Miracle-dz/UniFAR-FTUs huggingface dataset:
Single cycle to failure in bending of three standard and five locking plates and plate constructs

Summary Objective: To evaluate the biomechanical properties of standard and locking plates in bending. We hypothesised that titanium (Ti) constructs would have the greatest deformation and that String of Pearl (SOP) constructs would have the greatest strength and stiffness, and would behave differently compared to plates alone. Methods: Dynamic compression plates (DCP), stainless steel (SS) limited contact (LC)-DCP®, Ti LC-DCP, locking compression plates (LCP), 10 mm and 11 mm advanced locking plate system (ALPS 10 / 11), SOP and Fixin plates were evaluated individually and as constructs applied to a validated bone model simulating a bridging osteosynthesis. Bending stiffness and strength were compared using one-way ANOVA with post hoc Tukey, and un-paired t-test (p <0.05). Results: The SOP plates had significantly greater stiffness than all other plates Ti LCDCP, ALPS 10 and Fixin plates had significantly lower stiffness than all other plates. The SOP constructs had the highest mean bending stiffness, and strength that was significantly different from only the Ti LC-DCP, ALPS 10 and Fixin constructs. The ALPS 10 constructs had the lowest mean bending stiffness, and strength that was significantly different from only ALPS 11 and SOP constructs. Comparison of bending structural stiffness of plates versus constructs showed a significant difference in all plate pairs except for the DCP and ALPS 10. Clinical relevance: Due to differing plate construct properties inherent to these diverse implant systems, identical approaches to fracture management and plate application cannot be applied. Presented at the 38th Annual Conference of the Veterinary Orthopedic Society, Snowmass, CO, USA March 6, 2011 (Mark S. Bloomberg Memorial Research Award recipient).
Effect of fusaric acid and phytoanticipins on growth of rhizobacteria and Fusarium oxysporum.

Suppression of soilborne diseases by biocontrol agents involves complex interactions among biocontrol agents and the pathogen and between these microorganisms and the plant. In general, these interactions are not well characterized. In this work, we studied (i) the diversity among strains of fluorescent Pseudomonas spp. , Bacillus spp. , and Paenibacillus sp. for their sensitivity to fusaric acid (FAc) and phytoanticipins from different host plants, (ii) the diversity of pathogenic and nonpathogenic Fusarium oxysporum isolates for their sensitivity to phytoanticipins, and (iii) the influence of FAc on the production of pyoverdine by fluorescent Pseudomonas spp. tolerant to this compound. There was a great diversity in the response of the bacterial strains to FAc; however, as a group, Bacillus spp. and Paenibacillus macerans were much more sensitive to FAc than Pseudomonas spp. FAc also affected production of pyoverdine by FAc-tolerant Pseudomonas spp. strains. Phytoanticipins differed in their effects on microbial growth, and sensitivity to a phytoanticipin varied among bacterial and fungal strains. Biochanin A did not affect growth of bacteria, but coumarin inhibited growth of Pseudomonas spp. strains and had no effect on Bacillus circulans and P. macerans. Conversely, tomatine inhibited growth of B. circulans and P. macerans. Biochanin A and tomatine inhibited growth of three pathogenic isolates of F. oxysporum but increased growth of three nonpathogenic F. oxysporum isolates. Coumarin inhibited growth of all pathogenic and nonpathogenic F. oxysporum isolates. These results are indicative of the complex interactions that can occur among plants, pathogens, and biological control agents in the rhizosphere and on the root surface. Also, these results may help to explain the low efficacy of some combinations of biocontrol agents, as well as the inconsistency in achieving disease suppression under field conditions.
MiT family translocation renal cell carcinoma.

