Miracle-dz/UniFAR-FTUs huggingface dataset:
The importance of the dyad: Participant perspectives on sharing biomarker results in Alzheimer's disease research

In the asymptomatic “preclinical” phase of Alzheimer's disease (AD), abnormal biomarkers indicate risk for developing cognitive impairment. Biomarker information is increasingly being disclosed to participants in research settings, and biomarker testing and results disclosure will be implemented in clinical settings in the future. Biomarker disclosure has potential psychosocial benefits and harms, impacting affected individuals and their support person(s). Limited data are available about with whom research participants share their results, information that will be necessary to develop disclosure protocols and post‐disclosure resources. Additionally, existing research has been conducted in largely White cohorts, limiting applicability to future clinical populations.
D-dimer Levels in Predicting Severity of Infection and Outcome in Patients with COVID-19

COVID-19 disease began to spread all around the world in December 2019 until now; and in the early stage it may be related to high D-dimer level that indicates coagulation pathways and thrombosis activation that can be affected by some underlying diseases including diabetes, stroke, cancer, and pregnancy and it also can be associated with Chronic obstructive pulmonary disease (COPD). The aim of this article was to analyze D-dimer levels in COVID-19 patients, as D-dimer level is one of the measures to detect the severity and outcomes of COVID-19. According to the results of this study, there is a higher level of D-dimer as well as concentrations of fibrinogen in the disease onset and it seems that the poor prognosis is linked to a 3 to 4-fold increase in D-dimer levels. It is also shown that 76% of the patients with ≥1 D-dimer measurement, had elevated D-dimer and were more likely to have critical illness than those with normal D-dimer. There was an increase in the rates of adverse outcomes with higher D-dimer of more than 2000 ng/mL and it is associated with the highest risk of death at 47%, thrombotic event at 37.8%, and critical illness at 66%. It also found that diabetes and COPD had the strongest association with death in COVID-19. So, it is necessary to measure the D-dimer levels and parameters of coagulation from the beginning as well as pay attention to comorbidities that can help control and management of COVID-19 disease.
“We are their eyes and ears here on the ground, yet they do not appreciate us”—Factors influencing the performance of Kenyan community health volunteers working in urban informal settlements

This study explored factors that influence CHV performance in urban informal settlements (UIS) within Nairobi Kenya and ways in which CHVs can be supported to enhance their wellbeing and strengthen community strategies. The study was undertaken in two UIS within Nairobi County. Thirteen focus group discussions and three key informant interviews were conducted with a range of respondents. Various topics covering the design of the Community Health Strategy (CHS) and broader contextual factors that affect CHVs’ performance, were discussed and data analysed using a framework analysis approach. The key programme design factors identified as influencing the performance of CHVs working in UIS included: CHV recruitment; training; availability of supplies and resources; and remuneration of CHVs. Health system factors that influenced CHVs performance included: nature of relationship between healthcare workers at local referral facilities and community members; availability of services and perceived corruption at referral facilities; and CHV referral outside of the local health facility. Whereas the broader contextual factors that affected CHV performance included: demand for material or financial support; perceived corruption in community programmes; and neighbourhood insecurity. These findings suggest that CHVs working in UIS in Kenya face a myriad of challenges that impact their wellbeing and performance. Therefore, to enhance CHVs’ well-being and improve their performance, the following should be considered: adequate and timely remuneration for CHVs, appropriate holistic training, adequate supportive supervision, and ensuring a satisfactory supply of resources and supplies. Additionally, at the facility level, healthcare workers should be trained on appropriate and respectful relations with both the community and the CHVs, clarity of roles and scope of work, ensure availability of services, and safeguard against corrupt practices in public health facilities. Lastly, there’s a need for improved and adequate security measures at the community level, to ensure safety of CHVs as they undertake their roles.
Carbon Life Cycle Assessment for Prairie as a Crop in Reclaimed Mine Land

A life cycle assessment with carbon (C) as the reference unit was used to balance the benefits of land preparation practices of establishing tall‐grass prairies as a crop for reclaimed mine land with reduced environmental damage. Land preparation and management practices included disking with sub‐soiling (DK‐S), disking only (DK), no tillage (NT), and no tillage with grazing (NT‐G). To evaluate the C balance and energy use of each of the land preparations, an index of sustainability (Is = CO/CI, Where: CO is the sum of all outputs and CI is the sum of all inputs) was used to assess temporal changes in C.
Amelioration of non-alcoholic fatty liver disease by targeting adhesion G protein-coupled receptor F1 (Adgrf1)

