Miracle-dz/UniFAR-FTUs huggingface dataset:
Homeobox-A13 acts as a functional prognostic and diagnostic biomarker via regulating P53 and Wnt signaling pathways in lung cancer.

BACKGROUND The prognosis of lung cancer patients is poor without useful prognostic and diagnostic biomarker. To search for novel prognostic and diagnostic markers, we previously found homeobox-A13 (HOXA13) as a promising candidate in lung cancer. OBJECTIVE To determine the precisely clinical feature, prognostic and diagnostic value, possible role and mechanism of HOXA13. METHODS Gene-expression was explored by real-time quantitative-PCR, western-blot and tissue-microarray. The associations were analyzed by Chi-square test, Kaplan-Meier and Cox-regression. The roles and mechanisms were evaluated by MTS, EdU, transwell, xenograft tumor and luciferase-reporter assays. RESULTS HOXA13 expression is increased in tumors, and correlated with age of patients. HOXA13 expression is associated with unfavorable overall survival and relapse-free survival of patients in four cohorts. Interestingly, HOXA13 has different prognostic significance in adenocarcinoma (ADC) and squamous-cell carcinoma (SCC), and is a sex- and smoke-related prognostic factor only in ADC. Importantly, HOXA13 can serve as a diagnostic biomarker for lung cancer, especially for SCC. HOXA13 can promote cancer-cell proliferation, migration and invasion in vitro, and facilitate tumorigenicity and tumor metastasis in vivo. HOXA13 acts the oncogenic roles on tumor growth and metastasis by regulating P53 and Wnt/β-catenin signaling activities in lung cancer. CONCLUSIONS HOXA13 is a new prognostic and diagnostic biomarker associated with P53 and Wnt/β-catenin signaling pathways.
Concentration-dependent mode of binding of drug oxatomide with DNA: multi-spectroscopic, voltammetric and metadynamics simulation analysis

Abstract The interaction between antihistaminic drug oxatomide (OXT) and calf-thymus DNA (CT-DNA) has been investigated in a physiological buffer (pH 7.4) using UV–Vis, fluorescence, 1H NMR and circular dichroism spectral techniques coupled with viscosity measurements, KI quenching, voltammetry and in silico molecular modeling studies. OXT binds with CT-DNA in a concentration-dependent manner. At a lower [Drug]/[CT-DNA] molar ratio (0.6–0.1), OXT intercalates into the base pairs of CT-DNA, while at a higher [Drug]/[CT-DNA] molar ratio (13–6), the drug binds in the minor grooves of CT-DNA. The binding constants for the interaction are found to be in the order of 103–105 M−1, and the groove binding mode of interaction exhibits a slightly higher binding constant than that of intercalative mode. Thermodynamic analysis of binding constants at three different temperatures suggests that both these modes of binding are mainly driven by hydrophobic interactions (ΔH o > 0 and ΔS o > 0). Voltammetric investigations indicate that the electro-reduction of OXT is an adsorption controlled process and shifts in reduction peak potentials reiterate the concentration-dependent mode of binding of the drug with CT-DNA. The free energy landscape obtained at the all-atom level, using metadynamics simulation studies, revealed two major binding forces: partial intercalation and minor groove binding, which corroborate well with the experimental results. Communicated by Ramaswamy H. Sarma
Diaphragm function in acute respiratory failure and the potential role of phrenic nerve stimulation

Purpose of review The aim of this review was to describe the risk factors for developing diaphragm dysfunction, discuss the monitoring techniques for diaphragm activity and function, and introduce potential strategies to incorporate diaphragm protection into conventional lung-protective mechanical ventilation strategies. Recent findings It is increasingly apparent that an approach that addresses diaphragm-protective ventilations goals is needed to optimize ventilator management and improve patient outcomes. Ventilator-induced diaphragm dysfunction (VIDD) is common and is associated with increased ICU length of stay, prolonged weaning and increased mortality. Over-assistance, under-assistance and patient-ventilator dyssynchrony may have important downstream clinical consequences related to VIDD. Numerous monitoring techniques are available to assess diaphragm function, including respiratory system pressures, oesophageal manometry, diaphragm ultrasound and electromyography. Novel techniques including phrenic nerve stimulation may facilitate the achievement of lung and diaphragm-protective goals for mechanical ventilation. Summary Diaphragm protection is an important consideration in optimizing ventilator management in patients with acute respiratory failure. The delicate balance between lung and diaphragm-protective goals is challenging. Phrenic nerve stimulation may be uniquely situated to achieve and balance these two commonly conflicting goals.
Comparison of outcomes of peritoneal dialysis between patients after failed kidney transplant and transplant-naïve patients: a meta-analysis of observational studies

