Miracle-dz/UniFAR-FTUs huggingface dataset:
Linker domain function predicts pathogenic MLH1 missense variants

The pathogenic consequences of 369 unique human HsMLH1 missense variants has been hampered by the lack of a detailed function in mismatch repair (MMR). Here single-molecule images show that HsMSH2-HsMSH6 provides a platform for HsMLH1-HsPMS2 to form a stable sliding clamp on mismatched DNA. The mechanics of sliding clamp progression solves a significant operational puzzle in MMR and provides explicit predictions for the distribution of clinically relevant HsMLH1 missense mutations.
Aquazol as a consolidant for matte paint on Vietnamese paintings

This article describes the consolidation of two Vietnamese portrait paintings that had suffered flaking paint, tenting and blind cleavage. Scientific analysis revealed the presence of zinc sulfates as a result of the degradation processes. This posed consolidation issues since zinc sulfates are very water soluble. A discussion of paint characteristics demonstrates the particular requirements of consolidants. The effect of consolidants and their manner of application on matte paint films is elucidated, followed by a description of testing of consolidants. The only consolidant suitable for use was found to be Aquazol, hence this was tested at length before being used to consolidate the paint layers. Aquazol was also used as a filling and retouching medium. The properties of Aquazol are discussed, and two potential methods of identification of Aquazol, when used as a conservation material, were demonstrated; using Fourier transform infra-red spectroscopy (FTIR) and pyrolysis gas chromatography mass spectrometry (Py-GCMS).
Sex-Specific Risk Profiles for Suicide Among Persons with Substance Use Disorders in Denmark.

BACKGROUND AND AIMS Persons with substance use disorders (SUDs) are at elevated risk of suicide death. We identified novel risk factors and interactions that predict suicide among men and women with SUD using machine learning. DESIGN Case-cohort study. SETTING Denmark. PARTICIPANTS The sample was restricted to persons with their first SUD diagnosis during 1995-2015 (n = 13,179). Cases were persons who died by suicide in Denmark during 1995-2015 (n = 2,774) and the comparison subcohort was a 5% random sample of individuals in Denmark drawn on January 1, 1995. MEASUREMENTS Suicide death was recorded in the Danish Cause of Death Registry. Predictors included social and demographic information, mental and physical health diagnoses, surgeries, medications, and poisonings. FINDINGS Persons among the highest risk for suicide, as identified by the classification trees, were men prescribed antidepressants in the 4 years before suicide and had a poisoning diagnosis in the 4 years before suicide; and women who were 30+ years old and had a poisoning diagnosis 4 years before and 12 months before suicide. Among men with SUD, the random forest identified five variables that were most important in predicting suicide: reaction to severe stress and adjustment disorders, drugs used to treat addictive disorders, age 30+ years, antidepressant use, and poisoning in the 4 prior years. Among women with SUD, the random forest found that the most important predictors of suicide were prior poisonings and reaction to severe stress and adjustment disorders. Individuals in the top 5% of predicted risk accounted for 15% of all suicide deaths among men and 24% of all suicides among women. CONCLUSIONS In Denmark, prior poisoning and comorbid psychiatric disorders may be among the most important indicators of suicide risk among persons with substance use disorders, particularly among women.
Stories of professional development in physiotherapy education

ABSTRACT This study examines graduating physiotherapy students’ narratives related to their professional development. The data comprised interviews with 33 graduating physiotherapy students. The data were analyzed using the narrative analysis approach. As a result, five different story models were identified. The descriptive story models were named: 1) “Study path dominated by life changes”; 2) “Realizing the connection between physiotherapy theory and practice”; 3) “Self-regulated and practical-oriented learning path”; 4) “Becoming a critical developer”; and 5) “Multiprofessional working towards expertise”. In students’ stories, there appeared different turning points that illustrated especially meaningful episodes during the process of their professional development to be a physiotherapist. From a pedagogical point of view, two important features appeared: the importance of connecting theory and practice and the role of clinical supervisors.
DIELECTRIC PROPERTIES OF ALKANEDIOL/WATER MIXTURES