Background: Recent research has shown that the adhesion G protein-coupled receptor F1 (Adgrf1; also known as GPR110; PGR19; KPG_012; hGPCR36) is an oncogene. The evidence is mainly based on high expression of Adgrf1 in numerous cancer types, and knockdown Adgrf1 can reduce the cell migration, invasion, and proliferation. Adgrf1 is, however, mostly expressed in the liver of healthy individuals. The function of Adgrf1 in liver has not been revealed. Interestingly, expression level of hepatic Adgrf1 is dramatically decreased in obese subjects. Here, the research examined whether Adgrf1 has a role in liver metabolism. Methods: We used recombinant adeno-associated virus-mediated gene delivery system, and antisense oligonucleotide was used to manipulate the hepatic Adgrf1 expression level in diet-induced obese mice to investigate the role of Adgrf1 in hepatic steatosis. The clinical relevance was examined using transcriptome profiling and archived biopsy specimens of liver tissues from non-alcoholic fatty liver disease (NAFLD) patients with different degree of fatty liver. Results: The expression of Adgrf1 in the liver was directly correlated to fat content in the livers of both obese mice and NAFLD patients. Stearoyl-coA desaturase 1 (Scd1), a crucial enzyme in hepatic de novo lipogenesis, was identified as a downstream target of Adgrf1 by RNA-sequencing analysis. Treatment with the liver-specific Scd1 inhibitor MK8245 and specific shRNAs against Scd1 in primary hepatocytes improved the hepatic steatosis of Adgrf1-overexpressing mice and lipid profile of hepatocytes, respectively. Conclusions: These results indicate Adgrf1 regulates hepatic lipid metabolism through controlling the expression of Scd1. Downregulation of Adgrf1 expression can potentially serve as a protective mechanism to stop the overaccumulation of fat in the liver in obese subjects. Overall, the above findings not only reveal a new mechanism regulating the progression of NAFLD, but also proposed a novel therapeutic approach to combat NAFLD by targeting Adgrf1. Funding: This work was supported by the National Natural Science Foundation of China (81870586), Area of Excellence (AoE/M-707/18), and General Research Fund (15101520) to CMW, and the National Natural Science Foundation of China (82270941, 81974117) to SJ.
De novo assembly and annotation of the Amblyomma hebraeum tick midgut transcriptome response to Ehrlichia ruminantium infection

The South African bont tick Amblyomma hebraeum is a hematophagous vector for the heartwater disease pathogen Ehrlichia ruminantium in southern Africa. During feeding, the tick’s enterocytes express proteins that perform vital functions in blood digestion, including proteins that may be involved in E. ruminantium acquisition, colonization or immunity. To delineate the molecular mechanism of midgut response to E. ruminantium infection, we performed comparative analyses of midgut transcriptomes of E. ruminantium infected engorged A. hebraeum nymphs, and infected adult male and female ticks with their corresponding matched uninfected controls, before and during feeding. A total of 102,036 unigenes were annotated in public databases and their expression levels analyzed for engorged nymphs as well as unfed and partly-fed adult ticks. There were 2,025 differentially expressed genes (DEGs) in midguts, of which 1,225 unigenes were up-regulated and 800 unigenes were down-regulated in the midguts of infected ticks. Annotation of DEGs revealed an increase in metabolic and cellular processes among E. ruminantium infected ticks. Notably, among the infected ticks, there was up-regulation in the expression of genes involved in tick immunity, histone proteins and oxidative stress responses. We also observed up-regulation of glycoproteins that E. ruminantium could potentially use as docking sites for host cell entry. Insights uncovered in this study offer a platform for further investigations into the molecular interaction between E. ruminantium and A. hebraeum.
Micro-earthquakes beneath Ice Streams Β and C, West Antarctica: observations and implications

