Miracle-dz/UniFAR-FTUs huggingface dataset:
Thrombosis and Major Bleeding Risk After Primary PCI Among Patients With Multivessel Coronary Artery Disease

Background and Aim This study aimed to develop and validate separate risk prediction models for thrombosis events (TEs) and major bleeding (MB) in patients with multivessel coronary artery lesions who had undergone primary percutaneous coronary intervention (PCI). Methods and Results Thrombosis events (TEs) were defined as the composite of myocardial infarction recurrence or ischemic cerebrovascular events, whereas MB was defined as the occurrence of bleeding academic research consortium (BARC) three or five bleeding. The derivation and validation cohorts comprised 2,976 patients who underwent primary PCI between January 2010 and June 2017. At a median follow-up of 3.07 years (1,122 days), TEs and MB occurred in 167 and 98 patients, respectively. Independent predictors of TEs were older age, prior PCI, non-ST elevated MI (NSTEMI), and stent thrombosis (ST). Independent predictors of MB were triple therapy at discharge, coronary artery bifurcation lesions, lesion restenosis, target lesion of the left main coronary artery, stent thrombosis, non-use of IABP during primary PCI, type A/B according to the American College of Cardiology classification of the coronary lesion, and PTCA. In the derivation and validation cohorts, the areas under the curve were 0.817 and 0.82 for thrombosis and 0.886 and 0.976 for bleeding, respectively. In the derivation cohort, high thrombotic risk (n = 755) was associated with higher 3-year incidence of TEs, major adverse cardiovascular events (MACEs), and all-cause death compared to low risk (n = 1,275) (p = 0.0022, 0.019, and 0.012, respectively). High bleeding risk (n = 1,675) was associated with higher incidence of bleeding, MACEs, and cardiac death compared to low risk (n = 355) (p < 0.0001). Conclusion Simple risk scores can be useful in predicting risks of ischemic and bleeding events after primary PCI, thereby stratifying thrombotic or MB risks and facilitating clinical decisions.
Combinatorial Approaches for Efficient Design of Photoswitchable Protein-Protein Interactions as In Vivo Actuators

Light switchable two-component protein dimerization systems offer versatile manipulation and dissection of cellular events in living systems. Over the past 20 years, the field has been driven by the discovery of photoreceptor-based interaction systems, the engineering of light-actuatable binder proteins, and the development of photoactivatable compounds as dimerization inducers. This perspective is to categorize mechanisms and design approaches of these dimerization systems, compare their advantages and limitations, and bridge them to emerging applications. Our goal is to identify new opportunities in combinatorial protein design that can address current engineering challenges and expand in vivo applications.
In Silico Infection Analysis (iSFA) Identified Coronavirus Infection and Potential Transmission Risk in Mammals

Coronaviruses are a great source of threat to public health which could infect various species and cause diverse diseases. However, the epidemic’s spreading among different species remains elusive. This study proposed an in silico infection analysis (iSFA) system that includes pathogen genome or transcript mining in transcriptome data of the potential host and performed a comprehensive analysis about the infection of 38 coronaviruses in wild animals, based on 2,257 transcriptome datasets from 89 mammals’ lung and intestine, and revealed multiple potential coronavirus infections including porcine epidemic diarrhea virus (PEDV) infection in Equus burchellii. Then, through our transmission network analysis, potential intermediate hosts of five coronaviruses were identified. Notably, iSFA results suggested that the expression of coronavirus receptor genes tended to be downregulated after infection by another virus. Finally, binding affinity and interactive interface analysis of S1 protein and ACE2 from different species demonstrated the potential inter-species transmission barrier and cross-species transmission of SARS-CoV-2. Meanwhile, the iSFA system developed in this study could be further applied to conduct the source tracing and host prediction of other pathogen-induced diseases, thus contributing to the epidemic prevention and control.
Preparation and Characterization of Vancomycin Hydrochloride-Loaded Mesoporous Silica Composite Hydrogels

