Miracle-dz/UniFAR-FTUs huggingface dataset:
Bcl-xL activity influences outcome of the mitotic arrest

Microtubule-targeting (MT) drugs taxanes and vinca alkaloids are widely used as chemotherapeutic agents against different tumors for more than 30 years because of their ability to block mitotic progression by disrupting the mitotic spindle and activating the spindle assembly checkpoint (SAC) for a prolonged period of time. However, responses to mitotic arrest are different—some cells die during mitotic arrest, whereas others undergo mitotic slippage and survive becoming able for proliferation. Using normal fibroblasts and several cancer cell types we determined two critical doses, T1 and T2, of mitotic inhibitors (nocodazole, Taxol, and vinorelbine). T1 is the maximal dose cells can tolerate undergoing normal division, and T2 is the minimal mitostatic dose, wherein > 90% of mitotic cells are arrested in mitosis. In all studied cell lines after treatment with mitotic inhibitors in a dose above T2 cells had entered mitosis either die or undergo mitotic slippage. We show that for all three drugs used cell death during mitotic arrest and after slippage proceeded via mitochondria-dependent apoptosis. We determined two types of cancer cells: sensitive to mitotic arrest, that is, undergoing death in mitosis (DiM) frequently, and resistant to mitotic arrest, that is, undergoing mitotic slippage followed by prolonged survival. We then determined that inhibition of Bcl-xL, but not other anti-apoptotic proteins of the Bcl-2 group that regulate MOMP, make resistant cells susceptible to DiM induced by mitotic inhibitors. Combined treatment with MT drugs and highly specific Bcl-xL inhibitors A-1155643 or A-1331852 allows achieving 100% DiM in a time significantly shorter than maximal duration of mitotic arrest in all types of cultured cells tested. We further examined efficacy of sequential treatment of cultured cells using mitotic inhibitors followed by inhibitors of Bcl-xL anti-apoptotic protein and for the first time show that sensitivity to Bcl-xL inhibitors rapidly declines after mitotic slippage. Thus sequential use of mitotic inhibitors and inhibitors of Bcl-xL anti-apoptotic protein will be efficient only if the Bcl-xL inhibitor will be added before mitotic slippage occurs or soon afterward. The combined treatment proposed might be an efficient approach to anti-cancer therapy.
Continuous theta-burst stimulation over the left posterior inferior frontal gyrus induced compensatory plasticity in the language network

Introduction Continuous theta-burst stimulation (cTBS) has been used as an effective tool in inducing inhibitory aftereffect within a short time periods in the motor cortex; this has been demonstrated in the language network to a limited degree with controversial effect. In this study, we aimed to delineate the offline effect of cTBS-induced changes to the left posterior inferior frontal gyrus (pIFG) in healthy subjects using functional magnetic resonance imaging (fMRI). Methods Twenty healthy, normal subjects (mean age: 30.84 years) were recruited. They all were right-handed and had no contra-indications for fMRI or cTBS. They were randomly assigned into the treatment group or the sham control group. Results ANOVA showed that cTBS had a significant main effect only when the sham treatment was subtracted from the real stimulation in left superior temporal, left inferior frontal gyrus, thalamus, and right insular cortex (uncorrected p < 0.002). The subjects' post-cTBS condition differed significantly from their pre-cTBS condition in the left pIFG (uncorrected p < 0.002). There were interactions in the pIFG, bilateral superior parietal lobules, left superior temporal, left supramarginal, and left cuneus areas. The application of cTBS induced increased BOLD signals in language-related networks by stimulating the left pIFG (BA 44). This implies that inhibiting the pIFG led to increased use of language network resources. Conclusion This study demonstrated cTBS-induced changes in the language network caused by stimulation of the left pIFG. Based on these findings, future studies on the therapeutic effects of cTBS on the right Broca's homolog area are warranted.
COVID-19 related disruption in higher education students' health and wellbeing: Implications for university action

