Miracle-dz/UniFAR-FTUs huggingface dataset:
Establishment of an in vitro culture system to study the developmental biology of Onchocerca volvulus with implications for anti-Onchocerca drug discovery and screening

Background Infections with Onchocerca volvulus nematodes remain a threat in Sub-Saharan Africa after three decades of ivermectin mass drug administration. Despite this effort, there is still an urgent need for understanding the parasite biology especially the mating behaviour and nodule formation as well as the development of more potent drugs that can clear the developmental (L3, L4, L5) and adult stages of the parasite and inhibit parasite reproduction and behaviour. Methodology/Principal findings Prior to culture, freshly harvested O. volvulus L3 larvae from dissected Simulium damnosum flies were purified by centrifugation using a 30% Percoll solution to eliminate fly tissue debris and contaminants. Parasites were cultured in both cell-free and cell-based co-culture systems and monitored daily by microscopic visual inspection. Exhausted culture medium was replenished every 2–3 days. The cell-free culture system (DMEM supplemented with 10% NCS) supported the viability and motility of O. volvulus larvae for up to 84 days, while the co-culture system (DMEM supplemented with 10% FBS and seeded on LLC-MK2 feeder cells) extended worm survival for up to 315 days. Co-culture systems alone promoted two consecutive parasite moults (L3 to L4 and L4 to L5) with highest moulting rates (69.2±30%) observed in DMEM supplemented with 10% FBS and seeded on LLC-MK2 feeder cells, while no moult was observed in DMEM supplemented with 10% NCS and seeded on LEC feeder cells. In DMEM supplemented with 10% FBS and seeded on LLC-MK2 feeder cells, O. volvulus adult male worms attached to the vulva region of adult female worms and may have mated in vitro. Apparent early initiation of nodulogenesis was observed in both DMEM supplemented with 10% FBS and seeded on LLC-MK2 and DMEM supplemented with 10% NCS and seeded on LLC-MK2 systems. Conclusions/Significance The present study describes an in vitro system in which O. volvulus L3 larvae can be maintained in culture leading to the development of adult stages. Thus, this in vitro system may provide a platform to investigate mating behaviour and early stage of nodulogenesis of O. volvulus adult worms that can be used as additional targets for macrofilaricidal drug screening.
A Privacy-Preserving Key Management Scheme with Support for Sybil Attack Detection in VANETs

Vehicular ad hoc networks (VANETs) face two important and conflicting challenges with regards to security: preserve the privacy of vehicles in order to prevent malicious entities from tracking users and detect and remove bad actors that attempt to game the system for their own advantage. In particular, detecting Sybil attacks, in which one node attempts to appear as many, seemingly conflicts with the goal of privacy preservation, and existing schemes fail on either one or both accounts. To fill this gap, we present a hierarchical key management system which uses short group signatures to preserve member privacy at lower levels while allowing mid-level nodes to detect Sybil attacks and highly trusted nodes at the top of the hierarchy to completely reveal the real identities of malicious nodes in order to prevent them from rejoining the system and for use by legal authorities. In addition, we present an argument for relaxing the requirement of backward secrecy in VANET groups in the case when no malicious activity has been detected.
Evaluation of the Performance of Manual Antimicrobial Susceptibility Testing Methods and Disk Breakpoints for Stenotrophomonas maltophilia

