published: October 2022

AbstractProgress towards the 2030 End TB goals has seen severe setbacks due to disruptions arising from the COVID-19 pandemic. For governments and international partner organizations supporting the global TB response, there is a need to assess what level of effort is now needed to reach these goals. Using mathematical modelling, we addressed this question for the countries being supported by the United States Agency for International Development (USAID). We aggregated the 24 countries in the USAID portfolio into three geographical country groups: South Asia; sub-Saharan Africa; and Central Asian Republics/Europe (CAR/EU). From 2023 onwards we modelled a combination of interventions acting at different stages of the care cascade, including improved diagnostics; reducing the patient care seeking delay; and the rollout of a disease-preventing vaccine from 2025 onwards. We found that in all three country groups, meeting the End TB goals by 2030 will require a combination of interventions acting at stages of the TB care cascade. Specific priorities may depend on country settings, for example with public-private mix playing an important role in countries in South Asia and elsewhere. When a vaccine becomes available, its required coverage to meet the 2030 goals will vary by setting, depending on the amount of preventive therapy that has already been implemented. Monitoring the number-needed-to-test to identify 1 person with TB in community settings can provide a useful measure of progress towards the End TB goals.
Association of indoor use of pesticides with CKD of unknown origin
Authors: Alvand Saba , Alatab Sudabeh , Dalvand Sahar , Shahraki-Sanavi Fariba , Kaykhaei Mahmoud Ali , Shahraki Elham , Barar Erfaneh , Sepanlou Sadaf G , Ansari-Moghaddam Alireza 
Published: October 2022

AbstractDiabetes mellitus and hypertension are the two main etiologies of chronic kidney disease (CKD). However, CKD subjects of unknown origin (CKDu) have been recognized recently. One of the proposed causes is pesticide use in farmers. On the other hand, house use of pesticides has never been investigated in developing countries. In this study, we aimed to investigate the association between house use of pesticide and their exposure time with CKDu. This study is part of the population-based cohort of Prospective Epidemiological Research Studies in Iran. We used the baseline data of the Zahedan Adult Cohort Study. We dropped all subjects with diabetes mellitus and/ or hypertension, egfr 60-89 ml/min/1.73 m2, and unavailable creatinine measurement. Subjects with egfr of less than 60 ml/min/1.73 m2through MDRD equations were defined as CKDu and compared with subjects with egfr of more than 90 ml/min/1.73 m2. The house use of pesticides and exposure time were asked through a questionnaire. In this study 10072 participants enrolled, and 1079 remained in the final sample after appliance the exclusion criteria. Female sex, single marital status, low physical activity, TG more than 150 mg/dl, BMI of more than 25, non-smokers, house use of pesticide, and more time exposed to pesticides were associated with CKDu. The effects of age, female sex, TG more than 150 mg/dl, pesticide use (1.36;95%CI 1.01-1.84), and the third tertile of exposure time compared to non-users (1.64;95%CI 1.07-2.51) remained significant in multivariable analysis. We found a positive association between the use and exposure time with kidney function in cases without diabetes mellitus and hypertension. Further longitudinal studies should be carried out to assess this effect.
Mechano-Cas12a Assisted Tension Sensor (MCATS) for Massively Amplified Cell Traction Force Measurements
Authors: Duan Yuxin , Szlam Fania , Hu Yuesong , Chen Wenchun , Li Renhao , Ke Yonggang , Sniecinski Roman , Salaita Khalid 
Published: October 2022

AbstractCells transmit piconewton forces to mediate essential biological processes such as coagulation. One challenge is that cell-generated forces are infrequent, transient, and difficult to detect. Here, we report the development of Mechano-Cas12a Assisted Tension Sensor (MCATS) that utilizes CRISPR-Cas12a to transduce and amplify the molecular forces generated by cells. We demonstrate the power of MCATS by detecting the forces generated by as few as ~103human platelets in a high-throughput manner. Platelet forces are significantly inhibited when blood samples are treated with FDA-approved drugs such as aspirin, eptifibatide(integrilin®), 7E3(Reopro®), and ticagrelor (Brelinta®). Because MCATS requires <5uL of blood/measurement, a single blood draw can generate a personalized dose-response curve and IC50for this panel of drugs. Platelet activity and force-generation are tightly associated, and hence MCATS was used to quantify platelet dysfunction following cardiopulmonary bypass (CPB) in a pilot study of 7 cardiac patients. We found that MCATS detected platelet dysfunction which strongly correlated with the need for platelet transfusion to limit bleeding. These results indicate MCATS may be a useful assay for clinical applications.
Hexanucleotide repeat expansions in C9orf72 alter microglial responses and prevent a coordinated glial reaction in ALS
Authors: Masrori Pegah , Bijnens Baukje , Davie Kristofer , Poovathingal Suresh Kumar , Storm Annet , Hersmus Nicole , Fumagalli Laura , Van Den Bosch Ludo , Fiers Mark , Thal Dietmar Rudolf , Mancuso Renzo , Van Damme Philip 
Published: October 2022

