Miracle-dz/UniFAR-FTUs huggingface dataset:
Bisphosphonate-related osteonecrosis of the jaw: the Florence experience.

Aims. Bisphosphonates (BPs) are important therapeutic drugs in multiple myeloma and cancers with bone metastases. Bisphosphonate-Related Osteonecrosis of the Jaw (BRONJ) has been described as a potential side effect of the last generation BPs. The Authors evaluated clinical features, preventing measures and treatment strategies.Patients and methods. The Authors retrospectively analyzed 19 patients affected by malignant cancer in endovenous treatment with BPs. Fourteen patients were treated with zoledronate, 1 with pamidronate and 4 with both drugs for breast cancer (9 patients), multiple myeloma (6 patients), prostatic cancer (3 patients) and colon cancer (1 patient). Results. The lenght of therapy was 5-36 months before osteonecrosis was observed; in 15 patients BRONJ involved the mandible, in 2 the maxilla and in 2 both jaws. The trigger factors were tooth extractions, inadequate removable total denture, basic and advanced surgery, root canal treatment. Ten patients received non-surgical treatment, 7 patients minor surgical procedures and 2 patients a partial maxillectomy. Healing was achieved in all maxillary localization, and in one mandibular localization with partial maxillectomy.Conclusions. Prevention is the best important phase in the management of this pathology. Risk factors are the type of bisphosphonate and the length of exposure, while dental surgical procedures are trigger factors. Conservative treatment seems to be the best way to control BRONJ, but bone resection and soft tissue closure have to be performed when the lesion is refractory to conservative approach.
Testosterone replacement in hypogonadal men alters the HDL proteome but not HDL cholesterol efflux capacity[S]

The effects of androgens on cardiovascular disease (CVD) risk in men remain unclear. To better characterize the relationship between androgens and HDL, we investigated the effects of testosterone replacement on HDL protein composition and serum HDL-mediated cholesterol efflux in hypogonadal men. Twenty-three older hypogonadal men (ages 51–83, baseline testosterone < 280 ng/dl) were administered replacement testosterone therapy (1% transdermal gel) with or without the 5α-reductase inhibitor dutasteride. At baseline and after three months of treatment, we determined fasting lipid concentrations, HDL protein composition, and the cholesterol efflux capacity of serum HDL. Testosterone replacement did not affect HDL cholesterol (HDL-C) concentrations but conferred significant increases in HDL-associated paraoxonase 1 (PON1) and fibrinogen α chain (FGA) (P = 0.022 and P = 0.023, respectively) and a decrease in apolipoprotein A-IV (apoA-IV) (P = 0.016). Exogenous testosterone did not affect the cholesterol efflux capacity of serum HDL. No differences were observed between men who received testosterone alone and those who also received dutasteride. Testosterone replacement in older hypogonadal men alters the protein composition of HDL but does not significantly change serum HDL-mediated cholesterol efflux. These effects appear independent of testosterone conversion to dihydrotestosterone. Further research is needed to determine how changes in HDL protein content affect CVD risk in men.
Valence, arousal and word associations

This study aimed at testing the relative effects of valence and arousal on the generation of unusual first associates in response to non-emotional inducers. To examine this question, four specific moods varying along both the valence and the arousal dimensions were induced: happiness (positive mood, high arousal), serenity (positive mood, low arousal), anger (negative mood, high arousal) and sadness (negative mood, low arousal). The results indicate that the uniqueness of word-associations is influenced by arousal levels rather than by the valence of mood. No matter what the valence, high-arousing moods enhanced the production of unusual associates in contrast to low-arousing moods.
The Interstellar Carbon Budget and the Role of Carbon in Dust and Large Molecules

