Miracle-dz/UniFAR-FTUs huggingface dataset:
Cytoprotective effects of molsidomine against methotrexate-induced hepatotoxicity: an experimental rat study

Introduction and aim Methotrexate (Mtx) is an antineoplastic and immunosuppressive drug that may cause hepatotoxicity, whereas molsidomine (Mol) is a vasodilating and antioxidant agent. This study aimed to investigate the potential protective effects of Mol in Mtx-induced liver toxicity in rats. Materials and methods Forty Wistar albino rats were equally divided into five groups: control, Mol, Mtx, Mol–Mtx, and Mtx–Mol. Following treatment, the animals were sacrificed, and liver tissue samples were histopathologically evaluated using Roening grading and Bcl-2 antibody staining. Tissue oxidants, antioxidants, and serum transaminases were measured and statistically compared across all groups. Results No hepatic fibrosis or steatosis was observed in any of the groups. In the Mtx group, grade 2 liver injury and score 2 Bcl-2 antibody staining were observed; however, in the Mol–Mtx group, these were lower (grade 1, score 1). There were no statistically significant differences in serum transaminase levels among groups. Malondialdehyde levels were higher in all rats that received Mtx, but no differences in myeloperoxidase levels were observed among the groups. Levels of tissue antioxidants, including superoxide dismutase, glutathione (GSH) peroxidase (GSH-Px), and reduced GSH, were significantly higher in the Mol-treated and Mol pre-treated groups. Catalase (CAT) levels were elevated in all Mol-treated groups, but only in that group were CAT levels statistically significantly higher than in the control group. Conclusion Our results suggest that some oxidant levels could increase following Mtx administration in the liver, possibly contributing to liver damage, whereas Mol could mitigate the histopathological and biochemical effects of hepatotoxicity. However, molecular studies are required to understand the exact mechanisms of these alterations.
Clinicians’ Perspectives of a Novel Home-Based Multidisciplinary Telehealth Service for Patients with Chronic Spinal Pain

Chronic spinal pain conditions can often be successfully managed by a non-surgical, multidisciplinary approach, however many individuals are unable to access such specialised services within their local community. A possible solution may be the delivery of care via telerehabilitation. This study aimed to evaluate clinicians' perspectives on providing clinical care via telerehabilitation during the early implementation of a novel spinal telerehabilitation service. Eight clinicians' were recruited, completing surveys at four separate time points. Confidence in providing treatment via telerehabilitation significantly improved with time (χ2(3)=16.22, p=0.001). Clinicians became significantly more accepting of telerehabilitation being a time- (χ2(3)=11.237, p=0.011), and cost-effective (χ2(3)=9.466, p=0.024) platform in which they could deliver care. Overall satisfaction was high, with technology becoming easier to use (p=0.026) and ability to establish rapport significantly improved with experience (p=0.043). Understanding clinicians' perspectives throughout the early implementation phase of a new telerehabilitation service is a critical component in determining long-term sustainability.
Emerging biomarkers for the diagnosis and monitoring of urothelial carcinoma

Urothelial carcinoma (UC) arises extensively from the renal pelvis, ureter, urinary bladder, and urethra. UC represents a clinical and social challenge because of its incidence, post-treatment recurrence rate, and prognosis. Combinations of urine cytology, cystoscopy, and conventional imaging such as computed tomography are currently used for diagnosis and monitoring modalities of UC. Both the poor diagnostic accuracy of urine cytology and poor cost performance of cystoscopy and conventional imaging modalities emphasize the urgent need for advancement in clinical guidance for UC. Urine- and blood-based biomarkers for detection of UC of the bladder and upper urinary tract represent a considerable research area. Biomarkers can help to improve UC diagnosis with the aim of replacing cystoscopy and other imaging examinations in future and may enable individualizing risk stratification regarding therapy and follow-up. Over the decades, numerous studies have focused on the potential application of biomarkers for UC, including urine, circulating tumor DNA, RNAs, proteins, and extracellular vesicles. Although some biomarkers such as ImmunoCyt/uCyt+, UroVysion, NMP-22, bladder tumor antigen, CxBladder, and Xpert Bladder Cancer are currently available in clinical practice, few biomarkers achieve high sensitivity and specificity. Emerging biomarkers are continuously developed and reported in medical journals. However, there is a significant lack on following external validation using different cohorts. The positive results are needed to be confirmed by more studies with large-scale cohorts and long follow-up periods to prove the true value of novel biomarkers, followed by their adoption in clinical practice. The present paper provides an overview of the evidence based on high-impact studies regarding urine- and blood-based biomarkers and their clinical applications in bladder cancer and upper tract UC.
Relationship between liver iron concentration determined by R2-MRI, serum ferritin, and liver enzymes in patients with thalassemia intermedia