At 25 °C the complex dielectric permittivity has been measured as a function of frequency ν (1 MHz ≤ ν ≤ 56 GHz) and mole fraction x (0 ≤ x ≤ 1) for mixtures of water with 1,3-propanediol, 1,4-butanediol, 1,5-pentanediol, and 1,7-heptanediol. Some parameters like the (extrapolated) static permittivity and the characteristic relaxation time can be directly taken from the spectra. But the spectra can be also analytically represented by semiempirical relaxation spectral functions. A function containing two relaxation terms, a high-frequency Cole−Cole term and a Debye term with smaller relaxation frequency, appears to be appropriate. The relaxation parameters of the water/diol mixtures have been evaluated and compared to other water/organic solvent systems to show that (i) a high degree of permanent electric dipole orientation correlation exists in the diols that is significantly reduced on addition of water, (ii) the characteristic relaxation time reflects a substantial effect of entropy in the mechanism of .
Nature of the Glass Transition and the Glassy State

The thermodynamic properties of amorphous phases of linear molecular chains are obtained from statistical mechanics by means of a form of the quasi‐lattice theory which allows for chain stiffness and the variation of volume with temperature. A second‐order transition is predicted for these systems.This second‐order transition has all the qualitative features of the glass transition observed experimentally. It occurs at a temperature which is an increasing function of both chain stiffness and chain length and a decreasing function of free volume.The molecular ``relaxation times'' are shown to increase rapidly as the second‐order transition temperature is approached from above.To permit quantitative application of the theory and determine the relationship between the second‐order transition and the glass transition observed in ``slow'' experiments these two transitions are tentatively identified. By this means quantitative predictions are made concerning the variations of (1) glass temperature with molecula.
Sex Differences in Heart Failure With Preserved Ejection Fraction

Background The female preponderance in heart failure with preserved ejection fraction (HFpEF) is a distinguishing feature of this disorder, but the association of sex with degree of diastolic dysfunction and clinical outcomes among individuals with HFpEF remains unclear. Methods and Results We conducted a prospective, multicenter, observational study of patients with HFpEF (PURSUIT‐HFpEF [Prospective Multicenter Observational Study of Patients with Heart Failure with Preserved Ejection Fraction]: UMIN000021831). Between 2016 and 2019, 871 patients were enrolled from 26 hospitals (follow‐up: 399±349 days). We investigated sex‐related differences in diastolic dysfunction and postdischarge clinical outcomes in patients with HFpEF. The echocardiographic end point was diastolic dysfunction according to American Society of Echocardiography/European Association of Cardiovascular Imaging criteria. The clinical end point was a composite of all‐cause death and heart failure readmission. Women accounted for 55.2% (481 patients) of the overall cohort. Compared with men, women were older and had lower prevalence rates of hypertension, coronary artery disease, and chronic kidney disease. Women had diastolic dysfunction more frequently than men (52.8% versus 32.0%, P<0.001). The incidence of the clinical end point did not differ between women and men (women 36.1/100 person‐years versus men 30.5/100 person‐years, P=0.336). Female sex was independently associated with the echocardiographic end point (adjusted odds ratio, 2.839; 95% CI, 1.884–4.278; P<0.001) and the clinical end point (adjusted hazard ratio, 1.538; 95% CI, 1.143–2.070; P=0.004). Conclusions Female sex was independently associated with the presence of diastolic dysfunction and worse clinical outcomes in a cohort of elderly patients with HFpEF. Our results suggest that a sex‐specific approach is key to investigating the pathophysiology of HFpEF. Registration URL: https://upload.umin. ac.jp; Unique identifier: UMIN000021831.
The glymphatic system and meningeal lymphatics of the brain: new understanding of brain clearance

