Miracle-dz/UniFAR-FTUs huggingface dataset:
Intercalary bone grafts for joint and limb preservation in 17 dogs with high-grade malignant tumors of the diaphysis.

OBJECTIVE To evaluate postoperative complications, limb function, and tumor control after intercalary resection and reconstruction for preservation of limb and joint function in dogs with high-grade malignant tumors of diaphyseal bone. STUDY DESIGN Retrospective study. ANIMALS Seventeen client-owned dogs. METHODS The bone tumor database and medical records were reviewed (1986-2002) for dogs with diaphyseal tumors treated with intercalary resection and reconstruction with either an allograft or irradiated autograft. Clinical presentation, diagnostic findings, surgical management, and outcome were determined from medical records and telephone interviews with veterinarians and owners. Statistical analyses included chi2 to test associations between intra- and postoperative variables with complications, and Kaplan-Meier survival analysis for disease-free interval, metastasis-free interval (MFI), and median survival time. RESULTS Intercalary limb-sparing surgery was performed in 17 dogs with diaphyseal tumors: osteosarcoma (OSA) (15), histiocytic sarcoma (1), and solitary metastasis from a pulmonary adenocarcinoma (1). One dog was excluded from further analysis when the spared limb was amputated 4 days postoperatively because of incomplete tumor resection. In 16 dogs, limb function was good to excellent. Complications occurred in 5 dogs (31.3%) and included superficial infection in 2 dogs (12.5%) and implant failure in 4 dogs (25%). All implant failures occurred in the ulna and there was a significant association between implant failure and non-cemented allografts (P=.042). Non-union of 1 or both osteotomies was diagnosed in 10 dogs (83.3%) and, despite lack of clinical signs in all cases, was significantly associated with the use of intracavitary locally released cisplatin (P=.046) and cemented intercalary grafts (P=.046). Local tumor recurrence was diagnosed in 1 dog (6.3%) and metastatic disease in 12 dogs (75.0%), including 10 dogs with OSA. The median MFI was 137 days. The local disease-free and overall limb-salvage rate was 94% and 100%, respectively. Overall median survival time was 393 days and the median survival time for dogs with OSA was 449 days. CONCLUSION Intercalary limb-sparing surgery results in better postoperative limb function with fewer and less severe complications than historical reports of dogs treated with non-intercalary limb-sparing surgery. CLINICAL RELEVANCE In dogs with diaphyseal tumors, intercalary limb-sparing surgery preserves normal joint function and results in good to excellent limb use with few complications and good local tumor control.
Frequent detection of human rhinoviruses, paramyxoviruses, coronaviruses, and bocavirus during acute respiratory tract infections

Viruses are the major cause of pediatric acute respiratory tract infection (ARTI) and yet many suspected cases of infection remain uncharacterized. We employed 17 PCR assays and retrospectively screened 315 specimens selected by season from a predominantly pediatric hospital‐based population. Before the Brisbane respiratory virus research study commenced, one or more predominantly viral pathogens had been detected in 15.2% (n = 48) of all specimens. The Brisbane study made an additional 206 viral detections, resulting in the identification of a microbe in 67.0% of specimens. After our study, the majority of microbes detected were RNA viruses (89.9%). Overall, human rhinoviruses (HRVs) were the most frequently identified target (n = 140) followed by human adenoviruses (HAdVs; n = 25), human metapneumovirus (HMPV; n = 18), human bocavirus (HBoV; n = 15), human respiratory syncytial virus (HRSV; n = 12), human coronaviruses (HCoVs; n = 11), and human herpesvirus‐6 (n = 11). HRVs were the sole microbe detected in 37.8% (n = 31) of patients with suspected lower respiratory tract infection (LRTI). Genotyping of the HRV VP4/VP2 region resulted in a proposed subdivision of HRV type A into sublineages A1 and A2. Most of the genotyped HAdV strains were found to be type C. This study describes the high microbial burden imposed by HRVs, HMPV, HRSV, HCoVs, and the newly identified virus, HBoV on a predominantly paediatric hospital population with suspected acute respiratory tract infections and proposes a new formulation of viral targets for future diagnostic research studies. J. Med. Virol. 78:1232–1240, 2006. © 2006 Wiley‐Liss, Inc.
Evaluation of the effect of one large dose of erythropoietin against cardiac and cerebral ischemic injury occurring during cardiac surgery with cardiopulmonary bypass: a randomized double‐blind placebo‐controlled pilot study

