Miracle-dz/UniFAR-FTUs huggingface dataset:
Evaluation of structural valve deterioration and bioprosthetic valve failure utilizing the new European consensus definition in patients undergoing TAVI with first-generation devices: Outcomes beyond 5 years from a single center in Turkey.

OBJECTIVE The long-term durability of transcatheter aortic bioprosthetic valves continues to be a major concern. Standardized criteria of the structural valve deterioration (SVD) and bioprosthetic valve failure (BVF) have recently been defined. Limited studies have evaluated the long-term durability of transcatheter aortic valve implantation (TAVI) according to these new definitions. We aim to analyze the durability of TAVI beyond 5 years and to report the frequency of SVD and BVF. METHODS A total of 89 patients who had undergone TAVI and had theoretically completed at least 5 years after the procedure were included. Either a Medtronic CoreValve or an Edwards SAPIEN XT valve were implanted in the patients. New standardized definitions were used to evaluate SVD and BVF. RESULTS The mean age of the patients was 78.70±6.95 years. SVD occured in 4 (4.5%) patients during 6 years of follow-up. Severe SVD was observed in 2 patients (2.2%), and these patients had the New York Heart Association class II symptoms. Both patients with severe SVD also met the criteria of BVF. Moderate SVD was observed in 2 patients (2.2%), and these patients had no valve-related symptoms. Of the 4 SVD cases, 2 were associated with increased mean transaortic gradients, whereas the remaining 2 cases were associated with intraprosthetic aortic regurgitation. All patients with SVD are still alive, and none of them have required aortic valve reintervention. CONCLUSION Although first-generation TAVI devices were used, we determined the low rate of SVD and BVF at the 6-year follow-up. It may be suggested that there is no major concern associated with TAVI even with first-generation devices regarding long-term durability.
Bacterial lysis, autophagy and innate immune responses during adjunctive phage therapy in a child

Adjunctive phage therapy was used in an attempt to avoid catastrophic outcomes from extensive chronic Pseudomonas aeruginosa osteoarticular infection in a 7‐year‐old child. Monitoring of phage and bacterial kinetics allowed real‐time phage dose adjustment, and along with markers of the human host response, indicated a significant therapeutic effect within two weeks of starting adjunctive phage therapy. These findings strongly suggested the release of bacterial cells or cell fragments into the bloodstream from deep bony infection sites early in treatment. This was associated with transient fever and local pain and with evidence of marked upregulation of innate immunity genes in the host transcriptome. Adaptive immune responses appeared to develop after a week of therapy and some immunomodulatory elements were also observed to be upregulated.
Respiratory Nurses Have Positive Attitudes But Lack Confidence in Advance Care Planning for Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (COPD) is a progressive, life-limiting illness. Despite significant symptom burden, access to advance care planning (ACP) and palliative care are limited. Early initiation of ACP enables patients to articulate the values that underpin the decisions they would make if, in the future, they are unable to speak for themselves. Nurses constitute the majority of health care workforce and are well placed to initiate these discussions. This study explored knowledge, attitudes, and practice regarding ACP for patients with COPD among Australian and New Zealand respiratory nurses. A cross-sectional online survey tested knowledge about ACP and canvassed attitudes about current practice. Data were analyzed using descriptive statistics and content analysis of text data. The 112 participating respiratory nurses had substantial knowledge and positive attitudes regarding ACP in COPD; however, they lacked confidence and clarity regarding their role. Despite advances in end-of-life care provision for chronic disease, well-established barriers remained (inadequate training, fear of distressing patients, and time), and discussion triggers were still linked to acute deterioration, diagnosis of severe disease, and patient initiation. Better articulating the role of the respiratory nurse in ACP and building capacity and confidence within this workforce may improve ACP access for people living with COPD.
A Super-Resolved View of the Alzheimer’s Disease-Related Amyloidogenic Pathway in Hippocampal Neurons

