Miracle-dz/UniFAR-FTUs huggingface dataset:
Decision making for the surgical approach of posterior petrous bone meningiomas.

OBJECT The authors undertook this study to examine the surgical approaches used to treat posterior petrous bone meningiomas at a single institution and retrospectively evaluate their surgical strategy based on a previously published classification. METHODS Cases in which craniotomies were performed to treat posterior petrous bone meningiomas between 2002 and 2010 were retrospectively reviewed. Data were examined from 57 patients who were treated for 59 tumors. The tumors were classified into 3 types according to the location of their primary dural attachment: Type A, located around the porus trigeminus (33 tumors); Type M, located at the level of the porus of the internal auditory canal (IAC) (12 tumors); and Type P, located laterally to the IAC (14 tumors). The median tumor diameter was 34 mm (range 20-67 mm). RESULTS The choice of the approach was based on tumor location, as the displacement of vascular structures and cranial nerves was primarily determined by the site of dural attachment on the posterior petrous bone. An anterior petrosectomy was performed in 82% of Type A meningiomas, and a retrosigmoid approach was used in 86% of Type P meningiomas. The spectrum of approaches was less uniform for Type M meningiomas. Overall, total resection was obtained in 39% of all cases, and in 18%, 50%, and 86% of Type A, Type M, and Type P tumors, respectively. The postoperative mortality rate was 8.8% (5 deaths among 57 patients), and all 5 patients who died during the early postoperative period had large Type A tumors. At last follow-up, the functional preservation of the facial nerve was excellent in 49 (94%) of the 52 surviving patients. CONCLUSIONS The authors believe that proper selection of the approach favorably impacts functional outcome in patients undergoing surgery for the treatment of skull base tumors. In the authors' case series of posterior petrous bone meningiomas, Type P and most Type M tumors were safely managed through a regular retrosigmoid approach, whereas Type A tumors were optimally treated via an epidural anterior petrosectomy.
Morphine inhibits VEGF expression in myocardial ischemia.

BACKGROUND Vascular endothelial growth factor (VEGF) may contribute to the resolution of myocardial ischemia by stimulating collateral circulation. Morphine analgesia after myocardial ischemia is thought to increase infarct size. We hypothesize that morphine inhibits myocardial VEGF expression by inhibiting hypoxia-induced factor 1alpha (HIF-1alpha) and the signal transduction mechanisms involving Erk-1,2 MAP kinase (p42/p44), and PI3 kinase activity (phospho-Akt). METHODS (1) In vitro: primary cultures of rat cardiac myocytes; (2) in vivo: rat coronary ligation model; (3) mRNA measurement: real-time reverse transcriptase-polymerase chain reaction; (4) protein measurements: enzyme-linked immunosorbent assay, Western immunoblot, electromobility shift assay (EMSA), and immunohistochemistry. RESULTS Using rat cardiac myocytes in vitro, we show that morphine: (1) decreases hypoxia-induced VEGF(121) and VEGF(165) mRNA expression and VEGF protein concentration through an opioid receptor mechanism; (2) decreases HIF-1alpha protein expression (immunoblot) and nuclear protein binding to the VEGF HIF-1alpha DNA response element (EMSA); and (3) inhibits phospho-Erk-1,2 MAP kinase (immunoblot) and phospho-Akt kinase activity (immunoblot). Using a rat coronary ligation model, we show that morphine treatment: (1) decreases myocardial VEGF protein expression (immunohistochemistry); (2) decreases HIF-1alpha protein expression (immunoblot); and (3) decreases phospho-Erk-1,2 and phospho-Akt expression. CONCLUSIONS (1) Morphine inhibits hypoxia-induced VEGF transcription, in part, through an HIF-1alpha-mediated mechanism and (2) morphine inhibition of hypoxia-induced HIF-1alpha may be mediated by inhibition of ERK 1,2 MAP kinase activity and PI3 kinase activity.
A novel approach to predicting protein structural classes in a (20–1)‐D amino acid composition space

