Temporal properties of preparation phase for arm-pointing movements in various directions and distances.

In this study, we investigated how the temporal properties of the preparation phase for upper limb movements are affected by the reaching direction and distance. Twelve right-handed participants performed three motor tasks: two types of reaching movements and one finger-lifting movement. The reaching movements were performed from the home position to 15 target locations (five directions and three distances) as quickly and precisely as possible under two conditions: pre-cueing the target to allocate the sufficient time for the motor-planning process before movement initiation, and no-cuing. The finger lifting movement was performed by lifting the index finger (from the home position) upward in the air as quickly as possible. The reaction time (RT), movement time (MT), and kinematics of the index finger were obtained for each condition. In addition, differential RTs (DRT) were calculated by subtracting the RT for no-cue lifting from that for no-cue reaching, thereby implicitly representing the time required for the motor-planning process for reaching movements. The results indicated the anisotropy of the DRTs being larger in the forward and left-forward directions than that in the right-forward direction, and larger in the forward direction than that in the right direction for the middle distance. It is suggested that the temporal costs of the motor-planning process depend on the movement direction and distance. In the kinematic analysis, the MTs showed the anisotropy being the largest in the left-forward among all directions. Meanwhile, the time from peak velocity to terminate the movement (TFPV) was significantly longer in the left-forward direction when no-cueing the target than when pre-cueing. These results suggest that reaching movement is refined during the online-control process to accomplish the intended performance if a reaching movement under the no-cue condition is initiated before building sufficient motor planning, especially in the direction requiring large temporal costs. It is likely that humans achieve their intended movements by allocating the temporal costs required before and after movement initiation according to the difficulty of motor control which varies with the direction and distance.

Selection of appropriate location based on signed distance based ranking approach with interval type-2 trapezoidal fuzzy preference relations.

In real life situation, it is often difficult to judge the relative importance of different parameters being considered for evaluating some alternatives. In the context of fuzzy sets, it is a situation where it is difficult to define precise membership grades for attribute values. Here we require more generalized type of fuzzy sets which have a greater representational power than ordinary fuzzy sets. For this purpose we use "interval type-2 trapezoidal fuzzy preference relations (IT2TrFPRs)" in this article as a generalization of fuzzy preference relations and consider the environment discussed above, where there is no information on priority weights. A collective decision matrix will be constructed on the basis of hybrid averages using weighted averaging and signed distance based OWA operation. Then a least deviation model will be employed in order to determine the priority weight vectors. Finally, the alternatives will be ranked on the basis of weighted normalized signed distance of each alternative from the ideal solution. Moreover, a real life example of location selection is illustrated to elaborate the effectiveness of the proposed scheme.

Prevalence, severity, and predictors of self-reported depression in ultra-distance runners: An online survey based on 265 athletes.

BACKGROUND: Literature suggests a high prevalence of mental health disorders among athletes practicing elite and extreme sports. One of the most commonly encountered disorders in this group of individuals is depression. OBJECTIVE: The aim of this study was to examine the prevalence, severity, and risk factors of symptoms of self-reported depression among ultra-distance runners. METHODS: Data was collected using an online survey (February to April 2023) and included 265 (age 48.35 ± 10.52 years) adult ultra-runners. The Beck Depression Inventory-II (BDI-II) was used to measure self-reported depression. Additional variables comprised basic sociodemographic information and information regarding training, ultramarathon experience, and previous injury. Descriptive and interferential statistics were performed using JASP Version 0.16.4. RESULTS: We found that 21.9 % (n = 58) of ultra-runners suffered from self-reported depression (i.e., BDI-II score ≥ 14) with an average BDI-II score of 22.7 ± 7.1 (moderately severe symptoms). Female ultra-runners had a higher prevalence (30.8 %) of self-reported depression than males (16.2 %, p = .001). Logistic regression revealed that ultra-runners without previous sports injury (p = .01) and those of increasing age (p = .003) had a significantly lower risk of self-reported depression. Similarly, linear regression showed the absence of injury (p < .001) and increasing age (p = .02) resulted in significantly lower BDI-II scores. Training volume in distance and hours per week as well as ultra-running experience did not show any significant association. CONCLUSIONS: Affecting more than one-fifth of our collective, depressive symptoms appear to be highly prevalent among ultra-runners. Our findings underline the importance of screening for clinical depression, especially among injured athletes. However, the previously assumed peculiarities of the sport in the area of high training volume do not appear to be a significant factor.

