Miracle-dz/UniFAR-FTUs huggingface dataset:
Defining the Minimal Clinically Important Difference and Patient-acceptable Symptom State Score for Disability Assessment in Surgical Patients

Background: The World Health Organization Disability Assessment Schedule 2.0 has been used to measure postoperative disability in several clinical trials and cohort studies. It is uncertain what the minimal clinically important difference or patient-acceptable symptom state scores are for this scale in patients recovering from surgery. Methods: The authors analyzed prospectively collected data from three studies that measured disability 3 and 6 months after surgery. Three distribution-based methods (0.3 multiplied by SD, standard error of the measurement, and 5% range) and two anchor-based methods (anchored to two patient-rated health status questions and separately to unplanned hospital readmission) were averaged to estimate the minimal clinically important difference for the World Health Organization Disability Assessment Schedule 2.0 score converted to a percentage scale. Scores consistent with a patient-acceptable symptom state and clinically significant disability were determined by an anchored 75th centile method. Results: Data from 4,361 patients were analyzed. The average minimal clinically important difference estimate for the World Health Organization Disability Assessment Schedule 2.0 was 5%, with similar estimates in patients with or without preoperative disability. The patient-acceptable symptom state score was 16%, and the score consistent with at least moderate clinically significant disability was 35%. Using these estimates, between baseline and 6 months after surgery, 21% of patients had a significant increase in disability, and 73% achieved a patient-acceptable symptom state. Conclusions: A change in World Health Organization Disability Assessment Schedule 2.0 score of 5% or more after surgery is consistent with a clinically important change in disability. Patients with a score less than 16% after surgery have an acceptable symptom state and can be considered as disability-free, whereas patients with a score of 35% or more can be considered as having at least moderate clinically significant disability. Using previously collected data from three studies across 4,361 patients, a 5% change in score after surgery is clinically important. Patients with a scaled disability score less than 16% after surgery have an acceptable symptom state and can be considered as disability-free. Supplemental Digital Content is available in the text.
Comparative Study on Mixing Behavior of Binary Mixtures of Cocoa Butter/Tristearin (CB/TS) and Cocoa Butter/Coconut Oil (CB/CO)

The comparative study between the mixing behavior of two binary mixtures of cocoa butter (CB)/tristearin (TS) and cocoa butter (CB)/coconut oil (CO) was investigated by using differential scanning calorimetry (DSC). The DSC profile for CB/TS blends resulted in a monotectic temperature–concentration (T–X) phase diagram, whereas a phase diagram of eutectic type was observed for CB/CO blends at 65 wt % of CO and 35 wt % CB; this suggests that the eutectic crystal can be formed when the saturated fat (blue = CO) is smaller in size compared to monounsaturated fat (orange = CB), whereas, for similar and larger size (red = TS) to CB, phase separation under crystallization is likely to occur (as shown in the graphical abstract). In order to understand the interaction between the binary systems, the profile of the phase diagram was fitted with Bragg–Williams approximation for estimation of the nonideality mixing parameter. Moreover, the morphology of the two different systems by polarized light microscopy (PLM) also depicted the variations in phase behavior by showing a significant change in CB morphology from spherulitic, grainy to granular and needlelike after the addition of TS and CO, respectively. Our findings emphasize the fundamental understanding of the interaction of bulk fat/fat and fat/oil system.
High-risk Human Papillomavirus Messenger RNA Testing in Wet and Dry Self-collected Specimens for High-grade Cervical Lesion Detection in Mombasa, Kenya