The MiT subfamily of transcription factors includes TFE3, TFEB, TFC, and MiTF. Gene fusions involving two of these transcription factors have been identified in renal cell carcinoma (RCC). The Xp11 translocation RCCs were first officially recognized in the 2004 WHO renal tumor classification, and harbor gene fusions involving TFE3. The t(6;11) RCCs harbor a specific Alpha-TFEB gene fusion and were first officially recognized in the 2013 International Society of Urologic Pathology (ISUP) Vancouver classification of renal neoplasia. These two subtypes of translocation RCC have many similarities. Both were initially described in and disproportionately involve young patients, though adult translocation RCC may overall outnumber pediatric cases. Both often have unusual and distinctive morphologies; the Xp11 translocation RCCs frequently have clear cells with papillary architecture and abundant psammomatous bodies, while the t(6;11) RCCs frequently have a biphasic appearance with both large and small epithelioid cells and nodules of basement membrane material. However, the morphology of these two neoplasms can overlap, with one mimicking the other. Both of these RCCs underexpress epithelial immunohistochemical markers like cytokeratin and epithelial membrane antigen (EMA) relative to most other RCCs. Unlike other RCCs, both frequently express the cysteine protease cathepsin k and often express melanocytic markers like HMB45 and Melan A. Finally, TFE3 and TFEB have overlapping functional activity as these two transcription factors frequently heterodimerize and bind to the same targets. Therefore, on the basis of clinical, morphologic, immunohistochemical, and genetic similarities, the 2013 ISUP Vancouver classification of renal neoplasia grouped these two neoplasms together under the heading of "MiT family translocation RCC. " This review summarizes our current knowledge of these recently described RCCs.
Factors associated with difficulties encountered by nurses in the care of terminally ill cancer patients in hospitals in Japan

Objective: To identify the factors associated with difficulties encountered by nurses working in general wards in hospitals in Japan. Methods: Questionnaires including items regarding difficulties in providing care to terminally ill cancer patients, the existence of a mentor regarding end-of-life issues, awareness of end-of-life issues, and demographic factors were administered to 375 staff nurses working in general in-patient wards. Multivariate regression analyses were employed to investigate correlations between factors. Results: Multivariate regression analysis revealed that the existence of a mentor for end-of-life issues was associated with fewer difficulties in all areas other than “Knowledge and skill of nurses. ” Clinical experience was inversely related to difficulties in “Communication with patients and families” and “Personal issues. ” Greater awareness of end-of-life issues was related to higher difficulties in most areas. Significance of results: The existence of a mentor was correlated with fewer difficulties in most areas. Support by a palliative care team might be effective in reducing difficulties experienced by nurses and in improving care for terminally ill cancer patients. Basic communication training undertaken sooner after registration might be also useful.
68Ga-Labeled Bombesin Studies in Patients with Gastrointestinal Stromal Tumors: Comparison with 18F-FDG

Dynamic PET studies with a 68Ga-bombesin analog, DOTA-PEG2-[d-Tyr6, β-Ala11,Thi13,Nle14] BN(6-14) amide (68Ga-BZH3; DOTA is 1,4,7,10-tetraazacyclododecane-N,N′,N″,N‴-tetraacetic acid, and PEG is ethylene glycol [2-aminoethyl-carboxymethyl ether]), were performed on patients with gastrointestinal stromal tumors (GIST) to investigate the impact of complementary receptor scintigraphy on diagnosis and the potential of a radionuclide treatment. Furthermore, dynamic 18F-FDG studies were performed on the same patients. Methods: This study comprised 17 patients with GIST. All patients were scheduled for therapy with imatinib because of unresectable primary or recurrent GIST or because of metastatic disease. Dynamic PET scans using 68Ga-BZH3 and 18F-FDG were obtained on 2 consecutive days. Multivariate analysis was used to evaluate the kinetic data. Standardized uptake values (SUVs) were calculated, and a compartmental model (2-tissue) and noncompartmental model were used for data evaluation of both tracers. Results: Fourteen of 17 patients (25/30 lesions) were positive for uptake on 18F-FDG imaging, whereas 68Ga-BZH3 demonstrated an enhanced accumulation in 7 of 17 patients (8/30 lesions). Thirteen lesions were confirmed by histologic examination, and the remaining 17 were confirmed by follow-up. One recurrent tumor in the stomach could not be delineated on 18F-FDG imaging but showed enhanced 68Ga-BZH3 uptake. The median SUV for 68Ga-BZH3 was 3.3, in comparison with 7.9 for 18F-FDG. Best-subset analysis demonstrated that the global SUV (55–60 min after injection) for 18F-FDG was primarily dependent on k3, followed by k1. Multivariate analysis did not show a significant correlation between the kinetic parameters (k1–k4, fractional blood volume, and SUV) for 18F-FDG and bombesin. Conclusion: 68Ga-BZH3 may be helpful for diagnostic reasons in a subgroup of patients with GIST, as in the case of negative 18F-FDG findings and suspicion of viable tumor tissue. The meaning of the enhanced 68Ga-BZH3 uptake is open at the moment.
Spoof Plasmon-Based Slow-Wave Excitation of Dielectric Resonator Antennas

