dataesr/scientific-paragraphs-categorization huggingface dataset:
Ongoing clinical trials Official sources list 15 ongoing (not terminated, withdrawn, suspended, or completed) clinical trials launched after January 1 2012 that are aimed at assessing the safety and antineoplastic activity of bortezomib as an off-label therapeutic intervention, i. e. , in patients affected by malignancies other than MM and MCL (http://www. clinicaltrials. gov/) (Table  2 ). In particular, bortezomib is being tested in individuals with: (1) relapsed or refractory acute lymphoblastic leukemia (ALL), in combination with doxorubicin, dexamethasone, vincristine (a microtubular poison currently licensed for the treatment of several malignancies),  [343] [344] [345]  and pegylated asparaginase (a recombinant enzyme commonly employed for this oncologic indication) (NCT01769209); (2) acute myeloid leukemia (AML), in combination with arsenic trioxide (NCT01950611), sorafenib (a FDAapproved multikinase inhibitor)  [346] [347] [348]  and decitabine (a nucleoside analog employed for the treatment of AML and MDS)  301, 349  (NCT01861314), liposomal doxorubicin (NCT01736943), or sorafenib plus the HDAC inhibitor vorinostat  350  (NCT01534260); (3) DLBCL, either as a stand-alone maintenance therapy (NCT01902862), or as an induction therapy in combination with rituximab, dexamethasone, cytarabine, and cisplatin (a platinum derivative commonly employed against several solid neoplasms)  [351] [352] [353] [354]  prior to high-dose chemotherapy and autologous stem cell transplantation (NCT01805557), or combined with rituximab, cyclophosphamide, doxorubicin, and prednisone (NCT01848132); (4) low-or intermediate-risk MDS, as a single agent (NCT01891968); (5) Waldenstr€ om's macroglobulinemia (WM), combined with cyclophosphamide, rituximab and dexamethasone (NCT01788020) or with cyclophosphamide, rituximab, and fludarabine (NCT01592981); and (6) various hematologic malignancies, in combination with the experimental inhibitor of aurora kinase A (AURKA) alisertib and rituximab (NCT01695941) or a multicomponent chemotherapeutic cocktail (NCT02112916).
Moreover, the therapeutic potential of bortezomib is being investigated in subjects with relapsed or refractory neuroblastoma, who receive it in combination with the ornithine decarboxylase inhibitor eflornithine (which is currently approved as a topical intervention against facial hirsutism and as a systemic treatment for sleeping sickness)  [355] [356] [357] [358]  (NCT02139397), and in NSCLC patients bearing KRAS mutations or with a limited smoking history, who are treated with bortezomib plus acyclovir (a guanosine analog currently approved for the treatment of herpes simplex virus infection)  [359] [360] [361] [362]  (NCT01833143).
e. , in patients affected by neoplasms other than MM (http://www. clinicaltrials. gov/) (Table  4 ). Carfilzomib is being evaluated as a stand-alone therapeutic intervention in patients with (1) relapsed or refractory MCL (NCT02042950); (2) refractory renal cell carcinoma (NCT01775930); or (3) advanced malignancies (NCT01949545). Moreover, the safety and efficacy of carfilzomib are being tested in (1) patients with relapsed or refractory DLBCL, receiving carfilzomib in the context of rituximab-based chemotherapy (NCT01959698; NCT02073097); (2) subjects with relapsed or refractory MCL, who are treated with carfilzomib plus lenalidomide and rituximab (NCT01729104); (3) patients with relapsed or refractory NHL, receiving carfilzomib in combination with an FDAapproved histone deacetylase inhibitor (belinostat)  271,396-398 (NCT02142530)  or bendamustine and rituximab (NCT02187133); (4) patients with relapsed WM, with carfilzomib, rituximab, and dexamethasone (NCT01813227); (  5 ) subjects with cutaneous TCL, receiving carfilzomib plus the FDA-approved HDAC inhibitor romidepsin 397-400 (NCT01738594); and (6) MCL, TCL, and DLBCL patients, who are treated with carfilzomib and dexamethasone as consolidation therapy after autologous stem cell transplantation (NCT01926665).