A study of female sex workers in Mombasa, Kenya, found that self-collected specimens stored-dry performed similarly to specimens stored-wet for human papillomavirus messenger RNA testing to detect high-grade squamous intraepithelial lesions. Supplemental digital content is available in the text. Background Self-collection for high-risk human papillomavirus (hr-HPV) messenger RNA (mRNA) testing may improve cervical cancer screening. High-risk HPV mRNA with self-collected specimens stored dry could enhance feasibility and acceptance of specimen collection and storage; however, its performance is unknown. We compared the performance of hr-HPV mRNA testing with dry- as compared with wet-stored self-collected specimens for detecting high-grade squamous intraepithelial lesion or more severe (≥HSIL). Methods A total of 400 female sex workers in Kenya participated (2013–2018), of which 50% were HIV positive based on enrollment procedures. Participants provided 2 self-collected specimens: one stored dry (sc-DRY) using a Viba brush (Rovers) and one stored wet (sc-WET) with Aptima media (Hologic) using an Evalyn brush (Rovers). Physician-collected specimens were collected for HPV mRNA testing (Aptima) and conventional cytology. We estimated test characteristics for each hr-HPV screening method using conventional cytology as the reference standard (≥HSIL detection). We also examined participant preference for sc-DRY and sc-WET collection. Results High-risk HPV mRNA positivity was higher in sc-WET (36.8%) than sc-DRY samples (31.8%). Prevalence of ≥HSIL was 6.9% (10.3% HIV positive, 4.0% HIV negative). Sensitivity of hr-HPV mRNA for detecting ≥HSIL was similar in sc-WET (85%; 95% confidence interval [CI], 66%–96%), sc-DRY specimens (78%; 95% CI, 58%–91%), and physician-collected specimens (93%; 95% CI, 76%–99%). Overall, the specificity of hr-HPV mRNA for ≥HSIL detection was similar when comparing sc-WET with physician collection. However, specificity was lower for sc-WET (66% [61%–71%]) than sc-DRY (71% [66%–76%]). Women preferred sc-DRY specimen collection (46.1%) compared with sc-WET (31.1%). However, more women preferred physician collection (63.9%) compared with self-collection (36.1%). Conclusions Self-collected stored-dry specimens seemed to perform similarly to sc-WET for the detection of ≥HSIL.
Deconstructing eye contact perception: Measuring perceptual precision and self-referential tendency using an online psychophysical eye contact detection task

Eye contact perception—the ability to accurately and efficiently discriminate others’ gaze directions—is critical to understanding others and functioning in a complex social world. Previous research shows that it is affected in multiple neuropsychiatric disorders accompanied by social dysfunction, and understanding the cognitive processes giving rise to eye contact perception would help advance mechanistic investigations of psychopathology. This study aims to validate an online, psychophysical eye contact detection task through which two constituent cognitive components of eye contact perception (perceptual precision and self-referential tendency) can be derived. Data collected from a large online sample showed excellent test-retest reliability for self-referential tendency and moderate reliability for perceptual precision. Convergence validity was supported by correlations with social cognitive measures tapping into different aspects of understanding others. Hierarchical regression analyses revealed that perceptual precision and self-referential tendency explained unique variance in social cognition, suggesting that they measure unique aspects of related constructs. Overall, this study provided support for the reliability and validity of the eye contact perception metrics derived using the online Eye Contact Detection Task. The value of the task for future psychopathology research was discussed.
Fetal diagnosis of KCNQ1‐variant long QT syndrome using fetal echocardiography and magnetocardiography

A pregnant woman with KCNQ1 variant long QT syndrome (LQTS) underwent fetal magnetocardiography (fMCG) after atrioventricular (AV) block was noted during fetal echocardiogram—atypical for LQTS type 1. Concern for fetal LQTS on fMCG prompted monitoring of maternal labs, change of maternal beta blocker therapy, and frequent fetal echocardiograms. Collaboration between obstetricians, neonatologists, and pediatric cardiologists ensured safe delivery. Beta blocker therapy was initiated after birth, and postnatal evaluation confirmed genotype and phenotype positive LQTS in the infant. Our experience suggests diagnosis and evaluation of fetal LQTS can alter antenatal management to reduce risk of poor fetal and postnatal outcomes.
The Lateral Leaflet Suppression 1 (LLS1), encoding the MtYUCCA1 protein, regulates lateral leaflet development in Medicago truncatula.

