Miracle-dz/UniFAR-FTUs huggingface dataset:
The sonic hedgehog-GLI1 signaling pathway in brain tumor development

Introduction: The sonic hedgehog (Shh) pathway is a regulatory network involved in development and cancer. Proteins like Ptch, SMO, and Gli are central to the Shh pathway. Other proteins like HHIP, SUFU, Bmi-1, Cyclin D2, Plakoglobin, PAX6, Nkx2.2, and SFRP1 are not so well understood in Shh regulation as Gli-1 downstream target genes. Areas covered: In this review we try to explain the Shh pathway components and their role in development and cancer, mainly of the brain. A summary of each of the proteins is presented together with an overview of their involvement in cancer. Expert opinion: Genetic alterations of the Shh pathway have been detected in cancer stem cells, a subgroup of tumor cells implicated in the origin and maintenance of tumors, being responsible for cancer recurrence and chemotherapy resistance. Cancer stem cells constitute a novel target for biomedical researchers. Specifically, the Shh pathway is being explored as a new opportunity for targeted therapies against tumors. Therefore, a better knowledge of every of the regulators of the Shh pathway is needed.
Ocular Involvement in Hospitalized Patients with Candidemia: Analysis at a Boston Tertiary Care Center

Purpose: To study the prevalence, microbial profile, and risk factors for ocular involvement in patients with candidemia. Methods: The records of all inpatient consultations requested at the Brigham and Women’s Hospital from October 2009 to June 2011 to evaluate for ocular involvement in patients with candidemia were retrospectively reviewed. Results: Forty-nine consults were requested to rule out ocular involvement in patients with candidemia. The mean patient age was 55 years. In decreasing frequency, the organisms isolated were Candida albicans (42%), Candida parapsilosis (23%), Candida glabrata (17%), Candida tropicalis (8%), Candida dublinensis (5%), Candida krusei (3%), and Candida lusitaniae (3%). All patients were on antifungal treatment at the time of their initial ophthalmologic examination. One patient had evidence of chorioretinitis, and 3 patients had nonspecific fundus findings. Common risk factors included presence of an intravenous catheter, malignancy, and abdominal surgery. Conclusions: Ocular involvement is rare among patients with systemic Candida infection.
Effect of Submucosal Resection and Submucosal Diathermy on Nasal Airflow in Inferior Turbinate Hypertrophy

ubmucosal resection and submucosal diathermy are common procedures in the treatment of inferior turbinate hypertrophy. Nonetheless, there is still a debate on the safety and efficacy between these two surgical techniques. We aimed at comparing the effectiveness and safety of submucosal diathermy and submucosal resection in the treatment of inferior turbinate hypertrophy. Sixty patients with nasal obstruction due to inferior turbinate hypertrophy were randomly divided into two groups; submucosal resection and submucosal diathermy groups. Gertner-Podoshin plate was used for measurement of nasal airflow before operation and 2 months postoperative. Significant resolution of the obstruction reported by the patients was similarly detected in diathermy (93.1%) and resection groups (96%, P>0.05). According to the Gertner-Podoshin measurements, both diathermy and resection techniques similarly resulted in good nasal airflow two month postoperative (86.2% vs. 89.2%, respectively; P>0.05). Postoperative bleeding was more common in the resection group compared with the diathermy group (P=0.002). Moreover, patients in the diathermy group suffered from pain more than the resection group (P=0.01). Both submucosal resection and submucosal diathermy techniques result in similar postoperative outcomes in treatment of inferior turbinate hypertrophy, although postoperative bleeding and pain was more in submucosal resection and submucosal diathermy techniques, respectively. Keywords : Inferior turbinate hypertrophy; nasal airflow; side effects; submucosal diathermy; submucosal resection
National Implementation of Response to Intervention (RTI): Research Summary