The COVID 19 pandemic has led to substantial disruptions in the lives of students in higher education. Partial or full closures of institutions for face-to-face teaching or consultations over a long-lasting period of time in many countries have had significant consequences on the psychosocial health and wellbeing of many students. This perspectives article summarizes the implications on mental, social, and behavioral aspects of students' wellbeing. Moreover, the need for health promoting und supportive services, programmes, structures, and policies is outlined with recommendations for institutional actions on the level of teaching practice, counseling services, and health monitoring, and with the call to re-affirm the wider policy-oriented approach of the Health Promoting University.
The use of the Decision Regret Scale in non-clinical contexts

The Decision Regret Scale (DRS) was assessed for its psychometric qualities in measuring decision regret in ordinary life scenarios. Although the scale has typically been used with patients and in the context of medical decision-making in earlier studies, this contribution shows that the instrument may have a variety of uses, retaining excellent metric properties even in non-medical contexts. The tool showed good fits with both the CFA and the gender Measurement Invariance. A non-probabilistic selection of 2,534 Italian university students was conducted. The internal consistency measures were found to be completely appropriate. Correlations with the General Decision-Making Style (GDMS) and Scale of Regulatory Modes were used to check for convergent validity (SRM). Convergence analysis showed that participants with higher regret scores were those who favored a rational decision-making style, while lower regret scores correlated with avoidant and spontaneous styles. With regard to the regulatory modes, the relationship between regret and locomotion was positive. Overall, the directions of association point to an interesting predictive measure of a person’s decision-making and self-regulatory orientation through the evaluation of regret using the DRS. The excellent psychometric properties found foreshadow a reliable use in various contexts where knowledge of post-decisional attitude becomes important: school, university, professional orientation, marketing studies, relationship choices, as well as for use in research.
Satisfaction and associated factors among psychiatry service users at Amanuel mental specialized hospital. Addis Ababa, Ethiopia

Background Patient service satisfaction is the central point for the health system. Worldwide, around 450 million people suffer from mental and behavioral disorders. Clients who are dissatisfied with the service will miss appointments, abandon the treatment plan, and eventually relapse from the illness. Despite improved access to health services, the satisfaction from health institution services was decreasing from time to time and there is little information on health service consumer satisfaction. Objective To assess the satisfaction and associated factors among psychiatric service consumers at Amanuel Mental Specialized Hospital, Addis Ababa, Ethiopia, 2021/2022. Methods and materials An institutional-based cross-sectional study was conducted among 420 psychiatric service users from December 15 to January 16, 2021/2022. Systematic random sampling was used. A face-face interview technique and chart review were used to collect the data and a standard and validated tool called the mental health service satisfaction scale (MHSSS) was used to measure satisfaction. The collected data was entered into EPI info version 7 and exported to SPSS version 22 for analysis. The binary logistic regression model was used to analyze the data and bivariable and multivariable logistic regression analyses were conducted to identify associated factors with satisfaction. The level of significance was reported at P < 0.05. Results The study showed that the magnitude of patient satisfaction was 63.3% [95% CI 58.3–67.9%). Sex (AOR = 1.7, 95% CI (1.072–2.88)], educational status (AOR 4.2, 95% CI 1.64–1.8), residency [AOR = 1.8, 95% CI (1.098–3.19)], distance from the hospital [AOR 0.56, (0.34–0.93)] were significantly associated with patient satisfaction at p < 0.05. Conclusion The magnitude of patient satisfaction was high. The study showed that Sex, educational status, residence, and distance from the hospital were significantly associated with satisfaction. Prioritizing care for female patients and those coming from a distance is necessary. More ever, it is preferable to routinely and continually monitor healthcare facilities so that timely feedback can be given and problems that affect patient satisfaction can be resolved.
Status and epidemiological characteristics of high-risk human papillomavirus infection in multiple centers in Shenyang