In species with compound leaves, the positions of leaflet primordia initiation are associated with local peaks of auxin accumulation. However, the role of auxin during the late developmental stages and outgrowth of compound leaf remains largely unknown. Using genome resequencing approaches, we identified insertion sites at four alleles of the LATERAL LEAFLET SUPPRESSION1 (LLS1) gene, encoding the auxin biosynthetic enzyme YUCCA1 in Medicago truncatula. Linkage analysis and complementation tests showed that the lls1 mutant phenotypes were caused by the Tnt1 insertions that disrupted the LLS1 gene. The transcripts of LLS1 can be detected in primordia at early stages of leaf initiation and later in the basal regions of leaflets, and finally in vein tissues at late leaf developmental stages. The vein numbers and auxin level are reduced in lls1-1 mutant. Analysis of the lls1 sgl1 and lls1 palm1 double mutants uncovered that SGL1 is epistatic to LLS1, and LLS1 works with PALM1 in an independent pathway to regulate the growth of lateral leaflets. Our work demonstrates that the YUCCA1/YUCCA4 subgroup plays very important roles in the outgrowth of lateral leaflets during the compound leaf development of M. truncatula, in addition to leaf venation.
tugHall: a simulator of cancer-cell evolution based on the hallmarks of cancer and tumor-related genes

Abstract Summary The flood of recent cancer genomic data requires a coherent model that can sort out the findings to systematically explain clonal evolution and the resultant intra-tumor heterogeneity (ITH). Here, we present a new mathematical model designed to computationally simulate the evolution of cancer cells. The model connects the well-known hallmarks of cancer with the specific mutational states of tumor-related genes. The cell behavior phenotypes are stochastically determined, and the hallmarks probabilistically interfere with the phenotypic probabilities. In turn, the hallmark variables depend on the mutational states of tumor-related genes. Thus, our software can deepen our understanding of cancer-cell evolution and generation of ITH. Availability and implementation The open-source code is available in the repository https://github.com/nagornovys/Cancer_cell_evolution. Contact mamkato@ncc.go. jp Supplementary information Supplementary data are available at Bioinformatics online.
A Key Management Scheme Based on Pairing-Free Identity Based Digital Signature Algorithm for Heterogeneous Wireless Sensor Networks

The secure transmission of data within a network has received great attention. As the core of the security management mechanism, the key management scheme design needs further research. In view of the safety and energy consumption problems in recent papers, we propose a key management scheme based on the pairing-free identity based digital signature (PF-IBS) algorithm for heterogeneous wireless sensor networks (HWSNs). Our scheme uses the PF-IBS algorithm to complete message authentication, which is safer and more energy efficient than some recent schemes. Moreover, we use the base station (BS) as the processing center for the huge data in the network, thereby saving network energy consumption and improving the network life cycle. Finally, we indirectly prevent the attacker from capturing relay nodes that upload data between clusters in the network (some cluster head nodes cannot communicate directly). Through performance evaluation, the scheme we proposed reasonably sacrifices part of the storage space in exchange for entire network security while saving energy consumption.
Oxytocin has sex-specific effects on social behaviour and hypothalamic oxytocin immunoreactive cells but not hippocampal neurogenesis in adult rats