Stenotrophomonas maltophilia is an emerging cause of serious infections with high associated mortality in immunocompromised patients. Treatment of S. maltophilia infections is complicated by intrinsic resistance to many antimicrobials, including carbapenems, aminoglycosides, and some cephalosporins. ABSTRACT Stenotrophomonas maltophilia is an emerging cause of serious infections with high associated mortality in immunocompromised patients. Treatment of S. maltophilia infections is complicated by intrinsic resistance to many antimicrobials, including carbapenems, aminoglycosides, and some cephalosporins. Despite this, >90% of isolates are susceptible to trimethoprim-sulfamethoxazole (SXT), which is the front-line therapy for this organism. Side effects of SXT include bone marrow suppression, which precludes its use for many neutropenic patients. In this population, levofloxacin (LEV), minocycline (MIN), ceftazidime (CAZ), ciprofloxacin (CIP), and tigecycline (TIG) are used as alternative therapies, all of which require testing to inform susceptibilities. The reference standard method for testing S. maltophilia is broth microdilution (BMD), but very few clinical laboratories perform reference BMD. Furthermore, interpretive criteria are not available for CIP or TIG for S. maltophilia, although generic pharmacokinetic/pharmacodynamic (PK/PD) MIC breakpoints are available for these drugs. We assessed performance of disk and gradient diffusion tests relative to BMD for 109 contemporary isolates of S. maltophilia. Categorical agreement values for SXT, LEV, and MIN disk diffusion were 93%, 89%, and 95%, respectively. Categorical agreement values for SXT, LEV, MIN, and CAZ gradient strips were 98%, 85%, 93%, and 71%, respectively, by Etest (bioMerieux) and 98%, 83%, 99%, and 73% by the MIC test strip (MTS; Liofilchem). CIP and TGC, two clinically valuable alternatives to SXT, did not demonstrate promising disk-to-MIC correlates using CLSI document M100-ED30 (Clinical and Laboratory Standards Institute, Performance Standards for Antimicrobial Susceptibility Testing, M100-ED30, 2020) P. aeruginosa or PK/PD breakpoints. Manual commercial tests perform well for S. maltophilia, with the exception of tests for LEV and CAZ, for which high error rates were observed.
Overview of a Life Skills Coaching Program for Adults on the Autism Spectrum: Coaches’ Perspectives

There is considerable need to identify effective service provision models to support adults on the autism spectrum as they seek to lead independent lives. This study outlines an individualized life skills coaching program for adults with autism, “LifeMAP”, and the experiences and perspectives of the coaches. Responses on a tailored questionnaire provided detailed insight into how the coaches were performing their job, the strategies they utilized, reasons for client success and difficulty, challenges faced by the coaches, and ways they were supported by program staff. Coaches’ job self-efficacy and satisfaction were also examined. This study serves as a preliminary examination of individualized coaching for adults with autism from the coaches’ perspective.
Nitrogen, phosphorus, potassium, magnesium, and sulphur requirements for maize grain production

Abstract Nitrogen, phosphorus, potassium, magnesium, and sulphur requirements for maize grain production were investigated at 7 sites selected in the Waikato, Bay of Plenty, and Poverty Bay to provide a range in soil nutrient status. High grain yields were achieved without pre-plant or starter fertiliser in Poverty Bay and using only 20–25 kg of Nand P as starter in the Waikato and the Bay of Plenty. It was concluded that no pre-plant P is required if the Olsen P test is 15 or above, and no pre-plant K is required if the K soil test is above 4. No evidence was found to support Mg or S applications to maize. The influence of soil N on the chemical composition of the maize plant, and its implications in diagnosis of nutrient deficiencies using tissue analysis, is discussed.
Rapid decline of resting heart rate trajectories from childhood to young adulthood is paradoxically associated with increased cardiac mass

