Miracle-dz/UniFAR-FTUs huggingface dataset:
Fatty acid binding protein 7 as a marker of glioma stem cells

Glioblastomas are the most aggressive brain tumors. Glioblastoma stem cells (GSCs) are thought to be responsible for the recurrence, chemoresistance, and poor prognosis of glioblastoma. Fatty acid binding protein 7 (FABP7), which is a cellular chaperone for a variety of omega‐3 fatty acids, is a known marker for neural stem cells. In this study, using a newly developed anti‐FABP7 antibody and patient‐derived GSC lines, we evaluated the expression of FABP7 in GSCs. Using immunocytochemistry, Western blotting, and qPCR analyses, FABP7 was found to be highly enriched in GSCs and its localization was found in cytosol and nuclei. FABP7 expression was significantly downregulated in differentiated GSCs induced by the addition of serum. In the glioma surgical specimens, FABP7 was highly expressed in the majority of glioblastoma. Double immunostaining for FABP7 and Sox2 showed that FABP7+Sox2+ tumor cells were significantly increased in glioblastoma (grade IV) compared with diffuse astrocytoma (grade II) and anaplastic astrocytoma (grade III). Our data introduces FABP7 as a marker for GSCs and further highlights its possible significance for glioma diagnosis and treatment.
Antithyroid Drug Use in Pregnancy and Birth Defects: Why Some Studies Find Clear Associations, and Some Studies Report None.

BACKGROUND Rare cases of birth defects after the use of methimazole (MMI) or carbimazole to treat hyperthyroidism in early pregnancy have been reported since 1972, whereas propylthiouracil (PTU) has not been considered teratogenic. Recently, two studies reported birth defects after the use of MMI in early pregnancy to affect 2-4% of exposed children, and one study also found birth defects after the use of PTU. On the other hand, some published studies did not find associations between the use of thionamides and birth defects. SUMMARY The methods used in the two positive and the four negative reports are reviewed. The two positive studies included a sufficient number of children exposed to MMI (n = 1231 and 1097) to evaluate the studied outcomes, whereas the four negative studies included a much lower number of exposed children (n = 73, 108, 30, and 124). Considering PTU, the birth defects observed in one study were in general milder and tended to be diagnosed and registered only when they resulted in complications and led to surgery after one year of age. None of the negative studies has investigated outcomes after one year of age. CONCLUSION Studies finding no associations between early pregnancy exposure to antithyroid drugs and birth defects were either not sufficiently powered or did not study outcomes at optimal ages.
Understanding the role of doxycycline in the inhibition of osteoarthritis

ecent research developments have supported the use 1–14 mutation developed OA in the knee and temporomandibular R of doxycycline to treat osteoarthritis. The purpose of this article is to concisely present the laboratory and clinical studies, as well as the molecular mechanisms, that provide an explanation for doxycycline’s efficacy. Doxycycline has been shown to reduce the severity of articular cartilage breakdown in osteoarthritis (OA) and has been recommended for treatment of OA. A decrease in matrix metalloproteinase-13 (MMP-13) collagenase production by chondrocytes in response to treatment with doxycycline has been observed. In addition, doxycycline was shown to inhibit digestion of type XI collagen, while also inhibiting type II collagen synthesis. A mutation in the gene encoding type XI collagen causes OA in the knee joints of mice and humans. Moreover, type II collagen has recently been shown to act as a ligand for the cell surface collagen receptor discoidin domain receptor-2 (DDR-2), which in turn induces MMP-13, leading to cartilage destruction. In 1991, doxycycline was shown to inhibit digestion of type XI collagen in vitro. Subsequently, collagenolytic activity in cartilage extracts from OA knees of untreated dogs was observed to be five-fold greater than extracts from dogs given doxycycline. Doxycycline also has been found to reduce extracellular matrix breakdown in adult periodontitis. A study involving femoral heads obtained from patients after arthroplasty showed that 5 days of doxycycline treatment inhibited collagenase activity in human OA cartilage. A clinical study involving arthroscopic evaluation of temporomandibular joints in patients receiving doxycycline showed a dramatic reduction in collagenase activity. MMP-13 was measured in chondrocytes isolated from areas of OA cartilage after treatment with doxycycline, showing a reduction in MMP-13 synthesis. A study involving rats receiving doxycycline showed a protective action of doxycycline on articular cartilage. A randomized, placebo-controlled, double-blind trial was performed on large numbers of obese women who received 30 months of treatment with doxycycline. Tibiofemoral joint space narrowing was then measured showing that the loss of joint space width in the doxycycline group was 40% less than that in the placebo group. Type XI collagen is part of the network of collagen fibrils that helps retain proteoglycans and contributes to mechanical stability. Mice with a loss of function of type XI collagen
Prognostic Significance of TERT Promoter Mutations in Papillary Thyroid Carcinomas in a BRAF(V600E) Mutation-Prevalent Population.