Finally, the clinical profile of carfilzomib is being assessed in (1) previously untreated subjects affected by extensive stage small-cell lung cancer, who are treated with carfilzomib plus carboplatin (a platinum derivative employed for the treatment of multiple solid tumors, including ovarian carcinoma)  [401] [402] [403]  and etoposide (NCT01987232); (2) subjects with relapsed lung cancer, receiving carfilzomib in combination with irinotecan (a topoisomerase I inhibitor mainly used for the treatment of colorectal carcinoma)  404, 405  (NCT01941316); and (3) patients with metastatic castration-resistant prostate cancer,  335  who are treated with carfilzomib, dexamethasone, and acyclovir (NCT02047253).
Clinical studies Marizomib-based monotherapy has been associated with a promising safety profile (no evidence of thrombocytopenia and peripheral neuropathy) and clinical efficacy in Phase I trials enrolling relapsed and refractory MM patients. 80, 407, 411, 428 In addition, the combination of marizomib and vorinostat was well tolerated by patients with advanced solid tumors. 429 According to official sources (http://www. clinicaltrials. gov/, ongoing trials initiated after January 1 2012), the safety and antineoplastic activity of marizomib are currently being assessed in relapsed or refractory MM patients, receiving marizomib either as a standalone therapeutic intervention (NCT00461045) or in combination with pomalidomide (an immunomodulatory agent approved by the US FDA for the treatment of MM)  110, [430] [431] [432] [433]  and lowdose dexamethasone (NCT02103335) (Table  5 ).
The safety and tolerability of ixazomib have been evaluated in several Phase I clinical trials enrolling subjects with relapsed/ refractory MM. [434] [435] [436] [437] [438] [439] [440]  In 2 of these studies, 15-18% of patients were reported to achieve at least a partial response to therapy,  434, 435  supporting further clinical development. Along similar lines, ixazomib (co-administered with dexamethasone and lenalidomide) was well tolerated by individuals with previously untreated MM and exerted some degree of clinical activity. 441, 442 According to official sources, no fewer than 14 clinical trials have been initiated after January   4 ) in combination with dexamethasone and panobinostat (an experimental non-selective HDAC inhibitor)  397, 398  in subjects with relapsed and/or refractory MM (NCT02057640); (5) in combination with dexamethasone and pomalidomide in refractory (NCT02004275) or relapsed/refractory (NCT02119468) MM patients; (6) with lenalidomide only, as a maintenance regimen upon autologous stem cell transplantation in MM patients (NCT01718743); (7)  with lenalidomide and dexamethasone, in patients with either newly diagnosed (NCT01850524, NCT01936532) or relapsed/ refractory (NCT01564537, NCT01645930) MM.
Moreover, ixazomib monotherapy is being evaluated in non-MM patients, including (1) subjects with relapsed or refractory AML (NCT02030405); (2) individuals with relapsed/refractory cutaneous and peripheral TCL (NCT02158975); (3) patients with relapsed/refractory follicular lymphoma (NCT01939899); (4) subjects with hematologic malignancies or advanced solid tumors (NCT01912222); and (5) individuals with lymphomas or advanced solid tumors (NCT01953783). Finally, ixazomib is being assessed in combination with (1) mitoxantrone (an FDAapproved immunogenic anthracycline used for the therapy of NHL, AML, and breast carcinoma),  [443] [444] [445] [446]  etoposide, and intermediate-dose cytarabine in relapsed/refractory AML patients (NCT02070458); (2) vincristine, doxorubicin, pegylated-asparaginase, and dexamethasone in subjects with relapsed/refractory ALL or lymphoma (NCT01887587); and (3) vorinostat, in individuals with advanced solid tumors (NCT02042989) (Table  5 ).
The safety and tolerability of oprozomib have been evaluated in Phase I studies performed on patients with hematologic malignancies and advanced solid tumors. 447, 448 ccording to official sources (http://www. clinicaltrials. gov/, ongoing trials initiated after January 1 2012), the clinical profile of oprozomib is being investigated in (1) transplantineligible patients with newly diagnosed MM, receiving oprozomib plus dexamethasone and lenalidomide (NCT01881789), or dexamethasone and oral cyclophosphamide (NCT01881789), or prednisone and melphalan (NCT02072863), (2) relapsed and/or refractory MM patients, treated with oprozomib plus dexamethasone (NCT01832727); and (3) subjects with primary refractory or relapsed/refractory MM, receiving oprozomib with pomalidomide and dexamethasone (NCT01999335) (Table  5 ).