The development of prediction methods based on statistical theory generally consists of two parts: one is focused on the exploration of new algorithms, and the other on the improvement of a training database. The current study is devoted to improving the prediction of protein structural classes from both of the two aspects. To explore a new algorithm, a method has been developed that makes allowance for taking into account the coupling effect among different amino acid components of a protein by a covariance matrix. To improve the training database, the selection of proteins is carried out so that they have (1) as many non‐homologous structures as possible, and (2) a good quality of structure. Thus, 129 representative proteins are selected. They are classified into 30 α, 30 β, 30 α + β, 30 α/β, and 9 ζ (irregular) proteins according to a new criterion that better reflects the feature of the structural classes concerned. The average accuracy of prediction by the current method for the 4 × 30 regular proteins is 99.2%, and that for 64 independent testing proteins not included in the training database is 95.3%. To further validate its efficiency, a jackknife analysis has been performed for the current method as well as the previous ones, and the results are also much in favor of the current method. To complete the mathematical basis, a theorem is presented and proved in Appendix A that is instructive for understanding the novel method at a deeper level. © 1995 Wiley‐Liss, Inc.
Quality of life in caregivers providing care for lung transplant candidates.

CONTEXT Caregivers are essential members of the health care team who provide care, valued at more than $250 billion each year, to millions of persons who require assistance with health and daily care. Patients with respiratory diseases who are waiting for a lung transplant are required to have an identified caregiver. The caregivers are rarely studied. OBJECTIVE To explore the relationships among the health status of caregivers of lung transplant candidates, caregivers' reaction to caregiving, and caregivers' perceived quality of life. DESIGN This descriptive study examined the quality of life of lung transplant caregivers from a multidimensional perspective. SETTING AND PARTICIPANTS Twenty-nine dyads of lung transplant candidates and their caregivers were recruited from a Midwestern medical center. MEASURES Data were collected by self-report: caregivers completed the Quality of Life Index, SF-12 health survey, Profile of Mood States-Short Form, and the Caregiver Reaction Assessment. RESULTS Caregivers reported favorable levels of quality of life, physical health, and mood during the pretransplant waiting phase. However, problem areas for caregivers during this time included fatigue, depression, and the financial impact of the transplant. Data analyses indicated that depression, caregiver general health, impact on finances, and lack of family support had the greatest effect on caregivers' quality of life. Nurses are urged to recognize the role of caregivers in the transplant process, ask about and listen to caregivers' needs, and include caregivers in the plan of care.
A systematic review on zinc for the prevention and treatment of age-related macular degeneration.

PURPOSE The objective of this systematic review was to examine the evidence on zinc intake from foods and supplements in the primary prevention and treatment of AMD. METHODS Randomized controlled trials (RCTs), prospective cohort, retrospective cohort, and case-control studies that investigated zinc intake from foods and/or supplements, and AMD in men and women with a mean age of 50 years or older were included. Medline and Cochrane Central were searched from inception to February 2012 and November 2012, respectively. Data extraction and quality appraisal were done on all eligible studies. RESULTS TEN STUDIES WERE INCLUDED: four RCTs, four prospective cohort, and two retrospective cohort studies. Age-related Eye Disease Study (AREDS) showed zinc treatment to significantly reduce the risk of progression to advanced AMD. The risk of visual acuity loss was of similar magnitude, but not statistically significant. Two RCTs reported statistically significant increases in visual acuity in early AMD patients and one RCT showed no effect of zinc treatment on visual acuity in advanced AMD patients. Results from six cohort studies on associations between zinc intake and incidence of AMD were inconsistent. CONCLUSIONS Current evidence on zinc intake for the prevention of AMD is inconclusive. Based on the strength of AREDS, we can conclude that zinc treatment may be effective in preventing progression to advanced AMD. Zinc supplementation alone may not be sufficient to produce clinically meaningful changes in visual acuity.
Differential expression of Zif268 and c‐Fos in the primary visual cortex and lateral geniculate nucleus of normal Cebus monkeys and after monocular lesions