This study aims to explore the feasibility of the novel temperature-sensitive hydrogel-based dual sustained-release system (Van/SBA-15/CS-GP-SA) in the repair and treatment of infectious jaw defects. Van/SBA-15 was prepared using the mesoporous silica (SBA-15) as a carrier for vancomycin hydrochloride (Van), and Van/SBA-15 was characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy dispersive spectrometry (EDS), X-ray photoelectron spectroscopy (XPS), Fourier transform infrared (FTIR), Brunauer–Emmett–Teller (BET), and Barrett–Joyner–Halenda (BJH). The characterization results confirm that Van is loaded in SBA-15 successfully. Van/SBA-15/CS-GP-SA is constructed by encapsulating Van/SBA-15 in chitosan–sodium glycerophosphate–sodium alginate hydrogel (CS-GP-SA). The microstructures, sustained-release ability, biocompatibility, and antibacterial properties of Van/SBA-15/CS-GP-SA were systematically studied. Van/SBA-15/CS-GP-SA is found to have promising sustained-release ability, outstanding biocompatibility, and excellent antibacterial properties. This study provides new ideas for the management of infectious jaw defects.
Bumetanide for Irritability in Children With Sensory Processing Problems Across Neurodevelopmental Disorders: A Pilot Randomized Controlled Trial

Background Treatment development for neurodevelopmental disorders (NDDs) such as autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) is impeded by heterogeneity in clinical manifestation and underlying etiologies. Symptom traits such as aberrant sensory reactivity are present across NDDs and might reflect common mechanistic pathways. Here, we test the effectiveness of repurposing a drug candidate, bumetanide, on irritable behavior in a cross-disorder neurodevelopmental cohort defined by the presence of sensory reactivity problems. Methods Participants, aged 5–15 years and IQ ≥ 55, with ASD, ADHD, and/or epilepsy and proven aberrant sensory reactivity according to deviant Sensory Profile scores were included. Participants were randomly allocated (1:1) to bumetanide (max 1 mg twice daily) or placebo tablets for 91 days followed by a 28-day wash-out period using permuted block design and minimization. Participants, parents, healthcare providers, and outcome assessors were blinded for treatment allocation. Primary outcome was the differences in ABC-irritability at day 91. Secondary outcomes were differences in SRS-2, RBS-R, SP-NL, BRIEF parent, BRIEF teacher at D91. Differences were analyzed in a modified intention-to-treat sample with linear mixed models and side effects in the intention-to-treat population. Results A total of 38 participants (10.1 [SD 3.1] years) were enrolled between June 2017 and June 2019 in the Netherlands. Nineteen children were allocated to bumetanide and nineteen to placebo. Five patients discontinued (n = 3 bumetanide). Bumetanide was superior to placebo on the ABC-irritability [mean difference (MD) −4.78, 95%CI: −8.43 to −1.13, p = 0.0125]. No effects were found on secondary endpoints. No wash-out effects were found. Side effects were as expected: hypokalemia (p = 0.046) and increased diuresis (p = 0.020). Conclusion Despite the results being underpowered, this study raises important recommendations for future cross-diagnostic trial designs.
Analysis of the Complete Plastomes of 31 Species of Hoya Group: Insights Into Their Comparative Genomics and Phylogenetic Relationships

Hoya is a genus in Apocynaceae-Asclepiadoideae, known for its showy wax flowers, making it a popular ornamental plant. However, phylogenetic relationships among most Hoya species are not yet fully resolved. In this study, we sequenced 31 plastomes of Hoya group species using genome skimming data and carried out multiple analyses to understand genome variation to resolve the phylogenetic positions of some newly sequenced Chinese endemic species. We also screened possible hotspots, trnT-trnL-trnF, psba-trnH, and trnG-UCC, ndhF, ycf1, matK, rps16, and accD genes that could be used as molecular markers for DNA barcoding and species identification. Using maximum likelihood (ML) and Bayesian Inference (BI), a species phylogeny was constructed. The newly assembled plastomes genomes showed the quasi-tripartite structure characteristic for Hoya and Dischidia with a reduced small single copy (SSC) and extremely enlarged inverted repeats (IR). The lengths ranged from 175,404 bp in Hoya lacunosa to 179,069 bp in H. ariadna. The large single copy (LSC) regions ranged from 80,795 bp (Hoya liangii) to 92,072 bp (Hoya_sp2_ZCF6006). The massively expanded IR regions were relatively conserved in length, with the small single-copy region reduced to a single gene, ndhF. We identified 235 long dispersed repeats (LDRs) and ten highly divergent hotspots in the 31 Hoya plastomes, which can be used as DNA barcodes for species identification. The phylogeny supports Clemensiella as a distinct genus. Hoya ignorata is resolved as a relative to Clade VI species. This study discloses the advantages of using Plastome genome data to study phylogenetic relationships.
An Increased Anticholinergic Drug Burden Index Score Negatively Affect Nutritional Status in Older Patients Without Dementia