Abstract The glymphatic system and meningeal lymphatics have recently been characterized. Glymphatic system is a glia-dependent system of perivascular channels, and it plays an important role in the removal of interstitial metabolic waste products. The meningeal lymphatics may be a key drainage route for cerebrospinal fluid into the peripheral blood, may contribute to inflammatory reaction and central nervous system (CNS) immune surveillance. Breakdowns and dysfunction of the glymphatic system and meningeal lymphatics play a crucial role in age-related brain changes, the pathogenesis of neurovascular and neurodegenerative diseases, as well as in brain injuries and tumors. This review discusses the relationship recently characterized meningeal lymphatic vessels with the glymphatic system, which provides perfusion of the CNS with cerebrospinal and interstitial fluids. The review also presents the results of human studies concerning both the presence of meningeal lymphatics and the glymphatic system. A new understanding of how aging, medications, sleep and wake cycles, genetic predisposition, and even body posture affect the brain drainage system has not only changed the idea of brain fluid circulation but has also contributed to an understanding of the pathology and mechanisms of neurodegenerative diseases.
Head Impact Exposures Among Youth Tackle and Flag American Football Athletes

Background: Promoted as a safer alternative to tackle football, there has been an increase in flag football participation in recent years. However, examinations of head impact exposure in flag football as compared with tackle football are currently limited. Hypothesis: Tackle football athletes will have a greater number and magnitude of head impacts compared with flag football athletes. Study Design: Cohort study. Level of Evidence: Level 4. Methods: Using mouthguard sensors, this observational, prospective cohort study captured data on the number and magnitude of head impacts among 524 male tackle and flag football athletes (6-14 years old) over the course of a single football season. Estimates of interest based on regression models used Bayesian methods to estimate differences between tackle and flag athletes. Results: There were 186,239 head impacts recorded during the study. Tackle football athletes sustained 14.67 (95% CI 9.75-21.95) times more head impacts during an athletic exposure (game or practice) compared with flag football athletes. Magnitude of impact for the 50th and 95th percentile was 18.15g (17.95-18.34) and 52.55g (51.06-54.09) for a tackle football athlete and 16.84g (15.57-18.21) and 33.51g (28.23-39.08) for a flag football athlete, respectively. A tackle football athlete sustained 23.00 (13.59-39.55) times more high-magnitude impacts (≥40g) per athletic exposure compared with a flag football athlete. Conclusion: This study demonstrates that youth athletes who play tackle football are more likely to experience a greater number of head impacts and are at a markedly increased risk for high-magnitude impacts compared with flag football athletes. Clinical Relevance: These results suggest that flag football has fewer head impact exposures, which potentially minimizes concussion risk, making it a safer alternative for 6- to 14-year-old youth football athletes.
The pharmacotherapeutic management of hyperkalemia in patients with cardiovascular disease

ABSTRACT Introduction: Patients with cardiovascular diseases (CVD) are at increased risk of hyperkalemia, particularly when treated with renin-angiotensin-aldosterone inhibitors (RAASIs). Because the occurrence or fear of hyperkalemia, RAASIs are frequently down-titrated or discontinued in patients with CVD, with consequent worse outcomes than patients who remain on maximum doses. Areas covered: This article reviews potassium homeostasis, epidemiology, risk factors, and outcomes of hyperkalemia, and efficacy and safety of the drugs used for acute and chronic treatment of hyperkalemia. A literature search was carried out using the PubMed and guidelines for the management of hyperkalemia. Expert opinion: The emergency treatment of hyperkalemia is not supported by high-quality evidence and clinical trials did not report drug effects on clinical outcomes. Two potassium binders, patiromer and sodium zirconium cyclosilicate, represent a new approach in the treatment of chronic hyperkalemia as they may allow the titration and maintenance of guidelines-recommended doses of RAASIs in patients with CVD who otherwise would not tolerate them due to the risk of hyperkalemia. Further studies are needed to evaluate the safety and efficacy of drug therapy and support the development of guidelines for acute and chronic hyperkalemia.
Mortality risk stratification using artificial intelligence-augmented electrocardiogram in cardiac intensive care unit patients.