Background Iron overload is a risk factor affecting all patients with thalassemia intermedia (TI). We aimed to determine whether there is a relationship of serum ferritin (SF) and alanine aminotransferase (ALT) with liver iron concentration (LIC) determined by R2 magnetic resonance imaging (R2-MRI), to estimate the most relevant degree of iron overload and best time to chelate in patients with TI. Methods In this cross-sectional study, 119 patients with TI (mean age years) were randomly selected and compared with 120 patients who had a diagnosis of thalassemia major (TM). Correlations of LIC, as determined by R2-MRI, with SF and ALT levels, were assessed in all participants. A P-value <0.05 was considered statistically significant. Results SF and LIC levels were lower in patients with TI than in those with TM; only ferritin values were significant. We found a statistically significant relationship between SF and LIC, with cut-off estimates of SF in patients with TI who had splenectomy and those who entered puberty spontaneously (916 and 940 ng/mL, respectively) with LIC >5 mg Fe/g dry weight (P<0.0001). A significant relationship was also found for patients with TI who had elevated ALT level (63.5 U/L), of 3.15 times the upper normal laboratory limit, using a cut-off for LIC ≥5 mg Fe/g dry weight. Conclusion We determined the cut-off values for ALT and SF indicating the best time to start iron chelation therapy in patients with TI, and found significant correlations among iron overload, SF, and ALT.
Pity: a qualitative study on Iranian women with breast cancer

Background Women with breast cancer (BC) are commonly confronted with others' pity. However, there is limited information about pity in Iranian women with BC. The aim of this study was to explore perceptions, reactions, coping strategies, and consequences of pity among Iranian women with BC. Methods This qualitative study was carried out from March 2016 till October 2017. A purposive sample of 36 women with BC was selected with maximum variation from three health care centers in Alborz Province, Iran. Data were collected using semistructured interviews and analyzed using a conventional content-analysis approach. Results Our findings indicated that Iranian women with BC experienced received pity and perceived unusual attention from others as due to certain reasons. Others' pity caused negative emotional reactions in them. They used self-protection strategies against others' pity. The consequences of self-protection against pity were normalizing the patient's flow of life and/or social isolation. Conclusion Pity is a serious psychosocial challenge in Iranian women with BC, with negative effects on quality of life. Therefore, pity should be considered in counseling and psychosocial screening of patients.
Personality and Social Capital

While previous research has shown that personality shapes social networks, we know very little about the relationship between these important psychological characteristics and the creation of social capital. In this article, we argue that personality shapes individuals’ ability to create social capital, and we predict positive associations between each of the Big Five personality traits and social capital. We tested our hypotheses using the Social Survey of the Networks of the Dutch, 2014, which contains data on about 1,069 respondents, including social capital and Big Five personality measures. Our findings showed that personality and social capital were related such that extraversion and openness predicted instrumental social capital, and extraversion, emotional stability, and agreeableness predicted expressive social capital. Conscientiousness benefited instrumental social capital when respondents were older or when social capital was accessed via weak ties. We discuss these findings in light of existing explanations of the creation of social capital.
Influence of Xiaoyaosan on depressive-like behaviors in chronic stress-depressed rats through regulating tryptophan metabolism in hippocampus

