Miracle-dz/UniFAR-FTUs huggingface dataset:
A Fast and Interpretable Deep Learning Approach for Accurate Electrostatics-Driven pKa Predictions in Proteins

Existing computational methods for estimating pKa values in proteins rely on theoretical approximations and lengthy computations. In this work, we use a data set of 6 million theoretically determined pKa shifts to train deep learning models, which are shown to rival the physics-based predictors. These neural networks managed to infer the electrostatic contributions of different chemical groups and learned the importance of solvent exposure and close interactions, including hydrogen bonds. Although trained only using theoretical data, our pKAI+ model displayed the best accuracy in a test set of ∼750 experimental values. Inference times allow speedups of more than 1000× compared to physics-based methods. By combining speed, accuracy, and a reasonable understanding of the underlying physics, our models provide a game-changing solution for fast estimations of macroscopic pKa values from ensembles of microscopic values as well as for many downstream applications such as molecular docking and constant-pH molecular dynamics simulations.
Inducing and Recording Acute Stress Responses on a Large Scale With the Digital Stress Test (DST): Development and Evaluation Study

Background Valuable insights into the pathophysiology and consequences of acute psychosocial stress have been gained using standardized stress induction experiments. However, most protocols are limited to laboratory settings, are labor-intensive, and cannot be scaled to larger cohorts or transferred to daily life scenarios. Objective We aimed to provide a scalable digital tool that enables the standardized induction and recording of acute stress responses in outside-the-laboratory settings without any experimenter contact. Methods On the basis of well-described stress protocols, we developed the Digital Stress Test (DST) and evaluated its feasibility and stress induction potential in a large web-based study. A total of 284 participants completed either the DST (n=103; 52/103, 50.5% women; mean age 31.34, SD 9.48 years) or an adapted control version (n=181; 96/181, 53% women; mean age 31.51, SD 11.18 years) with their smartphones via a web application. We compared their affective responses using the international Positive and Negative Affect Schedule Short Form before and after stress induction. In addition, we assessed the participants’ stress-related feelings indicated in visual analogue scales before, during, and after the procedure, and further analyzed the implemented stress-inducing elements. Finally, we compared the DST participants’ stress reactivity with the results obtained in a classic stress test paradigm using data previously collected in 4 independent Trier Social Stress Test studies including 122 participants overall. Results Participants in the DST manifested significantly higher perceived stress indexes than the Control-DST participants at all measurements after the baseline (P<.001). Furthermore, the effect size of the increase in DST participants’ negative affect (d=0.427) lay within the range of effect sizes for the increase in negative affect in the previously conducted Trier Social Stress Test experiments (0.281-1.015). Conclusions We present evidence that a digital stress paradigm administered by smartphone can be used for standardized stress induction and multimodal data collection on a large scale. Further development of the DST prototype and a subsequent validation study including physiological markers are outlined.
Hippocampal dentate gyrus integrity revealed with ultrahigh resolution diffusion imaging predicts memory performance in older adults

Medial temporal lobe (MTL) atrophy is a core feature of age‐related cognitive decline and Alzheimer's disease (AD). While regional volumes and thickness are often used as a proxy for neurodegeneration, they lack the sensitivity to serve as an accurate diagnostic test and indicate advanced neurodegeneration. Here, we used a submillimeter resolution diffusion weighted MRI sequence (ZOOMit) to quantify microstructural properties of hippocampal subfields in older adults (63–98 years old) using tensor derived measures: fractional anisotropy (FA) and mean diffusivity (MD). We demonstrate that the high‐resolution sequence, and not a standard resolution sequence, identifies dissociable profiles for CA1, dentate gyrus (DG), and the collateral sulcus. Using ZOOMit, we show that advanced age is associated with increased MD of the CA1 and DG as well as decreased FA of the DG. Increased MD of the DG, reflecting decreased cellular density, mediated the relationship between age and word list recall. Further, increased MD in the DG, but not DG volume, was linked to worse spatial pattern separation. Our results demonstrate that ultrahigh‐resolution diffusion imaging enables the detection of microstructural differences in hippocampal subfield integrity and will lead to novel insights into the mechanisms of age‐related memory loss.
Synchronous or collision solid neoplasms and lymphomas: A systematic review of 308 case reports