Abstract Background Little is known about the varied resting heart rate (RHR) trajectory patterns from childhood to young adulthood and their clinical significance. We aim to identify RHR trajectories from childhood to young adulthood, and to determine their relationship with left ventricular mass (LVM) index. Methods RHR was measured up to 15 times over a 21-year period in 759 participants from childhood to young adulthood. LVM was measured using echocardiography and was normalised to body surface area to obtain LVM index in 546 participants. Results Using latent class models, three trajectory groups in RHR from childhood to young adulthood were identified, including high-decreasing group (HDG), moderate-decreasing group (MDG), and low-decreasing group (LDG). We found that trajectory of RHR was a significant predictor of LVM index with faster decrease of RHR associated with higher levels of total peripheral resistance (P for trend <0.001) and LVM index (P for trend <0.001). Compared to the LDG, individuals in the HDG showed higher LVM index (β = 6.08, p < 0.001). In addition, the interactions between race and RHR trajectories for LVM index was significant (p < 0.05). Conclusion Our findings show an association between RHR trajectories from childhood to young adulthood with cardiac mass, suggesting that monitoring RHR may help identify subpopulation at high cardiovascular risk.
A Cell-Penetrating Peptide That Blocks Toll-Like Receptor Signaling Protects Kidneys against Ischemia-Reperfusion Injury

Renal ischemia-reperfusion injury (IRI) is involved in the majority of clinical conditions that manifest as renal function deterioration; however, specific treatment for this type of injury is still far from clinical use. Since Toll-like receptor (TLR)-mediated signaling is a key mediator of IRI, we examined the effect of a multiple-TLR-blocking peptide named TLR-inhibitory peptide 1 (TIP1), which exerts the strongest action on TLR4, on renal IRI. We subjected C57BL/6 mice to 23 min of renal pedicle clamping preceded by intraperitoneal injection with a vehicle or TIP1. Sham control mice underwent flank incision only. Mouse kidneys were harvested after 24 h of reperfusion for histology, western blot, RT-PCR, and flow cytometry analysis. Pretreatment with TIP1 lowered the magnitude of elevated plasma creatinine levels and attenuated tubular injury. TIP1 treatment also reduced mRNA expression of inflammatory cytokines and decreased apoptotic cells and oxidative stress in post-ischemic kidneys. In kidneys pretreated with TIP1, the infiltration of macrophages and T helper 17 cells was less abundant than those in the IRI only group. These results suggest that TIP1 has a potential beneficial effect in attenuating the degree of kidney damage induced by IRI.
Dietary fat intake and liver cancer incidence: A population‐based cohort study in Chinese men

To date, limited studies have focused on the association between dietary fat and liver cancer risk, especially in China. Our study aims to evaluate the association between dietary fat intake and liver cancer incidence risk in men. Dietary fat intake was obtained through a validated food frequency questionnaire in a Chinese prospective cohort. The Cox regression model was utilized to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). After exclusion, 59 998 recruitments were finally analyzed with a total follow‐up time of 714 339 person‐years, 431 incident liver cancer cases were newly identified among them. The adjusted HRs (95% CIs) for the highest vs lowest quartile of total fat, saturated fat, monounsaturated fat (MUFA), and polyunsaturated fat (PUFA) were 1.33 (1.01‐1.75), 1.50 (1.13‐1.97), 1.26 (0.96‐1.65), and 1.41 (1.07‐1.86), and the corresponding P‐trend values were . 008, . 005, . 034, and . 005, respectively. In the secondary analysis among participants tested for hepatitis B virus, we found that higher intakes of saturated fat and PUFA were also associated with increased liver cancer risks. Besides, high risks of per standard deviation alterations of the total fat, saturated fat and MUFA were detected in liver cancer, and these results were similar to those concluded from the full‐cohort analysis. In conclusion, dietary intakes of total fat, saturated fat, PUFA, and probably MUFA might increase liver cancer risks. Our study provides suggestive advice to public administration on dietary suggestions, and related measures taken from managing dietary fat intake might reduce liver cancer incidence.
Separating Algorithms from Questions and Causal Inference with Unmeasured Exposures: An Application to Birth Cohort Studies of Early BMI Rebound.