Background Tryptophan metabolism has always been considered to play a vital role in mental disorder diseases, and how traditional Chinese formula Xiaoyaosan regulates the tryptophan metabolism is a complement to the pathogenesis of depression. This study established a depression rat model by the chronic immobilization stress (CIS) method and observed the change in tryptophan metabolism in hippocampus and the effects of Xiaoyaosan. Methods Forty-eight male Sprague Dawley (SD) rats were randomly divided into the following four groups: control group, CIS group, Xiaoyaosan group, and fluoxetine group. The depression model was established by the 21-day CIS. The food intake and body weight were recorded, and the sucrose preference test (SPT), novelty suppressed feeding (NSF) test and open field test (OFT) were also used to evaluate the model. Then, the contents of tryptophan and 5-hydroxytryptamine (5-HT) in hippocampus were detected by the ELISA method, and the expression levels of tryptophan hydrogenase 2 (TPH2) and indoleamine 2,3-dioxygenase 1 (IDO1) in hippocampus were determined by quantitative reverse transcriptase polymerase chain reaction reaction (qRT-PCR) and Western blot methods. Results The behavioral data showed a significant difference between the model group and the normal group. The 5-HT content in the hippocampi of CIS rats was significantly reduced, whereas the tryptophan content in the hippocampi of model rats was significantly increased. The TPH2 level in hippocampus of the model group was significantly decreased, and the IDO1 level was significantly increased. Xiaoyaosan and fluoxetine could significantly reverse these changes and had obvious curative effects. Conclusion The abnormal tryptophan metabolism existed in the hippocampi of chronic stress-depressed rats, which was closely related to the pathogenesis of depression. Xiaoyaosan could improve the tryptophan metabolism by regulating the expression levels of TPH2 and IDO1, thus exerting an antidepressant-like effect.
Evaluation of TNF-α cytokine production in patients with tuberculosis compared to healthy people

Background: Mycobacterium tuberculosis (TB) is one of the most important causes of human mortality. Approximately one-third of the world’s population is infected with TB and 5–10% of them develop the active form of the disease. Cytokines play a major role in the host defense process against Mycobacterium infections. Among these cytokines, tumor necrosis factor alpha (TNF-α) has a prominent role in the defense of and pathological responses to tuberculosis. Materials and methods: A case-control study was carried out from May 2016 to June 2017. 45 patients with diagnosis of tuberculosis (smear and positive culture) were included as case group and 45 healthy subjects as control group. The serum levels of TNF-α were determined with the enzyme-linked immunosorbent assay (ELISA) method. Results: The concentration of TNF-α in patients with TB was significantly higher than in the control group (P<0.05). However, the difference was only significant in the age groups 20–30 and 50–60 years; in the age groups 30–40, 40–50 and 50–70 years, the difference was not significant, although certain trends were apparent. Discussion and conclusion: Since the level of serum TNF-α is higher in patients with pulmonary tuberculosis than in individuals without it, the measurement of TNF-α levels can be useful as a probable marker for the diagnosis of tuberculosis.
Correlation between vertical components and skeletal Class II malocclusion in ethnic Javanese

Introduction The dentoskeletal morphology of Class II malocclusion has been analyzed in several cephalometric investigations. It is crucially important to understand the vertical components in orthodontic treatment. Defining the facial type of an individual is an essential key to obtain an accurate orthodontic diagnosis. Aim The aim of this study was to understand the correlation of vertical components in Class II skeletal malocclusion. Materials and methods This is a observational descriptive study. This study used lateral cephalograms of Class II skeletal malocclusion from Universitas Airlangga Dental Hospital, between April 2015 and 2016. Cephalometric analysis was performed using digital software by a single examiner. This analysis measured gonial (Go), upper gonial (Go1), lower gonial (Go2), Yaxis-SN angle, the length of anterior face height, and posterior face height. The correlation between each variable was analyzed using the Pearson correlation test (P<0.01). Results There was a correlation between vertical components and Class II skeletal malocclusion. Conclusion Vertical components were correlated with Class II skeletal malocclusion. The greater ANB angle will be followed by greater Go2, which worsens the condition of Class II skeletal malocclusion.
Doxorubicin-loaded quaternary ammonium palmitoyl glycol chitosan polymeric nanoformulation: uptake by cells and organs

