Miracle-dz/UniFAR-FTUs huggingface dataset:
Corynoxine Protects Dopaminergic Neurons Through Inducing Autophagy and Diminishing Neuroinflammation in Rotenone-Induced Animal Models of Parkinson’s Disease

Recent studies have shown that impairment of autophagy is related to the pathogenesis of Parkinson’s disease (PD), and small molecular autophagy enhancers are suggested to be potential drug candidates against PD. Previous studies identified corynoxine (Cory), an oxindole alkaloid isolated from the Chinese herbal medicine Uncaria rhynchophylla (Miq.) Jacks, as a new autophagy enhancer that promoted the degradation of α-synuclein in a PD cell model. In this study, two different rotenone-induced animal models of PD, one involving the systemic administration of rotenone at a low dosage in mice and the other involving the infusion of rotenone stereotaxically into the substantia nigra pars compacta (SNpc) of rats, were employed to evaluate the neuroprotective effects of Cory. Cory was shown to exhibit neuroprotective effects in the two rotenone-induced models of PD by improving motor dysfunction, preventing tyrosine hydroxylase (TH)-positive neuronal loss, decreasing α-synuclein aggregates through the mechanistic target of the rapamycin (mTOR) pathway, and diminishing neuroinflammation. These results provide preclinical experimental evidence supporting the development of Cory into a potential delivery system for the treatment of PD.
Personal Metaphors as Motivational Resources: Boosting Anticipated Incentives and Feelings of Vitality Through a Personal Motto-Goal

Motto-goals describe a desired mind-set and provide a person with a guiding principle of how to approach a personal goal or obligation (e.g., with the inner strength of a bear I am forging ahead). We propose that motto-goals can be conceptionalized as individually created metaphors and that the figurative, metaphorical language and the characteristics of the formation process make them effective in changing the perception of unpleasant personal obligations as more inherently enjoyable and raise vitality levels. To test whether a newly devised minimalistic motto-goal intervention can make goal striving more attractive (stronger anticipation of activity related incentives) and energize goal-oriented action (increase vitality) in relation to an unpleasant obligation, two experimental studies were conducted. In Study 1 the motto-goal condition led to stronger anticipation of activity related incentives and vitality compared to a distraction task. The effect on vitality was partially mediated by a change in feelings of autonomy. Study 2 replicated the effects compared to a placebo intervention and further found motto-goals to be specifically effective in increasing the anticipation of activity related incentives as opposed to outcome related incentives. The results support that applying motto-goals built with a newly developed minimalist motto-goal intervention can influence the subjective experience of individuals faced with a previously unpleasant obligation.
Medication-Related Hospital Readmissions Within 30 Days of Discharge: Prevalence, Preventability, Type of Medication Errors and Risk Factors

Background: Hospital readmission rates are increasingly used as a measure of healthcare quality. Medicines are the most common therapeutic intervention but estimating the contribution of adverse drug events as a cause of readmissions is difficult. Objectives: To assess the prevalence and preventability of medication-related readmissions within 30 days after hospital discharge and to describe the risk factors, type of medication errors and types of medication involved in these preventable readmissions. Design: A cross-sectional observational study. Setting: The study took place across the cardiology, gastroenterology, internal medicine, neurology, psychiatry, pulmonology and general surgery departments in the OLVG teaching hospital, Netherlands. Participants: Patients with an unplanned readmission within 30 days after discharge from an earlier hospitalization (index hospitalization: IH) were reviewed. Measurements: The prevalence and preventability of medication-related readmissions were assessed by residents in multidisciplinary meetings. A senior internist and hospital pharmacist reassessed the prevalence and preventability of identified cases. Generalized estimating equation with logistic regression was performed to identify risk factors of potentially preventable medication-related readmissions. Results: Of 1,111 included readmissions, 181 (16%) were medication-related, of which 72 (40%) were potentially preventable. The number of medication changes at IH (Adjusted odds ratio [ORadj]: 1.14; 95% CI: 1.05–1.24) and having ≥3 hospitalizations 6 months before IH (ORadj: 2.11; 95% CI: 1.12–3.98) were risk factors of a preventable medication-related readmission. Of these preventable readmissions, 35% were due to prescribing errors, 35% by non-adherence and 30% by transition errors. Medications most frequently involved were diuretics and antidiabetics. Conclusion: This study shows that 16% of readmissions are medication-related, of which 40% are potentially preventable. If the results are confirmed in larger multicentre studies, this may indicate that more attention should be paid to medication-related harm in order to lower the overall readmission rates.
Blockade of TRPM7 Alleviates Chondrocyte Apoptosis and Articular Cartilage Damage in the Adjuvant Arthritis Rat Model Through Regulation of the Indian Hedgehog Signaling Pathway