Background: Processing of the amyloid-β protein precursor (AβPP) is neurophysiologically important due to the resulting fragments that regulate synapse biology, as well as potentially harmful due to generation of the 42 amino acid long amyloid β-peptide (Aβ42), which is a key player in Alzheimer’s disease. Objective: Our aim was to clarify the subcellular locations of the fragments involved in the amyloidogenic pathway in primary neurons with a focus on Aβ42 and its immediate substrate AβPP C-terminal fragment (APP-CTF). To overcome the difficulties of resolving these compartments due to their small size, we used super-resolution microscopy. Methods: Mouse primary hippocampal neurons were immunolabelled and imaged by stimulated emission depletion (STED) microscopy, including three-dimensional three-channel imaging, and quantitative image analyses. Results: The first (β-secretase) and second (γ-secretase) cleavages of AβPP were localized to functionally and distally distinct compartments. The β-secretase cleavage was observed in early endosomes in soma, where we were able to show that the liberated N- and C-terminal fragments were sorted into distinct vesicles budding from the early endosomes. Lack of colocalization of Aβ42 and APP-CTF in soma suggested that γ-secretase cleavage occurs in neurites. Indeed, APP-CTF was, in line with Aβ42 in our previous study, enriched in the presynapse but absent from the postsynapse. In contrast, full-length AβPP was not detected in either the pre- or the postsynaptic side of the synapse. Furthermore, we observed that endogenously produced and endocytosed Aβ42 were localized in different compartments. Conclusion: These findings provide critical super-resolved insight into amyloidogenic AβPP processing in primary neurons.
Emulating an RCT in observational research in chest trauma: The target trial approach

BACKGROUND While the concept of a “target trial”—optimizing the quality of observational studies by attempting to emulate the ideal world conditions of a randomized controlled trial—was first expounded over a decade ago, the take up of this concept in the design and analysis of trials in trauma is lacking. The target trial approach avoids common errors in observational research to increase its scientific validity as well as potentially enable causal questions to be answered without the expense and intricacies of a randomized controlled trial. This review article briefly introduces the reader to the concepts and utility of a “target trial” approach before providing demonstrations of its application in the subject area of chest trauma. METHODS Four articles published in the last 5 years—two case control and two cohort studies—are chosen and considered in terms of their causal question; study population; inclusion and exclusion criteria; designation of time 0; clarity of the follow-up period; study outcomes; methods to minimize confounding; results; overall issues regarding study time; and the presence of avoidable errors such as introduction of immortal time bias or information bias. RESULTS Two of the studies had an unclear causal question; none of the studies designated a time 0; the follow-up period was unclear for all but one of the studies; and one study had a serious issue with information bias resulting from differential misclassification. CONCLUSION Failure to emulate a “target trial” framework may lead to serious methodologic issues in observational research. Expansion of the awareness of this approach in trauma literature will improve the quality of our observational research and potentially translate into significant benefits for our patients.
Streblus asper attenuates alloxan-induced diabetes in rats and demonstrates antioxidant and cytotoxic effects

Abstract Context Streblus asper Lour. (Moraceae) is used for the treatment of different ailments, including diabetes, and requires scientific validation. Objective The study evaluates antidiabetic effects, antioxidant potential, and cytotoxicity of leaf and bark extracts of S. asper. Materials and methods Antidiabetic effects were assessed by inducing diabetes in Wistar albino rats (n = 5, six groups included 30 rats) by injecting alloxan [0.25 mg/kg body weight (bw)] intraperitoneally, and efficacy of methanol extracts of leaf and bark, and aqueous extract of leaves were evaluated by oral administration of 300 mg/kg bw of extracts for 3 weeks. Glibenclamide (Dibenol™) was used as a control (10 mg/kg bw). Antioxidant properties were examined by DPPH free radical scavenging activity, and cytotoxicity was investigated using a brine shrimp lethality assay. Results Methanol extracts of leaves and bark, and the aqueous extract of leaves of S. asper, caused significant reductions in blood glucose levels in diabetic rats of 36.83, 70.33, and 52.71%, respectively, after 21 days of treatment. IC50 values in DPPH radical scavenging assessment for those extracts were 58.92, 88.54, and 111.36 µg/mL, respectively. LC50 values for brine shrimp lethality for the extracts were 173.80, 32.36, and 3235.9 µg/mL, respectively. Discussion and conclusions The methanol bark extract of S. asper showed significant antidiabetic activity. This study will significantly contribute to establishing the plant as an alternative medicinal resource for rural populations of Bangladesh and provides an opportunity for further research to identify the primary active compound(s) and establish new drug candidates.
Hypothalamic‐Pituitary‐Adrenal Activity in Adverse Events Reporting After Placebo Administration