BACKGROUND The role of telomerase reverse transcriptase (TERT) promoter mutations in differentiated thyroid cancer has been well established. These mutations have a significantly higher prevalence in aggressive thyroid tumors, including widely invasive oncocytic carcinomas, poorly differentiated carcinomas, and anaplastic thyroid carcinomas. Interestingly, in some studies, TERT mutations were found to be more common in tumors with a BRAF(V600E) mutation. However, mutational analysis of TERT promoter mutations in thyroid tumors has not been previously performed for patients in Korea, where the BRAF(V600E) mutation in papillary thyroid carcinoma (PTC) is particularly prevalent. This study analyzed TERT promoter mutations in various thyroid tumors and examined their relationship with clinicopathologic factors and the BRAF(V600E) mutation in PTC cases. METHODS Using 242 preoperative fine-needle aspiration biopsy specimens (including 207 PTCs) with confirmed histopathological diagnosis of the biopsied thyroid nodules, the TERT promoter status (C228T and C250T) was analyzed, and the relationship with clinicopathologic factors and the BRAF(V600E) mutation in PTC cases was examined. RESULTS Of 242 patients, 14.5% (30/207), 26.7% (4/15), 50% (1/2), and 60% (2/5) of PTCs, follicular thyroid carcinomas, poorly differentiated carcinomas, and anaplastic thyroid carcinomas harbored a TERT(C228T) mutation, respectively. The TERT(C228T) mutation was associated with recurrence (p = 0.03). However, no association with other clinicopathologic factors in PTC was found. Coexistence of TERT(C228T) and BRAF(V600E) mutations was found in 13.0% of PTCs and was significantly associated with older age and advanced stage compared with the group negative for either mutation. The TERT(C228T) mutation status was an independent prognostic factor for recurrence-free survival (hazard ratio = 3.08 [confidence interval 1.042-9.079]; p = 0.042) in patients with PTC in multivariate analysis. CONCLUSIONS Identification of TERT promoter mutations in preoperative fine-needle aspiration biopsy specimens may help in better characterizing the prognosis and triaging thyroid cancer patients for appropriate treatment.
Disinfection of stethoscopes: Gap between knowledge and practice in an Indian tertiary care hospital

Context: Stethoscopes are used primarily to assess the health of patients and are one of the most commonly used medical devices. Thus, are the prominent tools for the spread of health-care associated infections (HAIs). Aims: The study was conducted to assess the knowledge and awareness about handling of the stethoscope and cleaning practices followed among the healthcare workers (HCWs). Materials and Methods: A total of 80 participants were included during a 4-month study period at a tertiary care hospital in Ujjain. A semi-structured questionnaire was distributed to HCWs and the surface of the diaphragm of their stethoscopes were swabbed for bacteriological analysis using standard techniques. Results: Out of total 80 stethoscopes, 69 (86%) were found to be contaminated with at least one type of microorganism. Pseudomonas aeruginosa was the most predominant bacterial species found on 58 stethoscopes, followed by Bacillus subtilis (n = 21) and Staphylococcus spp. (n = 16). Out of total 10 S. aureus isolated, 3 were methicillin-resistant S. aureus ( MRSA). Majority (97%) of the HCWs had good knowledge about the topic, but only 22 (27%) reported to apply it in the practice. Conclusions: Our study confirmed that majority of the stethoscopes were contaminated with microorganisms. Besides having knowledge about the importance of cleaning the stethoscopes, lower percentage of HCWs reported to follow it in practice. Thus, the authors recommend regularization of reminders such as circulars, motivating posters for the HCWs to clean the diaphragm of the stethoscopes.
Screening of BCOR‐CCNB3 sarcoma using immunohistochemistry for CCNB3: A clinicopathological report of three pediatric cases

