Miracle-dz/UniFAR-FTUs huggingface dataset:
The molecular function of kallikrein‐related peptidase 14 demonstrates a key modulatory role in advanced prostate cancer

Kallikrein‐related peptidase 14 (KLK14) is one of the several secreted KLK serine proteases involved in prostate cancer (PCa) pathogenesis. While relatively understudied, recent reports have identified KLK14 as overexpressed during PCa development. However, the modulation of KLK14 expression during PCa progression and the molecular and biological functions of this protease in the prostate tumor microenvironment remain unknown. To determine the modulation of KLK14 expression during PCa progression, we analyzed the expression levels of KLK14 in patient samples using publicly available databases and immunohistochemistry. In order to delineate the molecular mechanisms involving KLK14 in PCa progression, we integrated proteomic, transcriptomic, and in vitro assays with the goal to identify substrates, related‐signaling pathways, and functional roles of this protease. We showed that KLK14 expression is elevated in advanced PCa, and particularly in metastasis. Additionally, KLK14 levels were found to be decreased in PCa tissues from patients responsive to neoadjuvant therapy compared to untreated patients. Furthermore, we also identified that KLK14 expression reoccurred in patients who developed castrate‐resistant PCa. The combination of proteomic and transcriptomic analysis as well as functional assays revealed several new KLK14 substrates (agrin, desmoglein 2, vitronectin, laminins) and KLK14‐regulated genes (Interleukin 32, midkine, SRY‐Box 9), particularly an involvement of the mitogen‐activated protein kinase 1 and interleukin 1 receptor pathways, and an involvement of KLK14 in the regulation of cellular migration, supporting its involvement in aggressive features of PCa progression. In conclusion, our work showed that KLK14 expression is associated with the development of aggressive PCa suggesting that targeting this protease could offer a novel route to limit the progression of prostate tumors. Additional work is necessary to determine the benefits and implications of targeting/cotargeting KLK14 in PCa as well as to determine the potential use of KLK14 expression as a predictor of PCa aggressiveness or response to treatment.
Validity, functional impairment and complications related to Internet gaming disorder in the DSM-5 and gaming disorder in the ICD-11

Background: Many concerns have been raised regarding the Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5) criteria for Internet gaming disorder and International Classification of Diseases, 11th Revision (ICD-11) criteria for gaming disorder. Aims: In this study, we demonstrated the diagnostic validity of each criterion for Internet gaming disorder in the DSM-5 in terms of their intensity and frequency thresholds and evaluated functional impairments, unhealthy behaviors and complications among adults with Internet gaming disorder and gaming disorder. Methods: We recruited 69 subjects with Internet gaming disorder, 69 regular gamers and 69 controls without regular gaming based on diagnostic interviewing conducted by a psychiatrist according to the DSM-5 Internet gaming disorder criteria. Results: Except for the ‘deceiving’ and ‘escapism’ criteria, all criteria for Internet gaming disorder had a diagnostic accuracy ranging from 84.7% to 93.5% in differentiating between adults with Internet gaming disorder and regular gamers. A total of 44 participants with Internet gaming disorder (63.8%) fulfilled the gaming disorder criteria. In addition, 89% and 100% of the Internet gaming disorder and gaming disorder groups, respectively, had academic, occupational or social functional impairment. Both the Internet gaming disorder and gaming disorder groups had higher rates of delayed sleep phase syndrome and insomnia. The gaming disorder group also had a higher obesity proportion. Conclusion: The ‘deceiving’ and ‘escapism’ criteria had relatively lower diagnostic accuracy. Both the Internet gaming disorder and gaming disorder groups demonstrated functional impairments and unhealthy behaviors. They also exhibited complications, such as obesity and sleep disorders. These results support the utility of the DSM-5 Internet gaming disorder and ICD-11 gaming disorder criteria in identifying individuals who need treatment for both gaming addiction symptoms and complications resulting from the addiction.
The effect of cricoid and paralaryngeal force on upper oesophageal occlusion during induction of anaesthesia: a randomised, crossover study