Participants of clinical trials who receive a placebo treatment often report a variety of adverse events, sometimes called nocebo effects. The reason why these adverse events occur is not clear, and understanding the underlying mechanisms represents a challenge that is likely to improve the interpretation of clinical trials as well as medical practice. Here, we studied 192 healthy subjects who received placebo oxygen through a mask after reading (READ) or not reading (NO‐READ) a list of possible adverse events of oxygen breathing: headache, chest pain, abdominal pain, and cough. The whole hypothalamus‐pituitary‐adrenal axis was assessed just before and right after placebo breathing by measuring the hypothalamic corticotropin‐releasing hormone (CRH), pituitary adrenocorticotropic hormone (ACTH), and adrenal cortisol (COR). In addition, both state and trait anxiety were assessed. We found that 64.5% of the NO‐READ group reported no adverse events, 30.2% had one, and only 5.2% had two adverse events. In contrast, only 20.8% of the READ group reported no adverse events, whereas 1, 2, 3, and 4 adverse events were reported with a frequency of 21.8%, 19.8%, 19.8%, and 17.7%, respectively. In addition, when the READ group reported three and four adverse events, CRH, ACTH, and COR were significantly increased compared to the NO‐READ group, along with an increase in state anxiety scores. These data indicate that hypothalamic‐pituitary‐adrenal activity and state anxiety are increased in those subjects who report many adverse events after reading a list of adverse events, thus highlighting a possible neuroendocrine mechanism after placebo administration.
YouTube as a platform for knowledge and awareness of peritoneal dialysis: A content analysis

Background: One of the main barriers to choosing peritoneal dialysis (PD) is the lack of awareness and PD knowledge. There is an increasing trend in the use of the internet as a search tool for health-related information. This study aims to determine how useful YouTube videos are to get information about PD. Methods: YouTube videos were evaluated independently by two nephrologists. The videos’ quality was assessed with DISCERN scoring system, global quality score (GQS) and the Journal of the American Medical Association (JAMA) scoring system. We determined the quartile (Q) of the videos as follows: most reliable top 25% videos Q1 and others Q2–4. Results: A total of 295 videos were evaluated. University or society-sourced videos made up 15% (n = 43) of all videos, and healthcare providers were the primary target audience compared to patients (p < 0.001). JAMA, GQS and DISCERN scores were significantly higher for the videos that were targeted healthcare providers compared to the patients (p < 0.001, for all). A total of 34% of the videos in Q1 were obtained from the university or society. Nevertheless, only 17% of the videos prepared for the patients were among the Q1. A small number of videos mentioned that PD maintains the residual kidney function (RKF) longer compared to haemodialysis. Conclusions: Universities and societies should upload videos to provide easy-to-understand information on PD. Also, the important benefits of PD, like the preservation of RKF, should be further highlighted in these videos. It may increase the PD penetrance by increasing patients’ awareness.
Applying Kurtosis as an Indirect Metric of Noise Temporal Structure in the Assessment of Hearing Loss Associated With Occupational Complex Noise Exposure