AIMS An artificial intelligence-augmented electrocardiogram (AI-ECG) algorithm can identify left ventricular systolic dysfunction (LVSD). We sought to determine whether this AI-ECG algorithm could stratify mortality risk in cardiac intensive care unit (CICU) patients, independent of the presence of LVSD by transthoracic echocardiography (TTE). METHODS AND RESULTS We included 11 266 unique Mayo Clinic CICU patients admitted from 2007 to 2018 who underwent AI-ECG after CICU admission. Left ventricular ejection fraction (LVEF) data were extracted for patients with a TTE during hospitalization. Hospital mortality was analysed using multivariable logistic regression. Mean age was 68 ± 15 years, including 37% females. Higher AI-ECG probability of LVSD remained associated with higher hospital mortality [adjusted odds ratio (OR) 1.05 per 0.1 higher, 95% confidence interval (CI) 1.02-1.08, P = 0.003] after adjustment for LVEF, which itself was inversely related with the risk of hospital mortality (adjusted OR 0.96 per 5% higher, 95% CI 0.93-0.99, P = 0.02). Patients with available LVEF data (n = 8242) were divided based on the presence of predicted (by AI-ECG) vs. observed (by TTE) LVSD (defined as LVEF ≤ 35%), using TTE as the gold standard. A stepwise increase in hospital mortality was observed for patients with a true negative, false positive, false negative, and true positive AI-ECG. CONCLUSION The AI-ECG prediction of LVSD is associated with hospital mortality in CICU patients, affording risk stratification in addition to that provided by echocardiographic LVEF. Our results emphasize the prognostic value of electrocardiographic patterns reflecting underlying myocardial disease that are recognized by the AI-ECG.
Immunotherapy and radiation therapy sequencing: State of the data on timing, efficacy, and safety

Radiation therapy exerts a tumoricidal local effect as well as both local and systemic immunomodulation. Immune checkpoint blockade has become a widely used treatment modality across cancer types with a rapidly growing list of agents and US Food and Drug Administration‐approved indications. Moreover, there may be synergy between radiation therapy and immune checkpoint blockade. Various strategies have been used, but the optimal sequencing of these therapies is unclear. In this review, the authors discuss the major mechanisms of available immune checkpoint inhibitors and explore the available preclinical and clinical evidence regarding treatment sequencing. They also review safety considerations and conclude with possible future directions.
Inﬂuence of transplanting time on essential oil yield and composition in Artemisia annua plants grown under the climatic conditions of sub-tropical north India

The yield and composition of the essential oil obtained by hydrodistillation of inﬂorescences from different populations of Artemisia annua L. (Asteraceae), transplanted during different months, was analysed using a combination of GC and GC–MS. Oil yield was found to range from 0.5 to as high as 1.6% (w/v), in which 24 constituents were identiﬁed, representing 84.4–92.2% of the total oil. Camphor was identiﬁed as the most abundant component in all the samples examined, followed by 1,8-cineole, except in June-transplanted plants, where b-caryophyllene was found to be the second most abundant compound. Camphor and 1,8-cineole alone constituted 44.7–65% of the total oil. The percentage occurrence of rest of the compounds was found to vary in different populations. Copyright © 2003 John Wiley & Sons, Ltd.
Accurate single-cell genotyping utilizing information from the local genome territory

Abstract Single-nucleotide variant (SNV) detection in the genome of single cells is affected by DNA amplification artefacts, including imbalanced alleles and early PCR errors. Existing single-cell genotyper accuracy often depends on the quality and coordination of both the target single-cell and external data, such as heterozygous profiles determined by bulk data. In most single-cell studies, information from different sources is not perfectly matched. High-accuracy SNV detection with a limited single data source remains a challenge. We developed a new variant detection method, SCOUT (Single Cell Genotyper Utilizing Information from Local Genome Territory), the greatest advantage of which is not requiring external data while base calling. By leveraging base count information from the adjacent genomic region, SCOUT classifies all candidate SNVs into homozygous, heterozygous, intermediate and low major allele SNVs according to the highest likelihood score. Compared with other genotypers, SCOUT improves the variant detection performance by 2.0–77.5% in real and simulated single-cell datasets. Furthermore, the running time of SCOUT increases linearly with sequence length; as a result, it shows 400% average acceleration in operating efficiency compared with other methods.
Farmers' behavior in reading and using risk information displayed on pesticide labels: a test with the theory of planned behavior.