Observational studies reporting adjusted associations between childhood body mass index (BMI) rebound and subsequent cardio-metabolic outcomes have often not given explicit attention to causal inference, including definition of a target causal effect and assumptions for unbiased estimation of that effect. Using data from 649 children in a Boston, Massachusetts-area cohort recruited in 1999-2002, we considered effects of stochastic interventions on a chosen subset of modifiable, yet unmeasured, exposures expected to be associated with early (< age 4 years) BMI rebound (a proxy) on adolescent cardiometabolic outcomes. We consider assumptions under which these effects may be identified with available data. This leads to an analysis where the proxy, rather than exposure, acts as exposure in the algorithm. We applied Targeted Maximum Likelihood Estimation, a doubly-robust approach that naturally incorporates machine learning for nuisance parameters (e.g. propensity score). We estimated a protective effect of an intervention that assigns modifiable exposures according to the distribution in the observational study of those without (vs. with) early BMI rebound for fat-mass index (-1.39 kg/m2; 95% CI -1.63,-0.72), but weaker or no effects for other cardiometabolic outcomes. Our results clarify distinctions between algorithms and causal questions, encouraging explicit thinking in causal inference with complex exposures.
Changing personality traits with the help of a digital personality change intervention

Significance Personality traits have consequences and are malleable throughout the lifespan. However, it is unclear if and how personality traits can be changed in desired directions. A 3-mo digital personality change intervention was deployed, and a large-scale randomized controlled trial (n = 1,523) was conducted to examine the effects of intended personality change in a nonclinical sample. The intervention group showed greater changes than the control group, and changes aligned with intended goals for change. Observers also perceived personality changes, but reported changes were less pronounced. Moreover, self- and observer-reported changes persisted until 3 mo after the end of the intervention. These findings provide the strongest evidence to date that normal personality traits can be changed through intervention in nonclinical samples. Personality traits predict important life outcomes, such as success in love and work life, well-being, health, and longevity. Given these positive relations to important outcomes, economists, policy makers, and scientists have proposed intervening to change personality traits to promote positive life outcomes. However, nonclinical interventions to change personality traits are lacking so far in large-scale naturalistic populations. This study (n = 1,523) examined the effects of a 3-mo digital personality change intervention using a randomized controlled trial and the smartphone application PEACH (PErsonality coACH). Participants who received the intervention showed greater self-reported changes compared to participants in the waitlist control group who had to wait 1 mo before receiving the intervention. Self-reported changes aligned with intended goals for change and were significant for those desiring to increase on a trait (d = 0.52) and for those desiring to decrease on a trait (d = −0.58). Observers such as friends, family members, or intimate partners also detected significant personality changes in the desired direction for those desiring to increase on a trait (d = 0.35). Observer-reported changes for those desiring to decrease on a trait were not significant (d = −0.22). Moreover, self- and observer-reported changes persisted until 3 mo after the end of the intervention. This work provides the strongest evidence to date that normal personality traits can be changed through intervention in nonclinical samples.
Training, Injury, and Lifestyle Characteristics of Recreational Triathletes

Abstract Triathlon is a popular sport among recreational and competitive athletes. As triathletes compete in races ranging from 16 to 140.6 miles and train in three disciplines simultaneously, it is difficult to identify injury risk factors. The aim of this study was to evaluate characteristics of a group of recreational triathletes regarding their medical history, training regimen, and injuries. Thirty-four triathletes completed this survey. We found a wide range of body types, training habits, and lifestyle characteristics. As in previous studies, we found a high rate of injuries in our surveyed triathletes. Injury rates were higher in athletes who had completed a longer race and those who reported higher training times per week. Additionally, many individuals have medical problems, use a variety of supplements, and follow specific dietary restrictions, which need to be considered in addition to training when assessing injury risk and recovery from injury.
Applied Methods for Estimating Transition Probabilities from Electronic Health Record Data