Chronic Adaptation of the Coracohumeral Space and Subscapularis Tendon in Professional Baseball Pitchers.

BACKGROUND: Pitchers frequently experience anterior shoulder pain, possibly associated with coracohumeral impingement; however, whether the coracohumeral distance (CHD) and/or subscapularis tendon adapt chronically (bilateral difference) due to pitching, and whether clinical measures are associated with CHD and subscapularis tendon organization have not been evaluated in professional pitchers. HYPOTHESIS: The authors hypothesized that dominant arm CHD would be smaller than the nondominant arm, dominant subscapularis tendon would have increased spatial frequency (ie, be more disorganized), and humeral retroversion (HR) would predict CHD and subscapularis tendon organization. LEVEL OF EVIDENCE: Level 4. METHODS: Healthy professional baseball pitchers were recruited during their preseason physical examination. Bilateral diagnostic ultrasound measured CHD, HR, and posterior capsule thickness (PCT), and quantified subscapularis tendon organization. External rotation, neutral, and crossbody CHD was measured. RESULTS: Overall, 52 healthy professional baseball pitchers participated. The dominant arm of pitchers demonstrated a significantly narrower CHD in all 3 positions (P < 0.01), increased scapular protraction (163 vs 156 mm; P < 0.01), and increased spatial frequency of the subscapularis tendon (1.8 vs 1.6 peaks/mm; P < 0.01). HR was associated with CHD in 30° of external rotation (R2 = 0.12; P < 0.01), neutral rotation (R2 = 0.11; P < 0.01), and the crossbody position (R2 = 0.28; P < 0.01). PCT was associated with CHD in 30° of external rotation (R2 = 0.16; P = 0.05). HR and CHD in 30° of external rotation was associated most strongly with subscapularis tendon organization (R2 = 0.11; P = 0.03). CONCLUSION: The dominant shoulder of professional pitchers presents with a smaller CHD, more scapular protraction, and more subscapularis tendon disorganization than the nondominant shoulder. CLINICAL RELEVANCE: Professional pitchers demonstrate chronic CHD and subscapularis tendon adaptations, which may increase their risk for anterior shoulder pain and subscapularis tendon injury.

Telemedicine as a counselling tool for nurses in Central Africa.

AIM: Compare the use and trend of a telemedicine tool for clinical advice among nurses and other Cameroonian healthcare providers and explore its feasibility and accessibility. DESIGN: A comparative observational descriptive study. METHODS: The sample includes all telemedicine users who request advice from volunteer medical specialists in Spain on clinical cases through the telemedicine tool "diagnosis assistance" (DA). It consisted of a total of 296 Cameroonian health professionals (59% women), of whom 77 were nurses. The variables in which the trend was explored (2013-2022) were DAs entered by nurses versus other healthcare professionals, compared by primary specialty, comments and documents attached. Feasibility and accessibility were explored through an anonymous survey. RESULTS: There were 2527 DAs between 2013 and 2022, of which nurses introduced 68%. There is an increasing trend in the nurse/other healthcare providers ratio, with significant differences in the chi-square of the linear trend between 2015 and 2022 (χ2 = 395.05; df = 7; p < .001). The probability that a DA was requested by nurses (PR >1) was observed in all years except for 2014, 2018 and 2019. The most tele-counselling requested by nurses was in the specialties of internal medicine, obstetrics and gynaecology, and dermatology. The exchange of comments and attachments was mainly conducted among nurses (74.9% and 50.4%, respectively). The users surveyed considered the tool valuable for diagnosis, applicable, with limitations due to cost, Internet quality or lack of time and effective at reducing hospital referrals. CONCLUSIONS: Telemedicine for clinical advice has been used mostly and with increasing tendency by nurses, mainly in internal medicine, gynaecology and dermatology, being a useful and feasible resource that can contribute to improving clinical decision-making by African nurses. IMPACT: The study addressed the problem of the shortage of health professionals in Central Africa and the search for alternatives that facilitate decision-making in this context. Tele-counselling tools through digital platforms that put Spanish specialists in contact with health professionals in Central Africa are mostly used by nurses working in rural health centres with a growing trend in their use. The research allows us to determine that tele-counselling tools constitute a well-accepted resource, which has a positive impact in environments with a shortage of human health resources, favouring the safety of both the nursing professional, through support in decision-making, and the populations to whom they provide care, who benefit from a multidisciplinary approach to their processes. REPORTING METHOD: The study has adhered to STROBE guidelines. PATIENT OR PUBLIC CONTRIBUTION: No Patient or Public Contribution.