Introduction/Aim Anticholinergic drugs, which have severe central and peripheric side effects, are frequently prescribed to older adults. Increased anticholinergic drug burden is associated with poor physical and cognitive functions. On the other side, the impact of anticholinergics on nutritional status is not elaborated in the literature. Therefore, this study was aimed to investigate the effect of the anticholinergic burden on nutrition. Materials and Methods Patients who underwent comprehensive geriatric assessment (CGA) 6 months apart were included in the study. Patients diagnosed with dementia were excluded because of the difference in the course of cognition, physical performance and nutrition. Nutritional status and global cognition were evaluated using Mini Nutritional Assessment-short form (MNA-SF), Mini-Mental State Examination (MMSE). Anticholinergic drug burden was assessed with the Drug Burden Index (DBI), enabling a precise dose-related cumulative exposure. Patients were divided into three groups according to DBI score: 0, no DBI exposure; 0–1, low risk; and ≥1, high risk. Regression analysis was performed to show the relationship between the difference in CGA parameters and the change in DBI score at the sixth month. Results A total of 423 patients were included in the study. Participants' mean age was 79.40 ± 7.50, and 68.6% were female. The DBI 0 score group has better MMSE and MNA-SF scores and a lower rate of falls, polypharmacy, malnutrition, and risk of malnutrition in the baseline. Having malnutrition or risk of malnutrition is 2.21 times higher for every one-unit increase in DBI score. Additionally, during the 6-month follow-up, increased DBI score was associated with decreased MNA-SF and MMSE score, albumin. Conclusions The harmful effects of anticholinergics may be prevented because anticholinergic activity is a potentially reversible factor. Therefore, reducing exposure to drugs with anticholinergic activity has particular importance in geriatric practice.
Understanding the Greenhouse Gas Impact of Deforestation Fires in Indonesia and Brazil in 2019 and 2020

Deforestation fires are hindering climate change mitigation efforts and compounding global environmental challenges. Indonesia and Brazil have experienced high rates of deforestation fires in recent years, with many of the fires burning in peatland-rich ecosystems. We quantify the greenhouse gas (GHG) emissions associated with the 2019 and 2020 deforestation fires in both countries and determine the share of emissions originating from peatlands. Specifically, we use publicly available data for deforested area estimates and quantify the above-ground biomass (AGB), dry matter, and peat soil emissions associated with these fires. We find that the cumulative emissions impact from deforestation fires in Indonesia and Brazil was 3.7 (±0.4) and 1.9 (±0.2) Gt CO2eq in 2019 and 2020, respectively. Nearly half of this GHG impact can be attributed to emissions from peatlands. However, real-time monitoring tools can underestimate these emissions as fires in peatlands smolder underground and can go undetected by satellites. We compare our results with publicly available land-use and fire emissions data and find that the magnitude of underestimation is of the order of 200–300% for severe fire years and highest in the peatland-rich Brazilian Pantanal. We identify the gaps in current policies that are exacerbating the GHG and climate impacts of deforestation fires in Indonesia and Brazil and emphasize the need for regular pre- and post-fire ground measurement, transparent data sharing, and robust policy enforcement for effective forest and peatland protection.
Impacts of Climate Change and Heat Stress on Farmworkers' Health: A Scoping Review