The transcription factors c‐Fos and Zif268 have been used as markers of neuronal activity, and they also have been implicated in neuronal plasticity. In this study, we investigated the expression of c‐Fos and Zif268 proteins in the lateral geniculate nucleus (LGN) and in the cortical primary visual area (V1) of normal adult Cebus apella monkeys and in animals with monocular lesions. In the LGN, the reaction for c‐Fos showed immunopositive cells in both magnocellular (M) and parvocellular (P) layers; however, the label was heavier in P layers. In animals that suffered monocular lesions, the immunocytochemistry for c‐Fos showed more labeling in layers related to the normal eye compared with those of the lesioned eye. No specific label was observed after the reaction for Zif268 in the LGN. In V1, the reaction for both Zif268 and c‐Fos showed a pattern of lamination in which heavier labeling was found in layers 2/3, 4A, 4C, and 6. After monocular lesions, we observed a clear pattern of ocular dominance columns in V1 for both c‐Fos and Zif268, in which the columns related to the normal eye are more heavily labeled than those related to the lesioned eye. This pattern is more evident in layer 4C after c‐Fos reaction, whereas, after Zif268, it is more clearly observed in layers 2/3. These results suggest that, in addition to be regulated by functional activity, these transcription factors are involved in different processes during cortical reorganization. J. Comp. Neurol. 482:166–175, 2005. © 2004 Wiley‐Liss, Inc.
Survival prediction of gastric cancer by a seven-microRNA signature

Aims Several microarray studies have reported microRNA (miRNA) expression signatures that classify cancer patients into different prognostic groups. No study has evaluated the association between miRNA expression patterns and gastric cancer prognosis. In this study, we developed a seven-miRNA signature that is closely associated with survival of patients with gastric cancer. Patients and methods MiRNA expression profile was analysed by real-time RT-PCR in 100 gastric cancer patients, which were randomly assigned to either the training set or the testing set. Cox proportional hazard regression and risk-score analysis were used to identify a stage-independent set of seven-miRNA signature in the training set that could classify patients with significantly different prognosis. This miRNA signature was further validated by the testing set and an independent cohort 60 patients. Results We have identified a seven-miRNA signature (miR-10b, miR-21, miR-223, miR-338, let-7a, miR-30a-5p, miR-126) for overall survival (p=0.0009) and relapse-free survival (p=0.0005) of gastric cancer patients. Multivariate analysis shown that the risk signature was an independent predictor of overall survival (HR=3.046; 95% CI, 1.246 to 7.445, p=0.015) and relapse-free survival (HR=3.337; 95% CI, 1.298 to 8.580, p=0.012). Furthermore, the predictive value of this seven-miRNA signature was validated in the testing set of 50 patients and an independent set of 60 patients. Conclusion Our seven-miRNA signature is closely associated with relapse-free and overall survival among patients with gastric cancer. The prognostic signature could be applicable to future decisions concerning treatment.
Lear homo-oligomeric helical bundles membrane proteins ? Perspectives from the study of How do helix – helix interactions help determine the folds of

The final, structure-determining step in the folding of membrane proteins involves the coalescence of preformed transmembrane helices to form the native tertiary structure. Here, we review recent studies on small peptide and protein systems that are providing quantitative data on the interactions that drive this process. Gel electrophoresis, analytical ultracentrifugation, and fluorescence resonance energy transfer (FRET) are useful methods for examining the assembly of homo-oligomeric transmembrane helical proteins. These methods have been used to study the assembly of the M2 proton channel from influenza A virus, glycophorin, phospholamban, and several designed membrane proteins—all of which have a single transmembrane helix that is sufficient for association into a transmembrane helical bundle. These systems are being studied to determine the relative thermodynamic contributions of van der Waals interactions, conformational entropy, and polar interactions in the stabilization of membrane proteins. Although the database of thermodynamic information is not yet large, a few generalities are beginning to emerge concerning the energetic differences between membrane and water-soluble proteins: the packing of apolar side chains in the interior of helical membrane proteins plays a smaller, but nevertheless significant, role in stabilizing their structure. Polar, hydrogen-bonded interactions occur less frequently, but, nevertheless, they often provide a strong driving force for folding helix–helix pairs in membrane proteins. These studies are laying the groundwork for the design of sequence motifs that dictate the association of membrane helices.
The causes of primary biliary cirrhosis: Convenient and inconvenient truths