Published data on stellar composition show that carbon in the sun is substantially more abundant than in other stars. A carbon abundance of 225 carbon atoms per 106 hydrogen atoms is representative of galactic stars, whereas published values for the sun range from 350 to 470 carbon atoms per 106 hydrogen atoms. Other elements are also present in enhanced quantities in the solar system, consistent with suggestions that a supernova event was closely associated with the formation of the solar system. The overabundance of carbon in the solar system has many important implications, including new constraints on nucleosynthesis models for supernovae and substantial modification of the so-called “cosmic” composition normally adopted in discussions of galactic and interstellar abundances. A reduction in the galactic carbon budget, as suggested by the stellar composition data, strongly constrains the quantity of carbon that is available for the formation of interstellar dust, and some dust models now appear implausible because they require more carbon than is available.
Towards automated assistance for operating home medical devices

To detect errors when subjects operate a home medical device, we observe them with multiple cameras. We then perform action recognition with a robust approach to recognize action information based on explicitly encoding motion information. This algorithm detects interest points and encodes not only their local appearance but also explicitly models local motion. Our goal is to recognize individual human actions in the operations of a home medical device to see if the patient has correctly performed the required actions in the prescribed sequence. Using a specific infusion pump as a test case, requiring 22 operation steps from 6 action classes, our best classifier selects high likelihood action estimates from 4 available cameras, to obtain an average class recognition rate of 69%.
Papillomavirus-like particle based vaccines: cervical cancer and beyond

Non-infectious human papillomavirus-like particles (VLP), composed of the L1 major capsid protein, are under active development as vaccines to prevent cervical cancer. They would presumably function primarily by generating virion-neutralising antibodies against the genital human papillomavirus (HPV) types that are the principal cause of most cervical cancers. Early phase clinical studies indicate that the VLP vaccines are well tolerated and able to consistently induce high titres of virus type-specific neutralising antibodies. Two types of second-generation VLP-based subunit vaccines with therapeutic implications, both related and unrelated to papillomavirus infection, are in preclinical development. One type seeks to induce cell-mediated immune responses, especially cytotoxic lymphocytes (CTL), against non-structural papillomavirus proteins, proteins of other viruses, or tumour associated antigens. The target antigen is incorporated into the VLPs as a fusion protein of L1 or the L2 minor capsid protein. In mouse models, this approach has generated potent CTL responses after low dose vaccination in the absence adjuvant. The second type of therapeutic VLP-based vaccine seeks to generate autoantibodies to self-antigens. The display of self polypeptides in the context of the highly ordered array of repetitive elements on the papillomavirus VLP surface abrogates the ability of the humoral immune system to functionally distinguish between foreign and self. High titre and high avidity auto-reactive IgG antibodies have been induced to both soluble (TNF-α) and cell surface (CCR5) central self-antigens. Vaccines based on this approach could potentially be effective alternatives to monoclonal antibody (mAb)-based therapies for a variety of disease targets.
A controlled trial of exercise rehabilitation after heart transplantation.

BACKGROUND In patients who have received a cardiac transplant, the denervated donor heart responds abnormally to exercise and exercise tolerance is reduced. The role of physical exercise in the treatment of patients who have undergone cardiac transplantation has not been determined. We assessed the effects of training on the capacity for exercise early after cardiac transplantation. METHODS Twenty-seven patients who were discharged within two weeks after receiving a heart transplant were randomly assigned to participate in a six-month structured cardiac-rehabilitation program (exercise group, 14 patients) or to undergo unstructured therapy at home (control group, 13 patients). Each patient in the exercise group underwent an individualized program of muscular-strength and aerobic training under the guidance of a physical therapist, whereas control patients received no formal exercise training. Cardiopulmonary stress testing was performed at base line (within one month after heart transplantation) and six months later. RESULTS As compared with the control group, the exercise group had significantly greater increases in peak oxygen consumption (mean increase, 4.4 ml per kilogram of body weight per minute [49 percent] vs. 1.9 ml per kilogram per minute [18 percent]; P=0.01) and workload (mean increase, 35 W [59 percent] vs. 12 W [18 percent]; P=0.01) and a greater reduction in the ventilatory equivalent for carbon dioxide (mean decrease, 13 [20 percent] vs. 6 [11 percent]; P=0.02). The mean dose of prednisone, the number of patients taking antihypertensive medications, the average number of episodes of rejection and of infection during the study period, and weight gain did not differ significantly between the groups. CONCLUSIONS When initiated early after cardiac transplantation, exercise training increases the capacity for physical work.
An experimental model of aortic surgery and the effect of Iloprost on lung injury

