Miracle-dz/UniFAR-FTUs huggingface dataset:
Generation and Characterization of Human Mesenchymal Stem Cell-Derived Smooth Muscle Cells

Cardiovascular diseases are the leading cause of death worldwide. A completely autologous treatment can be achieved by using elastogenic mesenchymal stem cell (MSC)-derived smooth muscle cells (SMC) at the affected tissue site of vascular diseases such as abdominal aortic aneurysms (AAA). Thus, our work focused on evaluating the efficacy of (a) the combination of various growth factors, (b) different time periods and (c) different MSC lines to determine the treatment combination that generated SMCs that exhibited the greatest elastogenicity among the tested groups using Western blotting and flow cytometry. Additionally, total RNA sequencing was used to confirm that post-differentiation cells were upregulating SMC-specific gene markers. Results indicated that MSCs cultured for four days in PDGF + TGFβ1 (PT)-infused differentiation medium showed significant increases in SMC markers and decreases in MSC markers compared to MSCs cultured without differentiation factors. RNA Seq analysis confirmed the presence of vascular smooth muscle formation in MSCs differentiated in PT medium over a seven-day period. Overall, our results indicated that origin, growth factor treatment and culture period played a major role in influencing MSC differentiation to SMCs.
Organizational Factors Moderating Changes in Tobacco Use Dependence Care Delivery Following a Comprehensive Tobacco-Free Workplace Intervention in Non-Profit Substance Use Treatment Centers

Although tobacco use is the leading preventable cause of death and is elevated among patients with substance use disorders, many substance use treatment centers (SUTCs) do not offer tobacco use interventions (i.e., screening and treatment). This study examined a key outcome of the implementation of a tobacco-free workplace program that provided education and specialized training to employees; namely, changes in clinician provision of the five As (Asking about tobacco use; Advising to quit; Assessing willingness to quit; Assisting with quitting; Arranging follow-up) from before to after the larger program implementation. The five As are a brief tobacco screening and treatment protocol that was taught as part of the program and that formed the basis for further intervention (e.g., provision of nicotine replacement therapies, Motivational Interviewing to enhance desire and willingness to make a quit attempt). Moreover, we also examined organizational moderators that may have impacted changes in the delivery of the five As over time among clinicians from 15 participating SUTCs. The number of the centers’ total and unique annual patient visits; full-time employees; and organizational readiness for implementing change were assessed as potential moderators of change in clinicians’ behaviors over time. Clinicians completed pre- and post-program implementation surveys assessing their provision of the five As. Results demonstrated significant increases in Asking (p = 0.0036), Advising (p = 0.0176), Assisting (p < 0.0001), and Arranging (p < 0.0001). SUTCs with higher Change Efficacy (p = 0.025) and lower Resource Availability (p = 0.019) had greater increases in Asking. SUTCs with lower Resource Availability had greater increases in Assessing (p = 0.010). These results help guide tobacco control program implementation to increase the provision of tobacco use interventions (i.e., the five As) to SUTC patients and elucidate Change Efficacy and Resource Availability as organizational factors promoting this clinician behavior change.
Empirical Study on the Impact of Urban and Rural Resident Basic Medical Insurance on Children's Educational Outcomes

This paper employs data from the 2016 and 2018 China Family Panel Studies (CFPS) to study the impact of participation in Urban and Rural Resident Basic Medical Insurance (URRBMI) on children's educational outcomes by using the logit model, double selection Lasso model, and propensity score matching. It is found that participating in URRBMI has no significant effect on children's Chinese performance, but has a significant negative effect on children's mathematics performance. The negative effect is more obvious for children who participating in the New Cooperative Medical Scheme (NCMS). The paper also studies the channel effects of participation in URRBMI on children's educational outcomes trough two different ways. It is noticed that both channel effects are not significant, that is, participation in URRBMI neither improves children's health nor changes household education expenditures.
Risk Factors for Perioperative Hemodynamic Instability in Pheochromocytoma: A Systematic Review and Meta-Analysis