Background: The presence of a lymphoma associated with a solid synchronous neoplasm or collision neoplasm has been rarely in the literature, and a detailed characterization of these cases is lacking to date. Objective: To describe the main clinicopathological features of synchronous/collision tumors. Methods: A systematic search in PubMed, Scielo, and Virtual Health Library literature databases for cases or case series of synchronous or collision lymphoma and other solid neoplasms reported up to March 2021 was performed. Three reviewers independently screened the literature, extracted data, and assessed the quality of the included studies. The systematic review was performed following the Preferred Reporting Items for Systematic Meta-Analyses guidelines. Results: Mean age of patients was 62.9 years (52.9% men). A total of 308 cases were included (62% synchronous and 38% collision). The most frequent location of both synchronous and collision tumors was the gastrointestinal tract with the most common solid neoplasm being adenocarcinoma, and the most frequent lymphoma diffuse large B-cell lymphoma (21.7%) and mucosa-associated lymphoid tissue lymphoma (20.4%). Of the total number of mucosa-associated lymphoid tissue lymphomas and gastric adenocarcinomas, the presence of Helicobacter pylori infection was documented in 47.3% of them. Only 2% of all cases had a previous history of lymphoma. Thus, in most cases (98%), lymphoma was discovery incidentally. In addition, nodal lymphoma was associated with metastasis in 29 (9.4%) cases as collision tumor, most commonly (90%) in locoregional lymph nodes of the solid neoplasm. Conclusions: The frequent association of some type of B-cell lymphoma and adenocarcinoma in synchronous/collision tumors of the gastrointestinal tract points to common pathogenic mechanisms in both neoplasia, particularly related to chronic inflammation in this location. In most cases, lymphoma identified in locoregional lymph nodes or distant of a carcinoma seems to represent an incidental finding during the carcinoma diagnostic/therapeutic approach. A synergy between carcinoma and lymphoma (involving inflammation and immunosuppression mechanisms) may favor tumor progression and dissemination. A better understating of the interactions lymphoma/carcinoma in the setting of synchronous/collision tumors may help to improve patient management and prognosis.
LncRNA MALAT1 inhibits the proliferation and invasiveness of laryngeal squamous cell carcinoma Hep-2 cells by modulating miR-362-3p.

OBJECTIVE To investigate the mechanism of lncRNA MALAT1 (MALAT1) inhibiting the proliferation and invasiveness of laryngeal squamous cell carcinoma (LSCC) Hep-2 cells by modulating miR-362-3p. METHODS We collected the expression profile of lncRNAs and miRNAs in LSCC downloaded from The Cancer Genome Atlas (TCGA) database as well as LSCC tissue samples and adjacent normal counterparts resected from LSCC patients in Lvliang People's Hospital and First Hospital of Shanxi Medical University between January 2018 and June 2020 for analysis. Human LSCC Hep-2 cells were selected for experiments. The expression of miR-362-3p and MALAT1 was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cells were subsequently transfected to knock out MALAT1, and the growth, metastasis and invasiveness of cells were evaluated by CCK-8 assay, plate clone formation, wound healing, and Transwell invasion assays respectively. The binding of MALAT1 to miR-362-3p was verified by RNA pull-down, RNA binding protein immunoprecipitation (RIP), and dual-luciferase reporter assays. RESULTS MALAT1 was highly expressed while miR-362-3p was lowly expressed in both LSCC tissues and cells compared with normal counterparts. MALAT1 knockdown inhibited the viability of Hep-2 cells, reducing the number of plate clone-forming cells as well as the number of migrated and invaded cells. Transfection of miR-362-3p inhibitor into Hep-2 cells treated by si-MALAT1 reversed the inhibition of si-MALAT1 on the proliferation of Hep-2 cells, and promoted cell invasiveness and migration. MALAT1 can sponge miR-362-3p and inhibit its expression. CONCLUSIONS Knockdown of MALAT can inhibit Hep-2 cell proliferation and reduce its invasiveness and migration by modulating miR-362-3p.
Oral digoxin effects on exercise performance, K+ regulation and skeletal muscle Na+,K+‐ATPase in healthy humans