Abstract Objectives. Ischemia/reperfusion (I/R) damage of the lung is a frequently encountered complication following aortic surgery. The aim of the present study is to investigate the histopathological effects of Iloprost on pulmonary damage developed after I/R. Design. Twenty-four Sprague-Dawley rats were randomly divided into 3 groups. In the control group, aortas were not clamped. In the I/R group, aortas were occluded, and after 1 h of ischemia, clamps were removed. After 2 h of reperfusion period, lungs of the rats were extracted. In the I/R + Iloprost group after 1 h of ischemia, Iloprost infusion was initiated, and maintained for the duration of 2 h reperfusion period. For histopathological scoring, density of polymorphonuclear leucocytes, congestion, interstitial edema, and bleeding were semiquantitatively evaluated, and histopathological changes were scored. Results. In the I/R group, multifocal-marked histopathological changes in 5 (62.5%), and multifocal-moderate histopathological changes in 3 (37.5%) rats were detected. In the I/R + Iloprost group, multifocal-moderate histopathological changes in 4 (50%), and multifocal-mild changes in 4 (50%) rats were detected. Conclusions. In the experimental rat model, administration of Iloprost has been shown to have preventive effects for pulmonary damage occurring after I/R generated by infrarenal aortic occlusion.
Do Porous Titanium Granule Grafts Affect Bone Microarchitecture at Augmented Maxillary Sinus Sites? A Pilot Split-Mouth Human Study

Background:The aim of this randomized controlled clinical study was to analyze the bone microarchitecture at augmented maxillary sinus sites by using different materials in patients to compare the effect of porous titanium granules as a sinus augmentation material with bone microstructural features. Materials and Methods:Eight subjects with bilateral atrophic posterior maxilla of residual bone height <4 mm included in this study and each patient was treated with bilateral sinus augmentation procedure using xenograft with equine origin (Apatos, Osteobiol; Tecnoss Dental) and xenograft (1 g) + porous titanium (1 g) granules (Natix; Tigran Technologies AB). Sixteen human bone biopsy samples were taken from patients receiving two-stage sinus augmentation therapy during implant installation and analyzed using microcomputerized tomography. Three-dimensional bone structural parameters were analyzed in details: tissue volume, bone volume, percentage of bone volume, bone surface and bone surface density, bone specific surface, trabecular thickness trabecular separation, trabecular number, trabecular pattern factor, structural model index, fractal dimension, and bone mineral density. Results:No statistically significant differences were found between groups according to bone structural parameters. Conclusions:Porous titanium grafts may ensure a space for new bone formation in the granules, which may be a clinical advantage for long-term success.
Time-course, negative-stain electron microscopy–based analysis for investigating protein–protein interactions at the single-molecule level