The current national trend in today’s schools is to meet the needs of struggling and at-risk learners through the implementation of multi-tiered response to intervention models. This research sought to better understand the national perspective of RTI by investigating the level of emphasis of current and projected state-wide efforts for implementing RTI from the perspectives of special education state department directors in all 50 states and the District of Columbia. An 86% response rate was obtained and every state indicated some emphasis on RTI either in current practice or in development. Statewide training efforts are underway in 90% of the states primarily emphasizing an overview of RTI, progress monitoring and the use of data-driven decision-making. The areas receiving less training emphasis include culturally responsive RTI and roles of educators in implementing response to intervention. Over one-third of the states indicated that they plan to use RTI, in part, as a replacement or supplement to the learning disability discrepancy model. In addition, most states indicated that they are or plan to use a combined problem solvingstandard treatment protocol model for making multi-tiered RTI decisions. Suggestions for additional research are also provided. Data were gathered during the spring and summer, 2007.
Differential expression of galectin-3, CK19, HBME1, and Ret oncoprotein in the diagnosis of thyroid neoplasms by fine needle aspiration biopsy

Background: Fine needle aspiration biopsy (FNAB) is a common and excellent procedure for the evaluation of thyroid lesions that require surgical resection. At times, the FNAB diagnosis can be difficult, particularly of follicular-patterned lesions. Previous studies have shown that some immunohistochemical (IHC) markers may be helpful in establishing more accurate diagnosis. In this study, our goal was to evaluate four of the recently investigated markers in differentiating benign from malignant thyroid nodules on FNABs. Materials and Methods: We performed IHC staining of galectin-3, Ret oncoprotein (Ret), HBME-1, and cytokeratin 19 (CK19), on cell block sections of thyroid FNAB cases that had corresponding surgical resections. They included 44 benign lesions (37 hyperplastic or cellular nodules, HN; and 7 follicular adenomas, FA) and 27 malignant tumors (6 follicular carcinoma, FC; 19 classic papillary carcinoma, PTC; and 2 follicular variant of papillary carcinoma, FVPC). The stains were done according to the standard avidin–biotin–peroxidase method. Results: Statistical analysis showed that immunoexpression was significantly higher in the malignant group for all four markers. The sensitivity for positive expression for all benign lesions versus malignant tumors was as follows: 10/44 (22.7%) versus 25/27 (92.6%) for galectin-3; 14/44 (31.8%) versus 23/27 (85%) for Ret; 12/44 (27.3%) versus 24/27 (88.8%) for HBME-1; and 13/44 (29.5%) versus 23/27 (85%) for CK19. The sensitivity and specificity was highest for galectin-3 (92.6% and 77.3%, respectively) followed by HMBE-1 (88.9% and 72.7%, respectively). When combining the markers' expressions, the panel of galectin-3 + HBME-1 showed the highest sensitivity and specificity (90.7% and 75%, respectively), but this was, however, lower than galectin-3 alone (92.3% and 77.3%, respectively). Conclusion: We conclude that galectin-3 is the best single marker in differentiating benign from malignant thyroid lesions with the highest sensitivity and specificity. The galectin-3 + HBME-1 was the best combination for distinguishing benign from malignant lesions. Because they were the best two independent and combined markers, we recommend the use of the galectin-3 + HBME-1 panel to enhance the diagnostic accuracy of follicular-patterned thyroid lesions on FNABs.
Interstitial lung diseases in Saudi Arabia: A single-center study

BACKGROUND: There are relatively few epidemiological studies on interstitial lung disease (ILD) worldwide. OBJECTIVE: To report the incident cases of ILD and compare our data with reports from other populations. METHODS: Newly diagnosed ILDs were prospectively collected at a single tertiary care hospital from January 2008 to December 2011. Detailed demographic and clinical data were collected at the time of diagnosis, along with the results from diagnostic procedures, including high-resolution computed tomography (HRCT), serological tests, bronchoalveolar lavage (BAL), transbronchial lung biopsy, endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and surgical lung biopsy. RESULTS: A total of 330 cases were included. The mean age was 55.4 ± 14.9 years. There was a slight predominance of females (202; 61.2%), and the male-to-female ratio was 1:1.37. The most frequent disease was connective tissue disease (CTD)-associated ILD (34.8%), followed by idiopathic pulmonary fibrosis (IPF) (23.3%), sarcoidosis (20%), and hypersensitivity pneumonitis (6.3%). Non-classifiable ILD was present in 1.8% of the total ILD cases. HRCT was performed in 97.3% of the cases, BAL in 17.5%, transbronchial lung biopsy in 21.8%, EBUS-TBNA in 4.5%, and surgical lung biopsy in 22.7% (38.6% of which were performed among the idiopathic interstitial pneumonia cases). CONCLUSIONS: CTD-ILD and IPF were the most frequently observed ILDs in this Saudi Arabian population. Similarities and differences were found with respect to the previous reports from other countries.
The doctoral experience: a bit of a curate's egg