Purpose This study was aimed to develop doxorubicin-loaded quaternary ammonium palmitoyl glycol chitosan (DOX–GCPQ) nanoformulation that could enable DOX delivery and noninvasive monitoring of drug accumulation and biodistribution at tumor site utilizing self-florescent property of doxorubicin. Materials and methods DOX–GCPQ amphiphilic polymeric nanoformulations were prepared and optimized using artificial neural network (ANN) and characterized for surface morphology by atomic force microscopy, particle size with polydispersity index (PDI), and zeta potential by dynamic light scattering. Fourier transformed infrared (FTIR) and X-ray diffractometer studies were performed to examine drug polymer interaction. The ANN-optimized nanoformulation was investigated for in vitro release, cellular, tumor, and tissue uptake. Results The optimized DOX–GCPQ nanoformulation was anionic spherical micelles with the hydrodynamic particle size of 97.8±1.5 nm, the PDI of <0.3, the zeta potential of 28±2 mV, and the encapsulation efficiency of 80%±1.5%. Nanoformulation demonstrated a sustained release pattern over 48 h, assuming Weibull model. Fluorescence microscopy revealed higher uptake of DOX–GCPQ in human rhabdomyosarcoma (RD) cells as compared to free DOX. In vitro cytotoxicity assay indicated a significant cytotoxicity of DOX–GCPQ against RD cells as compared to DOX and blank GCPQ (P<0.05). DOX–GCPQ exhibited low IC50 (1.7±0.404 µmol) when compared to that of DOX (3.0±0.968 µmol). In skin tumor xenografts, optical imaging revealed significantly lower DOX–GCPQ in heart and liver (P<0.05) and accumulated mainly in tumor (P<0.05) as compared to other tissues. Conclusion The features of nanoformulation, ie, small particle size, sustained drug release, and enhanced cellular uptake, potential to target tumor passively coupled with the possibility of monitoring of tumor localization by optical imaging may make DOX–GCPQ an efficient nanotheranostic system.
Preclinical quantification of air leaks in a physiologic lung model: effects of ventilation modality and staple design

Purpose Thoracic air leaks are a common complication following pulmonary resections. Limitations in clinical studies and preclinical models have hindered efforts to understand the pathophysiology of air leaks. With an emphasis on staple-line specific air leaks, we hypothesize that ventilation modality – intraoperative positive pressure vs postoperative negative pressure – and stapler design may play a role in air leaks. Methods Using a novel physiologic lung model, air leaks associated with graduated and uniform staple designs were evaluated under positive and negative pressure ventilation, simulating perioperative breathing in porcine lungs. Air leak incidence, air leak volume, and air leak rate were captured along with ventilation pressure and tidal volume. Results In all cases, negative pressure ventilation was associated with a higher occurrence of leaks when compared to positive pressure ventilation. Lungs leaked more air and at a faster rate under negative pressure ventilation compared to positive pressure ventilation. Graduated staple designs were associated with higher occurrence of leaks as well as larger leak rates when compared to uniform staples. Tissue thickness was not associated with differences in air leaks when tested with appropriate staple heights. Conclusion Using a novel lung model to investigate the pathophysiology of air leaks, we have identified breathing modality and staple design as two important variables that may impact air leaks. This work will help guide device design and drive future studies in human tissue, and it may help inform clinical practice to ultimately improve patient outcomes.
Sarcoidosis: patient treatment priorities

Sarcoidosis is a rare disease with the number of patients in the European Union (28 member states), Norway, Iceland and Lichtenstein estimated as ∼102 000 [1, 2]. Some 40% of individuals experience sarcoidosis as a chronic condition, while >60% of individuals find that the disease resolves within 2–5 years [3]. However, it has been shown that patients can still have symptoms that result in a reduced quality of life (QoL) even after clinical signs of disease have disappeared. These symptoms include fatigue, pain, everyday cognitive failure, small fibre neuropathy, exercise limitation and depressive symptoms [4, 5]. Findings from a recent survey of patients and their partners in the Netherlands also showed that sarcoidosis has a significant impact on their lives [6]. Sarcoidosis patient survey reveals QoL and functionality are required as core outcomes in treatment and care, along with more multidisciplinary working by clinicians and the establishment of specialist sarcoidosis centres in every European country http://ow.ly/DTvt30mQnqc
Effect of HMGB1 Polymorphisms on Urothelial Cell Carcinoma Susceptibility and Clinicopathological Characteristics