Several biophysical approaches are available to study protein–protein interactions. Most approaches are conducted in bulk solution, and are therefore limited to an average measurement of the ensemble of molecular interactions. Here, we show how single-particle EM can enrich our understanding of protein–protein interactions at the single-molecule level and potentially capture states that are unobservable with ensemble methods because they are below the limit of detection or not conducted on an appropriate time scale. Using the HIV-1 envelope glycoprotein (Env) and its interaction with receptor CD4-binding site neutralizing antibodies as a model system, we both corroborate ensemble kinetics-derived parameters and demonstrate how time-course EM can further dissect stoichiometric states of complexes that are not readily observable with other methods. Visualization of the kinetics and stoichiometry of Env–antibody complexes demonstrated the applicability of our approach to qualitatively and semi-quantitatively differentiate two highly similar neutralizing antibodies. Furthermore, implementation of machine-learning techniques for sorting class averages of these complexes into discrete subclasses of particles helped reduce human bias. Our data provide proof of concept that single-particle EM can be used to generate a “visual” kinetic profile that should be amenable to studying many other protein–protein interactions, is relatively simple and complementary to well-established biophysical approaches. Moreover, our method provides critical insights into broadly neutralizing antibody recognition of Env, which may inform vaccine immunogen design and immunotherapeutic development.
Percutaneous Revascularization of Grafts Versus Native Coronary Arteries in Postcoronary Artery Bypass Graft Patients

In patients with previous coronary artery bypass graft surgery, it is unknown whether better results may be obtained with percutaneous interventions of grafts versus native arteries. The clinical outcomes in 84 patients undergoing percutaneous interventions of either grafts (n = 31) or native arteries (n = 53) were compared. Procedural success rate was 95.3% (96.8% in the graft group vs 94.4% in the native group, P = .3). Mean follow-up was 19 ± 7 months. The incidence of major adverse events was 14.2% (12.9% vs 15.1% in the graft and native groups, respectively; P = .8), mortality rate was 3.5% (6.4% vs 1.8% in the graft and native groups, respectively; P = .3), and target-lesion revascularization was performed in 4.7% (6.4% vs 3.7% in the graft and native groups, respectively, P = .6). In conclusion, both graft or native percutaneous interventions were similar for immediate and midterm clinical outcomes. The relatively low risk need for target-lesion revascularization obtained with both strategies is encouraging.
Influence of combined thrombin stimulation, surface activation, and receptor occupancy on organization of GPIb/IX receptors on human platelets

Summary. Down‐regulation and clearance of as many as 60–80% of GPIb/IX receptors from exposed surfaces on thrombin‐activated platelets to channels of the open canalicular system (OCS) is considered to be a fundamental mechanism regulating platelet adhesivity in vitro and in vivo. The present study has combined thrombin stimulation in suspension, surface activation on formvar grids, receptor occupancy by von Willebrand factor (vWF) and exposure to anti‐vWF antibody in an effort to demonstrate the removal of GPIb/IX receptors from activated cells. Individually the stimuli failed to cause any change in the frequency of GPIb/ IX receptors. Combined, the stimuli were no more effective than when each was used alone. The only way to cause GPIb/IX to move was to add anti‐vWF to thrombin‐activated platelets allowed to spread on formvar grids and covered with multimers of ristocetin‐activated human or bovine vWF. Translocation of GPIb/IX‐vWF‐anti‐vWF complexes from peripheral margins into caps over cell centres, however, did not clear the peripheral zone of vWF binding capacity. Exposure of capped platelets after fixation to a second incubation with vWF demonstrated as many multimers extending from the central cap to the peripheral margins as were seen on platelets exposed a single time to vWF. Antibodies to GPIb, but not to GPIIb/IIIA, prevented the second labelling by vWF. Down‐regulation or clearance of GPIb/IX, in light of this study, does not appear to be a fundamental mechanism modulating platelet adhesivity.
Gonadal effects of cancer therapy in boys

A retrospective study of testicular histology was carried out in 21 prepubertal boys and in 11 intrapubertal or postpubertal boys who died from 1 day to 1 year after treatment with chemotherapy (CT) with or without radiation therapy (RT) for extragonadal solid tumors. Based on autopsy findings, profound histologic changes were found in six prepubertal boys and in all but one of the intrapubertal and postpubertal boys. For three of the prepubertal and five of the postpubertal boys with altered testicular histology, the contribution of pelvic RT could not be excluded. When prepubertal patients were evaluated according to nutritional status, a thickened tubular wall and absent or severely reduced spermatogonia were found in only 1 of 11 adequately nourished boys as compared with 5 of 10 malnourished boys. In intrapubertal and postpubertal boys, the tubular wall was thickened in six and these changes were independent of nutritional status. All malnourished intrapubertal and postpubertal patients demonstrated impaired spermatogenesis (versus 67% of age‐matched malnourished controls), whereas similar impairment was noted in 60% with adequate nutrition versus 20% of controls. The diffuse damage of germ cells and tubules in malnourished younger boys suggests that the prepubertal male is not necessarily protected against the reproductive effects of cancer therapy.
Platelet storage media