We investigated whether digoxin lowered muscle Na+,K+‐ATPase (NKA), impaired muscle performance and exacerbated exercise K+ disturbances. Ten healthy adults ingested digoxin (0.25 mg; DIG) or placebo (CON) for 14 days and performed quadriceps strength and fatiguability, finger flexion (FF, 105%peak‐workrate, 3 × 1 min, fourth bout to fatigue) and leg cycling (LC, 10 min at 33% VO2peak${\rm{V}}_{{{\rm{O}}}_{\rm{2}}{\rm{peak}}}$ and 67% VO2peak${\rm{V}}_{{{\rm{O}}}_{\rm{2}}{\rm{peak}}}$ , 90% VO2peak${\rm{V}}_{{{\rm{O}}}_{\rm{2}}{\rm{peak}}}$ to fatigue) trials using a double‐blind, crossover, randomised, counter‐balanced design. Arterial (a) and antecubital venous (v) blood was sampled (FF, LC) and muscle biopsied (LC, rest, 67% VO2peak${\rm{V}}_{{{\rm{O}}}_{\rm{2}}{\rm{peak}}}$ , fatigue, 3 h after exercise). In DIG, in resting muscle, [3H]‐ouabain binding site content (OB‐Fab) was unchanged; however, bound‐digoxin removal with Digibind revealed total ouabain binding (OB+Fab) increased (8.2%, P = 0.047), indicating 7.6% NKA–digoxin occupancy. Quadriceps muscle strength declined in DIG (−4.3%, P = 0.010) but fatiguability was unchanged. During LC, in DIG (main effects), time to fatigue and [K+]a were unchanged, whilst [K+]v was lower (P = 0.042) and [K+]a‐v greater (P = 0.004) than in CON; with exercise (main effects), muscle OB‐Fab was increased at 67% VO2peak${\rm{V}}_{{{\rm{O}}}_{\rm{2}}{\rm{peak}}}$ (per wet‐weight, P = 0.005; per protein P = 0.001) and at fatigue (per protein, P = 0.003), whilst [K+]a, [K+]v and [K+]a‐v were each increased at fatigue (P = 0.001). During FF, in DIG (main effects), time to fatigue, [K+]a, [K+]v and [K+]a‐v were unchanged; with exercise (main effects), plasma [K+]a, [K+]v, [K+]a‐v and muscle K+ efflux were all increased at fatigue (P = 0.001). Thus, muscle strength declined, but functional muscle NKA content was preserved during DIG, despite elevated plasma digoxin and muscle NKA–digoxin occupancy, with K+ disturbances and fatiguability unchanged.
Mid-late Holocene vegetation history of the Argive Plain (Peloponnese, Greece) as inferred from a pollen record from ancient Lake Lerna

This study provides a high-resolution reconstruction of the vegetation of the Argive Plain (Peloponnese, Greece) covering 5000 years from the Early Bronze Age onwards. The well dated pollen record from ancient Lake Lerna has been interpreted in the light of archaeological and historical sources, climatic data from the same core and other regional proxies. Our results demonstrate a significant degree of human impact on the environments of the Argive Plain throughout the study period. During the Early Bronze Age evidence of a thermophilous vegetation is seen in the pollen record, representing the mixed deciduous oak woodland of the Peloponnesian uplands. The plain was mainly used for the cultivation of cereals, whereas local fen conditions prevailed at the coring site. Towards the end of this period an increasing water table is recorded and the fen turns into a lake, despite more arid conditions. In the Late Bronze Age, the presence of important palatial centres modified the landscape resulting in decrease of mixed deciduous oak woodland and increase in open land, partly used for grazing. Possibly, the human management produced a permanent hydrological change at Lake Lerna. From the Archaic period onwards the increasing human pressure in association with local drier conditions caused landscape instability, as attested by a dramatic alluvial event recorded in the Pinus curve at the end of the Hellenistic Age. Wet conditions coincided with Roman times and favoured a forest regeneration pattern in the area, at the same time as we see the most intensive olive cultivation in the pollen record. The establishment of an economic landscape primarily based on pastures is recorded in the Byzantine period and continues until modern times. Overgrazing and fires in combination with arid conditions likely caused degradation of the vegetation into garrigue, as seen in the area of the Argive Plain today.
Factors Associated With Participation Rate and Predictive of Improvement After Cardiac Rehabilitation in Patients With Heart Failure