The high mobility group box 1 gene (HMGB1) plays a prominent role in cancer progression, angiogenesis, invasion, and metastasis. This study explored the effect of HMGB1 polymorphisms on clinicopathological characteristics of urothelial cell carcinoma (UCC). In total, 1293 participants (431 patients with UCC and 862 healthy controls) were recruited. Four single-nucleotide polymorphisms (SNPs) of HMGB1 (rs1412125, rs1360485, rs1045411, and rs2249825) were assessed using TaqMan real-time polymerase chain reaction assay. The results indicated that individuals carrying at least one T allele at rs1045411 had a lower risk of UCC than those with the wild-type allele [adjusted odds ratio = 0.722, 95% confidence interval (CI) = 0.565-0.924]. Furthermore, female patients with UCC carrying at least one T allele at rs1045411 were at a lower invasive tumor stage than those with the wild-type allele [odds ratio (OR) = 0.396, 95% CI = 0.169-0.929], similar to nonsmoking patients (OR = 0.607, 95% CI = 0.374-0.985). In conclusion, this is the first report on correlation between HMGB1 polymorphisms and UCC risk. Individuals carrying at least one T allele at rs1045411 are associated with a lower risk of UCC and a less invasive disease in women and nonsmokers.
Cancer/testis Antigen MAGEA3 Interacts with STAT1 and Remodels the Tumor Microenvironment

Cancer-testis antigen MAGEA3, being restrictedly expressed in testis and various kinds of tumors, has long been considered as an ideal target for immunotherapy. In this study, we report that MAGEA3 interacts with STAT1 and regulates the expression of tyrosine phosphorylated STAT1 (pY-STAT1) in tumor cells. We show that pY-STAT1 is significantly up-regulated when MAGEA3 is silenced by MAGEA3-specific siRNA. RNA sequencing analysis identified 274 STAT1-related genes to be significantly altered in expression level in MAGEA3 knockdown cells. Further analysis of these differentially expressed genes with GO enrichment and KEGG pathway revealed that they are mainly enriched in plasma membrane, extracellular region and MHC class I protein complex, and involved in the interferon signaling pathways, immune response, antigen presentation and cell chemotaxis. The differentially expressed genes associated with chemokines, antigen presentation and vasculogenic mimicry formation were validated by biological experiments. Matrigel matrix-based tube formation assay showed that silencing MAGEA3 in tumor cells impairs tumor vasculogenic mimicry formation. These data indicate that MAGEA3 expression in tumor cells is associated with immune cells infiltration into tumor microenvironment and anti-tumor immune responses, implying that it may play an important role in tumor immune escape. Our findings reveal the potential impact of MAGEA3 on the immunosuppressive tumor microenvironment and will provide promising strategies for improving the efficacy of MAGEA3-targeted immunotherapy.
Detection of bone marrow involvement with FDG PET/CT in patients with newly diagnosed lymphoma

Background Bone marrow involvement (BMI) affects the lymphoma stage, survival, and treatment. Bone marrow biopsy (BMB) and fluorodeoxyglucose (FDG) positron emission tomography- computed tomography (PET/CT) are useful techniques to detect BMI. Both have advantages and disadvantages. We aimed to identify factors that could be used to predict BMI with positive and negative results on PET/CT compare them with BMB in newly diagnosed patients with lymphoma. Methods We included 22 non-Hodgkin and 16 Hodgkin lymphoma patients in this single center study. All patients had PET/CT examination and BMB before treatment. BMI in BMB was reported as negative or positive. Bone marrow was classified into 3 types by FDG uptake on PT/CT; diffuse involvement, focal involvement, and normal bone marrow. Results PET/CT and BMB results were concordant (7 positive, 15 negative) in 22 patients (57%). We evaluated concordant and discordant patient characteristics and risk-stratified patients for BMI. Our findings suggest that patients with diffuse FDG uptake on PET/CT, especially patients with advanced age and low platelet and white blood cell counts, are likely to have BMI and could potentially forego BMB. Patients with negative PET/CT findings and no significant laboratory abnormalities are very unlikely to have BMI. Conclusion Our results suggest that BMI should not be decided solely based PET/CT or BMB findings. It is reasonable to use both diagnostic assays along with clinical and laboratory findings. PET/CT result, clinical and laboratory findings could be useful for predicting BMI in patient for whom BMB is contraindicated.