Objective: The association of occupational noise-induced hearing loss (NIHL) with noise energy was well documented, but the relationship between occupational noise and noise temporal structure is rarely reported. The objective of this study was to investigate the principal characteristics of the relationship between occupational NIHL and the temporal structure of noise. Methods: Audiometric and shift-long noise exposure data were collected from 3102 Chinese manufacturing workers from six typical industries through a cross-sectional survey. In data analysis, A-weighted 8-h equivalent SPL (LAeq.8h), peak SPL, and cumulative noise exposure (CNE) were used as noise energy indicators, while kurtosis (β) was used as the indicator of noise temporal structure. Two NIHL were defined: (1) high-frequency noise-induced hearing loss (HFNIHL) and (2) noise-induced permanent threshold shift at test frequencies of 3, 4, and 6 kHz (noise-induced permanent threshold shift [NIPTS346]). The noise characteristics of different types of work and the relationship between these characteristics and the prevalence of NIHL were analyzed. Results: The noise waveform shape, with a specific noise kurtosis, was unique to each type of work. Approximately 27.92% of manufacturing workers suffered from HFNIHL, with a mean NIPTS346 of 24.16 ± 14.13 dB HL. The Spearman correlation analysis showed that the kurtosis value was significantly correlated with the difference of peak SPL minus its LAeq.8h across different types of work (p < 0.01). For a kurtosis-adjusted CNE, the linear regression equation between HFNIHL% and CNE for complex noise almost overlapped with Gaussian noise. Binary logistic regression analysis showed that LAeq.8h, kurtosis, and exposure duration were the key factors influencing HFNIHL% (p < 0.01). The notching extent in NIPTS at 4 kHz became deeper with the increase in LAeq.8h and kurtosis. HFNIHL% increased most rapidly during the first 10 years of exposure. HFNIHL% with β ≥ 10 was significantly higher than that with β < 10 (p < 0.05), and it increased with increasing kurtosis across different CNE or LAeq.8h levels. When LAeq.8h was 80 to 85 dB(A), the HFNIHL% at β ≥ 100 was significantly higher than that at 10 ≤ β < 100 or β < 10 (p < 0.05 and p < 0.01, respectively). Conclusions: In the evaluation of hearing loss caused by complex noise, not only noise energy but also the temporal structure of noise must be considered. Kurtosis of noise is an indirect metric that is sensitive to the presence of impulsive components in complex noise exposure, and thus, it could be useful for quantifying the risk for NIHL. It is necessary to re-evaluate the safety of permissible exposure limit of 85 dB(A) as noise with a high kurtosis value can aggravate or accelerate early NIHL.
Oxidative stress and schizophrenia: A comparative cross‐sectional study of multiple oxidative markers in patients and their first‐degree relatives

Schizophrenia (SCZ) is a chronic, disruptive mental disorder with unknown pathogenic mechanisms. Several studies evidenced that oxidative stress (OS) may be one of the causal factors to play a role in the pathophysiology of the disease. Our study aims to contribute to the SCZ research by investigating a possible relationship between the severity of illness (scored with “The Positive and Negative Syndrome Scale [PANSS]”) and OS biomarkers in patients. We additionally assess the “first‐degree‐relatives (FDRs)” oxidative status with multiple parameters to test the idea of oxidative imbalance leads to disease progression as a genetical susceptibility factor.
Pseudopodium enriched atypical kinase 1(PEAK1) promotes invasion and of melanoma cells by activating JAK/STAT3 signals

ABSTRACT Pseudopodium enriched atypical kinase 1(PEAK1) is a non-receptor tyrosine kinase, which is enriched in the pseudopodia of migrating cells and plays an important role in regulating cell migration and proliferation. In the study, we investigate the therapeutic effect of PEAK1 on melanoma cells in vitro and in vivo. We used a lentiviral vector to express short hairpin RNAs (Lv-PEAK1 shRNA) for inhibiting PEAK1 expression in the melanoma SKMEL28 cells. A full-length PEAK1 gene was cloned into the pcDNA 3.1 (+) plasmid and used to infect the melanoma SKMEL19 cells. P6 (also known as Pyridines 6, EMD Chemicals), the Pan-JAK inhibitor, was used to inhibit the Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) pathway. The cell counting kit-8 (CCK-8), colony formation assay and transwell assay were used to detect cell proliferation, growth and invasion in vitro. The effect of PEAK1 on melanoma progression in vivo was also evaluated. Protein expression of PEAK1, E-cadherin, vimentin and JAK/STAT3 was measured using western blot assay or immunohistochemistry. The results showed that enforced PEAK1 expression facilitated melanoma cell growth, invasion and metastasis via activating JAK/STAT3 signals, and PEAK1 knockdown inhibited melanoma cell growth, invasion and metastasis via inactivating JAK/STAT3 signals. Further work demonstrated that P6 (500 nM) treatment reversed PEAK1-induced effect in melanoma cells. PEAK1 promotes tumorigenesis and metastasis via activating JAK/STAT3 signals, and PEAK1 knockdown reduced tumorigenesis and metastasis in melanoma via inactivating JAK/STAT3 signals, providing a novel therapeutic strategy for melanoma treatment.
The Influence of Substance Use on Side Effects of Olanzapine, Quetiapine, Risperidone, and Ziprasidone in Psychosis

