Miracle-dz/UniFAR-FTUs huggingface dataset:
Clinical Experience With Crizotinib in Patients With Advanced ALK-Rearranged Non-Small-Cell Lung Cancer and Brain Metastases.

PURPOSE Crizotinib is an oral kinase inhibitor approved for the treatment of ALK-rearranged non-small-cell lung cancer (NSCLC). The clinical benefits of crizotinib in patients with brain metastases have not been previously studied. PATIENTS AND METHODS Patients with advanced ALK-rearranged NSCLC enrolled onto clinical trial PROFILE 1005 or 1007 (randomly assigned to crizotinib) were included in this retrospective analysis. Patients with asymptomatic brain metastases (nontarget or target lesions) were allowed to enroll. Tumor assessments were evaluated every 6 weeks using RECIST (version 1.1). RESULTS At baseline, 31% of patients (275 of 888) had asymptomatic brain metastases; 109 had received no prior and 166 had received prior brain radiotherapy as treatment. Among patients with previously untreated asymptomatic brain metastases, the systemic disease control rate (DCR) at 12 weeks was 63% (95% CI, 54% to 72%), the intracranial DCR was 56% (95% CI, 46% to 66%), and the median intracranial time to progression (TTP) was 7 months (95% CI, 6.7 to 16.4). Among patients with previously treated brain metastases, the systemic DCR was 65% (95% CI, 57% to 72%), the intracranial DCR was 62% (95% CI, 54% to 70%), and the median intracranial TTP was 13.2 months (95% CI, 9.9 to not reached). Patients with systemic disease control were also likely to experience intracranial disease control at 12 weeks (correlation coefficient, 0.7652; P < .001). Among patients without baseline brain metastases who developed progressive disease (n = 253) after initiation of crizotinib, 20% were diagnosed with brain metastases. CONCLUSION Crizotinib was associated with systemic and intracranial disease control in patients with ALK-rearranged NSCLC who were ALK inhibitor naive and had brain metastases. However, progression of preexisting or development of new intracranial lesions while receiving therapy was a common manifestation of acquired resistance to crizotinib.
Influence of repeated porcine circovirus type 2 vaccination on sows’ immune response

In the last decade, the impact of the porcine circovirus type 2 (PCV-2)-associated diseases in pigs has consistently decreased due to the extensive application of PCV-2 vaccines in sows and piglets. However, clinical outbreaks of PCV-2 systemic diseases are still reported. For this reason, optimisation of vaccination schemes, which also evaluates vaccination of both sows and piglets, has been studied (Opriessnig and others 2010, Fraile and others 2012). A one-dose vaccine administered prior to mating in gilts and sows elicited a strong and homogeneous humoral response, and consequently, an increased colostral PCV-2 antibody concentration (Sibila and others 2013). The present paper aims at evaluating both the humoral and, for the first time, the cellular PCV-2-specific immune response in gilts and sows repeatedly vaccinated at each mating in order to contribute to a better knowledge on vaccination schemes in sows and in their offspring. In a randomised controlled field trial, two cohorts, each comprised by 46 gilts, were investigated. The study protocol was approved by the University of Parma Institutional Animal Care Committee. Animals, seven months old, originated from the same batch of replacements, were randomly allocated by lot either to group ‘VAC’ or to group ‘NV’. On the day of first mating, VAC sows were injected intramuscularly with 2 ml of a PCV-2 vaccine (Porcilis PCV, MSD Animal Health) (off-label use) and NV sows were injected with the adjuvant only. The same treatment was repeated on the day of mating after the weaning of their first and second litter. Blood samples were taken on the day of enrolment to the study, that is, …
Revisiting Li-Fraumeni Syndrome From TP53 Mutation Carriers.