Funding Authors are supported by the  European Commission (Art-Force) ;  Agence National de la Recherche (ANR) ;  Associazione Italiana per la Ricerca sul Cancro  (AIRC: MFAG 2013 # 14641  and triennial tellowship "  Antonietta Latronico " , 2014);  Italian Ministry of Health  ( GR-2011-02351355 ); Programma per i  Giovani Ricercatori "Rita Levi Montalcini " 2011;  Ligue Nationale  contre le Cancer;  Fondation pour la Recherche M edicale (FRM) ;  Institut National du Cancer (INCa) ;  Association pour la Recherche sur le Cancer (ARC) ,  LabEx Immuno-Oncologie ;  Fondation de France ;  Fondation Bettencourt-Schueller ; AXA Chair for Longevity Research;  Canc eropôle Ile-de-France, Paris Alliance of Cancer Research Institutes (PACRI)  and  Cancer Research for Personalized Medicine (CARPEM).
Design Our primary objective was to compare the clinical and economic outcomes of the LMWH dalteparin compared with UFH for the prevention of VTE in critically ill medical-surgical patients. We developed our analysis according to previously existing guidelines for economic evaluations  [9] [10] [11]  ; however, we used an in-hospital health care payer perspective to encompass all hospital costs, including physician and other personnel costs. PROTECT provided follow-up for patients until death or discharge from the hospital; therefore, our time horizon was from the period of randomization to hospital discharge or death. Our analysis plan was prespecified as part of the economic evaluation of the PROTECT protocol before trial completion and unblinding (clinical trials. gov NCT00182143). 2, 12, 13 All centers participating in this economic evaluation obtained research ethics approval to enroll patients in the trial, approval to include non-patient-based costing data, or both.
Characterics of Study Population Patient characteristics of the economic evaluation of the PROTECT trial are the same as those of the trial (3746 patients randomized to the LMWH dalteparin [1873] or UFH [1873]). The mean age was 61 years, 57% were men, 76% were admitted to the ICU for medical critical illness, and 90% required mechanical ventilation (eTable 1 in the Supplement). There were 22 patients (11 in each group) who, after randomization, were discovered to have exclusion criteria and were excluded from further daily data collection;however, these patients were not lost to follow-up and were included in the intention-to-treat analysis. 2 Therefore, 1862 patients in each group were used to determine resource use and cost calculations. As previously reported, 2 there were no statistically significant differences in rates of any thrombosis, DVT, and major bleeding; however, there were fewer episodes of pulmonary embolus and confirmed heparin-induced thrombocytopenia among patients who received dalteparin (eTable 2 in the Supplement).
In PROTECT, the numbers of heparin-induced thrombocytopenia and pulmonary embolus events were small, allowing only moderate confidence in estimates of superiority with LMWH. In this study, cost differences with LMWH were driven by apparent decreases in all thrombosis and heparin-induced a One patient was withdrawn from study at day 70 while still in the intensive care unit and final status information could not be collected; therefore, day 70 was designated the patient's intensive care unit and hospital discharge day. One patient was still in the hospital when the database was closed on January 24, 2011 (approximately 10 months after randomization). We used that day as the patient's intensive care unit and hospital discharge day. b Calculated as weight in kilograms divided by height in meters squared.
Although our methods attempted to total costs of care after randomization, it is likely that some were not captured. Further, our analyses were based on an in-hospital timehorizon (as opposed to lifetime) and were performed from the health care payer (as opposed to societal) perspective. Both were prespecified to focus on the effect-and cost-data-rich period of ICU and hospital admission. We did not incorporate health-related quality-of-life estimates in the form of measured utilities attributable to the in-hospital time horizon and focus on objective thrombotic events and their complications. However, findings from the in-hospital time horizon and health care system payer perspective are consistent with a pre-viously modeled lifetime horizon from a societal perspective using data from PROTECT and E-PROTECT that show a favorable incremental cost-effectiveness ratio for LMWH compared with UFH.
Dr Hall  reported receiving grants from the  Canadian Institutes of Health Research , the  Canadian Intensive Care Foundation , and the  Heart and Stroke Foundation  and serving as a commercial sponsor for an agent manufactured by  Portola. Dr Marshall  reported receiving research coodinator support from  McMaster University/ Canadian Institutes of Health Research  and receiving personal fees from AKPA,  Eli Lilly , and  Eisai. Dr Cook  reported that she is a Canada Research Chair of the  Canadian Institutes of Health Research. No other authors reported disclosures. Funding/Support: E-PROTECT was funded by the  Heart and Stroke Foundation (Ontario, Canada) , the  University of Toronto , and the  Canadian Intensive Care Foundation. PROTECT was funded by the  Canadian Institutes of Health Research , the  Heart and Stroke Foundation (Canada) , and the  Australian and New Zealand College of Anesthetists Research Foundation.