The different human papillomavirus (HPV) strains cause warts in various regions of the body. However, considering that the status and genotype distribution of HPV infection in women in Shenyang remain unknown, herein, we investigated the epidemiological characteristics of high-risk HPV (HR-HPV) infection in women in Shenyang, as well as the current state of HPV infection in Shenyang, to provide a theoretical basis for the prevention and treatment of cervical cancer. From December 2018 to December 2021, 6,432 urban and rural women from the Liaoning Cancer Hospital and the Sujiatun Women and Infants’ Hospital were assessed via the Thinprep cytology test (TCT) and HR-HPV detection. Of the 5,961 women enrolled, 739 were HPV positive (12.40%) and 562 were TCT positive (9.43%). Statistical analyses identified the following HPV risk factors: high school education or lower [OR = 1.426 (1.199–1.696), p < 0.001], age at first sexual encounter ≤ 19 years [OR = 1.496 (1.008–2.220), p = 0.046], and number of sexual partners > 1 [OR = 1.382 (1.081–1.768), p = 0.010], atypical squamous cells of undetermined significance (ASCUS) and above [OR = 10.788 (8.912–13.060), p < 0.001], non-condom-based contraception [OR = 1.437 (1.103–1.871), p = 0.007], nationalities other than Han [OR = 1.690 (1.187–2.406), p = 0.004], rural residence [OR = 1.210 (1.031–1.419), p = 0.020]. Compared to the HPV infection rate of women aged 56–65, that in women aged 35–45 [OR = 0.687 (0.549–0.860), p = 0.001] and 46–55 [OR = 0.740 (0.622–0.879), p = 0.001] decreased significantly. To conclude, risk factors of HPV infection among female patients include high school age and below, initial sexual encounter at age ≤ 19 years, number of sexual partners > 1, ASCUS and above, non-condom contraception, nationalities other than Han nationality and rural population. Collectively, this study provides insights for the improved prevention and treatment of cervical cancer.
Effects of a therapeutic exercise program in children with non-cystic fibrosis bronchiectasis: A pilot randomized controlled trial

Background In the absence of randomized controlled trials (RCTs) on the benefits of therapeutic exercise programs involving children with bronchiectasis, we undertook a pilot RCT to evaluate the effects of a play-based therapeutic exercise program on fundamental movement skill (FMS) proficiency. The effects of the program on cardiorespiratory fitness, perceived competence, and health-related quality of life (HR-QoL) were examined as secondary outcomes. Methods Children [median (IQR) age: 6.8 (5.3–8.8) years] with bronchiectasis unrelated to cystic fibrosis were randomized to a 7-week therapeutic exercise program (n = 11) or wait-list control (n = 10). The exercise program comprised 7 × 60-min weekly sessions and was supplemented by a home-based program 2-days/week. Participants were assessed on: FMS (locomotor and object control skills) using the Test of Gross Motor Development 2nd Edition (TGMD-2); cardiovascular fitness by calculating the percent change in heart rate (%ΔHR) from rest to completion of the first stage of a submaximal treadmill test; perceived competence using Harter’s athletic competence subscale; and QoL with the PedsQL. Results Significant group by time interactions were observed for locomotor and object control skills. Children completing the therapeutic exercise program exhibited significant improvements in both locomotor (pre 29.0 ± 2.0, post 35.2 ± 2.2, p = 0.01) and object control (pre 27.0 ± 2.0, post 35.5 ± 2.2, p = 0.01) skills, with no significant change in controls (pre 31.6 ± 2.1, post 31.8 ± 2.3 and pre 31.0 ± 2.1, post 32.3 ± 2.3, respectively). Among children completing the program, %ΔHR declined by 6% points, while %ΔHR declined only marginally among controls (0.9% points), but the group by time interaction was not statistically significant. The program had a small positive impact on competence perceptions (Cohen’s d = 0.2) and HR-QoL (Cohen’s d = 0.3). Conclusion This pilot RCT provides preliminary evidence for the efficacy of a play-based therapeutic exercise program to improve proficiency in FMS and fitness in children with bronchiectasis. The results are sufficiently positive to warrant conducting a larger RCT testing the efficacy of the exercise program in children with bronchiectasis and/or other chronic respiratory conditions.
Efficiency measures and influencing factors for rural land outsourcing: Evidence from China, 2003–2015

