Miracle-dz/UniFAR-FTUs huggingface dataset:
Determining the influence of agricultural land use on climate variables for the Canadian Prairies

Since the 1970s the Canadian Prairies have experienced a steady replacement of summer fallow with continuous cropping practices. It has been suggested that such regional scale changes in agricultural land use result in the modification of the regional climate and its variability. Our study explores this influence using linear discriminant analysis (LDA) to determine whether agricultural land use variables can discriminate the classes of exceedance (positive/negative beyond a given small scale variability range) found in the maximum and minimum daily temperature, diurnal temperature range (DTR), daily precipitation and daily incoming solar radiation. These classes of exceedance describe whether the climate was warmer/cooler, drier/wetter and sunnier/cloudier relative to the small scale variability range. The land use data consisted of summer fallow, annuals and perennials for the 127 ecodistricts in the Prairies ecozone. The climate data were neighbouring station data interpolated to the ecodistrict's centroid. Both data sets covered the period 1951–2006 and the analysis covered the entire data period with focus on 1971–2006 that coincided with the decline in summer fallow practice. It considered the primary growing season months of June, July and August and used the winter months of January and February as a contrast. Our approach showed that where large scale changes in agricultural land cover occurs we can establish a statistical relationship between such changes and the modification of the climate's variability. June coincided with the period of maximum positive growth rate and hence land cover change. The greatest discriminating power was therefore found to occur in June for the exceedance classes of maximum and minimum temperature and solar radiation over the 1971–2006 period with success rates ranging from 85 to 93%. The greatest success in discriminating the DTR classes was at 82% in July.
On convolutional neural networks for selection inference: Revealing the effect of preprocessing on model learning and the capacity to discover novel patterns

A central challenge in population genetics is the detection of genomic footprints of selection. As machine learning tools including convolutional neural networks (CNNs) have become more sophisticated and applied more broadly, these provide a logical next step for increasing our power to learn and detect such patterns; indeed, CNNs trained on simulated genome sequences have recently been shown to be highly effective at this task. Unlike previous approaches, which rely upon human-crafted summary statistics, these methods are able to be applied directly to raw genomic data, allowing them to potentially learn new signatures that, if well-understood, could improve the current theory surrounding selective sweeps. Towards this end, we examine a representative CNN from the literature, paring it down to the minimal complexity needed to maintain comparable performance; this low-complexity CNN allows us to directly interpret the learned evolutionary signatures. We then validate these patterns in more complex models using metrics that evaluate feature importance. Our findings reveal that preprocessing steps, which determine how the population genetic data is presented to the model, play a central role in the learned prediction method. This results in models that mimic previously-defined summary statistics; in one case, the summary statistic itself achieves similarly high accuracy. For evolutionary processes that are less well understood than selective sweeps, we hope this provides an initial framework for using CNNs in ways that go beyond simply achieving high classification performance. Instead, we propose that CNNs might be useful as tools for learning novel patterns that can translate to easy-to-implement summary statistics available to a wider community of researchers.
Unraveling lexical semantics in the brain: Comparing internal, external, and hybrid language models

To explain how the human brain represents and organizes meaning, many theoretical and computational language models have been proposed over the years, varying in their underlying computational principles and in the language samples based on which they are built. However, how well they capture the neural encoding of lexical semantics remains elusive. We used representational similarity analysis (RSA) to evaluate to what extent three models of different types explained neural responses elicited by word stimuli: an External corpus‐based word2vec model, an Internal free word association model, and a Hybrid ConceptNet model. Semantic networks were constructed using word relations computed in the three models and experimental stimuli were selected through a community detection procedure. The similarity patterns between language models and neural responses were compared at the community, exemplar, and word node levels to probe the potential hierarchical semantic structure. We found that semantic relations computed with the Internal model provided the closest approximation to the patterns of neural activation, whereas the External model did not capture neural responses as well. Compared with the exemplar and the node levels, community‐level RSA demonstrated the broadest involvement of brain regions, engaging areas critical for semantic processing, including the angular gyrus, superior frontal gyrus and a large portion of the anterior temporal lobe. The findings highlight the multidimensional semantic organization in the brain which is better captured by Internal models sensitive to multiple modalities such as word association compared with External models trained on text corpora.
Association of Male Sex and Microvascular Alterations on Optical Coherence Tomography Angiography in Diabetes