The aim of this study was to evaluate the effectiveness of cricoid and paralaryngeal force for oesophageal entrance occlusion during induction of anaesthesia. Seventy‐four patients were included in this randomised, crossover study. The relative position of the glottis and outer anteroposterior diameter of the upper oesophageal entrance were assessed at baseline, after the application of 30 N cricoid and paralaryngeal force, and after induction of anaesthesia. The occlusion rate of the oesophageal entrance with cricoid and paralaryngeal force was assessed during direct laryngoscopy. The relative position of the upper oesophageal entrance to the glottis changed in 45 out of 74 patients after induction of anaesthesia and during direct laryngoscopy compared with the awake state. The application of cricoid and paralaryngeal force decreased the mean (SD) diameter of the upper oesophageal entrance to a similar degree in awake (8.5 (2.1) mm to 6.4 (1.7) mm and 6.5 (1.6) mm, respectively; p < 0.001) and anaesthetised (8.7 (2.2) mm to 6.5 (1.7) mm and (6.7 (1.9) mm, respectively; p < 0.001) states. During direct laryngoscopy, the occlusion rate of the oesophageal entrance was greater with cricoid compared with paralaryngeal force (46/74 vs. 26/74, respectively; p = 0.002). The relative position of the upper oesophageal entrance to the glottis may change after induction of anaesthesia and during direct laryngoscopy. Cricoid and paralaryngeal force both decrease the diameter of the upper oesophageal entrance in awake and anaesthetised states. Occlusion of the oesophageal entrance is achieved more frequently with cricoid force compared with paralaryngeal force during direct laryngoscopy.
Monitoring glycation levels of a bispecific monoclonal antibody at subunit level by ultrahigh-resolution MALDI FT-ICR mass spectrometry

ABSTRACT Bispecific monoclonal antibodies (BsAbs) are engineered proteins with multiple functionalities and properties. The “bi-specificity” of these complex biopharmaceuticals is a key characteristic for the development of novel and more effective therapeutic strategies. The high structural complexity of BsAbs poses a challenge to the analytical methods needed for their characterization. Modifications of the BsAb structure, resulting from enzymatic and non-enzymatic processes, further complicate the analysis. An important example of the latter type of modification is glycation, which can occur in the manufacturing process, during storage in the formulation or in vivo after application of the drug. Glycation affects the structure, function, and stability of monoclonal antibodies, and consequently, a detailed analysis of glycation levels is required. Mass spectrometry (MS) plays a key role in the structural characterization of monoclonal antibodies and top-down, middle-up and middle-down MS approaches are increasingly used for the analysis of modifications. Here, we apply a novel middle-up strategy, based on IdeS digestion and matrix-assisted laser desorption ionization (MALDI) Fourier transform ion cyclotron resonance (FT-ICR) MS, to analyze all six different BsAb subunits in a single high-resolution mass spectrum, namely two light chains, two half fragment crystallizable regions and two Fd’ regions, thus avoiding upfront chromatography. This method was used to monitor glycation changes during a 168 h forced-glycation experiment. In addition, hot spot glycation sites were localized using top-down and middle-down MALDI-in-source decay FT-ICR MS, which provided complementary information compared to standard bottom-up MS.
Subjective Memory Complaints Are an Important Surrogate for Objective Cognitive Performance in African Americans

Supplemental Digital Content is available in the text. Purpose: Subjective memory complaints (SMCs) have been shown to be associated with lower neuropsychological test scores cross-sectionally. However, it remains unclear whether such findings hold true for African American (AA) older adults. Methods: Baseline visit data from the National Alzheimer’s Coordinating Center database collected from September 2005 to March 2018 were used. Generalized linear mixed models specifying binomial distributions were used to examine how neuropsychological test scores affect the likelihood of reporting SMCs. Patients: Inclusion criteria were participants who reported AA as their primary race, 60 to 80 years of age, were cognitively unimpaired, and had a Mini-Mental Status Examination score ≥26. A total of 1021 older AA adults without missing data met the criteria. Results: A total of 258 participants reported a SMC. SMCs were more likely with lower scores on measures of episodic memory and processing; however, SMCs were also more likely with higher scores on a measure of working memory. Working memory appeared to mediate reporting of SMC among participants with lower episodic memory scores. Discussion: These findings demonstrate that SMCs are associated with lower scores on objective neuropsychological measures among older AAs. Additional work is needed to determine whether SMCs are further associated with a risk for clinical transition to mild cognitive impairment or dementia among AA older adults.
Expression Levels of Microrna-125b in Serum Exosomes of Patients with Asthma of Different Severity and its Diagnostic Significance.