Articular cartilage damage with subsequent impairment of joint function is a common feature of articular diseases, in particular, rheumatoid arthritis and osteoarthritis. While articular cartilage injury mediated by chondrocyte apoptosis is a known major pathological feature of arthritis, the specific mechanisms remain unclear at present. Transient receptor potential melastatin-like seven channel (TRPM7) is reported to play an important regulatory role in apoptosis. This study focused on the effects of TRPM7 on arthritic chondrocyte injury and its underlying mechanisms of action. Sodium nitroprusside (SNP)-induced rat primary chondrocyte apoptosis and rat adjuvant arthritis (AA) were used as in vitro and in vivo models, respectively. Blockage of TRPM7 with 2-APB or specific siRNA resulted in increased chondrocyte viability and reduced toxicity of SNP. Moreover, treatment with 2-APB enhanced the Bcl-2/Bax ratio and reduced cleaved PARP and IL-6, MMP-13 and ADAMTS-5 expression in SNP-treated chondrocytes. Activation of Indian Hedgehog with purmorphamine reversed the protective effects of 2-APB on SNP-induced chondrocyte apoptosis. Blockage of TRPM7 with 2-APB relieved the clinical signs of AA in the rat model and reduced the arthritis score and paw swelling. Similar to findings in SNP-treated chondrocytes, 2-APB treatment increased the Bcl-2/Bax ratio and suppressed cleaved PARP, IL-6, MMP-13, ADAMTS-5, TRPM7, and Indian hedgehog expression in articular cartilage of AA rats. Our collective findings suggest that blockade of TRPM7 could effectively reduce chondrocyte apoptosis and articular cartilage damage in rats with adjuvant arthritis through regulation of the Indian Hedgehog signaling pathway.
Case Report: Blurred Vision and Eruptive Nevi - Bilateral Diffuse Uveal Melanocytic Proliferation With Mucocutaneous Involvement in a Lung Cancer Patient

We describe a case of a 65-year old patient presenting with unusual mucocutaneous melanocytic proliferations of a Bilateral Diffuse Uveal Melanocytic Proliferation (BDUMP) imitating a multifocal melanoma in situ, which improved dramatically after plasmapheresis. The patient first presented at the dermatology department due to rapidly evolving brown and black macules on the glans penis. Further skin involvement of the perineal and perianal region, mamillae and oral mucosa was stated. Histology from a penile biopsy was compatible with a melanoma in situ. Due to the distribution pattern and elevated serum tumor marker S100B, metastatic melanoma was considered. Staging examinations using PET-CT scan however, revealed a lung tumor, later confirmed as a Non-small-cell lung cancer (NSCLC). Primary radio chemotherapy was initiated to treat NSCLC. Shortly after initiation of radio chemotherapy the patient developed massive vision impairment and a NSCLC-associated BDUMP was diagnosed which led to the correct classification of melanocytic skin lesions as mucocutaneous BDUMP manifestation. Plasmapheresis was started resulting in a rapid improvement of vision starting ten days after the first plasmapheresis. In contrast skin manifestations started to disappear with a marked delay 4 months after the last plasmapheresis cycle. This case highlights the importance of memorizing multiple rapidly progressing melanocytic skin and/or mucous membrane spots together with visual impairment as a possible paraneoplastic BDUMP that needs a fundamentally different therapeutic approach compared to multifocal melanoma in situ. What is already known about this topic? Bilateral Diffuse Uveal Melanocytic Proliferation (BDUMP) is a paraneoplastic syndrome with melanocytic uveal proliferation leading to vision impairment. Extraocular manifestation is rare, mainly affect the subepidermal compartment and is hard to treat. Plasmapheresis has been shown to be an effective treatment mainly for vision improvement in some but not all cases. What does this study add? Our BDUMP case with widespread skin and mucosal involvement initially mimicked a multifocal melanoma in situ and showed an excellent treatment response to plasmapheresis. Improvement of mucocutaneous lesions has not been documented well in the literature so far. We show a more than one year lasting follow up still underlining the beneficial effect of plasmapheresis in this case. In-vitro data supports the hypothesis that plasma exchange eliminates a “Cultured melanocyte elongation and proliferation (CMEP)” factor out of patient blood leading to decreased melanocyte proliferation shown numerically in-vitro and clinically in-vivo. Our case clearly indicates that before establishing a definite diagnosis and therapy in patients with rapidly evolving melanocytic skin and/or mucosal lesions BDUMP mimicking multifocal melanoma in situ should be considered making a thorough diagnostic workup mandatory.
Decreased Treg Cell and TCR Expansion Are Involved in Long-Lasting Graves’ Disease