Abstract Purpose The influence of prior failed kidney transplants on outcomes of peritoneal dialysis (PD) is unclear. Thus, we conducted a systematic review and meta-analysis to compare the outcomes of patients initiating PD after a failed kidney transplant with those initiating PD without a prior history of kidney transplantation. Methods We searched PubMed, Embase, CENTRAL, and Google Scholar databases from inception until 25 November 2020. Our meta-analysis considered the absolute number of events of mortality, technical failures, and patients with peritonitis, and we also pooled multi-variable adjusted hazard ratios (HR). Results We included 12 retrospective studies. For absolute number of events, our analysis indicated no statistically significant difference in technique failure [RR, 1.14; 95% CI, 0.80–1.61; I2=52%; p = 0.48], number of patients with peritonitis [RR, 1.13; 95% CI, 0.97–1.32; I2=5%; p = 0.11] and mortality [RR, 1.00; 95% CI, 0.67–1.50; I2=63%; p = 0.99] between the study groups. The pooled analysis of adjusted HRs indicated no statistically significant difference in the risk of technique failure [HR, 1.25; 95% CI, 0.88–1.78; I2=79%; p = 0.22], peritonitis [HR, 1.04; 95% CI, 0.72–1.50; I2=76%; p = 0.85] and mortality [HR, 1.24; 95% CI, 0.77–2.00; I2=66%; p = 0.38] between the study groups. Conclusion Patients with kidney transplant failure initiating PD do not have an increased risk of mortality, technique failure, or peritonitis as compared to transplant-naïve patients initiating PD. Further studies are needed to evaluate the impact of prior and ongoing immunosuppression on PD outcomes.
Identification and Characteristics of Co-isolation of Multiple Nontuberculous Mycobacteria

Objective Although multiple nontuberculous mycobacteria (NTM) species can be isolated from the same patient, little has been reported on co-isolation. We clarified the trends and characteristics of the co-isolation of multiple NTM species. Methods To collect data on multiple NTM isolation, we first extracted all patients who visited our hospital from 2006 through 2015 with a diagnosis of NTM lung diseases other than Mycobacterium avium complex (MAC) and then reviewed their medical records to evaluate the co-isolation of multiple NTM species. Results Of 213 patients with non-MAC lung disease, the most common NTM species was M. gordonae (32%), followed by M. kansasii (20%) and M. abscessus (14%). Non-MAC NTM lung disease tended to be associated with middle age with a low body mass index and male predominance. Multiple NTM species were isolated from 55 (26%) of the 213 patients. The clinical characteristics associated with multiple NTM species isolation included female predominance, never smokers and the absence of cavity lesions in the lungs. The highest co-isolation rate was observed in patients with M. gordonae isolation (30%), followed by M. furtuitum isolation (26%) and M. abscessus isolation (20%). Only MAC was isolated when co-isolated with M. abscessus. Among M. szulgai, M. peregrinum and M. terrae isolation, no other NTM species were detected. Conclusion Co-isolation of multiple NTM species was not uncommon, with 26% of patients with non-MAC NTM lung diseases showing co-isolation with multiple NTM species. Each NTM species had distinct characteristics in terms of co-isolation.
Intrajejunal Infusion of Levodopa/Carbidopa for Advanced Parkinson's Disease: A Systematic Review