PURPOSE The aim of the study was to update the description of Li-Fraumeni syndrome (LFS), a remarkable cancer predisposition characterized by extensive clinical heterogeneity. PATIENTS AND METHODS From 1,730 French patients suggestive of LFS, we identified 415 mutation carriers in 214 families harboring 133 distinct TP53 alterations and updated their clinical presentation. RESULTS The 322 affected carriers developed 552 tumors, and 43% had developed multiple malignancies. The mean age of first tumor onset was 24.9 years, 41% having developed a tumor by age 18. In childhood, the LFS tumor spectrum was characterized by osteosarcomas, adrenocortical carcinomas (ACC), CNS tumors, and soft tissue sarcomas (STS) observed in 30%, 27%, 26%, and 23% of the patients, respectively. In adults, the tumor distribution was characterized by the predominance of breast carcinomas observed in 79% of the females, and STS observed in 27% of the patients. The TP53 mutation detection rate in children presenting with ACC or choroid plexus carcinomas, and in females with breast cancer before age 31 years, without additional features indicative of LFS, was 45%, 42% and 6%, respectively. The mean age of tumor onset was statistically different (P < .05) between carriers harboring dominant-negative missense mutations (21.3 years) and those with all types of loss of function mutations (28.5 years) or genomic rearrangements (35.8 years). Affected children, except those with ACC, harbored mostly dominant-negative missense mutations. CONCLUSION The clinical gradient of the germline TP53 mutations, which should be validated by other studies, suggests that it might be appropriate to stratify the clinical management of LFS according to the class of the mutation.
Psychosocial Treatments for Child and Adolescent Disorders: Empirically Based Strategies for Clinical Practice

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Pharmacokinetic study of benzylpenicillin potassium after intramuscular administration in rabbits

BOVINE respiratory disease (BRD) has a major economic impact in different cattle production systems worldwide (Griffin 1997, Pardon and others 2013, Lehenbauer 2014) and is the main reason of antimicrobial use in calves and youngstock (Pardon and others 2012). Public concern to reduce and rationalise veterinary antimicrobial use has markedly increased in the last decade (BelVetSac 2014, MARAN 2015). Veterinary formularies have been constructed which advise sampling, bacterial isolation and antimicrobial susceptibility testing before certain antimicrobial classes can be used (Haneveld 2014, AMCRA 2015). In human beings and different animal species bronchoalveolar lavage (BAL) is considered a safe and reliable sampling technique to identify causal organisms of pneumonia, because it directly samples the lung lobes (Wilkie and Markham 1979, Pringle and others 1988, Thomas and others 2002). Bronchial fluid can be obtained using an endoscope, enabling selection of the lung lobes to be sampled (Pringle and others 1988, Allen and others 1991). Disadvantages of the endoscopic guided BAL are the need for disinfecting the scope between two patients, the high purchase costs of the equipment and the risk for damage when using endoscopes on farm in cattle. For these reasons endoscopic guided BAL is not routinely applied to sample large groups of calves. Alternatively, with adequate training, BAL can be performed without endoscope using a BAL catheter. Advantages are that BAL catheters are cheap and can be sterilised and reused, making sampling of a representative number of animals in a limited time frame possible. However, there may be some drawbacks. It is unknown whether blind sampling with a BAL catheter does sample the ventrocranial lung parts, where the vast majority of bacterial pneumonias in calves are situated (Allan and others 1985, Allen and others 1991, Dagleish and others …
Epidemiology and Clinical Significance of Secondary and Therapy-Related Acute Myeloid Leukemia: A National Population-Based Cohort Study.