BACKGROUND This study aimed to investigate the expression levels of microRNA (miRNA)-125b in serum exosomes and its diagnostic efficacy for asthma severity. METHODS The study included 80 patients with untreated asthma and 80 healthy volunteers. The patients were divided into 4 groups according to disease severity: 20 with the intermittent state, 20 with the mildly persistent state, 20 with the moderately persistent state, and 20 with the severely persistent state. The expression levels of miRNA-125b in serum exosomes of each group were detected using quantitative polymerase chain reaction and compared. The Spearman correlation analysis was used to study the correlation between the expression levels of miRNA-125b in serum exosomes and asthma severity. The diagnostic efficacy of the expression levels of miRNA-125b in exosomes for asthma severity was evaluated using the Receiver Operating Characteristic (ROC) curve. RESULTS The expression levels of miRNA-125b in serum exosomes of patients with intermittent, mildly persistent, moderately persistent, and severely persistent asthma were all higher than those in the healthy control group, with statistically significant differences. The expression levels of miRNA-125b were also statistically significantly different among patients in each group. The Spearman correlation analysis showed a positive correlation of the relative expression of miRNA-125b in serum exosomes with asthma severity. The area under the ROC curve of the diagnostic efficacy of miRNA-125b in serum exosomes for patients with intermittent, mildly, moderately, and severe persistent asthma was 0.427, 0.541, 0.673, and 0.758, respectively. CONCLUSION The expression levels of miRNA-125b in serum exosomes had a high diagnostic efficacy and might serve as a noninvasive diagnostic marker for asthma severity.
Evolution of Aesthetic Dentistry

One of the main goals of dental treatment is to mimic teeth and design smiles in a most natural and aesthetic manner, based on the individual and specific needs of the patient. Possibilities to reach that goal have significantly improved over the last decade through new and specific treatment modalities, steadily enhanced and more aesthetic dental materials, and novel techniques and technologies. This article gives an overview of the evolution of aesthetic dentistry over the past 100 y from a historical point of view and highlights advances in the development of dental research and clinical interventions that have contributed the science and art of aesthetic dentistry. Among the most noteworthy advancements over the past decade are the establishment of universal aesthetic rules and guidelines based on the assessment of natural aesthetic parameters, anatomy, and physiognomy; the development of tooth whitening and advanced restorative as well as prosthetic materials and techniques, supported by the pioneering discovery of dental adhesion; the significant progress in orthodontics and periodontal as well as oral and maxillofacial surgery; and, most recently, the implementation of digital technologies in the 3-dimensional planning and realization of truly natural, individual, and aesthetic smiles. In the future, artificial intelligence and machine learning will likely lead to automation of aesthetic evaluation, smile design, and treatment-planning processes.
Expression profile of circular RNA s in TMJ osteoarthritis synovial tissues and potential functions of hsa_circ_0000448 with specific back-spliced junction.

OBJECTIVE As essential players in the occurrence and development of osteoarthritis, circular RNAs (circRNAs) have gradually received attention in recent years. However, their roles in temporomandibular joint osteoarthritis (TMJOA) featured with pain, restricted mouth opening and joint movement dysfunction, remains elusive. METHODS The expression profile of circRNAs in TMJ synovial tissues was analyzed by RNA-Seq. The differentially expressed circRNAs in the TMJOA were identified. The potential biological functions of these circRNAs were evaluated. RESULTS The expression profile of circRNAs in TMJ synovial tissues was stable and abundant, and most of which were newly discovered. A total of 58 differentially expressed circRNAs were identified in TMJOA, and four of which were identified by in vitro experiments. Among them, the up-regulated hsa_circ_0000448 with specific back-splice junction was involved in the TNF-α signaling pathway through CeRNA mechanism by targeting related microRNAs. Additionally, it was also predicted to bind several RNA binding proteins (RBPs), but almost had no protein-coding ability. CONCLUSION circRNAs in TMJ synovial tissue participate in the progression of TMJOA and may become a potential therapeutic target. The highly up-regulated has_circ_0000448 probably promotes TNF-α secretion of synovium through CeRNA mechanism in TMJOA.
Specific joint angle assessment of the shoulder rotators