The most difficult issue in autoimmunity remains etiology. Although data exist on effector mechanisms in many autoimmune diseases, the underlying cause or causes are still generically ascribed to genetics and environmental influences. Primary biliary cirrhosis (PBC) is considered a model autoimmune disease because of its signature antimitochondrial autoantibody (AMA), the homogeneity of clinical characteristics, and the specificity of biliary epithelial cell (BEC) pathology. Twenty years ago, we reported the cloning and identification of the E2 component of pyruvate dehydrogenase (PDC‐E2) as the immunodominant autoantigen of PBC, allowing for vigorous dissection of T and B lymphocyte responses against PDC‐E2 and development of several valid experimental models. There has also been considerable study of the biology of BECs, which has included the unique properties of apoptosis in which there is exposure of PDC‐E2 to the effector processes of the immune system. In this review, we present these data in the context of our proposal that the proximal cause of PBC is autoimmunity directed against well‐identified mitochondrially located autoantigens in individuals with inherited deficits of immune tolerance. We present these data under the umbrella of convenient truths that support this thesis as well as some inconvenient truths that are not readily accommodated by current theory. Conclusion: We emphasize that the potential initiator of PBC includes inter alia particular environmental xenobiotics; pathogenesis is aided and abetted by genetic weaknesses in mechanisms of immune regulation; and subsequent multilineage immunopathology impacts upon uniquely susceptible BECs to culminate clinically in the chronic autoimmune cholangiolitis of PBC. (HEPATOLOGY 2007.)
Proteome Analysis of Human Metaphase Chromosomes*

DNA is packaged as chromatin in the interphase nucleus. During mitosis, chromatin fibers are highly condensed to form metaphase chromosomes, which ensure equal segregation of replicated chromosomal DNA into the daughter cells. Despite >1 century of research on metaphase chromosomes, information regarding the higher order structure of metaphase chromosomes is limited, and it is still not clear which proteins are involved in further folding of the chromatin fiber into metaphase chromosomes. To obtain a global view of the chromosomal proteins, we performed proteome analyses on three types of isolated human metaphase chromosomes. We first show the results from comparative proteome analyses of two types of isolated human metaphase chromosomes that have been frequently used in biochemical and morphological analyses. 209 proteins were quantitatively identified and classified into six groups on the basis of their known interphase localization. Furthermore, a list of 107 proteins was obtained from the proteome analyses of highly purified metaphase chromosomes, the majority of which are essential for chromosome structure and function. Based on the information obtained on these proteins and on their localizations during mitosis as assessed by immunostaining, we present a four-layer model of metaphase chromosomes. According to this model, the chromosomal proteins have been newly classified into each of four groups: chromosome coating proteins, chromosome peripheral proteins, chromosome structural proteins, and chromosome fibrous proteins. This analysis represents the first compositional view of human metaphase chromosomes and provides a protein framework for future research on this topic.
A Prospective, Observational Study of Adverse Reactions to Drug Regimen for Multi-Drug Resistant Pulmonary Tuberculosis in Central India

Objective 1) To assess the adverse drug reactions (ADRs) of second-line anti-tubercular drugs used to treat Multi-drug resistant Tuberculosis (MDR-TB) in central India on the basis of causality, severity and avoidability scales. 2) To investigate the relationship of MDR-TB (primary or secondary) and the presence of diabetes mellitus (DM) with mean smear conversion time. Material and Methods: A prospective, observational study was carried out on diagnosed multidrug-resistant tuberculosis patients enrolled for DOTS-Plus regimen at TB and Chest Disease Department from January 2012 to December 2012 with a follow-up of nine months. Encountered ADRs were noted along with the time of sputum conversion. Results Total 64 ADRs were reported in 55 patients out of total 110 patients (n=110). As per the Naranjo causality assessment of ADRs, seven patients had definite, 45 had probable, and 3 had possible causal relation with drugs of DOTS-Plus regimen. As per the Hartwig’s severity assessment scale, there were total 7 ADRs in Level 1, 6 in Level 2, 33 in Level 3 and 9 in Level 4. Hallas avoidability assessment scale divided the ADRs as 3 being definitely avoidable, 26 possibly avoidable, 23 not avoidable and three not evaluable. Mean sputum smear conversion time was significantly higher in patients with a secondary type than that of primary type of MDR TB and in patients with DM than those without DM. Conclusion ADRs were common in patients of MDR-TB on DOTs-Plus drug regimen. It was due to lack of availability of safer and equally potent drugs in DOTs-Plus drug regimen compared to DOTS regimen in non-resistant TB. The frequency and severity of ADRs can be reduced by strict vigilance about known and unknown ADRs, monitoring their laboratory and clinical parameters and instituting appropriate measures.
Phase I clinical and pharmacokinetic study of oral S-1 in patients with advanced solid tumors.