PURPOSE Secondary and therapy-related acute myeloid leukemia (sAML and tAML, respectively) remain therapeutic challenges. Still, it is unclear whether their inferior outcome compared with de novo acute myeloid leukemia (AML) varies as a result of previous hematologic disease or can be explained by differences in karyotype and/or age. PATIENTS AND METHODS In a Danish national population-based study of 3,055 unselected patients with AML diagnosed from 2000 to 2013, we compared the frequencies and characteristics of tAML, myelodysplastic syndrome (MDS) -sAML, and non-MDS-sAML (chronic myelomonocytic leukemia and myeloproliferative neoplasia) versus de novo AML. Limited to intensive therapy patients, we compared chance of complete remission by logistic regression analysis and used a pseudo-value approach to compare relative risk (RR) of death at 90 days, 1 year, and 3 years, overall and stratified by age and karyotype. Results were given crude and adjusted with 95% CIs. RESULTS Overall, frequencies of sAML and tAML were 19.8% and 6.6%, respectively. sAML, but not tAML, was associated with low likelihood of receiving intensive treatment. Among intensive therapy patients (n = 1,567), antecedent myeloid disorder or prior cytotoxic exposure was associated with decreased complete remission rates and inferior survival (3-year adjusted RR for MDS-sAML, non-MDS-sAML, and tAML: RR, 1.14; 95% CI, 1.02 to 1.32; RR, 1.27; 95% CI, 1.16 to 1.34; and RR, 1.16; 95% CI, 1.03 to 1.32, respectively) compared with de novo AML. Among patients ≥ 60 years old and patients with adverse karyotype, previous MDS or tAML did not impact overall outcomes, whereas non-MDS-sAML was associated with inferior survival across age and cytogenetic risk groups (adverse risk cytogenetics: 1-year adjusted RR, 1.47; 95% CI, 1.23 to 1.76; patients ≥ 60 years old: 1-year adjusted RR, 1.31; 95% CI, 1.06 to 1.61). CONCLUSION Our results support that de novo AML, sAML, and tAML are biologically and prognostically distinct subtypes of AML. Patients with non-MDS-sAML have dismal outcomes, independent of age and cytogenetics. Previous myeloid disorder, age, and cytogenetics are crucial determinants of outcomes and should be integrated in treatment recommendations for these patients.
Decreased endovascular trophoblast invasion in first trimester pregnancies with high‐resistance uterine artery Doppler indices

BACKGROUND: Defective trophoblastic invasion in early pregnancy is involved in the pathogenesis of preeclampsia. This study investigates the relationship between Doppler assessment of uterine artery resistance and endovascular trophoblastic invasion in the first trimester of pregnancy. METHODS: Patients undergoing termination of pregnancy for non-medical reasons were categorized as having a low- or high-resistance uterine artery blood flow pattern by transabdominal Doppler ultrasound. Products of conception were examined histologically with regard to the extent of decidual endovascular trophoblast invasion. RESULTS: There were 14 low-resistance and 17 high-resistance uterine artery blood flow pregnancies identified at 10‐14 weeks of gestation. Normal intradecidual endovascular trophoblast invasion was identified with a similar frequency in both groups (P = 0.79). However, the proportion of decidual vessels with endovascular trophoblast invasion was significantly higher in the low-resistance pregnancies (49%) compared with the high-resistance ones (34%, P = 0.02). CONCLUSIONS: The findings of this study support the use of uterine artery Doppler investigation for the non-invasive assessment of trophoblast invasion in early pregnancy. Further studies are necessary to clarify the biological significance of these observations and their potential clinical applications.
Prevalence and risk factors of arternal hypertension among urban Africans workplace: The obsolete role of body mass index

ABSTRACT Background: Studies on the prevalence of hypertension among Africans in workplace did not deal with risk factors of hypertension. Thus there is a need to screen urban central Africans at workplace for environmental risk factors of hypertension. Method: A cross-sectional survey was conducted at the Kinshasa National Company of Electricity. A representative sample of 333 employees was screened. Tobacco, alcohol use and level of physical activity measures were obtained. Weight, height, BMI, waist, hip, conicity, blood pressure, pulse pressure and pulse rate were measured. Data were analysed using univariate and multivariate statistics. Results: The prevalence of hypertension was 21.3%. Hypertension was associated with aging, higher professional position, eastern origin, migration, alcohol use, wider pulse pressure >60mmHg, wider waist >90cm, wider hip >97cm, obesity, and left ventricle hypertrophy. Independent predictors of hypertension were age, wider waist, wider hip, alcohol intake, and left ventricle hypertrophy. In another logistic regression model, only waist>90 cm (OR=2.5 CI95% 1.3-4.9; p Nigerian Journal of Medicine Vol. 16 (1) 2007: pp. 42-49
Crescimento em meninos e meninas com puberdade precoce

Pubertal development is associated with increased growth velocity secondary to the interaction of three hormones: sex steroids, growth hormone and IGF-1. The pubertal spurt represents 16% of adult height. Precocious puberty (PP) may induce early fusion of growth plates, reducing growth duration and, consequently, adult height. Thus, the main objective of the treatment with GnRH analogues is to avoid the height commitment. It is important to emphasize that PP does not evolve uniformly, sometimes having a slow course (slow evolutive form), which does not require treatment. The authors discuss aspects of normal pubertal growth, precocious puberty and its variants, and the effects of treatment on final height. Special situations as early and fast puberty are also mentioned.
Creating new supramolecular materials by architecture of three-dimensional nanocrystal fiber networks.