Cardiac surgery and cardiopulmonary bypass (CPB) induce ischemia–reperfusion and subsequent cellular injury with inflammatory reaction. Clinical and experimental studies suggest that recombinant human erythropoietin (EPO) independently of its erythropoietic effect may be used as a cytoprotective agent against ischemic injury. We tested the hypothesis that one large dose of EPO administered shortly before CPB prevents the elevation of cardiac and cerebral ischemic blood markers as well as the systemic inflammatory response induced by cardiac surgery with CBP through this randomized double‐blind placebo‐controlled pilot trial. Fifty patients scheduled for coronary artery bypass graft (CABG) surgery with CPB were randomly allocated to EPO or control groups. EPO (800 IU/kg intravenously) or placebo (saline) was administered before CPB. The primary end point was to study the effect of EPO administration on several blood markers of myocardial and cerebral ischemia in relation to CABG with CPB. In both groups, surgery increased plasma concentrations of cardiac (troponin T, NT‐proBNP, and creatine kinase MB) and cerebral (S100β protein) markers ischemic as well as the pro‐inflammatory marker interleukin‐6. Compared with the placebo, EPO administration before CPB did not prevent an increase of all these markers following CPB. In conclusion, one large dose of EPO, given shortly before CPB, did not protect against cardiac and cerebral ischemia and inflammatory response occurring during CABG surgery with CPB. Although the long‐term clinical implications remain unknown, the findings do not support use of EPO at this dose as a cytoprotective agent in patients undergoing cardiac surgery.
Targeted Identification of SUMOylation Sites in Human Proteins Using Affinity Enrichment and Paralog-specific Reporter Ions*

Protein modification by small ubiquitin-like modifier (SUMO) modulates the activities of numerous proteins involved in different cellular functions such as gene transcription, cell cycle, and DNA repair. Comprehensive identification of SUMOylated sites is a prerequisite to determine how SUMOylation regulates protein function. However, mapping SUMOylated Lys residues by mass spectrometry (MS) is challenging because of the dynamic nature of this modification, the existence of three functionally distinct human SUMO paralogs, and the large SUMO chain remnant that remains attached to tryptic peptides. To overcome these problems, we created HEK293 cell lines that stably express functional SUMO paralogs with an N-terminal His6-tag and an Arg residue near the C terminus that leave a short five amino acid SUMO remnant upon tryptic digestion. We determined the fragmentation patterns of our short SUMO remnant peptides by collisional activation and electron transfer dissociation using synthetic peptide libraries. Activation using higher energy collisional dissociation on the LTQ-Orbitrap Elite identified SUMO paralog-specific fragment ions and neutral losses of the SUMO remnant with high mass accuracy (< 5 ppm). We exploited these features to detect SUMO modified tryptic peptides in complex cell extracts by correlating mass measurements of precursor and fragment ions using a data independent acquisition method. We also generated bioinformatics tools to retrieve MS/MS spectra containing characteristic fragment ions to the identification of SUMOylated peptide by conventional Mascot database searches. In HEK293 cell extracts, this MS approach uncovered low abundance SUMOylated peptides and 37 SUMO3-modified Lys residues in target proteins, most of which were previously unknown. Interestingly, we identified mixed SUMO-ubiquitin chains with ubiquitylated SUMO proteins (K20 and K32) and SUMOylated ubiquitin (K63), suggesting a complex crosstalk between these two modifications.
Cell cycle perturbation induced by gemcitabine in human tumor cells in cell culture, xenografts and bladder cancer patients: implications for clinical trial designs combining gemcitabine with a Chk1 inhibitor