Advanced Parkinson's disease is inconsistently defined, and evidence is lacking in relation to device‐aided therapies. To update existing reviews of intrajejunal infusion of levodopa/carbidopa (LCIG), we performed a literature search for relevant articles (to November 3, 2020) using PubMed supplemented by hand searching. Retrieved articles were categorized by relevance to identified research questions, including motor complications and symptoms; nonmotor symptoms; functioning, quality of life, and caregiver burden; optimal timing of treatment initiation and administration duration; discontinuation; and complications. Most eligible studies (n = 56) were open‐label, observational studies including relatively small patient numbers. LCIG consistently reduces OFF time and increased ON time without troublesome dyskinesia with varying effects regarding ON time with troublesome dyskinesia and the possibility of diphasic dyskinesia. More recent evidence provides some increased support for the benefits of LCIG in relation to nonmotor symptoms, quality of life, activities of daily living, and reduced caregiver burden. Patient age does not appear to significantly impact the effectiveness of LCIG. Discontinuation rates with LCIG (~17%–26%) commonly relate to device‐related issues, although the ability to easily discontinue LCIG may represent a potential benefit. LCIG may be a favorable option for patients with advanced Parkinson's disease who show predominant nonmotor symptoms and vulnerability to complications of other advanced therapy modalities. Larger, well‐controlled studies, including precise investigation of cost effectiveness, would further assist treatment selection. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society
A person-centered evaluation of subjective well-being using a latent profile analysis: Associations with negative life events, distress, and emotion regulation strategies.

The present study examined the structure of subjective well-being (SWB) using a person-centered approach, and tested whether SWB profiles differed in a number of self-reported negative life events, emotional distress, and cognitive emotion regulation strategies. The sample included a total of 945 undergraduate students from Serbia (78% female, Mage = 20.14 years). A 3-step latent profile analysis with partial conditional independence revealed four profiles, which have been tentatively labeled: low SWB (a combination of low life satisfaction, low positive affect, and high negative affect), mixed SWB (moderate to high life satisfaction, moderate to low positive affect, high negative affect), moderately low SWB (low life satisfaction, moderate to low positive affect, moderate negative affect), high SWB (high life satisfaction, high positive affect, low negative affect). A comparison of SWB profiles applied to symptoms of emotional distress, along with the number of self-reported negative life events and emotion regulation strategies, offered support to the validity of four SWB profiles. Our findings suggest that a person-centered perspective might be a valuable tool for understanding the structure of SWB. This article is protected by copyright. All rights reserved.
Predictive Classification System for Low Back Pain Based on Unsupervised Clustering

Study Design: Retrospective study. Objective: Lumbar magnetic resonance imaging (MRI) findings are believed to be associated with low back pain (LBP). This study sought to develop a new predictive classification system for low back pain. Method: Normal subjects with repeated lumbar MRI scans were retrospectively enrolled. A new classification system, based on the radiological features on MRI, was developed using an unsupervised clustering method. Results: One hundred and fifty-nine subjects were included. Three distinguishable clusters were identified with unsupervised clustering that were significantly correlated with LBP (P = .017). The incidence of LBP was highest in cluster 3 (57.14%), nearly twice the incidence in cluster 1 (30.11%). There were obvious differences in the sagittal parameters among the 3 clusters. Cluster 3 had the smallest intervertebral height. Based on follow-up findings, 27% of subjects changed clusters. More subjects changed from cluster 1 to clusters 2 or 3 (14.5%) than changed from cluster 2 or cluster 3 to cluster 1 (5%). Participation in sport was more frequent in subjects who changed from cluster 3 to cluster 1. Conclusion: Using an unsupervised clustering method, we developed a new classification system comprising 3 clusters, which were significantly correlated with LBP. The prediction of LBP is independent of age and better than that based on individual sagittal parameters derived from MRI. A change in cluster during follow-up may partially predict lumbar degeneration. This study provides a new system for the prediction of LBP that should be useful for its diagnosis and treatment.
Multiple Firm Livid Nodules on the Proximal Lower Leg: A Quiz