Objective: To evaluate the risk factors of perioperative hemodynamic instability in pheochromocytoma, we conducted a systematic search of the literature using the Preferred Reporting Items for Systematic Reviews and Meta-analysis. Methods: In April 2021, we systematically searched PubMed, the Cochrane library, and Scopus for relevant studies on the risk factors of perioperative hemodynamic instability of adrenalectomy in patients with pheochromocytoma, and we subjected the findings from those studies to formal meta-analysis. Results: Our systematic review identified 14 studies involving 1725 patients, of which nine studies with 967 patients were eligible for meta-analysis. The results of meta-analysis showed that tumor size (odds ratio (OR): 1.14 for each increased cm, 95% confidence interval (CI) 1.03–1.26, z = 2.57) and urinary norepinephrine (OR, 1.51: 95% CI 1.26–1.81; z = 4.50) were most closely associated with the occurrence of perioperative hemodynamic instability. Conclusion: These findings suggest that tumor size and urinary norepinephrine are important predictors and risk factors for perioperative hemodynamic instability in adrenalectomy for pheochromocytoma. Such findings may be of value to surgeons and anesthesiologists when considering or preparing for this procedure.
Study of Pavement Micro- and Macro-Texture Evolution Due to Traffic Polishing Using 3D Areal Parameters

Pavement micro- and macro-texture have significant effects on roadway friction and driving safety. The influence of traffic polish on pavement texture has been investigated in many laboratory studies. This paper conducts field evaluation of pavement micro- and macro-texture under actual traffic polishing using three-dimensional (3D) areal parameters. A portable high-resolution 3D laser scanner measured pavement texture from a field site in 2018, 2019, and 2020. Then, the 3D texture data was decomposed to micro- and macro-texture using Fourier transform and Butterworth filter methods. Twenty 3D areal parameters from five categories, including height, spatial, hybrid, function, and feature parameters, were calculated to characterize pavement micro- and macro-texture. The results demonstrate that the 3D areal parameters provide an alternative to comprehensively characterize the evolution of pavement texture under traffic polish from different aspects.
Awake Craniotomy for Resection of Cerebral Arteriovenous Malformation: Initial Experience From a Low- and Middle-Income Country

Global health has shown progress over the years; however, neurosurgical care has not followed the same trajectory due to it being presumably resource intensive. Awake craniotomy (AC) is a neurosurgical technique that can improve neurological outcomes, can potentially reduce costs and hospital stay, and can be easily employed in low- and middle-income countries (LMICs). It has proven to be beneficial in surgical resection of tumors located in the critical areas of the brain, but there is limited literature to support AC for resection of arteriovenous malformations (AVM). We present four cases of AVM that were successfully treated surgically under awake settings in a developing country. Two of the AVMs were Spetzler-Martin grade (SMG) 3, one was SMG 4, and one was SMG 1. All the patients underwent successful excision of AVMs, and the postoperative digital subtraction angiography (DSA) was negative for any residual. They had a total hospital stay of three to five days with a mean postoperative stay of two days. Only one patient showed transient conductive dysphasia, which resolved on subsequent follow-ups, and none of the patients developed any long-term neurological deficit. There are limited data from LMICs regarding the benefits of using AC for AVMs. However, our cases show that this technique can be applied for AVM resection, particularly in eloquent areas of the brain (parts of the cerebral cortex that control vision, language, sensory, and motor functions), to minimize potential neurological deficits. Even though it requires careful selection of cases, and needs a higher level of microsurgical and neuro-anesthesia expertise, it can lead to better postoperative outcomes, lesser morbidity, and a shorter hospital stay, contributing to low resource utilization, making it feasible in a resource-limited setting.
Knee Osteoarthritis Progression Is Delayed in Silent Information Regulator 2 Ortholog 1 Knock-in Mice