Established models of doctoral education in Australia are generally based on an apprenticeship model, where doctoral students learn from their advisors. However, these are slowly being reconsidered in light of low completion rates. This study investigated doctoral students' perceptions of their candidature by way of focus group interviews. The participants represented 17.9% of the doctoral students enrolled at a university. Three research questions constituted the interview schedule protocol: • What are some of the positives of your experience since you enrolled in the doctoral program? • What are some of the negatives of your experience since you enrolled in the doctoral program? • What are some of your recommendations for the future? Content analysis was employed to analyse interview transcripts and generate themes arising from each research question. The frequency with which such themes were cited were categorised by their incidence across the 18 schools represented in the study and across the whole sample of students to assess their prevalence. Key themes most often generated related to: • Generic skill courses; • Personal office space; • Supervision; • Social and academic/research culture; and • Communications. Results are discussed in relation to the future of doctoral education in Australia in an increasingly globalised competitive education sector.
Saudi guidelines on the diagnosis and treatment of pulmonary hypertension: 2014 updates

The Saudi Association for Pulmonary Hypertension (previously called Saudi Advisory Group for Pulmonary Hypertension) has published the first Saudi Guidelines on Diagnosis and Treatment of Pulmonary Arterial Hypertension back in 2008. [1] That guideline was very detailed and extensive and reviewed most aspects of pulmonary hypertension (PH). One of the disadvantages of such detailed guidelines is the difficulty that some of the readers who just want to get a quick guidance or looking for a specific piece of information might face. All efforts were made to develop this guideline in an easy-to-read form, making it very handy and helpful to clinicians dealing with PH patients to select the best management strategies for the typical patient suffering from a specific condition. This Guideline was designed to provide recommendations for problems frequently encountered by practicing clinicians involved in management of PH. This publication targets mainly adult and pediatric PH-treating physicians, but can also be used by other physicians interested in PH.
The role of sphingosine-1 phosphate and ceramide-1 phosphate in trafficking of normal stem cells and cancer cells

Introduction: A common feature of many types of cells is their responsiveness to chemotactic gradients of factors for which they express the corresponding receptors. The most studied chemoattractants so far are peptide-based growth factors and a family of cytokines endowed with strong chemotactic properties, called chemokines. However, additional evidence has accumulated that, in addition to these peptide-based chemoattractants, an important role in cell migration is played by bioactive lipids. Areas covered: Solid evidence has accumulated that two bioactive phosphorylated sphingolipids that are derivatives of sphingolipid metabolism, namely sphingosine-1-phosphate (S1P) and ceramide-1-phosphate (C1P), are potent chemoattractants for a variety of cells. In this review, we will discuss the effect of these two phosphorylated sphingolipids on the trafficking of normal and malignant cells, and, in particular, we will focus on their role in trafficking of normal hematopoietic stem/progenitor cells. Unlike other mediators, S1P under steady-state conditions maintain a steep gradient between interstitial fluid and peripheral blood and lymph across the endothelial barrier, which is important in the egress of cells from bone marrow. Both S1P and C1P may be upregulated in damaged tissues, which may result in reversal of this gradient. Expert opinion: S1P and C1P are important regulators of the trafficking of normal and malignant cells, and modification of their biological effects will have important applications in optimizing stem cell mobilization and homing, tissue organ/regeneration, and preventing cancer metastasis.
Acid-sensing ion channel 1a-mediated calcium influx regulates apoptosis of endplate chondrocytes in intervertebral discs