In the context of China’s vigorous promotion of its rural revitalization and land transfer policy, land outsourcing is a perspective worthy of attention to understand China’s rural land production and agricultural development. Based on rural land outsourcing in China from 2003 to 2015, this study adopts DEA efficiency analysis and Tobit regression analysis to measure the efficiency of rural land outsourcing in China as well as discuss its influencing factors. The results show that 1) from 2003 to 2015, the efficiency of rural land outsourcing in China has risen, especially in the eastern region, where the efficiency has the best performance. Overall, technical efficiency has hindered the improvement of rural land outsourcing efficiency. 2) The development of rural land outsourcing is restricted by factors such as the newly increased arable land area in rural areas, the foreign labor force, and rural managers, while land outsourcing income cannot significantly promote the expansion of land outsourcing. 3) Large rural agricultural enterprises or cooperatives enhance the efficiency of land outsourcing. Under the food security policy, realizing the technological increment of land outsourcing and land economy can effectively promote the scale and production efficiency of land outsourcing.
Temporal malleability to auditory feedback perturbation is modulated by rhythmic abilities and auditory acuity

Auditory feedback perturbation studies have indicated a link between feedback and feedforward mechanisms in speech production when participants compensate for applied shifts. In spectral perturbation studies, speakers with a higher perceptual auditory acuity typically compensate more than individuals with lower acuity. However, the reaction to feedback perturbation is unlikely to be merely a matter of perceptual acuity but also affected by the prediction and production of precise motor action. This interplay between prediction, perception, and motor execution seems to be crucial for the timing of speech and non-speech motor actions. In this study, to examine the relationship between the responses to temporally perturbed auditory feedback and rhythmic abilities, we tested 45 adult speakers on the one hand with a temporal auditory feedback perturbation paradigm, and on the other hand with rhythm perception and production tasks. The perturbation tasks temporally stretched and compressed segments (onset + vowel or vowel + coda) in fluent speech in real-time. This technique sheds light on the temporal representation and the production flexibility of timing mechanisms in fluent speech with respect to the structure of the syllable. The perception tasks contained staircase paradigms capturing duration discrimination abilities and beat-alignment judgments. The rhythm production tasks consisted of finger tapping tasks taken from the BAASTA tapping battery and additional speech tapping tasks. We found that both auditory acuity and motor stability in finger tapping affected responses to temporal auditory feedback perturbation. In general, speakers with higher auditory acuity and higher motor variability compensated more. However, we observed a different weighting of auditory acuity and motor stability dependent on the prosodic structure of the perturbed sequence and the nature of the response as purely online or adaptive. These findings shed light on the interplay of phonological structure with feedback and feedforward integration for timing mechanisms in speech.
Selective connectivity enhances storage capacity in attractor models of memory function

Autoassociative neural networks provide a simple model of how memories can be stored through Hebbian synaptic plasticity as retrievable patterns of neural activity. Although progress has been made along the last decades in understanding the biological implementation of autoassociative networks, their modest theoretical storage capacity has remained a major constraint. While most previous approaches utilize randomly connected networks, here we explore the possibility of optimizing network performance by selective connectivity between neurons, that could be implemented in the brain through creation and pruning of synaptic connections. We show through numerical simulations that a reconfiguration of the connectivity matrix can improve the storage capacity of autoassociative networks up to one order of magnitude compared to randomly connected networks, either by reducing the noise or by making it reinforce the signal. Our results indicate that the signal-reinforcement scenario is not only the best performing but also the most adequate for brain-like highly diluted connectivity. In this scenario, the optimized network tends to select synapses characterized by a high consensus across stored patterns. We also introduced an online algorithm in which the network modifies its connectivity while learning new patterns. We observed that, similarly to what happens in the human brain, creation of connections dominated in an initial stage, followed by a stage characterized by pruning, leading to an equilibrium state that was independent of the initial connectivity of the network. Our results suggest that selective connectivity could be a key component to make attractor networks in the brain viable in terms of storage capacity.
Establishment and validation of a radiological-radiomics model for predicting high-grade patterns of lung adenocarcinoma less than or equal to 3 cm