General Properties Yeast (unless mentioned otherwise, this means the budding yeast Saccharomyces cerevisiae) has been extensively used for understanding human diseases. As a simple and unicellular microrganism, it may seem quite different from humans and their diseases, but several important properties have made yeast a pivotal organism for many human studies and, as will be seen in Section 2. 3. 2, in particular for mitochondrial diseases: (i) Simplicity, rapidity and low cost. (ii) Highly developed genetics with a diverse and well-adapted toolbox. Thousands of mutations exist in practically every nuclear gene of the genome, and any new mutation can be created in vitro and reintroduced into the genome thanks to the rich collection of tools, which has been developed. (iii) A wealth of functional studies organized into an efficient database.
When the complete genome was published  [48] , we had some functional knowledge of about 30% of the roughly 5800 genes; the figure now reaches practically 85%. All information obtained is centralized in the Saccharomyces Genome Database or SGD, which is easy to use and kept up to date  [49]. (iv) Protein sequence conservation and heterologous complementation. All the properties I have described can be usefully exploited because bioinformatic analyses have revealed a high conservation thoughout eucaryotic evolution for many genes involved in basic cellular functions. As a consequence, we have gone a long way since the pioneering work of  [50]  on heterologous complementation of a yeast (S. pombe) mutation by a human gene. Recent orthology studies now show that nearly 1000 yeast genes are associated with human diseases  [51] , and in many cases the mammalian ortholog is functional and complements the yeast deletion mutant.
A multicenter prospective naturalistic study in antipsychotic naive children (ETAPE Study) In order to continue our safety monitoring project we have started a prospective, naturalistic and multicenter study to evaluate the incidence of adverse events related to the use of antipsychotic drugs in AP naive children and adolescents in France (ETAPE, Etude de la Tolérance des AntiPsychotiques chez l'Enfant)  [41, 42]. This study is funded by the French National Agency for Medicines and Health Products Safety (ANSM, Agence nationale de sécurité du médicament et des produits de santé) and is registered on ClinicalTrials. gov (NCT02007928)  [43]. The originality of this study lies in the inclusion of a AP naive pediatric population aged 6 to 18 years in 11 French pediatric psychiatry departments.
It was established in 1996 and is a voluntary network of countries, areas and organizations, dedicated to the promotion of public health surveillance and response in the Pacific. The core members are the 22 Ministries and Departments of Health in the Pacific Island countries and territories, and whose authority or consensus guides its work  [25]. The PPHSN is further supported by allied bodiesregional and international agencies, training institutions, laboratories, and other partners who can supplement the network with technical expertise, and in-kind and financial support. A Coordinating Body (CB) is drawn from each of these two groups, and consists of seven core and five allied body members. The CB membership is rotated in a staggered manner, with membership voted or endorsed by network and CB members.
Computational details The three dimentional structures of conjugates ABPI-NI1 and ABPI-NI2 were built with MOPAC program package using PM6 semiempirical method  [28]. The calculations were performed at optimized geometries, which reached gradient variations less than 0. 01 kcal/mol. The solvent effect was included in geometry optimizations following the «COnductorlike Screening Model» (COSMO) implemented in MOPAC. A dielectric constant of e = 40 and a refraction index of solvent (n) such that n 2 = 2 were used.
a The data for ABPI-NI1, NI1 and ABPI + NI1 were obtained using acetonitrile as a solvent and 360 nm excitation light (k ex ), the data for ABPI-NI2, NI2 and ABPI + NI2using dimethylsulfoxide and k ex = 340 nm. b Calculated from the absorption spectra of ABPI and emission spectra of compounds NI1 and NI2 (see Fig.
Data Collection Surveillance was based on data collected by sentinel general practitioners (SGP). Each participating SGP reported the number of cases that met the criteria, including the total number of patient visits on each reporting day. SGPs were expected to communicate encrypted data by cellular telephone (encrypted SMS) at least once a day, from Monday to Friday, because of health care center closures resulting from routine weekday-weekend schedules. If data from a sentinel center was not received by 10:00 a. m. , the IPD staff member contacted the sentinel center to obtain the missing data.