BCOR‐CCNB3 sarcoma is a recently recognized tumor morphologically and clinically simulating Ewing sarcoma. We herein retrospectively collected clinicopathologic data on BCOR‐CCNB3 sarcoma in the Kyoto University Hospital over the last 10 years. Three (20%) bone sarcomas were revealed to be diffusely positive for CCNB3 immunohistochemistry among 15 pediatric cases of undifferentiated sarcoma morphologically similar to Ewing sarcoma, while the other cases showed completely negative staining. The three patients with immunohistochemically CCNB3‐positive tumors were all male, aged between 11 and 17, and confirmed to have the BCOR‐CCNB3 fusion transcript by RT‐PCR. Radiologically, all cases had well‐demarcated solid masses with bone destruction. Although the tumors were basically small round cell tumors, less monomorphic histological patterns such as short spindle cells, a myxoid matrix, and hemangiopericytoma‐like pattern were also observed in both biopsy and resected specimens. Two patients achieved a complete response after chemotherapy for Ewing sarcoma and osteosarcoma, respectively. These results demonstrated that the application of CCNB3 immunostaining was useful for differentiating BCOR‐CCNB3 from a group of ‘Ewing‐like sarcomas’ and may contribute to the evaluation of treatment strategies for bone sarcomas.
Assessment of Depression, Anxiety, Quality of Life, and Coping in Long-Standing Multiple Endocrine Neoplasia Type 2 Patients.

BACKGROUND Data on psychological harm in multiple endocrine neoplasia type 2 (MEN2) are scarce. OBJECTIVES The aim of this study was to assess anxiety, depression, quality of life, and coping in long-standing MEN2 patients. PATIENTS AND METHODS Patients were 43 adults (age ≥18 years) with clinical and genetic diagnosis of MEN2 and long-term follow-up (10.6 ± 8.2 years; range 1-33 years). This was a cross-sectional study with qualitative and quantitative psychological assessment using semi-directed interviews and HADS, EORTC QLQ C30, and MINI-MAC scales. Adopting clinical criteria from 2015 ATA Guidelines on MEN2, biochemical cure (39%; 16/41), persistence/recurrence (61%; 25/41), and stable chronic disease (22/41) of medullary thyroid carcinoma (MTC) were scored. Pheochromocytoma affected 19 (44%) patients, with previous adrenalectomy in 17 of them. RESULTS Overall, anxiety (42%; mean score 11 ± 2.9; range 8-18; anxiety is defined as a score ≥8) and depression (26%; mean score 11 ± 3.8; range 8-20; depression is defined as a score ≥8) symptoms were frequent. Patients who transmitted RET mutations to a child had higher scores for weakness-discouragement/anxious preoccupation and lower scores for cognitive, emotional, and physical functioning (p < 0.05). Feelings of guilt were present in 35% of patients with mutation-positive children. Lower mean score values for depression and anxiety and higher scores for role, cognitive, and emotional functioning were noticed in 33 patients who were well-informed about their disease (p < 0.05). Fighting spirit was more frequently found in patients with multiple surgical procedures (p = 0.019) and controlled chronic adrenal insufficiency (p = 0.024). Patients with MEN2-related stress-inducing factors had lower scores for fighting spirit and cognitive functioning and higher scores for insomnia and dyspnea (p < 0.05). Eleven patients required sustained psychotherapeutic treatment. Mean global health status was relatively good in MEN2 cases (68.1 ± 22.3), and the cured group had higher physical functioning (p = 0.021). CONCLUSIONS Psychological distress is likely chronic in MEN2 patients. This study identified diverse MEN2-related factors (degree of information on disease, mutation-positive children, number of surgeries, comorbidities, stress-inducing factors, and cure) interfering positively or negatively with the results of the psychometrics scales. The active investigation of these factors and the applied psychological assessment protocol are useful to identify MEN2 patients requiring psychological assistance.
The impact of geropsychology training

What effect does a geropsychology practicum placement have on graduate students' knowledge of and attitudes toward older adults? Ninety psychology externs and interns were surveyed at the beginning of the training year and then 9 months later. About half of the trainees provided services in settings that served older adults, whereas the remainder did not. At the end of training, those with a geropsychology placement maintained higher interest in geropsychology, had lower negative attitudes toward older people, and had greater knowledge of mental health and aging than trainees without a geropsychology placement. There were no differences between the two placement groups in knowledge of general facts on aging and positive attitudes toward the aged. The implications of the findings for graduate program directors, training psychologists, and graduate students are discussed.
Towards Best Practices in the Treatment of Women With Addictive Disorders