Graves’ disease (GD) is a T cell-mediated organ-specific autoimmune disorder. GD patients who have taken anti-thyroid drugs (ATDs) for more than 5 years with positive anti-thyroid stimulating hormone receptor autoantibodies value were defined as persistent GD (pGD). To develop novel immunotherapies for pGD, we investigated the role of T cells in the long-lasting phase of GD. Clinical characteristics were compared between the pGD and newly diagnosed GD (nGD) (N = 20 respectively). Flow cytometric analysis was utilized to determine the proportions of Treg and Th17 cells (pGD, N = 12; nGD, N = 14). T cell receptor sequencing (TCR-seq) and RNA sequencing (RNA-seq) were also performed (pGD, N = 13; nGD, N = 20). Flow cytometric analysis identified lower proportions of Th17 and Treg cells in pGD than in nGD (P = 0.0306 and P = 0.0223). TCR-seq analysis revealed a lower diversity (P = 0.0025) in pGD. Specifically, marked clonal expansion, represented by an increased percentage of top V-J recombination, was observed in pGD patients. Interestingly, pGD patients showed more public T cell clonotypes than nGD patients (2,741 versus 966). Meanwhile, RNA-seq analysis revealed upregulation of the inflammation and chemotaxis pathways in pGD. Specifically, the expression of pro-inflammatory and chemotactic genes (IL1B, IL13, IL8, and CCL4) was increased in pGD, whereas Th17 and Treg cells associated genes (RORC, CARD9, STAT5A, and SATB1) decreased in pGD. Additionally, TCR diversity was negatively correlated with the expression of pro-inflammatory or chemotactic genes (FASLG, IL18R1, CCL24, and CCL14). These results indicated that Treg dysregulation and the expansion of pathogenic T cell clones might be involved in the long-lasting phase of GD via upregulating chemotaxis or inflammation response. To improve the treatment of pGD patients, ATDs combined therapies, especially those aimed at improving Treg cell frequencies or targeting specific expanded pathogenic TCR clones, are worth exploring in the future.
Biochemical Profiling for Antioxidant and Therapeutic Potential of Pakistani Chickpea (Cicer arietinum L.) Genetic Resource

In Pakistan, chickpeas (Cicer arietinum L.) are the largest grown legume crops, especially in desert areas. Along with an excellent source of nutrition, chickpea seeds have discernible medicinal and antioxidant characteristics. The diverse set of 90 chickpea genotypes (66 desi and 24 kabuli) were collected from different research zones in Pakistan, and seed flour was used for biochemical profiling. Genotypes were significantly different (Tukey HSD test, P < 0.05) for the traits under investigation. In non-enzymatic antioxidants, highest seed total phenolic contents (TPC) (34725 ± 275 μM/g s. wt.) was found in CM-98 (desi), ascorbic acid (AsA) (69.23 ± 2.25 μg/g s. wt.) in WH-3 (desi), and total flavonoid content (TFC) (394.98 ± 13.06 μg/mL sample) was detected in WH-11 (desi). In the class of enzymatic antioxidants, the highest seed ascorbate peroxidase (APX) (1680 ± 40 Units/g s. wt.) was detected in Tamman-2013 (kabuli), peroxidases (POD) (2564.10 ± 233.10 Units/g s. wt.) activity in CM1235/08 (desi), and superoxide dismutase (SOD) (279.76 ± 50 Units/g s. wt.) was detected in CH24/11 (desi). Highest seed catalase activity (CAT) (893 ± 50 Units/g s. wt.) and proline content (272.50 ± 20.82 μg/g s. wt.) was detected in an ICC-4951 (desi). In hydrolytic enzymes, the highest activity of esterase (37.05 μM/min/g s. wt) was found in, CH56/09(Kabuli), protease (11080 ± 10 Units/g s. wt.) in Karak-2 (desi), and α-amylase (213.02 ± 3.20 mg/g s. wt.) was observed in CH74/08 (kabuli). In other biochemical parameters, the highest seed total oxidant status (TOS) (356 ± 17.50 μM/g s. wt.) was detected in CM3457/91 (desi); malondialdehyde (MDA) content (295.74 ± 3.097 uM/g s. wt.) was observed in CM-2008 (kabuli), and total antioxidant capacity (TAC) (8.36 ± 0.082 μM/g s. wt.) was found in CM-72 (desi). In case of pigment analysis, Sheenghar-2000 (desi) depicted highest lycopene (12.579 ± 0.313 μg/g s. wt.) and total carotenoids (58.430.23 ± 0.569 μg/g s. wt.) contents. For seed therapeutic potential, the highest seed α-amylase inhibition (82.33 ± 8.06%) was observed in CM-88 (desi), while WH-1, WH-6, and ICCV-96030 (desi) depicted the highest value for seed anti-inflammatory potential (78.88 ± 0.55%). Genotypes with the highest antioxidant and therapeutic potential can be utilized as a natural antioxidant source and in breeding programs aimed at improving these traits in new breeding lines.
Similar Pain Intensity Reductions and Trunk Strength Improvements Following Whole-Body Electromyostimulation vs. Whole-Body Vibration vs. Conventional Back-Strengthening Training in Chronic Non-specific Low Back Pain Patients: A Three-Armed Randomized Controlled Trial