Purpose Epidemiologically, men have a higher incidence, severity, and progression of diabetic retinopathy (DR) than women. We investigated microvascular differences between men and women with diabetes on optical coherence tomography angiography (OCTA). Methods Three × 3 mm OCTA macula scans of non-diabetic and patients with diabetes were obtained. Vascular parameters included parafoveal vessel density (VD), vessel length density (VLD), and flow index (FI) of the superficial capillary plexus (SCP) and deep capillary plexus (DCP) as well as foveal avascular zone (FAZ) area and perimeter. Multivariable linear regression was used for statistical analysis. Results There were 1809 patients with diabetes and 217 non-diabetic participants that were included in this study. Diabetic individuals included those with no DR (n = 1356), mild non-proliferative DR (NPDR; n = 286), moderate NPDR (n = 126), and severe NPDR/proliferative DR (PDR; n = 41). Male sex was significantly associated with smaller FAZ area/perimeter and lower DCP VLD in both non-diabetic subjects and patients with diabetes. Male sex in the diabetic group was additionally associated with lower SCP VD/VLD and DCP VD. Addition of an interaction between male sex and diabetes status in the interaction analysis showed that being male and diabetic conferred increased reduction in DCP VD and VLD compared to sex-based changes in non-diabetics. Larger FAZ perimeter, lower SCP VD/VLD, and lower DCP VLD were associated with poorer visual acuity in diabetics. Conclusions On OCTA, male patients with diabetes may have more severe microvascular disease especially in the DCP compared to women. Translational Evidence Sex-based alterations in diabetic microvascular disease has the potential to influence future basic and clinical studies as well as the implementation of OCTA disease markers.
Host translation machinery is not a barrier to phages that interact with both CPR and non-CPR bacteria

ABSTRACT Within human microbiomes, Gracilibacteria, Absconditabacteria, and Saccharibacteria, members of Candidate Phyla Radiation (CPR), are increasingly correlated with human oral health and disease. We profiled the diversity of CRISPR-Cas systems in the genomes of these bacteria and sought phages that are capable of infecting them by matching their spacer inventories to large phage sequence databases. Gracilibacteria and Absconditabacteria recode the typical TGA stop codon to glycine and are putatively infected by phages that share their host’s alternate genetic code. Unexpectedly, however, other predicted phages of Gracilibacteria and Absconditabacteria do not use an alternative genetic code. Some of these phages may infect both alternatively coded CPR bacteria and standard-coded bacteria. These phages typically rely on other stop codons besides TGA and thus should be capable of producing viable gene products in either bacterial host type. By avoiding the acquisition of in-frame stop codons, these phages may have a broadened host range. Interestingly, we additionally predict that some phages of Saccharibacteria are targeted by spacers encoded in Actinobacteria, a phylum that includes known hosts for episymbiotic Saccharibacteria. IMPORTANCE Here, we profiled putative phages of Saccharibacteria, which are of particular importance as Saccharibacteria influence some human oral diseases. We additionally profiled putative phages of Gracilibacteria and Absconditabacteria, two Candidate Phyla Radiation (CPR) lineages of interest given their use of an alternative genetic code. Among the phages identified in this study, some are targeted by spacers from both CPR and non-CPR bacteria and others by both bacteria that use the standard genetic code as well as bacteria that use an alternative genetic code. These findings represent new insights into possible phage replication strategies and have relevance for phage therapies that seek to manipulate microbiomes containing CPR bacteria. Here, we profiled putative phages of Saccharibacteria, which are of particular importance as Saccharibacteria influence some human oral diseases. We additionally profiled putative phages of Gracilibacteria and Absconditabacteria, two Candidate Phyla Radiation (CPR) lineages of interest given their use of an alternative genetic code. Among the phages identified in this study, some are targeted by spacers from both CPR and non-CPR bacteria and others by both bacteria that use the standard genetic code as well as bacteria that use an alternative genetic code. These findings represent new insights into possible phage replication strategies and have relevance for phage therapies that seek to manipulate microbiomes containing CPR bacteria.
Validation of the Lithuanian multimorbidity treatment burden questionnaire (MTBQ) and its association with primary care patient characteristics