PURPOSE To investigate the side effects, determine the maximum-tolerated dose (MTD), and study the pharmacokinetics of S-1, an oral fluoropyrimidine-based antineoplastic agent consisting of the fluorouracil (5-FU) prodrug tegafur combined with two modulators, 5-chloro-2,4-dihydroxypyridine and potassium oxonate. PATIENTS AND METHODS Patients with advanced solid tumors received S-1 bid for 28 days, followed by 1 week of rest. 5-FU pharmacokinetics were investigated after a single initial dose of S-1 during the first 24 hours and weekly thereafter. RESULTS Twenty-eight patients received S-1 at the four consecutive dose levels of 25, 45, 35, and 40 mg/m(2). The MTD was initially found at 45 mg/m(2), with diarrhea as the dose-limiting toxicity (DLT). Diarrhea was also the DLT at the dose of 40 mg/m(2), which was the MTD for patients exposed to extensive prior chemotherapy. Other toxicities were generally mild. Two patients had a reduction of more than 50% in tumor dimension. Plasma pharmacokinetics of 5-FU were linear; at the highest S-1 dose level, 5-FU plasma peak concentrations reached 1 to 2 micromol/L, and the half-life of 5-FU was 3 to 4 hours. A statistically significant relationship was observed between the severity of diarrhea and pharmacokinetic parameters of 5-FU. CONCLUSION The recommended dose of S-1 in chemotherapy-naive or minimally chemotherapy-exposed patients is 40 mg/m(2) bid on 28 consecutive days, every 5 weeks. In heavily pretreated patients, the recommended dose is 35 mg/m(2) bid. Phase II trials are warranted in tumors known to be responsive to 5-FU treatment.
Neonatal Tolerization With Glutamic Acid Decarboxylase But Not With Bovine Serum Albumin Delays the Onset of Diabetes in NOD Mice

To test the role of glutamic acid decarboxylase (GAD65) or bovine serum albumin (BSA) autoimmunity in the pathogenesis of diabetes, GAD65 or BSA was injected intraperitoneally into neonatal female NOD mice (100 micrograms/mouse of each protein). Treatment with GAD65, but not with BSA, significantly delayed the onset of diabetes compared with control mice (P < 0.05). At 18 weeks, 6 of 10 control mice compared with 0 of 10 GAD65-treated mice (P = 0.005) and 7 of 14 BSA-treated mice had developed diabetes. However, after 79 weeks, 6 of 10 of the GAD65-treated mice were diabetic compared with 9 of 10 of the control mice and 12 of 14 of the BSA-treated mice. In GAD65-treated mice without diabetes, insulitis was markedly reduced compared with control or BSA-treated mice (P < 10−4). To further elucidate why GAD becomes an autoantigen, the expression in NOD mice islets was studied. Quantitative immunohistochemistry revealed that islet cell expression of GAD was increased in 5-week-old NOD mice compared with BALB/c mice (P = 0.02). With the occurrence of insulitis (9–15 weeks), the GAD expression was further increased relative to 5-week-old NOD mice (P < 0.02). In conclusion, GAD, but not BSA, autoimmunity is important for the development of diabetes in NOD mice. Furthermore, concordant with the appearance of insulitis, the GAD expression increased in NOD mouse islets, which could possibly potentiate the β-cell-directed autoimmunity.