Background: Acid-sensing ion channel 1a (ASIC1a), the primary acid sensors in the nervous system, has been studied earlier in various physiopathologic conditions. However, little is known about the role of ASIC1a in endplate chondrocytes in intervertebral discs (IVDs). Methods: The expression of ASICs was examined in rat endplate chondrocytes. Effects of treatment with ASIC1a small interfering RNA (siRNA) or selective blocker (PcTX1) on acid-induced intracellular Ca2+ concentration ([Ca2+]i) and cell apoptosis were investigated. ASIC1a involved in Ca2+-mediated apoptotic signals in acid-induced endplate chondrocyte apoptosis was also assessed. Results: We showed that ASIC1a is expressed in rat endplate chondrocytes, and blockade of ASIC1a using ASIC1a-siRNA or PcTX1 inhibited acid-induced cell apoptosis and elevation of [Ca2+]i. We also demonstrated that the acid-induced [Ca2+]i increase via ASIC1a is involved in endplate chondrocyte apoptosis. Moreover, blocking of ASIC1a-mediated [Ca2+]i elevation inhibited activation of acid-induced calcium-dependent proteases and decreased BAD phosphorylation in endplate chondrocytes. Similarly, extracellular acidosis induced cytochrome C translocation from the mitochondria to the cytoplasm and activation of caspase-9 and caspase-3, which was inhibited by ASIC1a-siRNA or PcTX1. Conclusion: ASIC1a activation in endplate chondrocytes may trigger Ca2+-dependent proteases activity and signaling, which leads to apoptosis of endplate chondrocytes in IVDs.
Incidence and risk factors predisposing anastomotic leak after transhiatal esophagectomy

OBJECTIVE: The objective of our study was to identify the incidence and risk factors of anastomotic leaks following transhiatal esophagectomy (THE). MATERIALS AND METHODS: A prospective study was conducted on 61 patients treated for carcinoma of the esophagus between 2006 and 2007. We examined the following variables: age, gender, preoperative cardiovascular function, intraoperative complications such as hypotension, arrhythmia, mediastinal manipulation period, blood loss volume, blood transfusion, duration of surgery, postoperative complications such as anastomotic leak, anastomotic stricture, requiring reoperation, respiratory complications, and total morbidity and mortality. Variables were compared between the patients with and without anastomotic leak. T-test for quantitative variables and Chi-square test for qualitative variables were used to find out any relationship. P value less than 0.05 was considered significant. RESULTS: Out of 61 patients, anastomotic leaks occurred in 13 (21.3%). Weight loss, forced expiratory volume (FEV1) <2 lit, preoperative albumin, intaoperative blood loss volume, and respiratory complication were associated with the anastomotic leak in patients undergoing THE. Anastomotic leaks were the leading cause of postoperative morbidity, anastomotic stricture, and reoperation. CONCLUSION: Anastomotic leakage is a life-threatening postoperative complication. Careful attention to the factors contributing to the development of a leak can reduce the incidence of anastomotic complications postoperatively.
Identification of a subset of patients with acute myeloid leukemia characterized by long-term in vitro proliferation and altered cell cycle regulation of the leukemic cells

Objective: The malignant cell population of acute myeloid leukemia (AML) includes a small population of stem/progenitor cells with long-term in vitro proliferation. We wanted to compare long-term AML cell proliferation for unselected patients, investigate the influence of endothelial cells on AML cell proliferation and identify biological characteristics associated with clonogenic capacity. Methods: Cells were cultured in medium supplemented with recombinant growth factors FMS-like tyrosine kinase-3 ligand, stem cell factor, IL-3, G-CSF and thrombopoietin. The colony-forming unit assay was used to estimate the number of progenitors in AML cell populations after 35 days of culture, and microarray was used to study global gene expression profiles between AML patients. Results: Long-term cell proliferation was observed in 7 of 31 patients, whereas 3 additional patients showed long-term proliferation after endothelial cell coculture. Patient-specific differences in constitutive cytokine release were maintained during cell culture. Patients with long-term proliferation showed altered expression in six cell cycle-related genes (HMMR, BUB1, NUSAP1, AURKB, CCNF, DLGAP5), two genes involved in DNA replication (TOP2A, RFC3) and one gene with unknown function (LHFPL2). Conclusion: We identified a subset of AML patients characterized by long-term in vitro cell proliferation and altered expression of cell cycle regulators that may be potential candidates for treatment of AML.
Circulating semaphorin-4D and plexin-B1 levels in postmenopausal women with low bone mass: the 3-month effect of zoledronic acid, denosumab or teriparatide treatment