A spoof plasmon (SP)-based slow-wave feeding configuration is proposed, experimentally verified and exploited to excite the fundamental horizontally polarized mode of dielectric resonator antennas (DRAs). As an example, a cylindrical DRA operating at 3 GHz is fed by the proposed feeding structure. The simulation and measurement evidence the unique features of TE01δ mode such as lower thickness-dependency of the resonant frequencies, superb miniaturization and ultra-compactness, and omnidirectional radiation for horizontally polarized waves. We anticipate that the ground-free SP-based feeding technique could be applied to effectively excite the more “unusual” modes of the isolated DRAs.
Phase II study of docetaxel, estramustine, and low-dose hydrocortisone in men with hormone-refractory prostate cancer: a final report of CALGB 9780. Cancer and Leukemia Group B.

PURPOSE To investigate the combination of docetaxel, estramustine (EM), and low-dose hydrocortisone in men with hormone-refractory prostate cancer (HRPC). PATIENTS AND METHODS Combinations of EM with other antimitotic agents such as docetaxel are synergistic in vitro and show significant clinical activity in patients with HRPC. We studied intravenous administration of docetaxel 70 mg/m(2), oral estramustine, and low-dose daily hydrocortisone in men with HRPC who demonstrated progression after initial hormone therapy. RESULTS Of the 47 men enrolled onto this multicenter cooperative group study, 46 were assessable for response and/or toxicity. In the 24 patients with measurable disease, there were three complete and nine partial responses for a measurable disease response rate of 50% (12 of 24 patients; 95% confidence interval [CI], 27% to 73%). In the 44 patients in whom pretreatment prostate-specific antigen (PSA) was elevated, 30 (68%) had a 50% or greater decrease, and 25 (57%) had a 75% or greater decrease in PSA. The combined measurable disease and biochemical response rate in all 46 assessable patients was 54% (three complete responses, 22 partial responses, 95% CI, 37% to 71%). The predominant toxicity was neutropenia, with 26% of patients having grade 3 and 30% having grade 4 granulocytopenia; there were no episodes of febrile neutropenia. Other common but mild adverse effects included malaise/fatigue, peripheral edema, and hyperglycemia. The incidence of thromboembolic events during therapy was 9%. With a median follow-up of 17 months, the median survival was 20 months. The median time to disease progression was 8 months for all patients, and 10 months for those with measurable disease. CONCLUSION This therapy is efficacious and moderately well tolerated in HRPC and should be compared in a phase III trial with mitoxantrone and prednisone.
Structural Adaptation of Vascular Networks: Role of the Pressure Response

Structural reductions in vessel luminal diameters in response to elevated pressure may play a role in the elevation of peripheral resistance generally observed in hypertension. In the present study, a theoretical model is used to simulate the effect of increased driving pressure on flow resistance in microvascular networks. The angioarchitecture (lengths and diameters of all segments, topology) of microvascular networks (n=6) in the rat mesentery was recorded by intravital microscopy. The model simulation of vascular adaptation in response to local wall shear stress, transmural pressure, and tissue Po2 was used to predict changes in network pressure drop and flow resistance for a given change of driving pressure (&Dgr;P). For &Dgr;P increasing from 15% to 190% of the normotensive value, a 3.3-fold increase in flow resistance was observed (structural autoregulation). If vascular reactivity to pressure was suppressed, the resistance increase was abolished. Suppressing pressure sensitivity also led to a rise in mean capillary pressure at normal driving pressure from 23.8±7.3 mm Hg to 34±6.9 mm Hg. These results indicate that low capillary pressure levels as well as structural autoregulation depend on vascular responses to circumferential wall stress (corresponding to pressure). This tendency of peripheral vascular beds to increase flow resistance for a given increase of bulk flow or driving pressure may amplify and stabilize blood pressure elevation in the development of hypertension.
A Role for TIC55 as a Hydroxylase of Phyllobilins, the Products of Chlorophyll Breakdown during Plant Senescence[OPEN]