SummaryNeuroinflammation is an important hallmark in amyotrophic lateral sclerosis (ALS). Experimental evidence has highlighted a role of microglia in the modulation of motor neuron degeneration. However, the exact contribution of microglia to both sporadic and genetic forms of ALS is still unclear. We generated single nuclei profiles of spinal cord and motor cortex from sporadic andC9orf72ALS patients, as well as controls. We particularly focused on the transcriptomic responses of both microglia and astrocytes. We confirmed thatC9orf72is highly expressed in microglia and shows a diminished expression in carriers of the hexanucleotide repeat expansion (HRE). This resulted in an impaired response to disease, with specific deficits in phagocytic and lysosomal transcriptional pathways. Astrocytes also displayed a dysregulated response inC9orf72ALS patients, remaining in a homeostatic state. This suggests that C9orf72 HRE alters a coordinated glial response, which ultimately would increase the risk for developing ALS. Our results indicate thatC9orf72HRE results in a selective microglial loss-of-function, likely impairing microglial-astrocyte communication and preventing a global glial response. This is relevant as it indicates that sporadic and familial forms of ALS may present a different cellular substrate, which is of great importance for patient stratification and treatment.
Species Richness and Speciation Rates for all Terrestrial Animals Emerge from a Synthesis of Ecological Theories
Authors: Fernandes Lucas D. , Hintzen Rogier E. , Thompson Samuel E. D. , Barychka Tatsiana , Tittensor Derek , Harfoot Mike , Newbold Tim , Rosindell James 
Published: October 2022

AbstractThe total number of species on earth and the rate at which new species are created are fundamental questions for ecology, evolution and conservation. These questions have typically been approached separately, despite their obvious interconnection. In this manuscript we approach both questions in conjunction, for all terrestrial animals, which enables a more holistic integration and generates novel emergent predictions. To do this, we combine two previously unconnected bodies of theory: general ecosystem modelling and individual based ecological neutral theory. General ecosystem models provide us with estimated numbers of individual organisms, separated by functional group and body size. Neutral theory, applied within a guild of functionally similar individuals, connects species richness, speciation rate and number of individual organisms. In combination, for terrestrial endotherms where species numbers are known, they provide us with estimates for speciation rates as a function of body size and diet class. Extrapolating the same rates to guilds of ectotherms enables us to estimate the species richness of those groups, including species yet to be described. We find that speciation rates per species per million years decrease with increasing body size. Rates are also higher for carnivores compared to omnivores or herbivores of the same body size. Our estimate for the total number of terrestrial species of animals is in the range 1.03 − 2.92 million species, a value consistent with estimates from previous studies, despite having used a fundamentally new approach. Perhaps what is most remarkable about these results is that they have been obtained using only limited data from larger endotherms and their speciation rates, with the rest of the predictive process being based on mechanistic theory. This work illustrates the potential of a new approach to classic eco-evolutionary questions, while also adding weight to existing predictions. As we now face an era of dramatic biological change, new methods will be needed to mechanistically model global biodiversity at the species and individual organism level. This will be a huge challenge but the combination of general ecosystem models and neutral theory that we introduce here could be the only way to tractably achieve it.
Intuitive interpretation of heterochromatin and euchromatin through rapid Hi-C analysis
Authors: Sumikama Takashi , Fukuma Takeshi 
Published: October 2022

AbstractHi-C is a technique that provides contact frequencies between pairs of loci on chromosomes. The conventional classification of heterochromatin and euchromatin based on Hi-C data is performed by principal component analysis; however, it requires long computational times and does not provide insight into the difference in contact frequencies between heterochromatin and euchromatin. Here, we propose a simple, intuitive and rapid method named the scaled contact number (SCN), which allows the contact frequencies to be visually interpreted and heterochromatin and euchromatin to be classified based on Hi-C results in a few minutes for long chromosomes at 1-kb resolution. The robustness of SCN was validated by confirming that SCN with reduced reads gives almost the same results as the original SCN. Overall, the approach described herein thus considerably decreases the time and computing power required to analyze Hi-C and further provides mechanistic insight indicating that euchromatin has more contacts than heterochromatin.
Detection of adaptation to light environment in myopia-associated loci Diversity of the myopia genetic background
Authors: Xia Tian , Nakayama Kazuhiro 
Published: October 2022