Abstract Background Side effects restrict the optimal use of antipsychotics. Little is known about the influence of substance use on side effects. The aim of this study was to compare antipsychotic side effects in patients with psychosis with and without substance use, while also taking medication history and diagnosis into consideration. Methods All patients (n = 226, mean age 34, females 33%) diagnosed with schizophrenia spectrum disorders (SSD; F20–F29) or other psychosis (F30-F32; F10-F19), were treated with olanzapine, quetiapine, risperidone or ziprasidone, and were assessed at baseline, 4-weeks, 14-weeks, and 27-weeks. The UKU-Side Effects Self-Rating Scale version was used to evaluate the side effect profiles, and the information on substance use was based on the Clinician Drug Use Scale. Results At baseline, 30% of the patients used substances, 54% were diagnosed with SSD, and 47% were antipsychotic naïve. The occurrence of side effects in total was not different in patients with substance use compared to without after 4-weeks of treatment, nor in the follow-up period. At 4-weeks there were some group differences in relation to substance use, diagnosis, and medication history for single side effects. Patients with substance use showed more increased dream activity, less reduced salivation, and more gynecomastia. Patients with SSD showed less neurological side effects, orgasm dysfunction, and tension/inner unrest. The medication naïve patients showed increased hypokinesia/akinesia. Conclusion Substance use alone does not influence the general magnitude of side effects of antipsychotic medication and does not indicate a different prescription practice in patients with psychosis and substance use.
Dietary supplementation with mung bean coat alleviates the disorders in serum glucose and lipid profile and modulates gut microbiota in high-fat diet and streptozotocin-induced prediabetic mice.

As amajor by-product of mung bean processing, mung bean coat (MBC), which is rich in polyphenols and dietary fiber, is deemed to be mainly responsible for the health benefits of mung bean. However, its beneficial effects on the hyperglycemia, hyperlipidemia, and gut microbiota composition in prediabetic mice is not fully understood. The objective of this study was to investigate the efficacy of MBC in alleviating high-fat diet and streptozotocin-induced prediabetes. Herein, compared with the model control, dietary supplementation with MBC (3%, w/w) for 12 weeks significantly decreased the fasting blood glucose (24.60%), total cholesterol (15.72%), triglyceride (14.41%), and low-density lipoprotein cholesterol (22.45%). Furthermore, the improvements in glucose tolerance were reflected in the reduction of the area under the curve (AUC) and incremental AUC by approximately 23.08% and 51.18%, respectively. 16S rRNA gene sequencing of fecal microbiota suggested that MBC promoted the enrichment of beneficial bacteria (Roseburia and Bifidobacterium) and the production of short-chain fatty acids. All of the results from this study provided a scientific reference for avoiding the functional ingredients waste of MBC and expanding its application value.
Bone density optimized pedicle screw instrumentation improves screw pull-out force in lumbar vertebrae

Abstract Pedicle screw instrumentation is performed in the surgical treatment of a wide variety of spinal pathologies. A common postoperative complication associated with this procedure is screw loosening. It has been shown that patient-specific screw fixation can be automated to match standard clinical practice and that failure can be estimated preoperatively using computed tomography images. Hence, we set out to optimize three-dimensional preoperative planning to achieve more mechanically robust screw purchase allowing deviation from intuitive, standard screw parameters. Toward this purpose, we employed a genetic algorithm optimization to find optimal screw sizes and trajectories by maximizing the CT derived bone mechanical properties. The method was tested on cadaveric lumbar vertebrae (L1 to L5) of four human spines (2 female/2 male; age range 60–78 years). The main boundary conditions were the predefined, level-dependent areas of possible screw entry points, as well as the automatically located pedicle structures. Finite element analysis was used to compare the genetic algorithm output to standard clinical planning of screw positioning in terms of the simulated pull-out strength. The genetic algorithm optimization successfully found screw sizes and trajectories that maximize the sum of the Young’s modulus within the screw’s volume for all 40 pedicle screws included in this study. Overall, there was a 26% increase in simulated pull-out strength for optimized compared to traditional screw trajectories and sizes. Our results indicate that optimizing pedicle screw instrumentation in lumbar vertebrae based on bone quality measures improves screw purchase as compared to traditional instrumentation.