Abstract Background The increasing prevalence of multimorbidity among older people in Lithuania and other Central-Eastern European countries leads to a greater patient treatment burden and puts additional pressure on healthcare services. Objectives This study aimed to validate the Lithuanian version of the Multimorbidity Treatment Burden Questionnaire (MTBQ). Methods The Lithuanian version of the MTBQ was tested (2021-2022) with 789 patients from seven Lithuanian primary care centres who had two or more long-term conditions. The questionnaire translation’s reliability, validity and dimensionality of the were assessed with Spearman’s rank correlation, Cronbach’s alpha, and factor reduction analysis. Treatment burden and its associations with sociodemographic and other indicators were analysed. Results Lithuanian version of MTBQ had good internal reliability (Cronbach’s alpha 0.711), validity, factor reduction applicability, and interpretability. The MTBQ scores of the questionnaire had a negative association with the quality-of-life scale (r=-0.327, 95% CI [-0.389, −0.264]) and positive associations with the self-rated health scores (r = 0.230, 95% CI [0.163, 0.297]) and with the number of comorbidities (r = 0.164, 95% CI [0.097, 0.233]). Distribution of treatment burden was identified (none (19,4%), low (46,6%), medium (25%), high (9%)). High treatment burden was found to be associated with having five or more long-term diseases, taking five or more medications, having anxiety or depression and living in a rural area. Conclusion The study’s findings show that the MTBQ is applicable in assessing the treatment burden of multimorbid patients in Lithuania. Furthermore, the study demonstrates that Lithuanian patients with multimorbidity have average treatment burden scores similar to or higher than participants in previous MTBQ validation studies. KEY MESSAGES • The Lithuanian version of MTBQ features good content validity, internal reliability, and construct validity, and is suitable for assessing treatment burden of patients with multimorbidity in Lithuania. • The study demonstrated that Lithuanian patients with multimorbidity had average treatment burden scores similar to or higher than participants in previous MTBQ validation studies.
The onset and interannual variability of the Asian summer monsoon in relation to land-sea thermal contrast

Abstract The onset and interannual variability of the Asian summer monsoon in relation to land–sea thermal contrast and its contributing factors are studied using a 14-yr (1979–1992) dataset. The onset of the Asian summer monsoon is concurrent with the reversal of meridional temperature gradient in the upper troposphere south of the Tibetan Plateau. The reversal is the result of large temperature increases in May to June over Eurasia centered on the Plateau with no appreciable temperature change over the Indian Ocean. In spring the Tibetan Plateau is a heat source that is distinctly separate from the heat source associated with the rain belt in the equatorial Indian ocean. The Tibetan heat source is mainly contributed by sensible heat flux from the ground surface, while the oceanic heat source is due to the release of latent heat of condensation. It is the sensible heating over the Plateau region in spring that leads to the reversal of meridional temperature gradient. Despite its intensity the condensatio.
Climate Model Biases in the Width of the Tropical Belt