AbstractThe time spent outdoors and exposure to bright sunlight have been reported to play important roles in preventing myopia progression. Myopia prevalence is generally low in Europe, and we hypothesized that local adaptation of ancestors in insufficient sunlight regions might underlie this low prevalence in Europeans. To verify this conjecture and understand how ancestry adaptation influenced on the diversity of myopia genetic background, polygenic risk scores (PRS) was calculated and revealed that the genetic risk of myopia increased as latitude decreased in the 1000 genome projects (1KGP) EUR, and we further determined selection signatures near the rhodopsin (RHO) coding region in 1KGP Finnish. The derived allele frequencies of identified loci correlated with sunshine duration worldwide, and the allele age was estimated to be ∼20,000 years, coincidently after the divergence of Europeans and East Asians.TSPAN10(rs9747347) is significantly associated with both myopia and pigmentation in Europeans, and we found selection favored the myopia risk allele in EUR. Haplotype comparison highlighted the divergence between EAS and EUR inRHOand pigmentation-associated loci, and the frequency diversity in Admixed American (AMR) of these loci was found to originate from recent admixture and local adaptation. We concluded that local adaptation played a role in myopia prevalence deviation, and selective pressure in the myopia-associated loci may originate from adaptation to sunlight environments rather than myopia itself. These findings reveal traces of evolution history of myopia’s genetic background, providing a new aspect of understanding the patterns and diversity of myopia prevalence.Author SummaryThe explanation for the distinct bias of myopia prevalence among ethnicities remains controversial, we took an evolutionary approach to understanding the history and diversity of the genetic background of myopia. We detected selection signatures of myopia-associated loci near the rhodopsin gene (RHO) in the 1000 Genome Project Europeans. Ambient light exposure is crucial for myopia;RHOis mainly expressed in rod cells and is extremely sensitive to light, indicating that local adaptation might contribute to myopia prevalence bias. Parallel geographical disposition of allele frequencies of myopia-associated loci inRHOand pigmentation-associated markers was observed, implying that selective pressure in myopia-associated loci may originate from adaptation events involved in sunlight exposure rather than myopia itself.
Engineering the substrate specificity of toluene degrading enzyme XylM using biosensor XylS and machine learning
Authors: Ogawa Yuki , Saito Yutaka , Yamaguchi Hideki , Katsuyama Yohei , Ohnishi Yasuo 
Published: October 2022

ABSTRACTEnzyme engineering using machine learning has been developed in recent years. However, to obtain a large amount of data on enzyme activities for training data, it is necessary to develop a high-throughput and accurate method for evaluating enzyme activities. Here, we examined whether a biosensor-based enzyme engineering method can be applied to machine learning. As a model experiment, we aimed to modify the substrate specificity of XylM, a rate-determining enzyme in a multistep oxidation reaction catalyzed by XylMABC inPseudomonas putida. XylMABC naturally converts toluene and xylene to benzoic acid and toluic acid, respectively. We aimed to engineer XylM to improve its conversion efficiency to a non-native substrate, 2,6-xylenol. Wild-type XylMABC slightly converted 2,6-xylenol to 3-methylsalicylic acid, which is the ligand of the transcriptional regulator XylS inP. putida. By locating a fluorescent protein gene under the control of thePmpromoter to which XylS binds, a XylS-producingEscherichia colistrain showed higher fluorescence intensity in a 3-methylsalicylic acid concentration-dependent manner. We evaluated the 3-methylsalicylic acid productivity of XylM variants using the fluorescence intensity of the sensor strain as an indicator. The obtained data provided the training data for machine learning for the directed evolution of XylM. Two cycles of machine learning-assisted directed evolution resulted in the acquisition of XylM-D140E-V144K-F243L-N244S with 15 times higher productivity than wild-type XylM. These results demonstrate that an indirect enzyme activity evaluation method using biosensors is sufficiently quantitative and high-throughput to be used as training data for machine learning. The findings expand the versatility of machine learning in enzyme engineering.
Theta phase specific modulation of hippocampal memory neurons
Authors: Rahsepar Bahar , Noueihed Jad , Norman Jacob F. , Lahner Benjamin , Quick Melanie H. , Ghaemi Kevin , Pandya Aashna , Fernandez Fernando R. , Ramirez Steve , White John A. 
Published: October 2022

I.AbstractThe theta rhythm, a quasi-periodic 4-10 Hz oscillation, is observed during memory processing in the hippocampus, with different phases of theta hypothesized to separate independent streams of information related to the encoding and recall of memories. At the cellular level, the discovery of hippocampal memory cells (engram neurons), as well as the modulation of memory recall through optogenetic activation of these cells, has provided evidence that certain memories are stored, in part, in a sparse ensemble of neurons in the hippocampus. In previous research, however, engram reactivation has been carried out using open loop stimulation at fixed frequencies; the relationship between engram neuron reactivation and ongoing network oscillations has not been taken into consideration. To address this concern, we implemented a closed-loop reactivation of engram neurons that enabled phase-specific stimulation relative to theta oscillations in the local field potential. Using this real-time approach, we tested the impact of activating engram neurons during the peak (encoding phase) and trough (recall phase) of theta oscillations. Consistent with previously hypothesized functions of theta oscillations in memory function, we show that stimulating engram neurons at the trough of theta is more effective in eliciting behavioral recall than either fixed frequency stimulation or stimulation at the peak of theta. Moreover, phase-specific trough stimulation is accompanied by an increase in the coupling between gamma and theta oscillations in CA1 hippocampus. Oure results provide a causal link between phase-specific activation of engram cells and the behavioral expression of memory.