Gemcitabine irreversibly inhibits ribonucleotide reductase and induces S phase arrest but whether this occurs in tumors in mice or patients has not been established. Tumor cells in culture were incubated with gemcitabine for 6 h to approximate the administration schedule in a patient. Concentrations that induced persistent S phase arrest thereafter correlated with cell killing. Administration of gemcitabine to mice also demonstrated a persistent S phase arrest in their tumor. The minimum dose that induced almost complete S phase arrest after 24 h (40 mg/kg) was well below the maximum tolerated dose in mice. S phase arrest was also observed in tumors of bladder cancer patients receiving gemcitabine. The Chk1 inhibitor MK-8776 sensitized cells to gemcitabine with the greatest cell killing when added 18 h after gemcitabine. In mice, the administration of MK-8776 18 h after gemcitabine elicited positivity for the DNA damage marker γH2AX; this also occurred at relatively low dose (40 mg/kg) gemcitabine. Hence, in both cell culture and xenografts, MK-8776 can markedly enhance cell killing of cells reversibly arrested in S phase by gemcitabine. Some cell lines are hypersensitive to MK-8776 as monotherapy, but this was not observed in xenograft models. Effective monotherapy requires a higher dose of Chk1 inhibitor, and target inhibition over a longer time period as compared to its use in combination. These results have important implications for combining Chk1 inhibitors with gemcitabine and suggest that Chk1 inhibitors with increased bioavailability may have improved efficacy both in combination and as monotherapy.
Non-ossicular signal transmission in human middle ears: Experimental assessment of the "acoustic route" with perforated tympanic membranes.

Direct acoustic stimulation of the cochlea by the sound-pressure difference between the oval and round windows (called the "acoustic route") has been thought to contribute to hearing in some pathological conditions, along with the normally dominant "ossicular route. " To determine the efficacy of this acoustic route and its constituent mechanisms in human ears, sound pressures were measured at three locations in cadaveric temporal bones [with intact and perforated tympanic membranes (TMs)]: (1) in the external ear canal lateral to the TM, P(TM); (2) in the tympanic cavity lateral to the oval window, P(OW); and (3) near the round window, P(RW). Sound transmission via the acoustic route is described by two concatenated processes: (1) coupling of sound pressure from ear canal to middle-ear cavity, H(P(CAV) ) identical withP(CAV)P(TM), where P(CAV) represents the middle-ear cavity pressure, and (2) sound-pressure difference between the windows, H(WPD) identical with(P(OW)-P(RW))P(CAV). Results show that: H(P(CAV) ) depends on perforation size but not perforation location; H(WPD) depends on neither perforation size nor location. The results (1) provide a description of the window pressures based on measurements, (2) refute the common otological view that TM perforation location affects the "relative phase of the pressures at the oval and round windows," and (3) show with an intact ossicular chain that acoustic-route transmission is substantially below ossicular-route transmission except for low frequencies with large perforations. Thus, hearing loss from TM perforations results primarily from reduction in sound coupling via the ossicular route. Some features of the frequency dependence of H(P(CAV) ) and H(WPD) can be interpreted in terms of a structure-based lumped-element acoustic model of the perforation and middle-ear cavities.
Use of gene tests to detect hereditary predisposition to cancer: What do we know about cost effectiveness?

Mutations in 4 genes associated with DNA repair have been shown to be associated with hereditary non‐polyposis colon cancer (HNPCC) in families which display unusually high risk for colorectal cancer. Laboratory tests for mutations in these genes will soon be commercially available, raising the possibility that population‐wide gene testing to identify individuals with an inherited susceptibility to colorectal cancer could be conducted. The purpose of our report is to explore the economic implications of conducting a program of population‐wide screening for HNPCC compared with alternative programs which would be restricted to families already known to be at high risk for HNPCC. Rather than provide a definitive answer to these questions, our purpose is to indicate priority areas of research which need to be conducted before such a definitive analysis can be done. An exploratory analysis has been conducted to determine which factors are most important in determining the cost‐effectiveness of a genetic testing program for HNPCC. The base case analysis focuses on current uncertainty about the population prevalence of the HNPCC genotype and phenotype, factors which are central to the cost‐effectiveness of population‐wide screening. Uncertainty in parameters related to the cost and effectiveness of screening and preventive interventions for HNPCC were explored using additional sensitivity analyses. Favorable levels of cost‐effectiveness for population‐wide screening are achieved only when the most favorable assumptions about HNPCC prevalence and the cost and effectiveness of screening and preventive interventions are made. © 1996 Wiley‐Liss, Inc.
Malignancies after mitoxantrone for multiple sclerosis