Light footprint of microalgae cultivation system addressed by modified Cornet model.

The cultivation of microalgae is significantly influenced by light intensity and utilization efficiency. This study developed a modified Cornet (M-Cornet) model to assess the distribution of light intensity and flux in microalgae cultivation systems. Algal biofilm cultivation represents a more concentrated approach of algal suspension cultivation. Both follow the M-Cornet model and exhibit the same growth rates when cultured under identical conditions. Algal pigments and morphologies greatly impact the light absorption and scattering, resulting in light attenuation in intensity, penetration distance and light flux distribution. Algae varieties exhibit diverse light flux characteristics. 37% - 90% of the incident light is absorbed, of which, 80% to 90% is dissipated as heat. 10% to 63% of the incident light is scattered off the photobioreactor. The overall light utilization efficiency ranges 6% to 13%. The light footprint using the M-Cornet model offers valuable insights for photobioreactors designing and cultivation operating.

Pulmonary Rehabilitation Once a Week for One Year in a Patient With Chronic Obstructive Pulmonary Disease.

Pulmonary rehabilitation (PR) has been shown to alleviate dyspnea, increase exercise capacity, and improve quality of life in patients with chronic obstructive pulmonary disease (COPD). However, such PR programs have focused on short-term effects. Thus, this study aimed to report our experience with a COPD patient who underwent PR once a week for one year. An 84-year-old male with stage II COPD, which was classified by the Global Initiative for Obstructive Lung Disease, presented symptoms of dyspnea while walking. The patient underwent PR once a week for one year, which included exercise training, self-management support, instructions on breathing during exertion, and respiratory muscle stretching. Before and after PR, we assessed the patient's physical function, dyspnea, and quality of life. For one year, no adverse events were recorded. We observed that the patient's physical function, dyspnea, and quality of life improved over time. In particular, his six-minute walking distance (6MWD) reached the minimal clinically important difference at three months and the predictive value of 6MWD for healthy adults at six months. The present case showed that a PR program conducted once a week for one year might be feasible and effective.

Spatiotemporal variation of microplastics along the long-distance raw water pipeline.

Raw water pipelines are considered a significant pathway for human exposure to microplastics (MPs, <5 mm) in surface water. However, there is currently very limited information on the longitudinal distribution characteristics of microplastics in raw water pipelines. This study assessed the abundance and distribution characteristics of microplastics in surface water from two different water sources in Jiangsu Province during different seasons. The correlation between conventional water quality indicators and microplastics was also explored. Specifically, the longitudinal variation of microplastics in raw water pipelines was investigated. Results showed that microplastics were detected in both basins during different seasons. In Basin 1, the abundance of MPs ranged from 34 ±â€¯1 to 58 ±â€¯2 n/L in March and from 3 ±â€¯1 to 6.7 ±â€¯4 n/L in June. In Basin 2, the abundance ranged from 6.5 ±â€¯1 to 14 ±â€¯1 n/L in March and from 2 ±â€¯1 to 7.7 ±â€¯1 n/L in June. The abundance of microplastics showed a decreasing trend along the pipeline. Polymethyl methacrylate (PMMA) was the main polymer type detected in both basins. Polyethylene terephthalate (PE) and polyurethane (PU) showed higher removal rates in the pipeline due to their higher density. The predominant size ranges of microplastics in the raw water were 10-50 µm and 50-100 µm. Additionally, the average particle size of MPs increased with the transportation distance, likely due to microbial colonization. This study is the first comprehensive investigation of the distribution characteristics of microplastics in raw water pipeline systems. The removal of microplastics in raw water pipelines contributes significantly to the elimination of microplastics at the source. This research helps to fill the knowledge gap regarding the fate of microplastics in raw water pipeline systems.

