Miracle-dz/UniFAR-FTUs huggingface dataset:
Adhesion strength and anti-tumor agents regulate vinculin of breast cancer cells

The onset and progression of cancer are strongly associated with the dissipation of adhesion forces between cancer cells, thus facilitating their incessant attachment and detachment from the extracellular matrix (ECM) to move toward metastasis. During this process, cancer cells undergo mechanical stresses and respond to these stresses with membrane deformation while inducing protrusions to invade the surrounding tissues. Cellular response to mechanical forces is inherently related to the reorganization of the cytoskeleton, the dissipation of cell–cell junctions, and the adhesion to the surrounding ECM. Moreover, the role of focal adhesion proteins, and particularly the role of vinculin in cell attachment and detachment during migration, is critical, indicating the tight cell–ECM junctions, which favor or inhibit the metastatic cascade. The biomechanical analysis of these sequences of events may elucidate the tumor progression and the potential of cancer cells for migration and metastasis. In this work, we focused on the evaluation of the spreading rate and the estimation of the adhesion strength between breast cancer cells and ECM prior to and post-treatment with anti-tumor agents. Specifically, different tamoxifen concentrations were used for ER+ breast cancer cells, while even concentrations of trastuzumab and pertuzumab were used for HER2+ cells. Analysis of cell stiffness indicated an increased elastic Young’s modulus post-treatment in both MCF-7 and SKBR-3 cells. The results showed that the post-treatment spreading rate was significantly decreased in both types of breast cancer, suggesting a lower metastatic potential. Additionally, treated cells required greater adhesion forces to detach from the ECM, thus preventing detachment events of cancer cells from the ECM, and therefore, the probability of cell motility, migration, and metastasis was confined. Furthermore, post-detachment and post-treatment vinculin levels were increased, indicating tighter cell–ECM junctions, hence limiting the probability of cell detachment and, therefore, cell motility and migration.
Ventricular arrhythmia and sudden cardiac death in hypertrophic cardiomyopathy: From bench to bedside

Patients with hypertrophic cardiomyopathy (HCM) mostly experience minimal symptoms throughout their lifetime, and some individuals have an increased risk of ventricular arrhythmias and sudden cardiac death (SCD). How to identify patients with a higher risk of ventricular arrythmias and SCD is the priority in HCM research. The American College of Cardiology/American Heart Association (ACC/AHA) and the European Society of Cardiology (ESC) both recommend the use of risk algorithms to identify patients at high risk of ventricular arrhythmias, to be selected for implantation of implantable cardioverters/defibrillators (ICDs) for primary prevention of SCD, although major discrepancies exist. The present SCD risk scoring systems cannot accurately identify early-stage HCM patients with modest structural remodeling and mild disease manifestations. Unfortunately, SCD events could occur in young asymptomatic HCM patients and even as initial symptoms, prompting the determination of new risk factors for SCD. This review summarizes the studies based on patients' surgical specimens, transgenic animals, and patient-derived induced pluripotent stem cells (hiPSCs) to explore the possible molecular mechanism of ventricular arrhythmia and SCD. Ion channel remodeling, Ca2+ homeostasis abnormalities, and increased myofilament Ca2+ sensitivity may contribute to changes in action potential duration (APD), reentry circuit formation, and trigger activities, such as early aferdepolarization (EAD) or delayed afterdepolarization (DAD), leading to ventricular arrhythmia in HCM. Besides the ICD implantation, novel drugs represented by the late sodium current channel inhibitor and myosin inhibitor also shed light on the prevention of HCM-related arrhythmias. The ideal prevention strategy of SCD in early-stage HCM patients needs to be combined with gene screening, hiPSC-CM testing, machine learning, and advanced ECG studies, thus achieving individualized SCD prevention.
Machine learning model for the prediction of prostate cancer in patients with low prostate-specific antigen levels: A multicenter retrospective analysis