Objective: To assess the therapy-related risk of malignancies in mitoxantrone-treated patients with multiple sclerosis. Methods: This retrospective observational cohort study included all mitoxantrone-treated patients with multiple sclerosis seen at our department between 1994 and 2007. We collected follow-up information on medically confirmed malignancies, life status, and cause of death, as of 2010. Malignancy rates were compared to the German national cancer registry matched for sex, age, and year of occurrence. Results: Follow-up was completed in 676 of 677 identified patients. Median follow-up time was 8.7 years (interquartile range 6.8–11.2), corresponding to 6,220 person-years. Median cumulative mitoxantrone dose was 79.0 mg/m2 (interquartile range 50.8–102.4). Thirty-seven patients (5.5%) were diagnosed with a malignancy after mitoxantrone initiation, revealing a standardized incidence ratio of 1.50 (95% confidence interval [CI] 1.05–2.08). Entities included breast cancer (n = 9), colorectal cancer (n = 7), acute myeloid leukemia (n = 4, 0.6%), and others (each entity n = 1 or 2). The standardized incidence ratio of colorectal cancer was 2.98 (95% CI 1.20–6.14) and of acute myeloid leukemia 10.44 (95% CI 3.39–24.36). It was not increased for other entities including breast cancer. Multivariate Cox regression identified higher age at treatment initiation but neither cumulative mitoxantrone dose (>75 vs ≤75 mg/m2) nor treatment with other immunosuppressive drugs or sex as a risk factor. Fifty-five patients had died, among them 12 of a malignancy and 43 reportedly of other causes. Conclusions: While the overall incidence of malignancies was only mildly increased, the risk of leukemia and colorectal cancer was heightened. If confirmed, posttherapy colonoscopy could become advisable.
The prevalence of chronic deep venous thrombosis in trauma: Implications for hospitals and patients

INTRODUCTION Deep venous thrombosis (DVT) is considered a preventable complication in trauma patients. Hospitals risk financial penalties for DVT rates above accepted benchmarks. These penalties do not apply to chronic DVT, which develops before admission. Lower-extremity duplex ultrasound (LEDUS) can detect characteristics of thrombus chronicity, allowing differentiation of chronic from acute DVT. The objective of this study was to determine the prevalence of chronic DVT in hospitalized trauma patients. METHODS We performed a retrospective review of trauma patients admitted to our Level I trauma center between July 1, 2006 and October 31, 2016 who had a DVT on initial screening LEDUS. Our center utilizes screening and surveillance LEDUS for patients admitted more than 48 hours. Definitions for chronic and acute DVT were extracted from existing literature. Patients with DVT on initial LEDUS underwent review of that LEDUS to assess clot chronicity and were classified as having acute DVT, chronic DVT, or DVT of indeterminate age. Demographic data, medical history, and injury characteristics were collected. Patients with acute DVT and those with chronic DVT were compared. RESULTS The prevalence of chronic DVT among patients with a DVT on initial LEDUS was 29.9%. Chronic DVT occurred in patients who were older and less severely injured. An above-knee component was significantly more common in chronic DVT (65%). Only 34 (41%) of those with chronic DVT reported a history of DVT. Among the patients with chronic DVT, 44 (53%) had a subsequent LEDUS, of whom 4 (9%) showed thrombus progression and 6 (14%) formed a new DVT. CONCLUSION Lower-extremity duplex ultrasound can identify chronic DVT, which represents nearly 30% of all DVT found on initial screening LEDUS in trauma patients. Those with chronic DVT should receive pharmacologic and mechanical prophylaxis because of the incidence of progression and new acute DVT. They should also be counseled regarding the possibilities of recurrence and chronic venous insufficiency. LEVEL OF EVIDENCE Diagnostic study, level III.
Update on antimicrobial agents: new indications of older agents

The discovery of newly recognised pathogens and the emergence of antimicrobial resistance have led to the development of new antimicrobial agents or to new indications for older agents. The indications have continued to increase because of new discoveries on the older agents’ antimicrobial and non-antimicrobial activities. Macrolides and tetracyclines have received attention for their non-antimicrobial properties and potential use in chronic inflammatory disorders. Doxycycline, minocycline and trimethoprim-sulfamethoxazole regained interest for their activity against methicillin-resistant Staphylococcus aureus, whereas colistin has regained interest for its activity against multiple drug-resistant, Gram-negative pathogens (i.e., Pseudomonas aeruginosa). Despite the recent development of new antimicrobial agents, older and less costly agents maintain an important role today in the treatment of infectious diseases.
Fas promoter -670 polymorphism is associated with development of anti-RNP antibodies in systemic lupus erythematosus.