Overexpression of silent information regulator 2 ortholog 1 (SIRT1) is associated with beneficial roles in aging-related diseases; however, the effects of SIRT1 overexpression on osteoarthritis (OA) progression have not yet been studied. The aim of this study was to investigate OA progression in SIRT1-KI mice using a mouse OA model. OA was induced via destabilization of the medial meniscus using 12-week-old SIRT1-KI and wild type (control) mice. OA progression was evaluated histologically based on the Osteoarthritis Research Society International (OARSI) score at 4, 8, 12, and 16 weeks after surgery. The production of SIRT1, type II collagen, MMP-13, ADAMTS-5, cleaved caspase 3, Poly (ADP-ribose) polymerase (PARP) p85, acetylated NF-κB p65, interleukin 1 beta (IL-1β), and IL-6 was examined via immunostaining. The OARSI scores were significantly lower in SIRT1-KI mice than those in control mice at 8, 12, and 16 weeks after surgery. The proportion of SIRT1 and type II collagen-positive-chondrocytes was significantly higher in SIRT1-KI mice than that in control mice. Moreover, the proportion of MMP-13-, ADAMTS-5-, cleaved caspase 3-, PARP p85-, acetylated NF-κB p65-, IL-1β-, and IL-6-positive chondrocytes was significantly lower in SIRT1-KI mice than that in control mice. The mechanically induced OA progression was delayed in SIRT1-KI mice compared to that in control mice. Therefore, overexpression of SIRT1 may represent a mechanism for delaying OA progression.
Machine Learning for Future Subtyping of the Tumor Microenvironment of Gastro-Esophageal Adenocarcinomas

Simple Summary We summarize the main components of the tumor microenvironment in gastro-esophageal adenocarcinomas (GEA). In addition, we highlight past and present applications of machine learning in GEA to propose ways to facilitate its clinical use in the future. Abstract Tumor progression involves an intricate interplay between malignant cells and their surrounding tumor microenvironment (TME) at specific sites. The TME is dynamic and is composed of stromal, parenchymal, and immune cells, which mediate cancer progression and therapy resistance. Evidence from preclinical and clinical studies revealed that TME targeting and reprogramming can be a promising approach to achieve anti-tumor effects in several cancers, including in GEA. Thus, it is of great interest to use modern technology to understand the relevant components of programming the TME. Here, we discuss the approach of machine learning, which recently gained increasing interest recently because of its ability to measure tumor parameters at the cellular level, reveal global features of relevance, and generate prognostic models. In this review, we discuss the relevant stromal composition of the TME in GEAs and discuss how they could be integrated. We also review the current progress in the application of machine learning in different medical disciplines that are relevant for the management and study of GEA.
Evidence for a Novel Antiviral Mechanism of Teleost Fish: Serum-Derived Exosomes Inhibit Virus Replication through Incorporating Mx1 Protein

Exosomes are associated with cancer progression, pregnancy, cardiovascular diseases, central nervous system-related diseases, immune responses and viral pathogenicity. However, study on the role of exosomes in the immune response of teleost fish, especially antiviral immunity, is limited. Herein, serum-derived exosomes from mandarin fish were used to investigate the antiviral effect on the exosomes of teleost fish. Exosomes isolated from mandarin fish serum by ultra-centrifugation were internalized by mandarin fish fry cells and were able to inhibit Infectious spleen and kidney necrosis virus (ISKNV) infection. To further investigate the underlying mechanisms of exosomes in inhibiting ISKNV infection, the protein composition of serum-derived exosomes was analyzed by mass spectrometry. It was found that myxovirus resistance 1 (Mx1) was incorporated by exosomes. Furthermore, the mandarin fish Mx1 protein was proven to be transferred into the recipient cells though exosomes. Our results showed that the serum-derived exosomes from mandarin fish could inhibit ISKNV replication, which suggested an underlying mechanism of the exosome antivirus in that it incorporates Mx1 protein and delivery into recipient cells. This study provided evidence for the important antiviral role of exosomes in the immune system of teleost fish.
Regulation of ER Composition and Extent, and Putative Action in Protein Networks by ER/NE Protein TMEM147