Society for Publication of Acta Dermato-Venereologica A 71-year-old male patient presented at the dermatology department with multiple firm livid cutaneous nodules on the proximal lower leg, scattered over an area approximately 15 × 25 cm (Fig. 1). The lesions initially appeared six weeks before presentation; they were painful on palpation and progressive in number and size. In addition, clinical examination and ultrasound scan revealed a firm subcutaneous lesion, approximately 5 cm diameter, in the affected area, and a superficial venous thrombosis of the adjacent great saphenous vein. Two punch biopsies of the cutaneous nodules, for histopathological evaluation, and a magnetic resonance imaging (MRI) scan were performed. Histopathology (Fig. 2A, B) showed a dermal, highly pleomorphic, heterochromatic tumour with high cell density, intense vascularization and extravasation of erythrocytes. The tumour cells had a varying size of nuclei and a high number of atypical mitotic figures. Immunohistochemistry (Fig. 2C–E) showed nuclear expression of ETS tran scription factor ERG (ERG), cytokeratin expression (AE1/AE3), positivity for cluster of differentiation 31 (CD31) and overexpression of MYC proto-oncogene (MYC). Furthermore, there was high proliferative activity (Ki67: 70%) and the tumour stained negative for calmodulin binding transcription activator 1 (CAMTA1), prostate specific antigen (PSA), S100 calcium binding protein (S100) and podoplanin (D2-40). The MRI scan showed a subcutaneous lesion, approximately 4.9 × 3.6 cm, medial to the popliteal area, and two more subcutaneous lesions, 14 mm and 7 mm diameter, in the upper thigh.
Electrocautery-enhanced Lumen-apposing Metal Stents in the Management of Symptomatic Pancreatic Fluid Collections

Background and Aims: Endoscopic decompression is considered a first-line treatment for symptomatic pancreatic fluid collections (PFCs). A lumen-apposing metal stent (LAMS) with an electrocautery-enhanced delivery system [electrocautery-enhanced lumen-apposing metal stent (ELAMS)] may facilitate this procedure. This study evaluated the safety and efficacy of ELAMS in the management of symptomatic PFCs. Patients and Methods: A multicenter, nonblinded, prospective, Food and Drug Administration (FDA)-approved, investigational device exemption clinical trial was conducted. Enrollment criteria included symptomatic PFCs ≥6 cm with ≥70% fluid fraction. Subjects were followed prospectively for safety, efficacy, and resolution of the collections. Primary endpoint success was defined as ≥50% reduction in PFC size. Clinical outcomes were compared with our previously published series of LAMS without the cautery-enhanced delivery system. Results: The target enrollment of 30 patients was achieved in 7 US tertiary care centers. All patients underwent successful placement of the ELAMS. The mean procedure duration, stent placement time, and fluoroscopy exposures were 28.1±12.5, 5.8±2.6, and 1.8±1.6 minutes, respectively. Eight patients had no fluoroscopy. The primary endpoint was achieved in 83.3% of patients. Two adverse events were attributed to the ELAMS: 1 bleeding upon stent removal and 1 stent migration. Relative to the comparator noncautery LAMS multicenter trial (N=33, 8 tertiary centers), there was a significantly shorter procedure duration [36 min (P<0.001)] with similar technical and clinical outcomes in the ELAMS cohort. Conclusion: LAMS placed using an electrocautery delivery system significantly reduce procedure duration and were safe and effective in the management of symptomatic PFCs.
Evaluation of mechanical properties of Ti-25Nb BCC porous cell structure and their association with structure porosity: A combined finite element analysis and analytical approach for orthopedic application