Abstract Micro-earthquakes have been monitored at two locations on Ice Stream Β and one on Ice Stream C using a seismographic array built specifically for that purpose. Subglacial micro-earthquakes arc 20 times more abundant beneath Ice Stream C than beneath Ice Stream B, despite the 100 times more rapid movement of Ice Stream B. Triangulation shows the foci beneath Ice Stream C, like those beneath Ice Stream B, to be within a few meters of the base of the ice, presumably within the uppermost part of the bed, and fault-plane analysis indicates slips on horizontal planes at about a 30° angle to the presumed direction of formerly active flow. Source parameters, computed from spectra of the arrivals, confirmed that the speed of slip is three orders of magnitude faster beneath Ice Stream C than beneath Ice Stream Β which means that a five orders-of-magnitude greater fraction of the velocity of Ice Stream C is contributed by the faulting, although that fraction is still small. We attribute the difference in activity beneath the two ice streams to the loss of dilatancy in the till beneath Ice Stream C in the process that led to its stagnation.
Amino acid–dependent regulation of insulin-like peptide signaling is mediated by TOR and GATA factors in the disease vector mosquito Aedes aegypti

Significance Aedes aegypti female mosquitoes are vectors of human viral diseases because they require vertebrate blood for their reproduction. Using CRISPR-Cas9 gene modification, transgenesis, and RNA interference in the mosquito, we identified the molecular mechanism underlying the nutritional pathway, in which the serine/tyrosine kinase target of rapamycin (TOR) mediates the amino acid (AA) signaling through GATA transcription factors and affects insulin-like peptides (ILP). GATA repressor (GATAr) inhibits the transcription of ilp4ilp6, and ilp7 genes. FoxO, a downstream TF in the insulin pathway, prevents the TOR-GATAr-mediated repression of these ilp genes. After the blood meal–mediated AA influx, GATA activator elevates the expression of ilp1ilp2ilp3ilp5, and ilp8 genes. Targeting AA-dependent reproductive processes may provide effective means in controlling mosquito population.
Variables related to bronchopulmonary dysplasia severity: a Six-Year retrospective study

Abstract Objectives This was a retrospective observational study conducted in a tertiary neonatal intensive care unit, in order to investigate factors which influenced the severity of bronchopulmonary dysplasia under NICHD new classification. Methods Six years of clinical data with different grades of bronchopulmonary dysplasia patients were collected and analyzed, bivariate ordinal logistic regression model and multivariable ordinal logistic regression model were used with sensitivity analyses. Results We identified seven variables were associated with the severity of BPD via a bivariate ordinal logistic regression model, including the level of referral hospital (OR 0.273；95% CI 0.117, 0.636), method of caffeine administration (OR 00.418；95% CI 0.177, 0.991), more than two occurrences of reintubation (OR 4.925；95% CI 1.878, 12.915), CPAP reapplication (OR 2.255；95% CI 1.059, 4.802), presence of positive sputum cultures (OR 2.574；95% CI 1.200, 5.519), the cumulative duration of invasive ventilation (OR 1.047；95% CI 1.017, 1.078), and postmenstrual age at the discontinuation of oxygen supplementation (OR 1.190；95% CI 1.027, 1.38). These seven variables were further analyzed via all multivariable ordinal logistic regression models, and we found that tertiary hospital birth and early administration of caffeine could reduce the severity of BPD by approximately 70% (OR 0.263；95% CI 0.090, 0.770) and 60% (OR 0.371；95% CI 0.138, 0.995), respectively. In contrast, multiple reintubations were related to higher BPD severity with an OR of 3.358 (95% CI 1.002, 11.252). Conclusion Improving perinatal care in level II hospitals, standardized caffeine administration, and optimized extubation strategy could potentially decrease the severity of BPD.
Segmentation of X‐ray coronary angiography with an artificial intelligence deep learning model: Impact in operator visual assessment of coronary stenosis severity

Visual assessment of the percentage diameter stenosis (%DSVE) of lesions is essential in coronary angiography (CAG) interpretation. We have previously developed an artificial intelligence (AI) model capable of accurate CAG segmentation. We aim to compare operators’ %DSVE in angiography versus AI‐segmented images.
Benzoates and in situ formed benzene in food supplements and risk assessment