Present platelet storage media often designated platelet additive solutions (PAS) basically contain acetate, citrate and phosphate and recently also potassium and magnesium. However, there seems to be an increasing interest in developing PASs that can be used also after further reduction of residual plasma content below 15–20% plasma. Inclusion of glucose but also calcium and bicarbonate in such solutions have been suggested to improve platelet (PLT) storage, especially when plasma content is reduced to very low levels. Results from a limited number of studies using novel PAS alternatives have been presented during the last years, such as InterSol‐G, PAS‐5, M‐sol, PAS‐G and SAS. Most of them are experimental solutions. The combined results presented in those studies suggest that presence of glucose may be necessary during PLT storage, primarily to maintain ATP at acceptable levels. At plasma inclusion below 15–20%, the content of glucose will generally be too low to support PLT metabolism for more than a few days making glucose addition in PAS necessary. Significant effects associated with presence of calcium was observed in PLTs stored in PAS with 5% inclusion but not with 20–35% plasma inclusion, suggesting that the content of plasma could be of importance. Bicarbonate only seems to be of importance for pH regulation, primarily when plasma inclusion is reduced to about 5%. Reduction in rate of glycolysis was observed in some PAS alternatives containing potassium and magnesium but not in others. Differences in pH or in concentrations of the various compounds included in PAS may be possible explanations. Additionally, novel PAS containing glucose, calcium and bicarbonate does not seem to be associated with improved in vitro results as compared to SSP+ or CompoSol when PLTs are stored with 35% plasma inclusion. The results would then also suggest that excess of glucose in novel PAS environment may not be associated with additional positive effects on PLT metabolism. This review is based on the few publications on novel PAS available, and additional studies would be needed in the future.
Expression of p53 and its homologues in primary and recurrent squamous cell carcinomas of the head and neck

The tumour‐suppressor protein p53 belongs to a family that includes 2 structurally related proteins, p63 and p73. Because of their structural homology, it has been hypothesized that both homologues serve as “spare mechanisms” in p53 mutations to regulate the cell cycle by inducing apoptosis. We investigated the mutational and protein expression status of p53 in correlation to its homologues, p73 and p63, in primary and recurrent squamous cell carcinomas of the head and neck (HNSCC) and corresponding nonneoplastic mucosa. Expression and mutation of p53 and its homologues p63 (including the 2 major isotypes TAp63 and ΔNp63) and p73 was examined by direct DNA sequencing and immunohistochemistry in 29 primary and 39 recurrent (secondary) HNSCCs after microdissection. Our results were correlated with pathohistologic stage and grade. p53 mutations were detected in 32/68 (47%) carcinomas of 17 patients, with a discordant mutation pattern of primary and consecutive tumours in all cases. Positive immunostaining for p63 was found in 55/68 (81%) carcinomas of 29 patients. Immunohistochemistry revealed p73 protein expression in 32/68 (47%) tumours. In normal mucosa, p63 and p73 were expressed in 40/68 (59%) and 12/68 (18%) cases, respectively. We failed to detect specific mutations of p73 or p63 in primary and recurrent carcinoma of the head and neck. p73 and p63 were rarely mutated in HNSCC, but both were expressed in a subset of tumours. The lack of correlation between p73/p63 and p53 protein expression suggests that neither p73 nor p63 can replace p53 when it is mutated. © 2002 Wiley‐Liss, Inc.