Background Electronic health record (EHR) data contain longitudinal patient information and standardized diagnostic codes. EHR data may be useful for estimating transition probabilities for state-transition models, but no guidelines exist on appropriate methods. We applied 3 potential methods to estimate transition probabilities from EHR data, using pediatric eating disorders (EDs) as a case study. Methods We obtained EHR data from PEDsnet, which includes 8 US children’s hospitals. Data included inpatient, outpatient, and emergency department visits for all patients with an ED. We mapped diagnoses to 3 ED health states: anorexia nervosa, bulimia nervosa, and other specified feeding or eating disorder. We estimated 1-y transition probabilities for males and females using 3 approaches: simple first-last proportions, a multistate Markov (MSM) model, and independent survival models. Results Transition probability estimates varied widely between approaches. The first-last proportion approach estimated higher probabilities of remaining in the same health state, while the MSM and independent survival approaches estimated higher probabilities of transitioning to a different health state. All estimates differed substantially from published literature. Limitations As a source of health state information, EHR data are incomplete and sometimes inaccurate. EHR data were especially challenging for EDs, limiting the estimation and interpretation of transition probabilities. Conclusions The 3 approaches produced very different transition probability estimates. Estimates varied considerably from published literature and were rescaled and calibrated for use in a microsimulation model. Estimation of transition probabilities from EHR data may be more promising for diseases that are well documented in the EHR. Furthermore, clinicians and health systems should work to improve documentation of ED in the EHR. Further research is needed on methods for using EHR data to inform transition probabilities.
Power Failure of Mitochondria and Oxidative Stress in Neurodegeneration and Its Computational Models

The brain needs more energy than other organs in the body. Mitochondria are the generator of vital power in the living organism. Not only do mitochondria sense signals from the outside of a cell, but they also orchestrate the cascade of subcellular events by supplying adenosine-5′-triphosphate (ATP), the biochemical energy. It is known that impaired mitochondrial function and oxidative stress contribute or lead to neuronal damage and degeneration of the brain. This mini-review focuses on addressing how mitochondrial dysfunction and oxidative stress are associated with the pathogenesis of neurodegenerative disorders including Alzheimer’s disease, amyotrophic lateral sclerosis, Huntington’s disease, and Parkinson’s disease. In addition, we discuss state-of-the-art computational models of mitochondrial functions in relation to oxidative stress and neurodegeneration. Together, a better understanding of brain disease-specific mitochondrial dysfunction and oxidative stress can pave the way to developing antioxidant therapeutic strategies to ameliorate neuronal activity and prevent neurodegeneration.
Global citation inequality is on the rise

Significance By analyzing a global sample of 4 million authors and 26 million scientific papers, this study finds that the top 1% most-cited scientists have increased their cumulative citation shares from 14 to 21% between 2000 and 2015 and that the Gini coefficient for citation imbalance has risen from 0.65 to 0.70. The growing citation concentration should be understood in the context of diverging trends in publication and collaboration activities for the top 1% compared to the “ordinary scientist. ” Our study raises intriguing questions about how rising inequalities will shape the evolution of science. Citations are important building blocks for status and success in science. We used a linked dataset of more than 4 million authors and 26 million scientific papers to quantify trends in cumulative citation inequality and concentration at the author level. Our analysis, which spans 15 y and 118 scientific disciplines, suggests that a small stratum of elite scientists accrues increasing citation shares and that citation inequality is on the rise across the natural sciences, medical sciences, and agricultural sciences. The rise in citation concentration has coincided with a general inclination toward more collaboration. While increasing collaboration and full-count publication rates go hand in hand for the top 1% most cited, ordinary scientists are engaging in more and larger collaborations over time, but publishing slightly less. Moreover, fractionalized publication rates are generally on the decline, but the top 1% most cited have seen larger increases in coauthored papers and smaller relative decreases in fractional-count publication rates than scientists in the lower percentiles of the citation distribution. Taken together, these trends have enabled the top 1% to extend its share of fractional- and full-count publications and citations. Further analysis shows that top-cited scientists increasingly reside in high-ranking universities in western Europe and Australasia, while the United States has seen a slight decline in elite concentration. Our findings align with recent evidence suggesting intensified international competition and widening author-level disparities in science.