ABSTRACT Upward trend in the use of food supplements urged the assessment of their safety. Eighty-eight liquid herbal supplements collected in Novi Sad (Serbia) in 2018 (36 samples) and 2021 (52 samples) were analysed for the presence of benzoates and sorbates (HPLC-UV) and benzene (HS-GC/MS). Benzoic acid varied from 599 to 9253 mg/kg and sorbic acid between 185 and 1658 mg/kg. The acceptable daily intake of sorbic acid was not reached, but in case of benzoic acid, it was exceeded by 5.3% of the samples. The presence of benzene was confirmed in 41.2% of benzoate preserved supplements (0.9–51.7 µg/kg). Benzene exposure revealed no health concern: maximum hazard quotients ranged from 0.39% (toddlers) to 0.84% (adolescents); minimum margins of exposure were between 35,680 (adolescents) and 77,419 (toddlers); estimates of lifetime cancer risk did not reach one extra cancer case per 100 000 persons. However, measures to mitigate benzene presence in food should be considered.
Evolutionary history of MEK1 illuminates the nature of deleterious mutations

Significance Genome sequencing has significantly improved diagnosis and treatment of genetic diseases and cancers; however, it produces many variants that cannot be easily interpreted. Automated bioinformatics tools can help predict functional consequences of variants of uncertain significance, but their accuracy is low. Here, by tracing precise evolutionary history of each amino acid position in MEK1 kinase (mutations in which cause neurodegenerative diseases and cancer), we can establish whether variants seen in humans are evolutionarily tolerant. Using published data and experiments, we show that evolutionarily tolerable variants in MEK1 are benign, whereas intolerable substitutions are damaging. Our approach will help in diagnostics of MEK1-associated diseases, it is generalizable to many other disease-associated genes, and it can help improve automated predictors.
The effectiveness of moderating harmful online content

In 2022, the European Union introduced the Digital Services Act (DSA), a new legislation to report and moderate harmful content from online social networks. Trusted flaggers are mandated to identify harmful content, which platforms must remove within a set delay (currently 24 h). Here, we analyze the likely effectiveness of EU-mandated mechanisms for regulating highly viral online content with short half-lives. We deploy self-exciting point processes to determine the relationship between the regulated moderation delay and the likely harm reduction achieved. We find that harm reduction is achievable for the most harmful content, even for fast-paced platforms such as Twitter. Our method estimates moderation effectiveness for a given platform and provides a rule of thumb for selecting content for investigation and flagging, managing flaggers’ workload.
Patients experience to inform decision-making and clinical follow-up: The example of total hip arthroplasty

Background The aim of this project was to enable patients and clinicians to benefit from previous patients experiences with total hip arthroplasty (THA) by seeking out patients views on what is important for them, leveraging registry data, and providing outcome information that is perceived as relevant, understandable, adapted to a specific patients profile, and readily available. Methods We created the information tool Patients like me in four steps. (1) The knowledge basis was the systematically collected detailed exposure and outcome information from the Geneva Arthroplasty Registry established 1996. (2) From the registry we randomly selected 275 patients about to undergo or having already undergone THA and asked them via interviews and a survey which benefits and harms associated with the operation and daily life with the prosthesis they perceived as most important. (3) The identified relevant data (39 predictor candidates, 15 outcomes) were evaluated using Conditional Inference Trees analysis to construct a classification algorithm for each of the 15 outcomes at three different time points/periods. Internal validity of the results was tested using bootstrapping. (4) The tool was designed by and pre-tested with patients over several iterations. Results Data from 6836 primary elective THAs operated between 1996 and 2019 were included. The trajectories for the 15 outcomes from the domains pain relief, activity improvement, complication (infection, dislocation, peri-prosthetic fracture) and what to expect in the future (revision surgery, need for contralateral hip replacement) over up to 20 years after surgery were presented for all patients and for specific patient profiles. The tool was adapted to various purposes including individual use, group sessions, patient-clinician interaction and surgeon information to complement the preoperative planning. The pre-test patients feedback to the tool was unanimously positive. They considered it interesting, clear, complete, and complementary to other information received. Conclusion The tool based on a survey of patients perceived concerns and interests and the corresponding long-term data from a large institutional registry makes past patients experience accessible, understandable, and visible for todays patients and their clinicians. It is a comprehensive illustration of trajectories of relevant outcomes from previous Patients like me. This principle and methodology can be applied in other medical fields.
How to enlarge lesion size in temperature control mode using an irrigation catheter with a flexible-tip of laser-cut kerfs