The study of addiction in women has been given increasing recent attention. Documented gender differences in a variety of domains, including substance craving, have prevention and treatment implications. This article reviews gender differences and sex-specific effects of addiction as they relate to treatment guidelines for women with substance-related disorders. Gender differences in the following domains are summarized: screening, physiological effects of substances, medical consequences, psychiatric comorbidity, craving, and family and developmental issues. Implications for future research and best practices are discussed, with the goal of improving women's mental health throughout the life cycle.
Role of tumor‐associated macrophages in human malignancies: friend or foe?

Tumor‐associated macrophages (TAMs) play a pivotal role in tumor growth in human malignancies. Published studies have analyzed the relationship between TAM infiltration and the prognosis of patients for many human tumors. Most studies reported a positive correlation between TAM density and a poor prognosis. Studies focusing on macrophage phenotypes emphasized the protumor role of M2 anti‐inflammatory macrophages in many types of human tumors. However, TAMs influence tumor progression in various ways that depend on differences in tumor sites, histology, and microenvironments. In this review, we summarize the function of TAMs in various human malignancies by reviewing the data provided in studies of TAMs in human malignancies.
Oestrogen‐receptor‐α gene polymorphism affects response in bone mineral density to oestrogen in post‐menopausal women

An oestrogen‐receptor‐α (ERα) gene polymorphism has been variably reported to be related to bone mass. To investigate whether this ERα gene polymorphism is associated with a functional difference, we assessed the response in bone mineral density (BMD) to oestrogen therapy in post‐menopausal women in relation to ERα gene polymorphism.
Inactivation of mTor arrests bovine oocytes in the metaphase‐I stage, despite reversible inhibition of 4E‐BP1 phosphorylation

The mammalian target of rapamycin (mTor), a Ser/Thr protein kinase, is implicated in the phosphorylation‐triggered inactivation of translation repressors, the so‐called eukaryotic initiation factor 4E (eIF4E)‐binding proteins (4E‐BPs). Previous observations in porcine and bovine oocytes revealed an increasing phosphorylation of 4E‐BP1 during meiotic maturation. This factor is hypophosphorylated in the germinal‐vesicle (GV) stage and its phosphorylation peaks in the metaphase II (M II) stage. In the present approach we intended to block 4E‐BP1 phosphorylation specifically to impair initiation of translation and elucidate effects on resumption of meiosis. Torin2, which acts as an active‐site mTor inhibitor, reduces 4E‐BP1 phosphorylation without any effect on eIF4E and arrests up to 60% of the oocytes in the M I stage. Effects of Torin2 treatment, analyzed by site‐specific substrate phosphorylation, were also observed at protein kinase B (Akt or PKB), and cyclin dependent kinases (CDKs). Only minor side effects were found at protein kinase A, C (PKA, PKC), ATM/ATR (Ataxia telangiectasia mutated/AT and Rad3‐related protein), and the mitogen activated protein kinases (MAPK) ERK1,2. The inhibition of 4E‐BP1 phosphorylation by Torin2 is reversible when cultivating oocytes for additional 24 hr in Torin2‐free medium. Even so, oocytes persist in the M I stage. This may indicate the necessity of spatiotemporally regulated translation during meiosis, which cannot be restored later. In conclusion, Torin2 enables an effective and specific inhibition of 4E‐BP1 phosphorylation, which may be valuable to investigate maturation specific protein synthesis in more detail. Mol. Reprod. Dev. 81: 363–375, 2014. © 2014 Wiley Periodicals, Inc.
Bcl‐2 family in non‐small cell lung cancer: its prognostic and therapeutic implications