Objective The aim of this study was to develop a predictive model to improve the accuracy of prostate cancer (PCa) detection in patients with prostate specific antigen (PSA) levels ≤20 ng/mL at the initial puncture biopsy. Methods A total of 146 patients (46 with Pca, 31.5%) with PSA ≤20 ng/mL who had undergone transrectal ultrasound-guided 12+X prostate puncture biopsy with clear pathological results at the First Affiliated Hospital of Guangxi Medical University (November 2015 to December 2021) were retrospectively evaluated. The validation group was 116 patients drawn from Changhai Hospital(52 with Pca, 44.8%). Age, body mass index (BMI), serum PSA, PSA-derived indices, several peripheral blood biomarkers, and ultrasound findings were considered as predictive factors and were analyzed by logistic regression. Significant predictors (P < 0.05) were included in five machine learning algorithm models. The performance of the models was evaluated by receiver operating characteristic curves. Decision curve analysis (DCA) was performed to estimate the clinical utility of the models. Ten-fold cross-validation was applied in the training process. Results Prostate-specific antigen density, alanine transaminase-to-aspartate transaminase ratio, BMI, and urine red blood cell levels were identified as independent predictors for the differential diagnosis of PCa according to multivariate logistic regression analysis. The RandomForest model exhibited the best predictive performance and had the highest net benefit when compared with the other algorithms, with an area under the curve of 0.871. In addition, DCA had the highest net benefit across the whole range of cut-off points examined. Conclusion The RandomForest-based model generated showed good prediction ability for the risk of PCa. Thus, this model could help urologists in the treatment decision-making process.
Protective effect of the curcumin-baicalein combination against macrovascular changes in diabetic angiopathy

Endothelial dysfunction is an early pathological event in diabetic angiopathy which is the most common complication of diabetes. This study aims to investigate individual and combined actions of Curcumin (Cur) and Baicalein (Bai) in protecting vascular function. The cellular protective effects of Cur, Bai and Cur+Bai (1:1, w/w) were tested in H2O2 (2.5 mM) impaired EA. hy926 cells. Wistar rats were treated with vehicle control as the control group, Goto-Kakizaki rats (n=5 each group) were treated with vehicle control (model group), Cur (150 mg/kg), Bai (150 mg/kg), or Cur+Bai (75 mg/kg Cur + 75 mg/kg Bai, OG) for 4 weeks after a four-week high-fat diet to investigate the changes on blood vessel against diabetic angiopathy. Our results showed that Cur+Bai synergistically restored the endothelial cell survival and exhibited greater effects on lowering the fasting blood glucose and blood lipids in rats comparing to individual compounds. Cur+Bai repaired the blood vessel structure in the aortic arch and mid thoracic aorta. The network pharmacology analysis showed that Nrf2 and MAPK/JNK kinase were highly relevant to the multi-targeted action of Cur+Bai which has been confirmed in the in vitro and in vivo studies. In conclusion, Cur+Bai demonstrated an enhanced activity in attenuating endothelial dysfunction against oxidative damage and effectively protected vascular function in diabetic angiopathy rats.
Indirect decompression via oblique lumbar interbody fusion is sufficient for treatment of lumbar foraminal stenosis

Oblique lumbar interbody fusion (OLIF) is a popular technique for the treatment of degenerative lumbar spinal disease. There are no clear guidelines on whether direct posterior decompression (PD) is necessary after OLIF. The purpose of this study was to analyze the effect of the indirect decompression obtained from OLIF in patients with lumbar foraminal stenosis. We retrospectively reviewed 33 patients who underwent OLIF surgery for degenerative lumbar spinal disease between 1 January 2018, and 30 June 2019. The inclusion criteria included patients who were diagnosed with lumbar foraminal stenosis by preoperative MRI. The exclusion criteria included the presence of central canal stenosis, spinal infection, vertebral fractures, and spinal malignancies. The clinical results, evaluated using the visual analogue scale of back pain (VAS-Back), VAS of leg pain (VAS-Leg), and Oswestry disability index (ODI), were recorded. The radiologic parameters were also measured. The VAS-Back, VAS-Leg, and ODI showed significant improvement in both the PD and non-posterior decompression (Non-PD) groups postoperatively (all, p < 0.05). Patients in the Non-PD group showed better results than those in the PD group in the VAS-Back at 12- and 24 months postoperatively (0.00 vs. 3.00 postoperatively at 12 months, p = 0.030; 0.00 vs. 4.00 postoperatively at 24 months, p = 0.009). In addition, the ODI at 24 months postoperatively showed better improvement in the Non-PD group (8.89 vs. 24.44, p = 0.038). The disc height in both the PD and the Non-PD groups increased significantly postoperatively (all, p < 0.05), but the restoration of foraminal height was significantly different only in the Non-PD group. There was no statistically significant difference in cage position, cage subsidence, fusion grade, or screw loosening between the PD and the Non-PD groups. Indirect decompression via OLIF for lumbar foraminal stenosis showed favorable outcomes. The use of interbody cages and posterior instrumentation was sufficient for relieving symptoms in patients with lumbar foraminal stenosis. Additional direct posterior decompression may deteriorate results in the follow-up period.
Ablation of cardiomyocyte-derived BDNF during development causes myocardial degeneration and heart failure in the adult mouse heart