A framework for modeling the impacts of adaptive search intensity on the efficiency of abundance surveys.

When planning abundance surveys, the impact of search intensity on the quality of the density estimates is rarely considered. We constructed a time-budget modeling framework for abundance surveys using principles from optimal foraging theory. We link search intensity to the number of sample units surveyed, searcher detection probability, the number of detections made, and the precision of the estimated population density. This framework allowed us to determine how a searcher should behave to produce optimized density estimates. Using data collected from quadrat and removal surveys of zebra mussels (Dreissena polymorpha) in central Minnesota, we applied this framework to evaluate potential improvements. We found that by tuning searcher behavior, density estimates from removal surveys of zebra mussels could be improved by up to 60% in some cases, without changing the overall survey time. Our framework also predicts a critical population density where the best survey method switches from removal surveys at low densities to quadrat surveys at high densities, consistent with past empirical work. In addition, we provide simulation tools to apply this form of analysis to a number of other commonly used survey designs. Our results provide insights into how to improve the performance of many survey methods in high-density environments by either tuning searcher behavior or decoupling the estimation of population density and detection probability.

A New Paradigm for High-dimensional Data: Distance-Based Semiparametric Feature Aggregation Framework via Between-Subject Attributes.

This article proposes a distance-based framework incentivized by the paradigm shift towards feature aggregation for high-dimensional data, which does not rely on the sparse-feature assumption or the permutation-based inference. Focusing on distance-based outcomes that preserve information without truncating any features, a class of semiparametric regression has been developed, which encapsulates multiple sources of high-dimensional variables using pairwise outcomes of between-subject attributes. Further, we propose a strategy to address the interlocking correlations among pairs via the U-statistics-based estimating equations (UGEE), which correspond to their unique efficient influence function (EIF). Hence, the resulting semiparametric estimators are robust to distributional misspecification while enjoying root-n consistency and asymptotic optimality to facilitate inference. In essence, the proposed approach not only circumvents information loss due to feature selection but also improves the model's interpretability and computational feasibility. Simulation studies and applications to the human microbiome and wearables data are provided, where the feature dimensions are tens of thousands.

A Quarter-Century of Online Informatics Education: Learners Served and Lessons Learned.

The value and methods of online learning have changed tremendously over the last 25 years. The goal of this paper is to review a quarter-century of experience with online learning by the author in the field of biomedical and health informatics, describing the learners served and the lessons learned. The author details the history of the decision to pursue online education in informatics, describing the approaches taken as educational technology evolved over time. A large number of learners have been served, and the online learning approach has been well-received, with many lessons learned to optimize the educational experience. Online education in biomedical and health informatics has provided a scalable and exemplary approach to learning in this field.

The impact of gender, psychology, and cultural dimensions on leadership development in distance education.