Oxytocin regulates social behaviours, pair bonding and hippocampal neurogenesis but most studies have used adult males. Our study investigated the effects of oxytocin on social investigation and adult hippocampal neurogenesis in male and female rats. Oxytocin has poor penetration of the blood-brain barrier, therefore we tested a nanoparticle drug, TRIOZANTM (Ovensa Inc.), which permits greater blood-brain-barrier penetration. Adult male and female rats were injected daily (i.p.) for 10 days with either: oxytocin in PBS (0.5 or 1.0 mg/kg), oxytocin in TRIOZANTM (0.5 or 1.0 mg/kg), or vehicle (PBS) and tested for social investigation. Oxytocin decreased body mass and increased social investigation and number of oxytocin-immunoreactive cells in the supraoptic nucleus (SON) of the hypothalamus in male rats only. In both sexes, oxytocin decreased the number of immature neurons (doublecortin+ cells) in the ventral hippocampus and reduced plasma 17β-estradiol levels in a dose- and delivery-dependent way. Oxytocin in TRIOZANTM reduced sedation observed post-injection and increased some central effects (oxytocin levels in the hypothalamus and ventral hippocampus neurogenesis) relative to oxytocin in PBS indicating that the nanoparticle may be used as an alternative brain delivery system. We showed that oxytocin has sex-specific effects on social investigation, body mass, sedation, and the oxytocin system. In contrast, similar effects were observed in both sexes in neurogenesis and plasma 17β-estradiol. Our work suggests that sex differences in oxytocin regulation of brain endpoints is region-specific (hypothalamus versus hippocampus) and that oxytocin does not promote social investigation in females.
Effectiveness of Two Types of Fixed Lingual Retainers in Preventing Mandibular Incisor Relapse.

OBJECTIVE To compare and evaluate the relapse tendency of two types of fixed lingual retainers using Little's irregularity index for a follow-up of one year. STUDY DESIGN Randomised clinical trial. PLACE AND DURATION OF STUDY Department of Orthodontics, Dr. Ishrat Ul Ebad Khan Institute of Oral Health Sciences and Dow Dental College in Dow University of Health Sciences, Karachi, Pakistan, from November 2017 to March 2019. METHODOLOGY A total of 54 patients were recruited and divided into two groups by random allocation. Subjects who have completed fixed appliance (MBT) orthodontic treatment and non extraction cases with moderate crowding in the lower arch were included. Subjects with caries, restoration, fracture or missing lower anterior teeth were excluded. Group 1 received fiber reinforced composite (FRC) retainers and group 2 received multistranded stainless steel (MSW) retainers. They were recalled after every three months interval for one year. Relapse tendency of retainers using Little's irregularity index was evaluated at each visit. RESULTS Comparison of relapse tendency between two retainers showed statistically significant results (p<0.05). The mean difference of CPD between two retainers at T0 was found to be 0.09 mm (p=0.01). At T1, it was determined to be 0.3 mm (p=0.022), and at T2 it was found to be 0.3 mm (p=0.008). At T3 and T4, it was found to be 0.5 mm (p<0.001) and 0.5 mm (p=0.002), respectively. All mean differences were statistically significant. CONCLUSION Fiber-reinforced retainers are more effective in preventing the mandibular incisor relapse. The results of the study also suggest that the irregularity of the dentition increases with the passage of time.
BEL β-Trefoil Reduces the Migration Ability of RUNX2 Expressing Melanoma Cells in Xenotransplanted Zebrafish

RUNX2, a master osteogenic transcript ion factor, is overexpressed in several cancer cells; in melanoma it promotes cells migration and invasion as well as neoangiogenesis. The annual mortality rates related to metastatic melanoma are high and novel agents are needed to improve melanoma patients’ survival. It has been shown that lectins specifically target malignant cells since they present the Thomsen–Friedenreich antigen. This disaccharide is hidden in normal cells, while it allows selective lectins binding in transformed cells. Recently, an edible lectin named BEL β-trefoil has been obtained from the wild mushroom Boletus edulis. Our previous study showed BEL β-trefoil effects on transcription factor RUNX2 downregulation as well as on the migration ability in melanoma cells treated in vitro. Therefore, to better understand the role of this lectin, we investigated the BEL β-trefoil effects in a zebrafish in vivo model, transplanted with human melanoma cells expressing RUNX2. Our data showed that BEL β-trefoil is able to spread in the tissues and to reduce the formation of metastases in melanoma xenotransplanted zebrafish. In conclusion, BEL β-trefoil can be considered an effective biomolecule to counteract melanoma disease.
The Myosin Family of Mechanoenzymes: From Mechanisms to Therapeutic Approaches.