Case definition The sentinel surveillance system in Senegal was based on clinical pre-diagnostic data using standard WHO case definitions to ensure comparability. Fever (the inclusion criterion was an axillary temperature of more than 37. 5uC) was the first symptom targeted. Three diseases associated with fever were selected for surveillance: confirmed malaria cases (the inclusion criteria were was fever and a positive result in a rapid diagnostic test); influenzalike illness (defined as fever with cough or fever with sore throat); and arbovirus infection (the inclusion criteria were fever without respiratory symptoms and at least two of the following symptoms: headache, arthralgia, myalgia-like backache, skin rash, retroorbital pain and hemorrhagic manifestations). Diarrheal disease was defined as three or more abnormally loose stools during the previous 24 hours.
Data analysis Data were available for analysis shortly after the patient's initial visit. A medical epidemiologist reviewed the output from all 11 primary health centers on a daily basis, and noted any changes in community-wide incidences of fever. Separate analyses were carried out for each syndrome category of interest, to look for changes in the distribution at each sentinel center. We estimated the proportion of all fever cases corresponding to each febrile syndrome at each sentinel center; we also estimated the proportion of all fever or diarrhea cases that were primary case encounters. Thus, various health service-based indicators were monitored daily, including the percentage of fever cases, confirmed malaria cases, influenza-like illness cases, suspected cases of arbovirus infection, and the number of cases with diarrhea and diarrhea with fever.
Ethical clearance The principles of the 4S network were approved by the Ministry of Health in its guidelines for influenza surveillance policy, finalized with the support of Pasteur Institute in Dakar and the Strengthening Influenza Sentinel Surveillance in Africa (SISA) project funded by the WHO  [10]. The protocol and oral consent were determined as routine surveillance activity, and therefore non-research by the Senegalese National Ethics committee and the steering committee for 4S network, an entity representing MoH, IPD, WHO and Clinicians in compliance with all applicable National regulations governing the protection of human subjects. Data were collected in an objective of surveillance and are anonymous. The information provided to participants was an informal description of the study.
Respiratory specimens were collected, only after informed consent was granted, verbally, to local health care workers by the patients or parents in the case of minors. Oral consent was documented in the patient form with two questions about received information and about oral consent. Patients could refuse to participate, no specimen will be taken. For the surveillance activities, written consent is judged not necessary by the Senegalese national ethics committee, which has also previously approved the work of the National Influenza Center  [11]. Collections of non-sensitive data or an observation from normal care in which participants remain anonymous do not require ethics committee review. The patients included in this study were of all ages and consulted the sentinel sites due to influenza-like symptoms; the patients, or parents in the case of minors, accept the tests for respiratory viruses largely because they are free and safe.
Description of the epidemiological indicators From week 11 in 2012 to week 35 in 2013, data was collected on a daily basis such that 101,640 visits were included in the study (Table1). The distribution by age group was 16,025 (15. 8%) less than 1-year olds, 27,937 (27. 5%) 1-4yr olds, 17,209 (16. 9%) 5-14yr olds, 12,093 (11. 9%) for 15-24yr olds and 28,373 (27. 9) over 24 yr olds. The age distribution at the various sentinel centers, is indicated in Table  2. In total, 22,662 cases (22. 3%) of fever were reported with the fewest (9. 9%) in Louga and the most (32. 3%) in Dakar Centre. ILI accounted for 22. 8% of fever cases (range: 8. 3% in Richard-Toll, in the north of the country, to 63% in Ziguinchor, in the south) (Table  1 ). The distribution of ILI cases by age group was 1,132 (22. 0%) among the under 1-year olds, 2,042 (39.
6%) among 1-4yr olds, 960 (18. 6%) among 5-14yr olds, 319 (6. 2%) among 15-24yr olds and 693 (13. 4%) among the over 24 yr olds (Table  3 ). Dengue-like syndromes accounted for 3. 4% of fever cases and suspected malaria cases for 39. 8%; 18. 1% of suspected malaria cases were confirmed (Table1). Diarrhea cases accounted for 5. 5% of visits and febrile diarrhoeas for 6. 1% of febrile syndromes and 24. 6% of diarrheas (Table  1 ). The epidemiological characteristics of groups with fever-related syndromes, such as those with ILI, identified by the sentinel surveillance system, were investigated graphically. Total daily counts (Figure  2 ), and daily and weekly counts for each sentinel center (data not shown), were plotted and analyzed. This revealed a peak in October 2012 corresponding to an increase in the number of febrile syndromes and ILI cases.