The research purpose is to evaluate the effectiveness of leadership in the process of distance learning from the perspective of the psychological theories of leadership, gender, and cross-cultural issues. The present research is based on such methods as surveys, testing, quantitative and qualitative analysis, and statistical data processing. The subjective (the experience of the respondents) and objective (machine calculation of clusters) assessments allowed the scholars to generate more arguments on leadership in the learning process. The sample consisted of 600 female and male students (300 from each sex, respectively) aged 18-20 years from Abu Dhabi University, American University in The Emirates, and the United Arab Emirates University. The research stated that the majority of students, regardless of gender, suppose that both sexes can develop similar leadership traits (80%). The research claims that female leaders have to be more dynamic and demonstrate higher intelligence (26% vs. 20%) and confidence (20% vs. 15%) than male leaders. Cultural and socio-demographic characteristics do not play a significant role in leadership development (10%). The main cause for the choice of a leader is behavioural and communication characteristics (50%) as well as personal qualities (35%). These results can be used for the online design of distance learning courses in universities (both group and individual), as well as for psychologists to study the aspect of individuals' predisposition to leadership. It makes sense for further research to explore the issue of differences in the perception of educational leadership in Asian and Western European countries based on the cross-cultural aspect, that is, the influence of national culture on the choice of leader in the educational environment.

Professional long distance runners achieve high efficiency at the cost of weak orbital stability.

Successful performance in long distance race requires both high efficiency and stability. Previous research has demonstrated the high running efficiency of trained runners, but no prior study quantitatively addressed their orbital stability. In this study, we evaluated the efficiency and orbital stability of 8 professional long-distance runners and compared them with those of 8 novices. We calculated the cost of transport and normalized mechanical energy to assess physiological and mechanical running efficiency, respectively. We quantified orbital stability using Floquet Multipliers, which assess how fast a system converges to a limit cycle under perturbations. Our results show that professional runners run with significantly higher physiological and mechanical efficiency but with weaker orbital stability compared to novices. This finding is consistent with the inevitable trade-off between efficiency and stability; increase in orbital stability necessitates increase in energy dissipation. We suggest that professional runners have developed the ability to exploit inertia beneficially, enabling them to achieve higher efficiency partly at the cost of sacrificing orbital stability.

The ultrametric backbone is the union of all minimum spanning forests.

Minimum spanning trees and forests are powerful sparsification techniques that remove cycles from weighted graphs to minimize total edge weight while preserving node reachability, with applications in computer science, network science, and graph theory. Despite their utility and ubiquity, they have several limitations, including that they are only defined for undirected networks, they significantly alter dynamics on networks, and they do not generally preserve important network features such as shortest distances, shortest path distribution, and community structure. In contrast, distance backbones, which are subgraphs formed by all edges that obey a generalized triangle inequality, are well defined in directed and undirected graphs and preserve those and other important network features. The backbone of a graph is defined with respect to a specified path-length operator that aggregates weights along a path to define its length, thereby associating a cost to indirect connections. The backbone is the union of all shortest paths between each pair of nodes according to the specified operator. One such operator, the max function, computes the length of a path as the largest weight of the edges that compose it (a weakest link criterion). It is the only operator that yields an algebraic structure for computing shortest paths that is consistent with De Morgan's laws. Applying this operator yields the ultrametric backbone of a graph in that (semi-triangular) edges whose weights are larger than the length of an indirect path connecting the same nodes (i.e. those that break the generalized triangle inequality based on max as a path-length operator) are removed. We show that the ultrametric backbone is the union of minimum spanning forests in undirected graphs and provides a new generalization of minimum spanning trees to directed graphs that, unlike minimum equivalent graphs and minimum spanning arborescences, preserves all max - min shortest paths and De Morgan's law consistency.

Children's ability to estimate approaching vehicle time-to-arrival following training in a virtual pedestrian environment.