Objective Brain-derived neurotrophic factor (BDNF) and its receptor TrkB-T1 were recently found to be expressed in cardiomyocytes. However, the functional role of cardiomyocyte-derived BDNF in heart pathophysiology is not yet fully known. Recent studies revealed that BDNF-TrkB pathway plays a critical role to maintain integrity of cardiac structure and function, cardiac pathology and regeneration of myocardial infarction (MI). Therefore, the BDNF-TrkB pathway may be a novel target for myocardial pathophysiology in the adult heart. Approach and results In the present study, we established a cardiomyocyte-derived BDNF conditional knockout mouse in which BDNF expression in developing cardiomyocytes is ablated under the control of the Myosin heavy chain 6 (MYH6) promoter. The results of the present study show that ablation of cardiomyocyte-derived BDNF during development does not impair survival, growth or reproduction; however, in the young adult heart, it causes cardiomyocyte death, degeneration of the myocardium, cardiomyocyte hypertrophy, left atrial appendage thrombosis, decreased cardiac function, increased cardiac inflammation and ROS activity, and metabolic disorders, leading to heart failure (HF) in the adult heart and eventually resulting in a decrease in the one-year survival rate. In addition, ablation of cardiomyocyte-derived BDNF during the developmental stage leads to exacerbation of cardiac dysfunction and poor regeneration after MI in adult hearts. Conclusion Cardiomyocyte-derived BDNF is irreplaceable for maintaining the integrity of cardiac structure and function in the adult heart and regeneration after MI. Therefore, the BDNF-TrkB pathway will be a novel target for myocardial pathophysiology in the adult heart.
Virus-to-prokaryote ratio in the Salar de Huasco and different ecosystems of the Southern hemisphere and its relationship with physicochemical and biological parameters

The virus-to-prokaryote ratio (VPR) has been used in many ecosystems to study the relationship between viruses and their hosts. While high VPR values indicate a high rate of prokaryotes' cell lysis, low values are interpreted as a decrease in or absence of viral activity. Salar de Huasco is a high-altitude wetland characterized by a rich microbial diversity associated with aquatic sites like springs, ponds, streams and a lagoon with variable physicochemical conditions. Samples from two ponds, Poza Rosada (PR) and Poza Verde (PV), were analyzed by epifluorescence microscopy to determine variability of viral and prokaryotic abundance and to calculate the VPR in a dry season. In addition, to put Salar de Huasco results into perspective, a compilation of research articles on viral and prokaryotic abundance, VPR, and metadata from various Southern hemisphere ecosystems was revised. The ecosystems were grouped into six categories: high-altitude wetlands, Pacific, Atlantic, Indian, and Southern Oceans and Antarctic lakes. Salar de Huasco ponds recorded similar VPR values (an average of 7.4 and 1.7 at PR and PV, respectively), ranging from 3.22 to 15.99 in PR. The VPR variability was associated with VA and chlorophyll a, when considering all data available for this ecosystem. In general, high-altitude wetlands recorded the highest VPR average (53.22 ± 95.09), followed by the Oceans, Southern (21.91 ± 25.72), Atlantic (19.57 ± 15.77) and Indian (13.43 ± 16.12), then Antarctic lakes (11.37 ± 15.82) and the Pacific Ocean (6.34 ± 3.79). Physicochemical variables, i.e., temperature, conductivity, nutrients (nitrate, ammonium, and phosphate) and chlorophyll a as a biological variable, were found to drive the VPR in the ecosystems analyzed. Thus, the viral activity in the Wetland followed similar trends of previous reports based on larger sets of metadata analyses. In total, this study highlights the importance of including viruses as a biological variable to study microbial temporal dynamics in wetlands considering their crucial role in the carbon budgets of these understudied ecosystems in the southern hemisphere.
Nonverbal synchrony in subjects with hearing impairment and their significant others