BACKGROUND Labels are the first source of information for the safe use of pesticides, but farmers rarely read labels before pesticide use. Using data from a sample of 300 orchard farmers in Meshginshar County, Iran, this study examined farmers' intention and behavior in reading and using risk information displayed on pesticide labels, using the theory of planned behavior (TPB). RESULTS Only 26% of the respondents mentioned that they read pesticide labels. Most farmers showed a low tendency towards reading pesticide labels due to low education, advanced age, and label-related problems, i.e., use of too technical language and unclear texts with small and illegible fonts. From the three basic variables of the TPB, subjective norms and perceived behavioral control (PBC) showed a significant impact on intention, while attitudes showed no significant impact. The three main variables of the TPB explained 90.2% of the variance in farmers' intention to read and use the labels. Furthermore, PBC and intention significantly affected farmers' actual behavior in reading and using the labels, explaining 78.5% of the variance in farmers' actual behavior. Age, experience in farming, and experience in spraying were negatively correlated with all variables of the TPB. CONCLUSION Findings provide new insights into farmers' behavior in reading pesticide labels by using for the first time the TPB. Pesticide manufacturers should consider the special conditions of subsistence farmers (low education and advanced age) when preparing pesticide labels and the extension services could use those findings to improve farmers' training in the use of pesticide labels. This article is protected by copyright. All rights reserved.
Theoretical explanation of the octahedral distortion in FeF2 and MgF2

Abstract The equilibrium geometries of rutile type FeF2 and MgF2 are determined using precise density functional theory calculations that lead to good agreement with experimental data. The strong deviation from the “ideal” octahedral geometry in FeF2 comes from the Fe2+ ion with the d6 configuration in the high-spin state, which would require a singly occupied spin-down d orbital. The stability can only be understood by going beyond the first coordination shell considering direct Fe–Fe interactions mainly along the c-axis. The orbital population of the various Fe-d orbitals is analyzed using constarint distortions between the ideal and the equilibrium structure. Above a critical Fe–Fe distance of about 3.15 Å the population numbers change drastically, a single Fe-d spin down orbital becomes occupied and the system can relax to an insulating state. In MgF2 no such d-orbitals are present and thus the distortions are much smaller.
Contributions of PCSS, CISS, and VOMS for Identifying Vestibular/Ocular Motor Deficits in Pediatric Concussions

Background: Vestibular/ocular motor dysfunction can occur in pediatric concussions, which can impair reading, learning, and participation in athletics. This study evaluated 3 clinical tools for identifying postconcussion vestibular/ocular motor dysfunction: (1) Post-Concussion Symptom Scale (PCSS), (2) Convergence Insufficiency Symptom Survey (CISS), and (3) Vestibular/Ocular Motor Screening (VOMS). Hypothesis: Evaluating vestibular/ocular motor dysfunction with multiple clinical tools will capture more symptomatic patients than any 1 tool alone. Study Design: Cross-sectional data from a prospective cohort study. Level of Evidence: Level 4. Methods: Patients were between 8 and 17 years old and seen in a tertiary care pediatric sports medicine clinic between August 2014 and February 2018. Data were collected from initial visit and included VOMS, PCSS, and CISS. Descriptive statistics, Pearson’s correlations, and logistic regressions were used to describe relationships between clinical tools. Results: Of the 156 patients (55.1% female; 14.35 ± 2.26 years old) included, this study identified 129 (82.7%) with vestibular/ocular motor dysfunction. Of these 129, 65 (50.4%) reported “visual problems” on PCSS, 93 (72.1%) had abnormal CISS, and 99 (76.7%) had abnormal VOMS. Together, VOMS and CISS identified 64 (49.6%) patients without reported “visual problems” on PCSS. Higher total PCSS scores predicted abnormal CISS (odds ratio [OR], = 1.11; 95% CI, 1.07-1.17) and abnormal VOMS (OR, 1.03; 95% CI, 1.01-1.06). “Visual problems” on PCSS did not predict abnormal CISS or VOMS. Conclusion: Vestibular/ocular motor dysfunction were identified in nearly 83% of study subjects when PCSS, CISS, and VOMS are used together. Clinical Relevance: These results suggest adding CISS and VOMS to the clinical evaluation of concussions can help clinicians identify post-concussion vestibular/ocular motor dysfunction.