Patients with heart failure (HF) are often limited in their ability to perform exercise. Cardiac rehabilitation (CR), recommended for stable HF patients, improves cardiorespiratory fitness; however, it is underutilized. This study explored the factors associated with CR participation and completion rates from a single center and predictive of improvement after CR. Purpose: Patients with heart failure (HF) are often limited in their ability to perform exercise. Cardiac rehabilitation (CR) improves aerobic capacity and quality of life (QOL) and is recommended for patients with clinically stable HF; however, it is underutilized. The aim of this study was to investigate the factors associated with participation and completion rates and predictive of improvement after phase II CR in patients with HF. Methods: Participation and completion rates were calculated for all patients with HF enrolled in a multidisciplinary management program from October 2008 to December 2018. Functional capacity and QOL were estimated. In patients undergoing CR, changes in peak oxygen uptake (V˙o2peak) were measured. Results: Of 662 patients enrolled, 448 (68%) completed the cardiopulmonary exercise test (CPX). Phase II CR was recommended in 411 patients, of whom 291 (71%) participated in CR. Participation was significantly related to sex and the time interval in days between hospital discharge and the CPX. Overall, 171 patients completed 36 sessions of CR (with a completion rate of 59%). During CR, there were 18 (6%) adverse events. Cardiac rehabilitation was associated with improvement in V˙o2peak from 1153 ± 393 to 1342 ± 470 mL/min (a 16% improvement; P < .001) and in QOL. The independent predictors of increase in V˙o2peak included sex, age, diabetes mellitus, and entry V˙o2peak. Conclusions: In patients with HF, factors associated with CR participation rate included sex and days between hospital discharge and the CPX. Participation in CR improved V˙o2peak and QOL. The improvement was related to male sex, younger age, no diabetes mellitus, and higher entry V˙o2peak.
Full Assessment of Lung Mechanics Using Computer‐Controlled, Forced Oscillation Technique

The forced oscillation technique (FOT) is a powerful and accurate method to quantify the mechanical properties of the airways and tissues of the respiratory system. Here we provide a detailed protocol for the measurement of mouse respiratory mechanical parameters. We present a procedure for mouse endotracheal intubation using a handcrafted intubation platform and confirmation module. The FlexiVentFX™ system (Scireq Inc.) is utilized for the thorough assessment of lung function with the FlexiWare™ software serving as a unit for the planning, experimentation, and analysis. The protocol has been standardized and adapted for use by our center for lung‐function phenotyping of mouse models generated for the International Mouse Phenotyping Consortium (IMPC). The simplified steps, technical considerations, and integrated hardware‐software demonstration make this protocol adaptable and implementable for researchers interested in using FOT for lung‐function evaluation. © 2022 The Authors. Current Protocols published by Wiley Periodicals LLC.
Documentation and Prediction of Increasing Groundwater Chloride in the Twin Cities, Minnesota

We provide a comprehensive overview of historic chloride concentrations in the groundwater of the Twin Cities metropolitan area (TCMA) in Minnesota, in order to define the extent of chloride contamination, due primarily to the seasonal application of deicing salt to roadways. Data collected from 1278 wells between 1965 and 2020 are representative of the major aquifers underlying the TCMA and establish a regional natural background chloride concentration of less than 10 mg/L. However, 55% of all measurements (1616 of 2943) are above 10 mg/L, with the highest concentrations found within the uppermost Quaternary aquifers. Chloride concentrations in underlying bedrock aquifers are negatively correlated with the thickness and clay composition of overlying materials. Most chloride measurements (92%) remain below chronic exposure limits set by state and federal authorities. Historical trends indicate that, if the current imbalance between chloride inputs and outflows persists, chloride concentrations in TCMA aquifers will surpass regulatory thresholds by midcentury as surface waters and Quaternary aquifer waters migrate into underlying bedrock aquifers. Most wells in this study are monitored annually, making it impossible to detect important sub‐annual fluctuations of chloride concentration that can exceed 40%.
The relationship between project team members’ effectiveness and acknowledgment of talent: Team members’ perspective