The aim of this multicenter trial was to compare the effects of whole-body electromyostimulation (WB-EMS) and whole-body vibration (WBV) with conventional back-strengthening training (CT) on changes in mean back pain intensity (MPI) and trunk strength in patients suffering from chronic non-specific low back pain (CNLBP). Two-hundred and forty CNLBP patients (40–70 years; 62% female) were randomly assigned to three intervention arms (WB-EMS: n = 80 vs. WBV: n = 80 vs. CT: n = 80). All training intervention programs were performed for 12 weeks in their usual commercial training setting. Before and during the last 4 weeks of the intervention, MPI was recorded using a 4-week pain diary. Additionally, maximal isometric trunk extension and -flexion strength was assessed on the BackCheck® machine. A moderate but significant decrease of MPI was observed in all groups (WB-EMS: 29.7 ± 39.1% (SMD 0.50) vs. WBV: 30.3 ± 39.3% (SMD 0.57) vs. CT: 30.5 ± 39.6% (SMD 0.59); p < 0.001). Similar findings were observed for maximal isometric strength parameters with a significant increase in all groups (extension: WB-EMS: 17.1 ± 25.5% vs. WBV: 16.2 ± 23.6% vs. CT: 21.6 ± 27.5%; p < 0.001; flexion: WB-EMS: 13.3 ± 25.6% vs. WBV: 13.9 ± 24.0% vs. CT: 13.9 ± 25.4%; p < 0.001). No significant interaction effects for MPI (p = 0.920) and strength parameters (extension: p = 0.436; flexion: p = 0.937) were observed. WB-EMS, WBV, and CT are comparably effective in improving MPI and trunk strength. However, training volume of WB-EMS was 43 or 62% lower, compared with CT and WBV.
An ω-3, but Not an ω-6 Polyunsaturated Fatty Acid Decreases Membrane Dipole Potential and Stimulates Endo-Lysosomal Escape of Penetratin

Although the largely positive intramembrane dipole potential (DP) may substantially influence the function of transmembrane proteins, its investigation is deeply hampered by the lack of measurement techniques suitable for high-throughput examination of living cells. Here, we describe a novel emission ratiometric flow cytometry method based on F66, a 3-hydroxiflavon derivative, and demonstrate that 6-ketocholestanol, cholesterol and 7-dehydrocholesterol, saturated stearic acid (SA) and ω-6 γ-linolenic acid (GLA) increase, while ω-3 α-linolenic acid (ALA) decreases the DP. These changes do not correlate with alterations in cell viability or membrane fluidity. Pretreatment with ALA counteracts, while SA or GLA enhances cholesterol-induced DP elevations. Furthermore, ALA (but not SA or GLA) increases endo-lysosomal escape of penetratin, a cell-penetrating peptide. In summary, we have developed a novel method to measure DP in large quantities of individual living cells and propose ALA as a physiological DP lowering agent facilitating cytoplasmic entry of penetratin.
Population-Based Comparison of Different Risk Stratification Systems Among Prostate Cancer Patients