Ti-based alloys have been commonly employed in manufacturing implants for orthopedic applications. Binary Titanium-Niobium (Ti-25Nb) alloy is a promising material for potential applications in orthopedics because of their lower elastic moduli and superior biocompatibility than the conventional Ti-based alloys. Implants with porous structures encourage bone ingrowth and reduce the effect of stress-shielding further. This study is aimed at establishing the relationship between the mechanical performance and structural parameters of porous body-centered-cubic (BCC) structures made up of Ti-25Nb (25% by wt.). Solid models of BCC porous structures were constructed (unit cell size: 2 mm; overall size: 8 × 8 × 8 mm3). Finite element analysis (FEA) of the BCC structures with porosity ranging from 29% to 79% (seven porosities) was conducted under tension, bending, and torsional loads. The Gibson-Ashby model and Exponential regression model were also employed to determine the stiffness of the above porous structures. The functional relationships between effective Young’s modulus, effective yield strength, and porosity generated from both the models were found to match the FEA results well. Results indicated that porosity in the range of 50%−70% can be used to design graded porous stems to mimic the mechanical properties of cortical bone.
The impact of race and ethnicity on lipoprotein(a) levels and cardiovascular risk

Purpose of review Lipoprotein(a) [Lp(a)] is a plasma circulating apoB100 (apoB) containing lipoprotein. It has a unique glycoprotein bound to the apoB100, apolipoprotein(a) [apo(a)]. The majority of the population expresses two apo(a) isoforms, when bound to apoB100 they create two circulating Lp(a) particles. Lp(a) levels are genetically determined and epidemiological studies have established elevated levels of Lp(a) to be a causal risk factor of cardiovascular disease (CVD). Lp(a) levels differ across racial groups and Blacks of Sub-Saharan decent have higher levels when compared to white. In comparison to white populations, studies in minorities are less represented in the published literature. Additionally, there is a lack of standardization in the commercial assays used to measured Lp(a) levels, and hence it is difficult to assess risk based on individual Lp(a) levels, but risk seems to occur in the upper percentiles of the population. Recent findings A recent study using data from the UK biobank highlights the racial differences in Lp(a) levels and the increase risk in CVD amongst all races. Summary This review will highlight Lp(a) biology and physiology with a focus on available data from racially diverse cohorts. There is a need to perform studies in diverse populations to understand if they are at higher risk than whites are.
TRIB3 promotes proliferation, migration, and invasion of retinoblastoma cells by activating the AKT/mTOR signaling pathway.

BACKGROUND Tribbles pseudokinase 3 (TRIB3) is a member of the tribbles-related family, which has been determined in various cancers, including renal cell carcinoma, acute promyelocytic leukemia, colorectal cancer, endometrial cancer, and glioma. However, its role in retinoblastoma (RB) has not yet been explored. METHODS The expression level of TRIB3 was detected in RB tissues and cell lines using qRT-PCR. The effects of TRIB3 on cell proliferation and invasion capacities were analyzed with MTT, crystal violet, and transwell assays. Western blot and rescue assays were conducted to explore the underlying mechanism. RESULTS This study found that TRIB3 was upregulated in human RB tissues compared to adjacent normal tissues both at the mRNA and protein levels. Overexpression of TRIB3 significantly promoted cell proliferation and invasion of RB cells, while TRIB3 knockdown inhibited these processes. Moreover, the mechanism deciphering experiments showed that TRIB3 overexpression can increase AKT and mTOR phosphorylation. Conversely, TRIB3 knockdown decreased the phosphorylation of AKT and mTOR. Additionally, MK2206, a potent AKT inhibitor, blocked the promotive effects of TRIB3 in RB cells. CONCLUSION This study demonstrated that TRIB3 acts as an oncogene and plays a crucial role in the proliferation and invasion of RB cells via regulating the AKT/mTOR signaling pathway. Therefore, TRIB3 may serve as a potential target in the diagnosis and/or treatment of RB.
Association of Preeclampsia With Incident Stroke in Later Life Among Women in the Framingham Heart Study

Key Points Question Is preeclampsia associated with later-life stroke among women after accounting for time-varying covariates? Findings In this cohort study of 1435 women with and without a history of preeclampsia who participated in the Framingham Heart Study, after adjustment for age and time-varying vascular risk factors, women with a history of preeclampsia had a more than 3-fold higher risk of experiencing a stroke in later life compared with women who did not have a history of preeclampsia. Meaning The findings suggest that preeclampsia may be an independent risk factor for later-life stroke among women after controlling for vascular risk factors across the life course.