Introduction Hearing loss has a great impact on the people affected, their close partner and the interaction between both, as oral communication is restricted. Nonverbal communication, which expresses emotions and includes implicit information on interpersonal relationship, has rarely been studied in people with hearing impairment (PHI). In psychological settings, non-verbal synchrony of body movements in dyads is a reliable method to study interpersonal relationship. Material and methods A 10-min social interaction was videorecorded in 39 PHI (29 spouses and 10 parent-child dyads) and their significant others (SOs). Nonverbal synchrony, which means the nonverbal behaviors of two interacting persons (referring to both general synchrony and the role of leading) and verbal interaction (percentage of speech, frequency of repetitions, and queries) were analyzed by computer algorithms and observer ratings. Hearing-related quality of life, coping mechanisms, general psychopathology, quality of relationship, and burden of hearing loss experienced by SOs were assessed using questionnaires. Results In the 39 dyads, true nonverbal synchrony differed from pseudosynchrony [t(43.4) = 2.41; p = 0.02] with a medium effect size (d = 0.42). Gender of PHI had a significant effect on general synchrony (p = 0.025) and on leading by SOs (p = 0.017). Age gap correlated with synchronic movements (p = 0.047). Very short duration of hearing impairment was associated with lower nonverbal synchrony in the role of leading by SOs (p = 0.031). Feeling of closeness by PHI correlated negatively with the role of leading by SOs (p > 0.001) and feeling of closeness by SOs was positively associated with leading by PHI (p = 0.015). No correlation was detected between nonverbal synchrony and other questionnaires. Burden experienced by the SOs was higher in SOs who reported less closeness (p = 0.014). Discussion A longer hearing impairment leads to more nonverbal leading by SOs compared to PHI with very short duration of hearing loss, possibly because of the long-lasting imbalance in communication. If PHI felt more closeness, SOs led less and vice versa. Burden experienced by SOs negatively correlated with closeness reported by SOs. Use of nonverbal signals and communication might help to improve benefits of auditory rehabilitation for PHI and decrease burden experienced by SOs.
Antimicrobial susceptibility profiles and tentative epidemiological cutoff values of Legionella pneumophila from environmental water and soil sources in China

Legionnaires’ disease (LD), caused by Legionella, including the most prevalent Legionella pneumophila, has been treated primarily with antibiotics. Environmental water and soil are the reservoirs for L. pneumophila. Studying antimicrobial susceptibility using a large number of isolates from various environmental sources and regions could provide an unbiased result. In the present study, antimicrobial susceptibility of 1464 environmental L. pneumophila isolates that were derived from various environmental water and soil sources of 12 cities in China to rifampin (RIF), erythromycin (ERY), clarithromycin (CLA), azithromycin (AZI), ciprofloxacin (CIP), moxifloxacin (MOX), levofloxacin (LEV), and doxycycline (DOX) was investigated, and minimum inhibitory concentration (MIC) data were obtained. We show that regarding macrolides, ERY was least active (MIC90 = 0.5 mg/L), while CLA was most active (MIC90 = 0.063 mg/L). A total of three fluoroquinolones have similar MICs on L. pneumophila. Among these antimicrobials, RIF was the most active agent, while DOX was the most inactive one. We observed different susceptibility profiles between serogroup 1 (sg1) and sg2-15 or between water and soil isolates from different regions. The ECOFFs were ERY and AZI (0.5 mg/L), RIF (0.002 mg/L), CIP, CLA and MOX (0.125 mg/L), LEV (0.063 mg/), and DOX (32 mg/L). Overall, two fluoroquinolone-resistant environmental isolates (0.14%) were first documented based on the wild-type MIC distribution. Not all azithromycin-resistant isolates (44/46, 95.65%) harbored the lpeAB efflux pump. The MICs of the ERY and CLA on the lpeAB + isolates were not elevated. These results suggested that the lpeAB efflux pump might be only responsible for AZI resistance, and undiscovered AZI-specific resistant mechanisms exist in L. pneumophila. Based on the big MIC data obtained in the present study, the same defense strategies, particularly against both CLA and RIF, may exist in L. pneumophila. The results determined in our study will guide further research on antimicrobial resistance mechanisms of L. pneumophila and could be used as a reference for setting clinical breakpoints and discovering antimicrobial-resistant isolates in the clinic, contributing to the antibiotic choice in the treatment of LD.
Establishing the Interaction between the Romanticization… Establishing the Interaction between the Romanticization of Suicide and the Paradigmatic Shift in Nigeria’s Sociocultural Values