AbstractEarth’s arid subtropics are situated at the edges of the tropical belt, which encircles the planet along the equator and covers half of its surface area. The climate of the tropical belt is strongly influenced by the Hadley cells, with their subsidence and easterly trade winds both sustaining the aridity at the belt’s edges. The understanding of Earth’s past, present, and future climates is contingent on understanding the dynamics influencing this region. An important but unanswered question is how realistically climate models reproduce the mean state of the tropical belt. This study augments the existing literature by examining the mean width and seasonality of the tropical belt in climate models from phase 5 of CMIP (CMIP5) and experiments from the second phase of the Chemistry–Climate Model Validation (CCMVal-2) activity of the Stratospheric Processes and Their Role in Climate (SPARC) project. While the models overall reproduce the structure of the tropical belt width’s seasonal cycle, they und.
Sustained response off‐treatment in eltrombopag‐treated adult patients with ITP who are refractory or relapsed after first‐line steroids: Primary, final, and ad‐hoc analyses of the Phase II TAPER trial

Immune thrombocytopenia (ITP) is characterized by reduced platelet count due to increased destruction and is categorized according to the time following diagnosis (newly diagnosed, persistent, chronic). First‐line corticosteroid therapy is associated with transient response, high relapse rates, and considerable toxicity. TAPER (NCT03524612) is a Phase II, prospective, single‐arm trial investigating whether eltrombopag can induce a sustained response off‐treatment (SRoT) in adult patients with ITP after first‐line corticosteroid failure. This study defines SRoT as an off‐treatment period wherein platelet count remains above 30 × 109/L in the absence of bleeding or rescue therapy. The primary endpoint was the proportion of patients who achieved SRoT until Month 12, which was 30.5% (n = 32/105; p < .0001 testing hypothesis H1: proportion >15%) following eltrombopag tapering and discontinuation, and median SRoT duration was ~8 months until Month 12. Median platelet count increased within 1 month of treatment and remained elevated until Month 12. Quality of life improved within 3 months and was maintained. Headache (21%) was the most common adverse event. None of the 4 deaths reported were considered treatment‐related. In summary, ~one‐third of patients achieved SRoT until Month 12 following eltrombopag tapering and discontinuation. An ad‐hoc early‐use analysis, stratified by ITP duration at baseline, assessed initial hematologic responses and safety. Results suggest that eltrombopag has similar efficacy in newly diagnosed and later stages of ITP. In follow‐up until Month 24, a median SRoT duration of ~22 months was observed (n = 20). The safety profile was comparable across analyses and ITP duration groups and aligned with its well‐established safety profile.
Superior Attentional Efficiency of Auditory Cue via the Ventral Auditory-thalamic Pathway

Abstract Auditory commands are often executed more efficiently than visual commands. However, empirical evidence on the underlying behavioral and neural mechanisms remains scarce. In two experiments, we manipulated the delivery modality of informative cues and the prediction violation effect and found consistently enhanced RT benefits for the matched auditory cues compared with the matched visual cues. At the neural level, when the bottom–up perceptual input matched the prior prediction induced by the auditory cue, the auditory-thalamic pathway was significantly activated. Moreover, the stronger the auditory-thalamic connectivity, the higher the behavioral benefits of the matched auditory cue. When the bottom–up input violated the prior prediction induced by the auditory cue, the ventral auditory pathway was specifically involved. Moreover, the stronger the ventral auditory-prefrontal connectivity, the larger the behavioral costs caused by the violation of the auditory cue. In addition, the dorsal frontoparietal network showed a supramodal function in reacting to the violation of informative cues irrespective of the delivery modality of the cue. Taken together, the results reveal novel behavioral and neural evidence that the superior efficiency of the auditory cue is twofold: The auditory-thalamic pathway is associated with improvements in task performance when the bottom–up input matches the auditory cue, whereas the ventral auditory-prefrontal pathway is involved when the auditory cue is violated.
Older adults' needs and preferences for a nutrition education digital health solution: A participatory design study