Non‐small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancers. Despite significant advances in its research of tumor biology and therapy, the prognosis for this neoplasm has still remained poor. The great majority of anticancer agents, regardless of their mechanisms of action, exert their lethal actions on cancer cells by inducing apoptosis following drug‐induced cellular damage. Many reported studies have evaluated the prognostic and therapeutic implications of apoptosis in lung cancer, but their exact clinical value has remained unclear. Therefore more prospective studies are currently required to further validate apoptosis as prognostic and predictive biomarkers in lung cancer patients. The current study reviewed the studies on the prognostic and predictive significances of Bcl‐2 family proteins in NSCLC. We also discussed potential treatment strategies which could target apoptotic proteins in lung carcinoma cells. Exception for Bcl‐2 itself, studies of the prognostic significance of other Bcl‐2 family proteins is markedly limited. The abundance of literature suggests that targeting apoptosis in NSCLC is feasible. However, many troubling questions arise with the use of new drugs or treatment strategies, and new biomarkers are needed.
Adaptivity in high-performance embedded systems: a reactive control model for reliable and flexible design

Abstract System adaptivity is increasingly demanded in high-performance embedded systems, particularly in multimedia system-on-chip (SoC), owing to growing quality-of-service requirements. This paper presents a reactive control model that has been introduced in Gaspard, our framework dedicated to SoC hardware/software co-design. This model aims at expressing adaptivity as well as reconfigurability in systems performing data-intensive computations. It is generic enough to be used for description in the different parts of an embedded system, for example, specification of how different data-intensive algorithms can be chosen according to some computation modes at the functional level; and expression of how hardware components can be selected via the usage of a library of intellectual properties according to execution performances. The transformation of this model toward synchronous languages is also presented, in order to allow an automatic code generation usable for formal verification, based on techniques such as model checking and controller synthesis, as illustrated in the paper. This work, based on Model-Driven Engineering and the standard UML MARTE profile, has been implemented in Gaspard.
O-0009QUANTITATIVE ANALYSIS OF THE IMPACT OF DEEPNESS OF RESPONSE ON POST-PROGRESSION SURVIVAL TIME FOLLOWING FIRST-LINE TREATMENT IN PATIENTS WITH MCRC

Background: The extent of tumor shrinkage in patients (pts) receiving chemotherapy with or without monoclonal antibodies is prognostic for progression-free survival (PFS) and overall survival (OS). The ‘Deepness of response (DpR)’ concept aims to relate tumor shrinkage to post-progression survival (PPS). If tumor shrinkage does take place, DpR is the percentage of tumor shrinkage observed at the nadir compared with baseline. DpR is 0 for no change and negative if the tumor load increases. Longest diameter (LD) based on RECIST or a calculated tumor volume (ASCO GI 2012 #635) can be used to quantify the tumor load. A joint model was presented (ASCO GI 2012 #580, ASCO 2012 #3603) which allows the prediction of PPS time for an individual patient based on DpR. Methods: Based on the data from the randomized CRYSTAL and OPUS trials, four treatment regimens (FOLFIRI +/- cetuximab and FOLFOX4 +/- cetuximab) were studied. A joint model was used to quantify individual changes in tumor size over time and relate these changes to PFS and OS. Relationships between baseline tumor load and DpR and PPS were studied. A Spearman correlation was used to study the relationship between DpR and PPS for KRAS wild-type pts with progressive disease. Results: Results are reported using LD-based measures for 841 pts with KRAS wild-type tumors and imaging data: 663 from the CRYSTAL study and 178 from the OPUS study. The 348 pts treated with FOLFIRI alone had a median DpR of 33.3% (interquartile range [IR]: 8.0%, 58.0%) while the 315 pts treated with FOLFIRI + cetuximab had a significantly higher median DpR of 50.9% (IR: 18.4%, 78.6%), p < 0.0001. The 96 pts treated with FOLFOX4 alone had a median DpR of 30.7% (IR: 4.0%, 55.9%) and the 82 pts treated with FOLFOX4 + cetuximab had a significantly higher median DpR of 57.9% (IR: 24.0%, 92.9%), p = 0.0008. Correlation between DpR and PPS for pts with documented disease progression was statistically significant in each of the two treatment groups and for both LD-based and volume-based measurements (p < 0.0001 for the CRYSTAL study and p < 0.005 for the OPUS study). The hazard ratios show a higher DpR to significantly favor a longer PPS time across the two studies and both treatment groups for both LD- and volume-based measurements. Conclusion: Our results emphasize the value of DpR as a new efficacy outcome measure for clinical trials. Furthermore the addition of cetuximab to chemotherapy was shown to significantly increase DpR with the prolongation of PPS and thus OS.