BACKGROUND: Independent peak torque (IPT) ratios may lead to misinterpretation of shoulder rotator imbalances. OBJECTIVE: To compare shoulder rotator IPT conventional ratio (CR) and dynamic control ratio (DCR) with ten-degree angle specific torque (AST) CR and DCR. METHODS: Twenty healthy adult males (24.65 ± 2.4 yrs) performed concentric (C) and eccentric (E) internal rotation (IR) and external rotation (ER) of the right shoulder on an isokinetic dynamometer at 60 ◦ /s and 180 ◦ /s through 150 ◦ of ROM. RESULTS: IPT DCR was significantly different than AST DCR at several angles at both test speeds. IPT CR were not significantly different than any AST CR at either speed. The last 3 ten degree AST DCR were also compared. AST DCR was significantly different at two angles at 60 ◦ /s and at three angles at 180 ◦ /s. CONCLUSION: DCR analysis should use a ten degree AST interpretative approach in order to avoid erroneous interpretations of shoulder rotator strength imbalances. IPT ratio tests should only be used to calculate CR.
Chromosome-level reference genome of Venturia effusa, causative agent of pecan scab.

Pecan scab, caused by Venturia effusa, is a devastating disease of pecan (Carya illinoinensis), which results in economic losses on susceptible cultivars throughout the southeastern U.S. To enhance our understanding of pathogenicity in V. effusa, we have generated a complete telomere-to-telomere reference genome of V. effusa isolate FRT5LL7-Albino. By combining Illumina MiSeq and Oxford Nanopore MinION data, we assembled a 45.2 Mb genome represented by 20 chromosomes and containing 10,820 putative genes, of which 7,619 have at least one functional annotation. The likely causative mutation of the albino phenotype was identified as a single base insertion and a resulting frameshift in the gene encoding the polyketide synthase ALM1. This genome represents the first full chromosome-level assembly of any Venturia species.
Glycemic Control and Complications in Type II Diabetes: Design of a feasibility trial

OBJECTIVE To determine, after 1 yr of follow-up in type II diabetes patients, whether a statistically and clinically significant difference can be achieved in HbA1c between a standard therapy group and an intensively treated group, while maintaining HbA1c levels in both groups within ranges acceptable in regular community practice. Secondary objectives include assessment of patient adherence to protocol, side effects, and accuracy of data collection. RESEARCH DESIGN AND METHODS This is a prospective, randomized, controlled VA CS conducted with 151 patients at five VAMCs. Patients are males, age 40–69 yr, treated at entry with a maximum dose of sulfonylurea or with insulin, exhibiting an HbA1c level > 3 SDs above the normal mean (5.05 + 3 × 0.50 = > 6.55%). Standard control is achieved with insulin and intensive control with a step-up regimen including insulin alone or insulin/glipizide combinations. Education and management of cardiovascular risk factors are handled similarly in both groups. Primary macrovascular end points are nonfatal myocardial infarction, congestive heart failure, stroke, amputation, and cardiovascular death. Primary microvascular end points are appearance and progression of retinopathy, documented by centrally read seven-field-stereo fundus photographs. Other measured indicators include resting and ambulatory ECGs, ventricular function (MUGA scan), serum lipid and apolipoprotein levels, plasma fibrinogen, nonsymptomatic peripheral vasculopathy, neuroautonomic status by heart-beat variation on Valsalva maneuver, and microalbuminuria. CONCLUSIONS This study may be the basis for a long-term trial, involving 1400 patients, to assess the long-term effects of metabolic control on macro- and microvascular end points.
Toddler affect with mothers and fathers: the importance of infant attachment