ABSTRACT The aim of this research is to investigate the relationship between the acknowledgment of team member’s talents and his/her effectiveness in construction projects. Talents were investigated in terms of ability, aspiration, and engagement dimensions while effectiveness was measured by both, the satisfaction and the communication dimensions. The data were collected by distributing questionnaires on the contracting companies who are executing large building construction. Multiple linear regression was used to test the main hypothesis. The results showed a statistically significant relation between acknowledgment of a team member’s talent and his/her effectiveness in performing their day-to-day tasks. The results of this research may serve as a motive for top management to lead their organization toward the adoption of talent management concept in which a clear definition of desired talents is required and a road map to talent acknowledgment is provided.
Isokinetic Muscle Strength in Elite Soccer Players 3 and 6 months After Anterior Cruciate Ligament Reconstruction

Abstract Milutinović, A, Jakovljević, V, Dabović, M, Faude, O, Radovanović, D, and Stojanović, E. Isokinetic muscle strength in elite soccer players 3 months and 6 months after anterior cruciate ligament reconstruction. J Strength Cond Res 37(4): e297–e304, 2023—The aim of this study was to evaluate interlimb symmetry in quadriceps and hamstring peak torque of elite soccer players at 3 months (stage 1) and 6 months (stage 2) after anterior cruciate ligament (ACL) reconstruction. Eight male professional soccer players competing at the highest level across different European countries, who had undergone ACL reconstruction, participated in this study. All patients underwent a supervised physiotherapy program after surgery. Data analyses included the use of separate two-way repeated-measures analyses of variance and effect sizes. Although knee extensor and flexor strength of the non-injured limb was found to be relatively unaltered (g = −0.10 to 0.00) between stage 1 and stage 2, comparisons across time points revealed moderate improvements in quadriceps peak torque (p = 0.01, g = 0.52), hamstring peak torque (p = 0.07, g = 0.51), and hamstring:quadriceps (H/Q) ratio (p = 0.03, g = −0.68) of the injured leg, as well as small-large improvements in the quadriceps (p = 0.004, g = 1.24) and hamstring limb symmetry index (LSI) (p = 0.056, g = 0.41). A time-dependent moderate-large asymmetry observed at stage 1 between the injured and noninjured leg in quadriceps peak torque (p < 0.001, g = −1.83), hamstring peak torque (p = 0.157, g = −0.67), and the H:Q ratio (p = 0.06, g = 1.01), as well as between the hamstring and quadriceps LSI (p = 0.03, g = −0.74) was eliminated at stage 2 (g = −0.31 to 0.42). Our findings indicate the importance of supervised and comprehensive therapy, as well as strength screening to assist in recovery aimed at optimizing identified strength deficits following ACL reconstruction.
Managing incontinence in low-and middle income-countries: A qualitative case study from Pakistan

Background Incontinence is a complex health and social issue, which involves the involuntary loss of urine or faeces or both. Individuals with disabilities are particularly vulnerable to incontinence. The management of incontinence has largely been overlooked in low and middle-income settings (LMICs). This study aimed to explore the incontinence management strategies employed by disabled people with severe incontinence and their caregivers in Sindh Province, Pakistan. Methods Incontinence management was explored through in-depth interviews with people with incontinence (PWI) and their caregivers, photovoice, and a market survey and product attribute assessment. Data was analysed thematically through inductive coding and evaluated against existing disability and caregiver frameworks. Results Incontinence management affected all aspects of daily life for PWI and caregivers. Effective management of incontinence was prioritised because caregivers viewed it to be part of their familial duty and a requirement for the household to remain pure in the eyes of God. Coping strategies included strict adherence to routines, reducing food and drink intake, creative uses of locally available natural resources, and a heavy reliance on soap and water for maintaining hygiene. Products such as adult diapers were largely unavailable, costly and were not deemed suitable for regular use. There were no social or medical interventions in the region to support incontinence management. The main impacts of incontinence on the household were social isolation, stigma, role shifts within the family, the development of physical ailments among caregivers, and decreased income. Conclusion The complex health, psychological, social, economic, and cultural impacts of incontinence are exacerbated in LMICs due a lack of recognition of the condition, the absence of social or medical interventions and limited access to basic WASH infrastructure, and assistive devices or products. Appropriate solutions need to be developed in partnership with PWI and caregivers and need to be contextualised, affordable and sustainable.