The architecture of three-dimensional interconnecting self-organized nanofiber networks from separate needlelike crystals of L-DHL (lanosta-8,24-dien-3beta-ol:24,25-dihydrolanosterol = 56:44) in di-isooctylphthalate has been achieved for the first time, on the basis of the completely new concept of branching creation by additives (branching promoters). [In this work, an additive, ethylene/vinyl acetate copolymer (EVACP), is used at a concentration of several 10 ppm. ] We demonstrate that this novel technique enables us to produce previously unknown self-supporting supramolecular functional materials with tailormade micro- or nanostructures, possessing significantly modified macroscopic properties, by utilizing materials thus far considered to be "useless". In addition, both the self-organized structure and the properties of the new materials can be fine-tuned by altering the processing conditions. Our results show that the formation of the interconnecting 3D self-organized network structure is controlled by a new mechanism, so-called crystallographic mismatch branching mechanism, as opposed to the conventionally adopted molecular self-assembly mechanism. The principles and criteria for the selection of branching promoters are also discussed from the point of view of molecular structures.
Deliberate design of ligand architecture yields dramatic enhancement of metal ion affinity.

Evaluation of the malonamide substructure with respect to binding site preorganization and complementarity for lanthanide metal ions suggests a new ligand architecture specifically designed to enhance lanthanide ion affinity. Consideration of conformational reorganization, restricted bond rotation, and donor group orientation suggests that typical malonamide structures, for example, N,N,N'N'-tetrahexylpropane-1,3-diamide (1), N,N'-dibutyl-N,N'-dimethyl-2-tetradecylpropane-1,3-diamide (2), or N,N,N'N'-tetramethylpropane-1,3-diamide (6), are poorly organized for metal ion complexation. Molecular mechanics analyses show that the unfavorable enthalpic and entropic terms are eliminated by the use of the novel bicyclic architecture found in 3,9-diaza-3,9-dimethylbicyclo[4.4. 0]decane-2,10-dione (7). Diamide 7 was prepared, and the X-ray crystal structure of the complex [Eu(7)(2)(NO(3))(3)] exhibits the same chelate conformation predicted by the molecular mechanics model. A hydrophobic derivative, 3,9-diaza-3,9-dioctylbicyclo[4.4. 0]decane-2,10-dione (8), was prepared, and solvent extraction studies reveal that the preorganized architecture of 8 gives a dramatic enhancement in binding affinity, exhibiting Eu(3+) distribution coefficients that are 7 orders of magnitude larger than a typical malonamide ligand, 1.
Financial Hardship Associated With Cancer in the United States: Findings From a Population-Based Sample of Adult Cancer Survivors.

PURPOSE To estimate the prevalence of financial hardship associated with cancer in the United States and identify characteristics of cancer survivors associated with financial hardship. METHODS We identified 1,202 adult cancer survivors diagnosed or treated at ≥ 18 years of age from the 2011 Medical Expenditure Panel Survey Experiences With Cancer questionnaire. Material financial hardship was measured by ever (1) borrowing money or going into debt, (2) filing for bankruptcy, (3) being unable to cover one's share of medical care costs, or (4) making other financial sacrifices because of cancer, its treatment, and lasting effects of treatment. Psychological financial hardship was measured as ever worrying about paying large medical bills. We examined factors associated with any material or psychological financial hardship using separate multivariable logistic regression models stratified by age group (18 to 64 and ≥ 65 years). RESULTS Material financial hardship was more common in cancer survivors age 18 to 64 years than in those ≥ 65 years of age (28.4% v 13.8%; P < .001), as was psychological financial hardship (31.9% v 14.7%, P < .001). In adjusted analyses, cancer survivors age 18 to 64 years who were younger, female, nonwhite, and treated more recently and who had changed employment because of cancer were significantly more likely to report any material financial hardship. Cancer survivors who were uninsured, had lower family income, and were treated more recently were more likely to report psychological financial hardship. Among cancer survivors ≥ 65 years of age, those who were younger were more likely to report any financial hardship. CONCLUSION Cancer survivors, especially the working-age population, commonly experience material and psychological financial hardship.
New aspects of hereditary ataxia in smooth-haired fox terriers