Due to the continuous rise of global temperatures and heatwaves worldwide as a result of climate change, concerns for the health and safety of working populations have increased. Workers in the food production chain, particularly farmworkers, are especially vulnerable to heat stress due to the strenuous nature of their work, which is performed primarily outdoors under poor working conditions. At the cross-section of climate change and farmworkers' health, a scoping review was undertaken to summarize the existing knowledge regarding the health impacts associated with climate change and heat stress, guide future research toward better understanding current and future climate change risks, and inform policies to protect the health and safety of agricultural workers. A systematic search of 5 electronic databases and gray literature websites was conducted to identify relevant literature published up until December 2021. A total of 9045 records were retrieved from the searches, of which 92 articles were included in the final review. The majority of the reviewed articles focused on heat-related illnesses (n = 57) and kidney diseases (n = 28). The risk factors identified in the reviewed studies included gender, dehydration, heat strain, wearing inappropriate clothing, workload, piece-rate payment, job decision latitude, and hot environmental conditions. On the other hand, various protective and preventive factors were identified including drinking water, changing work hours and schedule of activities, wearing appropriate clothing, reducing soda consumption, taking breaks in shaded or air-conditioned areas, and increasing electrolyte consumption in addition to improving access to medical care. This review also identified various factors that are unique to vulnerable agricultural populations, including migrant and child farmworkers. Our findings call for an urgent need to expand future research on vulnerable agricultural communities including migrant workers so as to develop effective policies and interventions that can protect these communities from the effects of heat stress.
A Competitive Assay Based on Dual-Mode Au@Pt-DNA Biosensors for On-Site Sensitive Determination of Carbendazim Fungicide in Agricultural Products

Carbendazim (CBZ), a systemic, broad-spectrum benzimidazole fungicide, is widely used to control fungal diseases in agricultural products. Its residues might pose risks to human health and the environment. Therefore, it is warranted to establish a rapid and reliable method for its residual quantification. Herein, we proposed a competitive assay that combined aptamer (DNA) specific recognition and bimetallic nanozyme gold@platinum (Au@Pt) catalysis to trace the CBZ residue. The DNA was labeled onto bimetallic nanozyme Au@Pt surface to produce Au@Pt probes (Au@Pt-DNA). The magnetic Fe3O4 was functionalized with a complementary strand of DNA (C-DNA) to form Fe3O4 probes (Fe3O4-C-DNA). Subsequently, the CBZ and the Fe3O4 probes competitively react with Au@Pt probes to form two Au@Pt-DNA biosensors (Au@Pt-ssDNA-CBZ and Au@Pt-dsDNA-Fe3O4). The Au@Pt-ssDNA-CBZ biosensor was designed for qualitative analysis through a naked-eye visualization strategy in the presence of CBZ. Meanwhile, Au@Pt-dsDNA-Fe3O4 biosensor was developed to quantitatively analyze CBZ using a multifunctional microplate reader. A competitive assay based on the dual-mode Au@Pt-DNA biosensors was established for onsite sensitive determination of CBZ. The limit of detection (LOD) and recoveries of the developed assay were 0.038 ng/mg and 71.88-110.11%, with relative standard deviations (RSDs) ranging between 3.15 and 10.91%. The assay demonstrated a good correlation with data acquired from liquid chromatography coupled with mass spectrometry/mass spectrometry analysis. In summary, the proposed competitive assay based on dual-mode Au@Pt-DNA biosensors might have a great potential for onsite sensitive detection of pesticides in agro-products.
Effects of 1,25-Dihydroxyvitamin D3 and 25-Hydroxyvitamin D3 on PBMCs From Dairy Cattle Naturally Infected With Mycobacterium avium subsp. paratuberculosis

The role of vitamin D3 in modulating immune responses has been well-established for over two decades; however, its specific functions have not been extensively detailed in cattle, particularly cattle in different stages of infection with Mycobacterium avium subspecies paratuberculosis (MAP). Consistent with previous work in our lab, the present study showed that infected cattle in the clinical stage of disease have reduced serum 25-hydroxyvitamin D3 [25(OH)D3]. Additionally, effects of vitamin D3 on peripheral blood mononuclear cells (PBMCs) from naturally infected dairy cattle in subclinical (n = 8) or clinical (n = 8) stages of infection were compared to non-infected control cows (n = 8). Briefly, PBMCs were isolated and cultured in vitro with 4 ng/ml 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] or 100 ng/ml 25(OH)D3. Treatment with 1,25(OH)2D3 resulted in decreased secretion for some pro-inflammatory cytokines in clinical animals, including IL-1β, IL-6, and IFN-γ. Similar responses for IL-1β and IL-6 were noted with the addition of 25(OH)D3. Additionally, pro-inflammatory cytokine gene expression tended to be upregulated in PBMCs from clinical animals after treatment with 1,25(OH)2D3. In contrast, PBMCs from clinical animals treated with 25(OH)D3 showed downregulation of pro-inflammatory cytokine gene expression, although only significant for IL1B. Following 25(OH)D3 treatment, clinical animals showed significant reduction in CD4+CD25+ T cells. CYP27B1 gene expression was notably decreased in clinical and control animals following 25(OH)D3 treatment but increased in subclinical cows. 1,25(OH)2D3 treatment reduced CYP24A1 gene expression in all groups, while 25(OH)D3 treatment only significantly reduced expression for control cows. Lastly, serum 25(OH)D3 levels were significantly lower in clinical animals. Taken together, these data show vitamin D3 modulates cytokine signaling in cattle at different stages of MAP infection and, therefore, may have implications on disease progression.
Operation of the Atypical Canonical Bone Morphogenetic Protein Signaling Pathway During Early Human Odontogenesis