OBJECTIVES: Child pedestrian injuries represent a significant public health challenge. Understanding the most complex cognitive skills required to cross streets helps us understand, improve, and protect children in traffic, as underdeveloped cognitive skill likely impacts children's pedestrian safety. One complex component of street-crossing is the cognitive-perceptual task of judging time-to-arrival of oncoming traffic. We examined capacity of 7- and 8-year-olds to judge time-to-arrival for vehicles approaching from varying distances and speeds, as well as improvement in those judgments following intensive street-crossing training in a virtual reality (VR) pedestrian simulator. METHODS: 500 seven- and eight-year-olds participated in a randomized trial evaluating use of a large kiosk VR versus smartphone-based VR headset to teach street-crossing skills. Prior to randomization into VR training condition and also prior to initiation of any training, children engaged in a video-based vehicle approach estimation task to assess ability to judge traffic time-to-arrival. They then engaged in multiple VR-based pedestrian safety training sessions in their randomly assigned condition until achieving adult functioning. Soon after training and again 6 months later, children repeated the vehicle estimation task. RESULTS: Prior to randomization or training, children were more accurate judging time to arrival for closer versus farther traffic, and rapidly-moving versus slower-moving traffic, but those results were subsumed by a speed x distance interaction. The interaction suggested distance cues were used more prominently than speed cues, and speed had varying effects at different distances. Training group had minimal effect on learning and all children became significantly better at judging vehicle arrival times following training. CONCLUSIONS: Children tend to underestimate vehicle arrival times. Distance cues are more impactful on time-to-arrival judgments than speed cues, but children's estimations based both on manipulations of vehicle speed and manipulations of vehicle distance improved post-training. Improvements were retained six months later. This finding is consistent with psychophysics research suggesting vehicle approach judgments rely on optical size and looming, which are impacted both by vehicle speeds and distances. Implementation of VR-based training for child pedestrian safety is recommended, as it may improve children's judgment of vehicle time-to-arrival, but it must be conducted cautiously to avoid iatrogenic effects.

Innovation Efficiency, Productive Performance and Undesirable Outputs across European Regions: Are there any missing links?

We introduce an analytical methodological framework that links knowledge generation efficiency with economic efficiency and the corresponding environmental impact for 199 European Regions during 2000-2018, using a benchmarking approach and especially a chain network DEA technique. A clear trade-off between knowledge generation efficiency and productive performance emerges. European regions which exhibit high innovation efficiency enjoy higher overall performance compared to their counterparts. In a second stage, we investigate the convergence patterns of the examined regions with respect to all the three facets of the estimated efficiency where the coexistence of multi-type convergence clubs is revealed.

MetaFluAD: meta-learning for predicting antigenic distances among influenza viruses.

Influenza viruses rapidly evolve to evade previously acquired human immunity. Maintaining vaccine efficacy necessitates continuous monitoring of antigenic differences among strains. Traditional serological methods for assessing these differences are labor-intensive and time-consuming, highlighting the need for efficient computational approaches. This paper proposes MetaFluAD, a meta-learning-based method designed to predict quantitative antigenic distances among strains. This method models antigenic relationships between strains, represented by their hemagglutinin (HA) sequences, as a weighted attributed network. Employing a graph neural network (GNN)-based encoder combined with a robust meta-learning framework, MetaFluAD learns comprehensive strain representations within a unified space encompassing both antigenic and genetic features. Furthermore, the meta-learning framework enables knowledge transfer across different influenza subtypes, allowing MetaFluAD to achieve remarkable performance with limited data. MetaFluAD demonstrates excellent performance and overall robustness across various influenza subtypes, including A/H3N2, A/H1N1, A/H5N1, B/Victoria, and B/Yamagata. MetaFluAD synthesizes the strengths of GNN-based encoding and meta-learning to offer a promising approach for accurate antigenic distance prediction. Additionally, MetaFluAD can effectively identify dominant antigenic clusters within seasonal influenza viruses, aiding in the development of effective vaccines and efficient monitoring of viral evolution.

Conductive single-phase SrMoO3 epitaxial films synthesized in pure Ar ambience via plasma-assisted radio frequency sputtering.