Background & Objectives: The TactiFlexTM SE irrigation catheter installs a laser-cut flexible tip with a thermocouple embedded 0.3mm from the tip, being used with temperature-control mode. We aimed to elucidate a safer method to enlarge the lesion size using this catheter. Methods: RF-applications were performed at a range of powers (35W, 40W, and 45W), CFs (10g/20g), and durations (60s, 120s, and 180s) using perpendicular/parallel catheter orientation with normal saline irrigation (NS-irrigation) and Half NS-irrigation (HNS-irrigation) in an ex-vivo model (Step 1). Further, similar RF-applications of 35W/40W/45W for 60s/120s/180 in NS-irrigation and 35W/40W for 60s/120s/180s in HNS-irrigation) were performed in 4 swine (Step 2). Lesion characteristics and the incidence of steam-pops were assessed. Results: In this ex-vivo experiment, 47(16.3%) steam-pops (13 in NS-irrigation vs 34 in HNS-irrigation, p=0.001) were observed in 288 lesions. In NS-irrigation group, the most aggressive setting (45W/180s, n=7/13, 54%) played a large part of steam-pop occurrence. Lesion size proportionally increased with longer ablation duration, but not with HNS-irrigation. The optimal cut-off of %impedance-drop to predict steam-pops was 20% with the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 78.3%, 80.6%, 43.4%, and 95.1%, respectively. In the in-vivo experiment, steam-pops were not observed with NS-irrigation (n=0/35), but were with HNS-irrigation (6/21, 29%). Lesion size proportionally increased with longer ablation duration, but not with HNS-irrigation partially because of the higher incidence of temperature-guard use (p=0.07). The optimal cut-off of %impedance-drop to predict steam-pops was 24% with the sensitivity= 83.0%, specificity=52.0%, PPV= 17.2%, and NPV= 96.3%, respectively, but 20% may be used with a safety margin. Conclusions: Although this novel catheter is generally safe, increasing ablation duration instead of using HNS-irrigation may be recommended for larger lesions.
Radical Group Transfer of Vinyl and Alkynyl Silanes Driven by Photoredox Catalysis

Radical group transfer is a powerful tool for the formation of C–C bonds. These processes typically involve radical addition to C–C π bonds, followed by fragmentation of the resulting cyclic intermediate. Despite the advantageous lability of organosilanes in this context, silicon-tethered radical acceptor groups have remained underexplored in radical group transfer reactions. We report a general photoredox-catalyzed protocol for the radical group transfer of vinyl and alkynyl silanes onto sp3 carbons, using activated and unactivated iodides as radical precursors. Our method displays high diastereoselectivity and excellent functional group tolerance, and enables direct formation of group transfer products by in situ ring opening. Mechanistic investigations revealed that the reaction proceeds via an unusual dual catalytic cycle, resulting in an overall redox-neutral process.
An Extremely Simple Algorithm for Source Domain Reconstruction

The aim of unsupervised domain adaptation (UDA) is to utilize knowledge from a source domain to enhance the performance of a given target domain. Due to the lack of accessibility to the target domain’s labels, UDA’s efficacy is highly reliant on the source domain’s quality. However, it is often impractical and expensive to obtain an appropriate transferable source domain. To address this issue, we propose a novel UDA setting, source domain reconstruction (SDR), which seeks to construct a new transferable source domain utilizing labeled source samples and unlabeled target samples. SDR has a significant advantage over the conventional method as it is much less expensive to construct a suitable pseudo-source domain rather than collecting an actual transferable source domain in real-world scenarios. To test the practice of SDR, we investigate SDR theoretically. We propose an easily implementable algorithm, the domain MixUp (DMU), which is motivated by the MixUp strategy, to solve the SDR problem. The algorithm can be used to design a UDA framework to significantly enhance the performance of several existing UDA algorithms. Results from extensive experiments conducted on seven benchmarks $(66$ UDA tasks) indicate that the reconstructed source domain has stronger transferability than the original source domain.