Hereditary ataxia was diagnosed in three smooth-haired fox terrier puppies from Sweden, 25 years after the previous known case in the breed. In addition to the characteristic spinal cord pathology, brain involvement was evident clinically, in the form of behavioural changes and bilaterally decreased menace responses, and histopathologically, with degenerative changes in the brainstem. The striking similarities to hereditary ataxia in the Jack Russell terrier suggest the same disease process in both breeds. A common ancestor, a female dog born in 1951 and considered a carrier of the disease at that time, was found in both the maternal and paternal lines of the three puppies.
WEE1 Kinase As a Target for Cancer Therapy.

Exploiting the complex machinery that regulates cell cycle checkpointsandDNArepair forcancertherapyhasbeenthefocusofmanypast and ongoing investigations; however, successful translation into patient care and meaningful impact on clinical outcomes have proven elusive. Eukaryotic cells rely on complex cell cycle checkpoint and DNA repair systems to ensure genomic integrity. In cells that have DNA damage (eg, after radiation or chemotherapy), several cell cycle checkpoints arrest cell cycle progression to allow for DNA repair. Historically these DNA repair pathways have been divided into two major arms consisting of ataxia telangiectasia and Rad3-related protein/checkpoint kinase 1 (ATR/ CHK1) and ataxia telangiectasia–mutated (ATM)/CHK2, although significant overlap exists and there is a high degree of redundancy (Fig 1). If DNA damage is too extensive for faithful repair, pathways leading to cell death are instigated. Before cells undergo mitosis, they progress through a tightly controlled cascade of G1-S, intra-S, and G2-M checkpoints. WEE1 kinase has emerged as a key G2-M checkpoint regulator. 1 This tyrosine kinase negatively regulates entry into mitosis by catalyzing an
Human exposures to immobilising agents: results of an online survey

Cases of human exposure to veterinary injectable anaesthetics were reviewed following a literature search and completion of an online questionnaire in an attempt to provide an objective approach to the problem. The modified Glasgow Coma Scale was used to rank cases according to their severity. From the cases examined, results showed that intoxication with potent opioids, such as etorphine, carfentanil and thiafentanil, need to be treated with antagonists such as naloxone, nalmefene or naltrexone, and not with antagonists with agonistic properties, such as diprenorphine. With regard to the α2-agonists xylazine, detomidine, medetomidine and romifidine, no antagonist is currently accredited for human use. Atipamezole, a specific α2-antagonist, is widely used in veterinary medicine and has been used experimentally to reverse dexmetomidine in a study in human medicine. The high concentrations of α2-agonists being used in zoo and wildlife medicine warrant the accreditation of atipamezole for use in cases of human exposure. Knowledge and availability of the appropriate antagonist are essential in cases of human intoxication with injectable anaesthetics. Preventive measures, such as wearing gloves and eye protection, need to be used more regularly to reduce the risk of exposure.
NOTES ON A SERIES OF INTRACRANIAL TUMORS AND CONDITIONS SIMULATING THEM: TUMOR SUSPECTS; TUMORS UNVERIFIED; TUMORS VERIFIED

This discussion may be opened by calling attention to Table 1 as a point of departure for the several matters I shall briefly touch on in connection with the patients with proved or presumptive tumors at present in the hospital wards. It gives in summary a working subdivision of the cases in our tumor series up to May 1 of this year. Table 1. —Cases in the Tumor Series Number Percentage Total Tumors histologically verified. 868 Gliomas (so diagnosed) of all types. 362 41.7 Adenomas (chiefly pituitary). 169 19.5 Meningiomas ("dural endotheliomas"). 99 11.4 Neurinomas (acoustic). 77 8.9 Congenital tumors. 54 6.2 Craniopharyngeal pouch cysts. 42 Cholesteatomas and dermoids. 8 Teratomas. 4 Granulomatous tumors. 36 4.2 Tuberculomas. 23 Syphilomas. 13 Metastatic and invasive tumors (varia). 34 3.9 Papillomas (choroid-plexus tumors). 13 1.5 Angiomas. 8 0.9 Miscellaneous and unclassified. 16 1.8 Tumors unverified but presence unquestioned. 476 Tumor suspects: probably not tumor