Background It is not known which risk stratification system has the best discrimination ability for predicting prostate cancer death. Methods We identified patients with non-metastatic primary prostate adenocarcinoma diagnosis between 2004 and 2015 using the Surveillance, Epidemiology, and End Results database. Patients were categorized in different risk groups using the three frequently used risk stratification systems of the National Comprehensive Cancer Network guideline (NCCN-g), American Urological Association guideline (AUA-g), and European Association of Urology guideline (EAU-g), respectively. Associations between risk classification and prostate cancer-specific mortality (PCSM) were determined using Kaplan–Meier analyses and multivariable regression with Cox proportional hazards model. Area under the receiver operating characteristics curve (AUC) analyses were used to test the discrimination ability of the three risk grouping systems. Results We analyzed 310,062 patients with a median follow-up of 61 months. A total of 36,368 deaths occurred, including 6,033 prostate cancer deaths. For all the three risk stratification systems, the risk groups were significantly associated with PCSM. The AUC of the model relying on NCCN-g, AUA-g, and EAU-g risk stratification systems for PCSM at specifically 8 years were 0.818, 0.793, and 0.689 in the entire population; 0.819, 0.795, and 0.691 in Whites; 0.802, 0.777, and 0.681 in Blacks; 0.862, 0.818, and 0.714 in Asians; 0.845, 0.806, and 0.728 in Chinese patients. Regardless of the age, marital status, socioeconomic status, and treatment modality, AUC of the model relying on NCCN-g and AUA-g for PCSM was greater than that relying on EAU-g; AUC of the model relying on NCCN-g system was greater than that of the AUA-g system. Conclusions The NCCN-g and AUA-g risk stratification systems perform better in discriminating PCSM compared to the EAU-g system. The discrimination ability of the NCCN-g system was better than that of the AUA-g system. It is recommended to use NCCN-g to evaluate risk groups for prostate cancer patients and then provide more appropriate corresponding treatment recommendations.
Measuring Consumer Engagement in Omnichannel Retailing: The Mobile In-Store Experience (MIX) Index

We draw insights from Activity Theory within the field of human-computer interaction to quantitatively measure a mobile in-store experience (MIX), which includes the suite of shopping activities and retail services that a consumer can engage in when using their mobile device in brick-and-mortar stores. We developed and validated a nine-item, formative MIX index using survey data collected from fashion consumers in the United States (n = 1,267), United Kingdom (n = 370), Germany (n = 362), and France (n = 219). As survey measures of consumer engagement in omnichannel retailing using a mobile device, the index items with stronger factor loadings described in-store shopping activities whereas those with weaker factor loadings described activities related to behavioral targeting and social networking. These results suggest that retailers should give consumers the autonomy to independently find, evaluate and purchase merchandise in brick-and-mortar stores, thereby enabling them to co-create personalized shopping experiences as active participants within an omnichannel retail servicescape. Our findings also suggest that retailers should provide consumers with more authentic ways to build community and brand affiliations than mobile marketing and social media promotions. In-store activities should not simply be a migration of pre-existing e-commerce capabilities onto mobile devices. An engaging mobile in-store experience should be an amalgam of physical and digital activities that produce a seamless shopping journey and leverage the unique properties of mobile devices – ultra-portability, location sensitivity, untetheredness, and personalization. Retail executives can use the validated MIX index to prepare strategic investments in mobile technology applications and capabilities for retail stores within their omnichannel operations. The nine-item MIX index is also well-suited for consumer surveys, which also makes it an attractive measure of consumer engagement in omnichannel retailing for future academic research.
Brain Density Clustering Analysis: A New Approach to Brain Functional Dynamics

Background A number of studies in recent years have explored whole-brain dynamic connectivity using pairwise approaches. There has been less focus on trying to analyze brain dynamics in higher dimensions over time. Methods We introduce a new approach that analyzes time series trajectories to identify high traffic nodes in a high dimensional space. First, functional magnetic resonance imaging (fMRI) data are decomposed using spatial ICA to a set of maps and their associated time series. Next, density is calculated for each time point and high-density points are clustered to identify a small set of high traffic nodes. We validated our method using simulations and then implemented it on a real data set. Results We present a novel approach that captures dynamics within a high dimensional space and also does not use any windowing in contrast to many existing approaches. The approach enables one to characterize and study the time series in a potentially high dimensional space, rather than looking at each component pair separately. Our results show that schizophrenia patients have a lower dynamism compared to healthy controls. In addition, we find patients spend more time in nodes associated with the default mode network and less time in components strongly correlated with auditory and sensorimotor regions. Interestingly, we also found that subjects oscillate between state pairs that show opposite spatial maps, suggesting an oscillatory pattern. Conclusion Our proposed method provides a novel approach to analyze the data in its native high dimensional space and can possibly provide new information that is undetectable using other methods.