Objective: The evaluation of circulating semaphorin-4D (sema4D) and plexin-B1 in postmenopausal women with low bone mass and the effect of antiresorptive or osteoanabolic treatment. Methods: Serum samples were obtained from postmenopausal women with low bone mass at baseline and 3 months after zoledronic acid infusion (n = 30), denosumab injection (n = 30) or teriparatide initiation (n = 28) and from controls matched for age, age at menopause and body mass index (n = 30) at the same time points. Main outcome measures: Circulating sema4D and plexin-B1. Results: Circulating sema4D increased following denosumab (p = 0.026), whereas decreased following teriparatide (p = 0.013). Sema4D/plexin-B1 ratio increased following denosumab (p = 0.004). At baseline, sema4D and plexin-B1 levels were higher in patients pre-treated with bisphosphonates compared to naïve ones (p < 0.001 and p = 0.001, respectively). In bivariate correlations sema4D was inversely correlated with serum carboxyterminal telopeptide of type 1 collagen (rs -0.282, p = 0.002), intact parathyroid hormone (rs -0.388, p < 0.001) and 25(OH)D (rs -0.316, p < 0.001), whereas there was a trend towards correlation with lumbar spine bone mineral density (rs -0.191, p = 0.053). Conclusions: Sema4D levels are independently associated with previous bisphosphonate treatment, intact parathyroid hormone and 25(OH)D levels. Denosumab and teriparatide seem to exert an opposite effect on circulating sema4D levels. Further studies are needed to evaluate whether sema4D mediates the coupling effect that occurs following both antiresorptive and osteoanabolic treatment.
Masterclass series in peripheral arterial disease

For the first time, the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC 7) has stated that peripheral arterial disease (PAD) is equivalent in risk to ischemic heart disease and that any class of antihypertensive drug can be used in most patients with PAD.1 While adding recommendations for the treatment of hypertension in patients with PAD is long overdue, the JNC 7 still falls short in their recommendations. There is a growing body of evidence that cardiovascular morbidity and mortality can be significantly lowered with an appropriate medical program including control of blood pressure to goal levels. Hypertension affects approximately 50 million Americans and 1 billion individuals worldwide.1 It is the most common primary diagnosis in the USA and accounts for 35 million office visits as the primary diagnosis.2 While recognition of high blood pressure among individual patients has increased, 30% are still unaware that they have hypertension and control rates to goal blood pressure are far below the Heathy People 2010 goal of 50% (Table 1). 1,3 It is hard to reconcile the fact that in the years 1999–2000, 66% of patients did not reach goal blood pressure levels when recent clinical trials have demonstrated that goal blood pressure can be achieved in most individuals when two or more antihypertensive medications are administered.4,5 The most common physician reasons for failure to achieve goal blood pressure are failure to prescribe lifestyle modifications, inappropriate antihypertensive drug doses or drug combinations and failure to use a diuretic in a multidrug regimen.
Leptin signaling as a therapeutic target of obesity

Introduction: Leptin is a hormone with a key role in food intake and body weight homeostasis. Congenital leptin deficiency (CLD) is a rare disease that causes hyperphagia and early severe obesity. However, common obesity conditions are associated with hyperleptinemia and leptin resistance. Areas covered: The main signaling pathways activated by leptin as well as the mechanisms underlying the regulatory actions of leptin on food intake and on lipid and glucose metabolism are reviewed. The potential mechanisms involving leptin resistance and the main regulatory hormonal and nutritional factors controlling leptin production/functions are also analyzed. The pathophysiology of leptin in human obesity, and especially the trials analyzing effects of leptin replacement therapy in patients with CLD or in subjects with common obesity and in post-obese weight-reduced subjects are also summarized. Expert opinion: The use of drugs or specific bioactive food components with anti-inflammatory properties to reduce the inflammatory state associated with obesity, especially at the hypothalamus, may help to overcome leptin resistance. Research should also be focused on investigating dietary strategies, food supplements or drugs capable of avoiding or reversing the leptin fall during weight management, in order to promote sustained body weight lowering and weight loss maintenance.