Objective We aimed to develop a Radiological-Radiomics (R-R) based model for predicting the high-grade pattern (HGP) of lung adenocarcinoma and evaluate its predictive performance. Methods The clinical, pathological, and imaging data of 374 patients pathologically confirmed with lung adenocarcinoma (374 lesions in total) were retrospectively analyzed. The 374 lesions were assigned to HGP (n = 81) and non-high-grade pattern (n-HGP, n = 293) groups depending on the presence or absence of high-grade components in pathological findings. The least absolute shrinkage and selection operator (LASSO) method was utilized to screen features on the United Imaging artificial intelligence scientific research platform, and logistic regression models for predicting HGP were constructed, namely, Radiological model, Radiomics model, and R-R model. Also, receiver operating curve (ROC) curves were plotted on the platform, generating corresponding area under the curve (AUC), sensitivity, specificity, and accuracy. Using the platform, nomograms for R-R models were also provided, and calibration curves and decision curves were drawn to evaluate the performance and clinical utility of the model. The statistical differences in the performance of the models were compared by the DeLong test. Results The R-R model for HGP prediction achieved an AUC value of 0.923 (95% CI: 0.891-0.948), a sensitivity of 87.0%, a specificity of 83.4%, and an accuracy of 84.2% in the training set. In the validation set, this model exhibited an AUC value of 0.920 (95% CI: 0.887-0.945), a sensitivity of 87.5%, a specificity of 83.3%, and an accuracy of 84.2%. The DeLong test demonstrated optimal performance of the R-R model among the three models, and decision curves validated the clinical utility of the R-R model. Conclusion In this study, we developed a fusion model using radiomic features combined with radiological features to predict the high-grade pattern of lung adenocarcinoma, and this model shows excellent diagnostic performance. The R-R model can provide certain guidance for clinical diagnosis and surgical treatment plans, contributing to improving the prognosis of patients.
Case Report: Necrotizing fasciitis caused by Staphylococcus aureus positive for a new sequence variant of exfoliative toxin E

Objectives: Necrotizing fasciitis (NF) caused by S. aureus is a rare, aggressive and rapidly progressing superficial fascia infection with a high mortality rate. The aim of this study was to identify virulence-related genes from a complete genome sequence of a methicillin-susceptible S. aureus (MSSA) isolate recovered from a monomicrobial case of NF. Materials and methods: The MSSA isolate UMCG579 was cultured from a pus collection from the subcutis of a patient with NF. The genome of isolate UMCG579 was sequenced using MinION (Oxford Nanopore) and MiSeq (illumina) platforms. Results: The genome of the UMCG579 isolate was composed of a 2,741,379 bp chromosome and did not harbor any plasmids. Virulence factor profiling identified multiple pore-forming toxin genes in the UMCG579 chromosome, including the Panton-Valentine leukocidin (PVL) genes, and none of the superantigen genes. The UMCG579 isolate harbored a new sequence variant of the recently described ete gene encoding exfoliative toxin (type E). A search in the GenBank database revealed that the new sequence variant (ete2) was exclusively found among isolates (n = 115) belonging to MLST CC152. While the majority of S. aureus ete-positive isolates were recovered from animal sources, S. aureus ete2-positive isolates originated from human carriers and human infections. Comparative genome analysis revealed that the ete2 gene was located on a 8777 bp genomic island. Conclusion: The combination of two heterogeneously distributed potent toxins, ETE2 and PVL, is likely to enhance the pathogenic ability of S. aureus isolates. Since anti-virulence therapies for the treatment of S. aureus infections continue to be explored, the understanding of specific pathogenetic mechanisms may have an important prophylactic and therapeutic value. Nevertheless, the exact contribution of ETE sequence variants to S. aureus virulence in NF infections must be determined.