The cubic perovskite SrMoO3 with a paramagnetic ground state and remarkably low room-temperature resistivity has been considered as a suitable candidate for the new-era oxide-based technology. However, the difficulty of preparing single-phase SrMoO3 thin films by hydrogen-free sputtering has hindered their practical use, especially due to the formation of thermodynamically favorable SrMoO4 impurity. In this work, we developed a radio frequency sputtering technology enabling the reduction reaction and achieved conductive epitaxial SrMoO3 films with pure phase from a SrMoO4 target in a hydrogen-free, pure argon environment. We demonstrated the significance of controlling the target-to-substrate distance (TSD) on the synthesis of SrMoO3; the film resistivity drastically changes from 1.46 × 105 µΩ·cm to 250 µΩ·cm by adjusting the TSD. Cross-sectional microstructural analyses demonstrated that films with the lowest resistivity, deposited for TSD = 2.5 cm, possess a single-phase SrMoO3 with an epitaxial perovskite structure. The formation mechanism of the conductive single-phase SrMoO3 films can be attributed to the plasma-assisted growth process by tuning the TSD. Temperature-dependent resistivity and Hall effect studies revealed metal-like conducting properties for low-resistive SrMoO3 films, while the high-resistive ones displayed semiconductor-like behavior. Our approach makes hydrogen-free, reliable and cost-efficient scalable deposition of SrMoO3 films possible, which may open up promising prospects for a wide range of future applications of oxide materials.

For the first time, we developed a plasma-assisted RF sputtering technology enabling the reduction reaction for the synthesis of single-phase conductive SrMoO₃ epitaxial films from insulating SrMoO₄ in pure-argon atmosphere.

Capillarity-powered and CRISPR/Cas12a-responsive DNA hydrogel distance sensor for highly sensitive visual detection of HPV DNA.

The rapid and specific identification and sensitive detection of human papillomavirus (HPV) infection is critical for preventing cervical cancer, particularly in resource-limited regions. In this work, we hope to propose a capillarity-powered and CRISPR/Cas12a-responsive DNA hydrogel distance sensor for point-of-care (POC) DNA testing. Using the thermal reversibility of DNA hydrogel and capillarity, the novel DNA hydrogel distance sensor can be rapidly and simply constructed by loading an ultra-thin CRISPR/Cas12a-responsive DNA-crosslinked hydrogel film at the end of the capillary tube. The target DNA-specific recombinase polymerase reaction (RPA) amplicons activate the trans-cleavage activity of the Cas12a enzyme, cleaving the crosslinked DNA in hydrogel film, and causing an increase of hydrogel's permeability. As a result, a sample solution containing target DNA travels into the capillary tube at a longer distance compared to the negative samples. Reading the solution traveling distance in capillary tubes, the novel sensor realizes target DNA detection without any special equipment. Benefiting from the exponential target amplification of RPA and multiple turnover response of trans-cleavage of CRISPR/Cas12a, the developed sensor can visually and specifically detect as low as 1 aM HPV 16 DNA within 30 min. These outstanding features, including exceptional sensitivity and specificity, simple and portable design, mild measurement conditions, quick turnaround time, and user-friendly read-out, make the novel distance sensor a promising option for POC diagnostic applications.

Building shape-focused pharmacophore models for effective docking screening.

The performance of molecular docking can be improved by comparing the shape similarity of the flexibly sampled poses against the target proteins' inverted binding cavities. The effectiveness of these pseudo-ligands or negative image-based models in docking rescoring is boosted further by performing enrichment-driven optimization. Here, we introduce a novel shape-focused pharmacophore modeling algorithm O-LAP that generates a new class of cavity-filling models by clumping together overlapping atomic content via pairwise distance graph clustering. Top-ranked poses of flexibly docked active ligands were used as the modeling input and multiple alternative clustering settings were benchmark-tested thoroughly with five demanding drug targets using random training/test divisions. In docking rescoring, the O-LAP modeling typically improved massively on the default docking enrichment; furthermore, the results indicate that the clustered models work well in rigid docking. The C+ +/Qt5-based algorithm O-LAP is released under the GNU General Public License v3.0 via GitHub ( https://github.com/jvlehtonen/overlap-toolkit ). SCIENTIFIC CONTRIBUTION: This study introduces O-LAP, a C++/Qt5-based graph clustering software for generating new type of shape-focused pharmacophore models. In the O-LAP modeling, the target protein cavity is filled with flexibly docked active ligands, the overlapping ligand atoms are clustered, and the shape/electrostatic potential of the resulting model is compared against the flexibly sampled molecular docking poses. The O-LAP modeling is shown to ensure high enrichment in both docking rescoring and rigid docking based on comprehensive benchmark-testing.