ABSTRACT The present study examined the degree to which toddlers’ affect at 20 months during the Parent Ignore Toddler Situation (PITS), a modified still-face paradigm, with mothers and fathers was predicted by attachment (12 and 14 months), temperamental negative reactivity (3, 5, 7, 12, and 14 months), and attachment X negative reactivity during infancy. Parents (N = 135) were predominantly Caucasian (90.3% of mothers and 87.4% of fathers). Results from multi-level models, controlling for baseline affect and current parent sensitivity, indicated several effects involving attachment, but not temperament. An Episode X Avoidant attachment interaction indicated that toddlers who were classified as avoidant with either parent during infancy showed a flattened pattern of positive affect across the PITS episodes compared with those classified as secure. In contrast, a Parent X Ambivalent attachment interaction indicated that toddler negative affect was higher when they had an ambivalent attachment with mothers but not fathers.
Changes in Exposure to Secondhand Smoke and Smoking Behavior

Aims: This study examines exposure to secondhand smoke and smoking behavior in the German general population before and after the introduction of new smoke-free laws in 2007 and 2008. Methods: Data came from the 2006 and 2009 German Epidemiological Survey of Substance Abuse (ESA). A propensity-score-matched subsample of n = 7,412 subjects between 18 and 64 years was used for the analysis. We employed multinomial logistic regression to examine changes in exposure to secondhand smoke at work, during leisure time, and at home among nonsmokers between 2006 and 2009. Logistic and ordinary least square regression were used to address changes in cigarette smoking prevalence and number of cigarettes smoked among smokers. Results: Exposure to secondhand smoke at work and during leisure time was substantially reduced in 2009 compared to 2006. The number of cigarettes smoked decreased in the same time period. No changes were found for exposure to secondhand smoke at home and cigarette smoking prevalence. However, se.
Adherence to Mediterranean diet of children living in small Southern Italian villages

Abstract A cross-sectional study was conducted in the primary schools of five small villages of Salento Peninsula to evaluate the adherence to the Mediterranean Diet (MD) of 282 6-8-years old children in relation to lifestyles and socio-economic factors. The parents of children completed a self-administered questionnaire to evaluate the prevalence of personal, behavioural and socio-economic factors of their sons. Children’s anthropometric measurements were also taken. The adherence to the MD was assessed using the Mediterranean Diet Quality Index for Children and Adolescents (KIDMED). The chi-square test was used to detect any differences among groups of children. Overall, 27.0% of children showed low adherence to the MD (KIDMED ≤3), 59.6% medium adherence (KIDMED 4–7) and 13.5% high adherence (KIDMED ≥8). The adherence to the MD was associated with the educational level (whether graduated or not) of the mother and the occupational status (whether employed or not) of both parents.
Zumba dancing and aerobic exercise can improve working memory, motor function, and depressive symptoms in female patients with Fibromyalgia

ABSTRACT Background: Patients suffering from the Fibromyalgia (FM) have impaired cognitive function, reduced physical activity and more marked depressive symptoms. While physical activity and exercise therapy are not typically part of the standard treatment for this syndrome, there is mounting evidence that regular participation in activities involving physical exertion has a positive impact on psychological functioning in people with FM. This study compares the impact of two different interventions, aerobic exercise training and Zumba dancing, on working memory, motor function and depressive symptoms among female patients with FM. The design also included a control condition. Method: A total of sixty middle-aged female patients with FM (mean age: 35.76 years) and undergoing standard care took part in the study. Participants were randomly assigned to one of the following three conditions: aerobic exercise training, Zumba dancing, or control. At baseline and 12 weeks later after the end of the intervention, participants’ working memory, motor function and depressive symptom severity were assessed. Results: Working memory, motor function and depressive symptoms improved over time, but only in the aerobic exercise training and Zumba dancing conditions than in the control condition. Post-hoc analyses showed that improvements were greatest among participants assigned to Zumba dancing, followed by participants who engaged in aerobic exercise training; the scores of the control group remained virtually unchanged. Conclusion: Aerobic exercise training and Zumba dancing can be recommended as add-ons to standard care to improve working memory and to reduce severity of depressive symptoms among female patients with FM. Although motor function improved in both intervention groups, the effects did not reach clinical relevance.