Myosins are among the most fascinating enzymes in biology. As extremely allosteric chemomechanical molecular machines, myosins are involved in myriad pivotal cellular functions and are frequently sites of mutations leading to disease phenotypes. Human β-cardiac myosin has proved to be an excellent target for small-molecule therapeutics for heart muscle diseases, and, as we describe here, other myosin family members are likely to be potentially unique targets for treating other diseases as well. The first part of this review focuses on how myosins convert the chemical energy of ATP hydrolysis into mechanical movement, followed by a description of existing therapeutic approaches to target human β-cardiac myosin. The next section focuses on the possibility of targeting nonmuscle members of the human myosin family for several diseases. We end the review by describing the roles of myosin in parasites and the therapeutic potential of targeting them to block parasitic invasion of their hosts. Expected final online publication date for the Annual Review of Biochemistry, Volume 89 is June 22, 2020. Please see http://www.annualreviews. org/page/journal/pubdates for revised estimates.
La Gestione Ambulatoriale Della Terapia Anticoagulante Orale (TAO) Nelle Cure Primarie: L'esperienza Dell'Associazione “Medicina di Gruppo di Masate”

Outpatient management of oral anticoagulation treatment (OAT) in general practice: the “Medicina di Gruppo di Masate” experience Oral anticoagulants are used for prophylaxis in thromboembolic conditions. Vitamin K antagonists (VKAs) such as warfarin, are commonly employed. The anticoagulation activity induced by VKAs is monitored by the prothrombin time test to determine the International Normalized Ratio (INR). Point-of-care testing (POCT) devices can be used to monitor anticoagulant therapy improving the quality of oral anticoagulation. This paper aims at describing the relevant experience of the “Medicina di Gruppo di Masate” in general practice. We also put this experience into the general context of the international evidence on the impact of POCT. Both our experience and the international evidence may support anticoagulant therapy management by GPs (General Practitioners).
Small molecule therapeutics to treat the β-globinopathies.

PURPOSE OF REVIEW The current review focuses on recent insights into the development of small molecule therapeutics to treat the β-globinopathies. RECENT FINDINGS Recent studies of fetal γ-globin gene regulation reveal multiple insights into how γ-globin gene reactivation may lead to novel treatment for β-globinopathies. SUMMARY We summarize current information regarding the binding of transcription factors that appear to be impeded or augmented by different hereditary persistence of fetal hemoglobin (HPFH) mutations. As transcription factors have historically proven to be difficult to target for therapeutic purposes, we next address the contributions of protein complexes associated with these HPFH mutation-affected transcription factors with the aim of defining proteins that might provide additional targets for chemical molecules to inactivate the corepressors. Among the enzymes associated with the transcription factor complexes, a group of corepressors with currently available inhibitors were initially thought to be good candidates for potential therapeutic purposes. We discuss possibilities for pharmacological inhibition of these corepressor enzymes that might significantly reactivate fetal γ-globin gene expression. Finally, we summarize the current clinical trial data regarding the inhibition of select corepressor proteins for the treatment of sickle cell disease and β-thalassemia.
Affibody Molecules as Targeting Vectors for PET Imaging

Affibody molecules are small (58 amino acids) engineered scaffold proteins that can be selected to bind to a large variety of proteins with a high affinity. Their small size and high affinity make them attractive as targeting vectors for molecular imaging. High-affinity affibody binders have been selected for several cancer-associated molecular targets. Preclinical studies have shown that radiolabeled affibody molecules can provide highly specific and sensitive imaging on the day of injection; however, for a few targets, imaging on the next day further increased the imaging sensitivity. A phase I/II clinical trial showed that 68Ga-labeled affibody molecules permit an accurate and specific measurement of HER2 expression in breast cancer metastases. This paper provides an overview of the factors influencing the biodistribution and targeting properties of affibody molecules and the chemistry of their labeling using positron emitters.