TIC55, a Rieske-type oxygenase previously described as a component of the chloroplast protein import machinery, also functions as a chlorophyll catabolite hydroxylase. Chlorophyll degradation is the most obvious hallmark of leaf senescence. Phyllobilins, linear tetrapyrroles that are derived from opening of the chlorin macrocycle by the Rieske-type oxygenase PHEOPHORBIDE a OXYGENASE (PAO), are the end products of chlorophyll degradation. Phyllobilins carry defined modifications at several peripheral positions within the tetrapyrrole backbone. While most of these modifications are species-specific, hydroxylation at the C32 position is commonly found in all species analyzed to date. We demonstrate that this hydroxylation occurs in senescent chloroplasts of Arabidopsis thaliana. Using bell pepper (Capsicum annuum) chromoplasts, we establish that phyllobilin hydroxylation is catalyzed by a membrane-bound, molecular oxygen-dependent, and ferredoxin-dependent activity. As these features resemble the requirements of PAO, we considered membrane-bound Rieske-type oxygenases as potential candidates. Analysis of mutants of the two Arabidopsis Rieske-type oxygenases (besides PAO) uncovered that phyllobilin hydroxylation depends on TRANSLOCON AT THE INNER CHLOROPLAST ENVELOPE55 (TIC55). Our work demonstrates a catalytic activity for TIC55, which in the past has been considered as a redox sensor of protein import into plastids. Given the wide evolutionary distribution of both PAO and TIC55, we consider that chlorophyll degradation likely coevolved with land plants.
Genetic basis for clinical response to CTLA-4 blockade in melanoma.

BACKGROUND Immune checkpoint inhibitors are effective cancer treatments, but molecular determinants of clinical benefit are unknown. Ipilimumab and tremelimumab are antibodies against cytotoxic T-lymphocyte antigen 4 (CTLA-4). Anti-CTLA-4 treatment prolongs overall survival in patients with melanoma. CTLA-4 blockade activates T cells and enables them to destroy tumor cells. METHODS We obtained tumor tissue from patients with melanoma who were treated with ipilimumab or tremelimumab. Whole-exome sequencing was performed on tumors and matched blood samples. Somatic mutations and candidate neoantigens generated from these mutations were characterized. Neoantigen peptides were tested for the ability to activate lymphocytes from ipilimumab-treated patients. RESULTS Malignant melanoma exomes from 64 patients treated with CTLA-4 blockade were characterized with the use of massively parallel sequencing. A discovery set consisted of 11 patients who derived a long-term clinical benefit and 14 patients who derived a minimal benefit or no benefit. Mutational load was associated with the degree of clinical benefit (P=0.01) but alone was not sufficient to predict benefit. Using genomewide somatic neoepitope analysis and patient-specific HLA typing, we identified candidate tumor neoantigens for each patient. We elucidated a neoantigen landscape that is specifically present in tumors with a strong response to CTLA-4 blockade. We validated this signature in a second set of 39 patients with melanoma who were treated with anti-CTLA-4 antibodies. Predicted neoantigens activated T cells from the patients treated with ipilimumab. CONCLUSIONS These findings define a genetic basis for benefit from CTLA-4 blockade in melanoma and provide a rationale for examining exomes of patients for whom anti-CTLA-4 agents are being considered. (Funded by the Frederick Adler Fund and others.).
Malaria control aimed at the entire population in KwaZulu-Natal negates the need for policies to prevent malaria in pregnancy.