Abstract Background The global population is ageing rapidly and there is a need for strategies to promote health and wellbeing among older adults. Nutrition knowledge is a key predictor of dietary intake; therefore, effective educational programmes are urgently required to rectify poor dietary patterns. Digital health technologies provide a viable option for delivering nutrition education that is cost‐effective and widely accessible. However, few technologies have been developed to meet the unique needs and preferences of older adults. Objective The aim of this study was to explore technology use among older adults and qualitatively determine the content needs and design preferences for an online nutrition education resource tailored to older adult consumers in Australia. Methods Twenty adult participants aged 55 years and older (95% female) participated in one of four 2‐h participatory design workshops. In each workshop, prompted discussion questions were used to explore participants' technology use and preferences and to explore content needs and design preferences for an online nutrition education resource specific to older adults. Results All participants were regularly using a range of different devices (e.g., smartphones, tablets and computers) and reported being comfortable doing so. Participants wanted a website that provided general nutrition information, practical advice and recipes. To enhance engagement, they sought a personalised resource that could be adjusted to suit their needs, included up‐to‐date information and allowed for easy sharing with others by exporting information as a PDF. Conclusions Participatory design methods generate new knowledge for designing and tailoring digital health technologies to be appropriate and useful for the target audience. Specifically, older adults seek an online resource that has large and simple fonts with clear categories, providing them with practical advice and general nutrition information that can be personalised to suit their own needs and health concerns, with the option to export and print information into a paper‐based format. Patient or Public Contribution Older adults actively participated in the development and evaluation process to generate ideas about potential features, functionalities, uses and practicalities of an online nutrition education resource.
Safety, pharmacokinetics, and target engagement of a brain penetrant RIPK1 inhibitor, SAR443820 (DNL788), in healthy adult participants

Abstract SAR443820 (DNL788) is a selective, orally bioavailable, brain penetrant inhibitor of receptor‐interacting serine/threonine protein kinase 1 (RIPK1). This phase I first‐in‐human healthy participant study (NCT05795907) was comprised of three parts: randomized, double‐blind, placebo‐controlled single ascending dose (SAD; part 1a); 14‐day multiple ascending dose (MAD; part 2) parts that evaluated safety, tolerability, pharmacokinetics (PK), and pharmacodynamics of SAR443820; and a separate open‐label, single‐dose part 1b (PK‐cerebrospinal fluid [CSF]) to assess SAR443820 levels in CSF. SAR443820 was well‐tolerated in healthy participants, and no treatment discontinuation related to an adverse event (AE) occurred. Most common AEs were dizziness and headache. No clinically meaningful changes were noted in laboratory values, vital signs, or electrocardiogram parameters. SAR443820 had a favorable PK profile, with plasma half‐lives (geometric mean) ranged between 5.7–8.0 h and 7.2–8.9 h after single and repeated doses, respectively. There were no major deviations from dose proportionality for maximum concentration and area under the curve across SAR443820 doses. Mean CSF‐to‐unbound plasma concentration ratio ranged from 0.8 to 1.3 over time (assessed up to 10 h postdose), indicating high brain penetrance. High levels of inhibition of activated RIPK1, as measured by decrease in pS166‐RIPK1, were achieved in both SAD and MAD parts, with a maximum median inhibition from baseline close to 90% at predose (Ctrough) after multiple dosing in MAD, reflecting a marked RIPK1 target engagement at the peripheral level. These results support further development of SAR443820 in phase II trials in amyotrophic lateral sclerosis (NCT05237284) and multiple sclerosis (NCT05630547).
Exposing the small protein load of bacterial life

Abstract The ever-growing repertoire of genomic techniques continues to expand our understanding of the true diversity and richness of prokaryotic genomes. Riboproteogenomics laid the foundation for dynamic studies of previously overlooked genomic elements. Most strikingly, bacterial genomes were revealed to harbor robust repertoires of small open reading frames (sORFs) encoding a diverse and broadly expressed range of small proteins, or sORF-encoded polypeptides (SEPs). In recent years, continuous efforts led to great improvements in the annotation and characterization of such proteins, yet many challenges remain to fully comprehend the pervasive nature of small proteins and their impact on bacterial biology. In this work, we review the recent developments in the dynamic field of bacterial genome reannotation, catalog the important biological roles carried out by small proteins and identify challenges obstructing the way to full understanding of these elusive proteins.