Bone morphogenetic protein (BMP) signaling plays essential roles in the regulation of early tooth development. It is well acknowledged that extracellular BMP ligands bind to the type I and type II transmembrane serine/threonine kinase receptor complexes to trigger the BMP signaling pathway. Then, the receptor-activated Smad1/5/8 in cytoplasm binds to Smad4, the central mediator of the canonical BMP signaling pathway, to form transfer complexes for entering the nucleus and regulating target gene expression. However, a recent study revealed the functional operation of a novel BMP-mediated signaling pathway named the atypical BMP canonical signaling pathway in mouse developing tooth, which is Smad1/5/8 dependent but Smad4 independent. In this study, we investigated whether this atypical BMP canonical signaling is conserved in human odontogenesis. We showed that pSMAD1/5/8 is required for the expression of Msh homeobox 1 (MSX1), a well-defined BMP signaling target gene, in human dental mesenchyme, but the typical BMP canonical signaling is in fact not operating in the early human developing tooth, as evidenced by the absence of pSMAD1/5/8-SMAD4 complexes in the dental mesenchyme and translocation of pSMAD1/5/8, and the expression of MSX1 induced by BMP4 is mothers against decapentaplegic homolog 4 (SMAD4)-independent in human dental mesenchymal cells. Moreover, integrative analysis of RNA-Seq data sets comparing the transcriptome profiles of human dental mesenchymal cells with and without SMAD4 knockdown by siRNA displays unchanged expression profiles of pSMAD1/5/8 downstream target genes, further affirming the functional operation of the atypical canonical BMP signaling pathway in a SMAD1/5/8-dependent but SMAD4-independent manner in the dental mesenchyme during early odontogenesis in humans.
Topological Abnormalities of Pallido-Thalamo-Cortical Circuit in Functional Brain Network of Patients With Nonchemotherapy With Non-small Cell Lung Cancer

Introduction Some previous studies in patients with lung cancer have mainly focused on exploring the cognitive dysfunction and deficits of brain function associated with chemotherapy. However, little is known about functional brain alterations that might occur prior to chemotherapy. Therefore, this study aimed to evaluate brain functional changes in patients with nonchemotherapy before chemotherapy with non-small cell lung cancer (NSCLC). Methods Resting-state functional MRI data of 35 patients with NSCLC and 46 matched healthy controls (HCs) were acquired to construct functional brain networks. Graph theoretical analysis was then applied to investigate the differences of the network and nodal measures between groups. Finally, the receiver operating characteristic (ROC) curve analysis was performed to distinguish between NSCLC and HC. Results Decreased nodal strength was found in the left inferior frontal gyrus (opercular part), inferior frontal gyrus (triangular part), inferior occipital gyrus, and right inferior frontal gyrus (triangular part) of patients with NSCLC while increased nodal strength was found in the right pallidum and thalamus. NSCLC also showed decreased nodal betweenness in the right superior occipital gyrus. Different hub regions distribution was found between groups, however, no hub regions showed group differences in the nodal measures. Furthermore, the ROC curve analysis showed good performance in distinguishing NSCLC from HC. Conclusion These results suggested that topological abnormalities of pallido-thalamo-cortical circuit in functional brain network might be related to NSCLC prior to chemotherapy, which provided new insights concerning the pathophysiological mechanisms of NSCLC and could serve as promising biological markers for the identification of patients with NSCLC.