The sudden rise in the number of suicides in Nigeria especially among the youths has become a source of grave concern in recent times. While many Nigerians have attributed this to the poor economic situation in the country, though this is certainly a factor, it does not sufficiently explain the situation as the accomplished and upwardly mobile are also in the statistics of those who have taken their own lives. This exploratory qualitative work examined the theory of suicide from both psychological and sociological perspectives. The psychological perspective holds that the incidence of suicide is directly proportional to the rate of insanity while the sociological perspective states that the suicide rate is closely linked to the relationship between individuals and society. The author posited that neither of these perspectives standing alone can adequately explain why people kill themselves, but if put together, they can offer a more holistic explanation for suicide. The study went further to examine some preeminent sociocultural values that were embedded into the Nigerian culture such as hard work, integrity, a sense of family/community, respect for elders/authority, among others which now appear anachronistic. The paper attempted to establish that the forces of globalization have eroded many of these values, gradually leading to cultural extinction which in turn has led to an increase in the rate of suicides in Nigeria by romanticizing suicide as a desirable solution to most unpalatable situations. Some of the recommendations made include an urgent renaissance of Nigeria’s sociocultural values, indigenous languages should be spoken and taught both at home and in school, and mental health issues should be destigmatized. Citation: Establishing the interaction between the romanticization of suicide and the paradigmatic shift in Nigeria's sociocultural values. Taxation
Atmosphere-cryosphere interactions at 21 ka BP in the European Alps

Evidence that during the Last Glacial Maximum (LGM) glaciers extended well into the piedmont planes is still identifiable in the alpine foreland as a system of well-preserved moraines. Glaciers are strongly affected by temperature and precipitation and therefore they are excellent indicators of climate change. Here we use a regional climate model (RCM) to investigate the physical processes sustaining the glacier extent during the LGM. We find a predominance of convection during summer and increased southwesterly stratiform precipitation over the southern Alps compared to pre-industrial conditions. This precipitation pattern, along with lower temperatures, determined summer snowfall extending to low elevations with a consequent substantial drop of the equilibrium line altitude (ELA) consistent with the estimated LGM glacier extent. Our RCM based estimates of the ELA at the LGM yield excellent consistency with Alpine glacier reconstructions, further demonstrating the great potential of this technique for use in paleoclimate studies. Alpine region, providing new detailed and physically-based information on the Alpine glacier extent at the LGM and at pre-industrial coditions . Our reconstruction matches with geomorphological evidence and resolves for the first time some shortcomings that occurred in previous LGM glacier reconstructions based on ice-flow dynamics. Our method is based only on simulated temperature and precipitation and is independent of local characteristics of the glacier site (dust, avalanches), In agreemtn with available literature, our results show much drier and colder LGM conditions (−6.6 °C on average) than today over the Alpine region. Differences in precipitation regimes across the Alps were caused by the southward displacement of the North Atlantic storm track, temperature differences controlling convective phenomena, and frequent and persistent occurrence of cyclones and anticyclones. In particular, in the northern Alps, precipitation was sparse and weak, as the Atlantic storm track was located south of the Alps and was subject only to a small seasonal variability caused by the