BACKGROUND South Africa has no policy to prevent malaria in pregnancy, despite the adverse effects of the disease in pregnancy. However, malaria control measures consisting of indoor residual spraying and specific antimalarial treatment have been in place since the 1970s. Information on the burden of malaria in pregnancy in South Africa is needed to indicate whether a specific policy for malaria prevention in pregnancy is necessary. OBJECTIVE To determine the burden of malaria in pregnancy in KwaZulu-Natal (KZN) province, South Africa. METHODS Pregnant women were enrolled at their first antenatal care visit to three health facilities in Umkhanyakude health district in northern KZN during May 2004 - September 2005 and followed up until delivery. Data collection included demographic details, current and previous malaria infection during pregnancy, haemoglobin concentrations and birth outcomes. RESULTS Of the 1 406 study participants, more than a quarter were younger than 20 years of age, and more than 90% were unemployed and unmarried. Although 33.2% of the women were anaemic, this was not related to malaria. The prevalence and incidence of malaria were very low, and low birth weight was only weakly associated with malaria (1/10). CONCLUSION The low burden of malaria in these pregnant women suggests that they have benefited from malaria control strategies in the study area. The implication is that additional measures specific for malaria prevention in pregnancy are not required. However, ongoing monitoring is needed to ensure that malaria prevalence remains low.
Hormone therapy and Alzheimer’s disease: benefit or harm?

Alzheimer’s disease (AD) is the most common cause of dementia. After menopause, circulating levels of oestrogens decline markedly and oestrogen influences several brain processes predicted to modify AD risk. For example, oestrogen reduces the formation of β-amyloid, a biochemical hallmark of AD. Oestrogen effects on oxidative stress and some effects on inflammation and the cerebral vasculature might also be expected to ameliorate risk. However, AD pathogenesis is incompletely understood and other oestrogen actions could be deleterious. Limited clinical trial evidence suggests that oestrogen therapy, begun after the onset of AD symptoms, is without substantial benefit or harm. Observational studies have associated oestrogen-containing hormone therapy with reduced AD risk. However, in the Women’s Health Initiative Memory Study – a randomised, placebo-controlled trial of women 65 – 79 years of age – oral oestrogen plus progestin doubled the rate of dementia, with heightened risk appearing soon after treatment was initiated. Based on current evidence, hormone therapy is thus not indicated for the prevention of AD. Discrepancies between observational studies and the Women’s Health Initiative clinical trial may reflect biases and unrecognised confounding factors in observational reports. Other explanations for divergent findings should be considered in future research, including effects of unopposed oestrogen or different hormone therapy preparations and the intriguing theoretical possibility that effects of hormone therapy on AD risk may be modified by the timing of use (e.g., initiation during the menopausal transition or early postmenopause versus initiation during the late postmenopause).
Identification and Replication of a Novel Obesity Locus on Chromosome 1q24 in Isolated Populations of Cilento

OBJECTIVE—Obesity is a complex trait with a variety of genetic susceptibility variants. Several loci linked to obesity and/or obesity-related traits have been identified, and relatively few regions have been replicated. Studying isolated populations can be a useful approach to identify rare variants that will not be detected with whole-genome association studies in large populations. RESEARCH DESIGN AND METHODS—Random individuals were sampled from Campora, an isolated village of the Cilento area in South Italy, phenotyped for BMI, and genotyped using a dense microsatellite marker map. An efficient pedigree-breaking strategy was applied to perform genome-wide linkage analyses of both BMI and obesity. Significance was assessed with ad hoc simulations for the two traits and with an original local false discovery rate approach to quantitative trait linkage analysis for BMI. A genealogy-corrected association test was performed for a single nucleotide polymorphism located in one of the linkage regions. A replication study was conducted in the neighboring village of Gioi. RESULTS—A new locus on chr1q24 significantly linked to BMI was identified in Campora. Linkage at the same locus is suggested with obesity. Three additional loci linked to BMI were also detected, including the locus including the INSIG2 gene region. No evidence of association between the rs7566605 variant and BMI or obesity was found. In Gioi, the linkage on chr1q24 was replicated with both BMI and obesity. CONCLUSIONS—Overall, our results confirm that successful linkage studies can be accomplished in these populations both to replicate known linkages and to identify novel quantitative trait linkages.