Nuclear envelope (NE) and endoplasmic reticulum (ER) collaborate to control a multitude of nuclear and cytoplasmic actions. In this context, the transmembrane protein TMEM147 localizes to both NE and ER, and through direct and indirect interactions regulates processes as varied as production and transport of multipass membrane proteins, neuronal signaling, nuclear-shape, lamina and chromatin dynamics and cholesterol synthesis. Aiming to delineate the emerging multifunctionality of TMEM147 more comprehensively, we set as objectives, first, to assess potentially more fundamental effects of TMEM147 on the ER and, second, to identify significantly TMEM147-associated cell-wide protein networks and pathways. Quantifying curved and flat ER markers RTN4 and CLIMP63/CKAP4, respectively, we found that TMEM147 silencing causes area and intensity increases for both RTN4 and CLIMP63, and the ER in general, with a profound shift toward flat areas, concurrent with reduction in DNA condensation. Protein network and pathway analyses based on comprehensive compilation of TMEM147 interactors, targets and co-factors then served to manifest novel and established roles for TMEM147. Thus, algorithmically simplified significant pathways reflect TMEM147 function in ribosome binding, oxidoreductase activity, G protein-coupled receptor activity and transmembrane transport, while analysis of protein factors and networks identifies hub proteins and corresponding pathways as potential targets of TMEM147 action and of future functional studies.
Artificial Intelligence in Thyroid Field—A Comprehensive Review

Simple Summary The incidence of thyroid pathologies has been increasing worldwide. Historically, the detection of thyroid neoplasms relies on medical imaging analysis, depending mainly on the experience of clinicians. The advent of artificial intelligence (AI) techniques led to a remarkable progress in image-recognition tasks. AI represents a powerful tool that may facilitate understanding of thyroid pathologies, but actually, the diagnostic accuracy is uncertain. This article aims to provide an overview of the basic aspects, limitations and open issues of the AI methods applied to thyroid images. Medical experts should be familiar with the workflow of AI techniques in order to avoid misleading outcomes. Abstract Artificial intelligence (AI) uses mathematical algorithms to perform tasks that require human cognitive abilities. AI-based methodologies, e.g., machine learning and deep learning, as well as the recently developed research field of radiomics have noticeable potential to transform medical diagnostics. AI-based techniques applied to medical imaging allow to detect biological abnormalities, to diagnostic neoplasms or to predict the response to treatment. Nonetheless, the diagnostic accuracy of these methods is still a matter of debate. In this article, we first illustrate the key concepts and workflow characteristics of machine learning, deep learning and radiomics. We outline considerations regarding data input requirements, differences among these methodologies and their limitations. Subsequently, a concise overview is presented regarding the application of AI methods to the evaluation of thyroid images. We developed a critical discussion concerning limits and open challenges that should be addressed before the translation of AI techniques to the broad clinical use. Clarification of the pitfalls of AI-based techniques results crucial in order to ensure the optimal application for each patient.
Neuroendocrine Carcinoma of the Larynx and Pharynx: A Clinical and Histopathological Study

Simple Summary Neuroendocrine carcinomas (NECs) of the head and neck are rare. The presented series of 20 patients with laryngeal and pharyngeal NECs is population-based and one of the largest published to date. We analyzed the treatment results according to the type of therapy and the role of various standard (synaptophysin-chromogranin-CD56, Ki-67, p16, HPV, and EBV) and some novel (INSM1 and PD-L1) neuroendocrine markers or potential prognosticators. The results indicate the following: (1) laryngeal and pharyngeal NECs accounted for 0.43% and 0.17% of the cases in the corresponding tumor groups, respectively; (2) neuroendocrine differentiation can be reliably determined by INSM1 immunohistochemistry; (3) the prognosis was determined by the nodal stage and TNM stage but not by the histological grade (which refers to moderately and poorly differentiated NECs); (4) except in well-differentiated NECs and early-stage (T1-2N0-1) moderately/poorly differentiated NECs, aggressive multimodal therapy is needed; and (5) the p16, HPV, and EBV statuses failed to show any prognostic value. Abstract Neuroendocrine carcinomas (NECs) of the head and neck are rare and the experience scanty. The Cancer Registry of Slovenia database was used to identify cases of laryngeal and pharyngeal NECs diagnosed between 1995–2020. Biopsies were analyzed for the expression of standard neuroendocrine markers (synaptophysin, chromogranin, CD56), INSM1, Ki-67, p16, and PD-L1 (using the combined positive score, CPS). In situ hybridization for human papillomavirus (HPV) and Epstein–Barr virus (EBV) was performed. Twenty patients (larynx, 12; pharynx, 8) were identified. One tumor was well differentiated (WD), five were moderately differentiated (MD), and 14 were poorly differentiated (PD). Disease control was achieved solely by surgery in 4/4 MD/PD T1-2N0-1 tumors. Eight patients died of the disease, seven of which were due to distant metastases. All three traditional markers were positive in 11/17 NECs and the INSM1 marker in all 20 tumors. Two of fourteen p16-positive tumors were HPV-positive, but all three nasopharyngeal NECs were EBV-negative. Three tumors had CPSs ≥ 1. In conclusion, INSM1 was confirmed to be a reliable marker of neuroendocrine differentiation. Except in WD and early-stage MD/PD tumors, aggressive multimodal therapy is needed; the optimal systemic therapy remains to be determined. p16, HPV, and EBV seem to bear no prognostic information.
Transcriptomic Profiling of Adult-Onset Asthma Related to Damp and Moldy Buildings and Idiopathic Environmental Intolerance