OBJECTIVE To evaluate whether the polymorphism of Fas promoter -670 is associated with susceptibility to systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) and their clinical features. METHODS A polymerase chain reaction of a genomic DNA-restriction fragment length polymorphism was used to determine genotypes of the Fas promoter -670 in 87 patients with SLE, 87 with RA, and 87 healthy controls. A second cohort of SLE patients (n = 85) was included. Clinical manifestations were analyzed in each patient and correlated with the genotypes. RESULTS The genotype distribution of the Fas promoter -670 did not differ between patients with SLE and control subjects (AA, GA, GG genotypes 31, 54, 15% vs 30, 55, 15% controls, respectively; chi-squared = 0.03, 2 df, p = 0.99) and between RA patients and controls (AA, GA, GG genotypes 38, 44, 18% vs 30, 55, 15% controls, respectively; chi-squared = 2.30, 2 df, p = 0.32). Regarding the clinical status of lupus patients according to Fas promoter -670 genotypes, there was no significant difference in age at onset, anti-dsDNA titer, C3, C4 level, renal involvement, number of American College of Rheumatology (ACR) criteria met, SLE Disease Activity Index, SLE International Collaborating Clinics/ACR Damage Index, or autoantibody profiles. However, the frequency of anti-RNP antibody was significantly different in the AA, GA, and GG groups (71, 25, 30%; chi-squared = 13.29, 2 df, p = 0.001). To confirm this finding, the Fas promoter -670 genotype was examined in a second cohort of SLE patients (n = 85). The result in the second cohort replicated the association shown in the first. In patients with RA, there was no significant difference in clinical and laboratory findings according to the Fas promoter -670 genotypes. CONCLUSION Our data suggest that the Fas promoter -670 polymorphism is associated with development of anti-RNP antibodies in SLE.
Ciclogénesis intensas en la cuenca occidental del Mediterráneo y temperatura superficial del mar: Modelización y evaluación de las áreas de recarga

Una caracteristica propia de las precipitaciones en el area del Mediterraneo Occidental es la torrencialidad. En el marco de unas precipitaciones anuales no muy abundantes, tipicas del clima mediterraneo, se registran fenomenos de precipitaciones torrenciales intensas en muchas zonas del Mediterraneo Occidental que provocan grandes danos economicos e incluso, en ocasiones, victimas. La cuenca mediterranea esta conformada por un mar profundo y semicerrado rodeado por una serie de cadenas montanosas, especialmente en su mitad occidental. Esta configuracion favorece el desarrollo de una dinamica atmosferica propia con algunos comportamientos particulares de esta region. Uno de los factores que pueden ser importantes en la genesis y desarrollo de las precipitaciones torrenciales es la interaccion entre el mar y la atmosfera con intercambios de humedad y calor que pueden inestabilizar la masa de aire que se desplaza sobre el mar. El Mediterraneo es un mar semicerrado con una circulacion propia y poco intercambio de masas de agua con otros mares u oceanos. A partir de datos de satelites se ha elaborado una climatologia de la temperatura superficial del Mediterraneo y se ha estudiado sus patrones de distribucion espacial en las diferentes epocas del ano. Como resultado de este analisis, se ha determinado la existencia de dos regimenes principales de distribucion de la temperatura superficial de mar en las epocas invernal y estival, con dos periodos de transicion entre ambas en primavera y otono. A partir del conocimiento de la climatologia de la temperatura superficial del mar y, especialmente, de su distribucion espacial se han seleccionado tres eventos de precipitaciones torrenciales en la Comunidad Valenciana para estudiar el efecto de las diferentes distribuciones de temperatura del mar en la simulacion de las lluvias torrenciales. Para ello, se ha seleccionado episodios de lluvia correspondientes a los regimenes invernal, estival y de transicion en otono. Para todos los eventos se ha realizado una simulacion de control con los datos de temperatura superficial del mar originales que actua como simulacion de control. Posteriormente se ha realizado simulaciones de cada evento en las que se perturbaba la temperatura superficial del mar en las zonas por las que se desplazaba la masa de aire que originaba las lluvias torrenciales a lo largo de su trayectoria en los dias previos. Se ha comprobado en los resultados del modelo meteorologico que la variacion de la temperatura superficial del mar en determinadas zonas, indicadas por su regimen de distribucion espacial, provoca importantes cambios en la precipitacion acumulada. Se ha podido identificar, por tanto, la existencia de areas de recarga donde la interaccion mar-atmosfera favorece el desarrollo de precipitaciones torrenciales en diferentes puntos de la cuenca mediterranea, en este caso la Comunidad Valenciana.