A subset of adult-onset asthma patients attribute their symptoms to damp and moldy buildings. Symptoms of idiopathic environmental intolerance (IEI) may resemble asthma and these two entities overlap. We aimed to evaluate if a distinct clinical subtype of asthma related to damp and moldy buildings can be identified, to unravel its corresponding pathomechanistic gene signatures, and to investigate potential molecular similarities with IEI. Fifty female adult-onset asthma patients were categorized based on exposure to building dampness and molds during disease initiation. IEI patients (n = 17) and healthy subjects (n = 21) were also included yielding 88 study subjects. IEI was scored with the Quick Environmental Exposure and Sensitivity Inventory (QEESI) questionnaire. Inflammation was evaluated by blood cell type profiling and cytokine measurements. Disease mechanisms were investigated via gene set variation analysis of RNA from nasal biopsies and peripheral blood mononuclear cells. Nasal biopsy gene expression and plasma cytokine profiles suggested airway and systemic inflammation in asthma without exposure to dampness (AND). Similar evidence of inflammation was absent in patients with dampness-and-mold-related asthma (AAD). Gene expression signatures revealed a greater degree of similarity between IEI and dampness-related asthma than between IEI patients and asthma not associated to dampness and mold. Blood cell transcriptome of IEI subjects showed strong suppression of immune cell activation, migration, and movement. QEESI scores correlated to blood cell gene expression of all study subjects. Transcriptomic analysis revealed clear pathomechanisms for AND but not AAD patients. Furthermore, we found a distinct molecular pathological profile in nasal and blood immune cells of IEI subjects, including several differentially expressed genes that were also identified in AAD samples, suggesting IEI-type mechanisms.
Adherence to Telemonitoring by Electronic Patient-Reported Outcome Measures in Patients with Chronic Diseases: A Systematic Review

Background: Effective telemonitoring is possible through repetitive collection of electronic patient-reported outcome measures (ePROMs) in patients with chronic diseases. Low adherence to telemonitoring may have a negative impact on the effectiveness, but it is unknown which factors are associated with adherence to telemonitoring by ePROMs. The objective was to identify factors associated with adherence to telemonitoring by ePROMs in patients with chronic diseases. Methods: A systematic literature search was conducted in PubMed, Embase, PsycINFO and the Cochrane Library up to 8 June 2021. Eligibility criteria were: (1) interventional and cohort studies, (2) patients with a chronic disease, (3) repetitive ePROMs being used for telemonitoring, and (4) the study quantitatively investigating factors associated with adherence to telemonitoring by ePROMs. The Cochrane risk of bias tool and the risk of bias in nonrandomized studies of interventions were used to assess the risk of bias. An evidence synthesis was performed assigning to the results a strong, moderate, weak, inconclusive or an inconsistent level of evidence. Results: Five studies were included, one randomized controlled trial, two prospective uncontrolled studies and two retrospective cohort studies. A total of 15 factors potentially associated with adherence to telemonitoring by ePROMs were identified in the predominate studies of low quality. We found moderate-level evidence that sex is not associated with adherence. Some studies showed associations of the remaining factors with adherence, but the overall results were inconsistent or inconclusive. Conclusions: None of the 15 studied factors had conclusive evidence to be associated with adherence. Sex was, with moderate strength, not associated with adherence. The results were conflicting or indecisive, mainly due to the low number and low quality of studies. To optimize adherence to telemonitoring with ePROMs, mixed-method studies are needed.