dataesr/scientific-paragraphs-categorization huggingface dataset:
77 In a two-dose regimen, where prime www. moleculartherapy. org Review vaccine administration was followed by a boost 28 days later, mild-tomoderate pain and tenderness remained the most common local adverse reaction, while headache, feeling feverish, chills, malaise, and muscle pain were reported as the most common systemic adverse reactions, similar to participants who received only a single dose of the vaccine. In a two-dose cohort, it was noticed that the reactogenicity profile (or the severity of adverse reactions) after administration of a booster dose of the vaccine was less severe, as compared with the severity of adverse reactions after the prime dose administration. In a recent report of data collected from the ongoing pivotal doubleblind, placebo-controlled phase III study, the safety and efficacy of AZD1222 was evaluated in 21,587 participants who received AZD1222 in a prime:boost regimen and in 10,792 participants who received placebo (NCT04516746).
172, 173 fety data for species D Ad26 vectors Similar to ChAdOx1, the rationale for use of Ad26 as a vaccine platform for SARS-CoV-2 was based on its low seroprevalence in humans,  152, 174  its established use in clinical trials,  76, 157, 161, 164, 165  and its prior approval by the EMA as a component in a vaccine against EBOV. 82, 87, 90, 91 The safety and efficacy of a single-dose COVID-19 vaccine Ad26. COV2. S, based on rare human adenovirus Ad26 (developed and distributed by Janssen and Johnson & Johnson), was evaluated in a series of randomized, placebo-controlled clinical trials. Initial studies analyzed two different doses of the vaccine as well as one-or two-dose regimens, where vaccines were administered 56 days apart (NCT04436276). 175 In the report of the interim results of a phase I/IIa trial of Ad26.
In this study, participants of 18-55 years of age reported fever as a frequent solicited AE. In this age group, 15% of participants in the low-vaccine-dose group and 39% of participants in the high-dose group reported grade 1 and 2 fevers. Grade 3 fever was reported by 5% and 9% of participants after receiving low and high vaccine doses, respectively. In a group of 65 years and older, grade 3 fever was not observed in participants who received low dose of the vaccine and was observed in 1% of participants who received high vaccine dose. After the second dose of the vaccine, no grade 3 fever was observed in any of the groups and there was no participant discontinuation due to an AE. 175  a subsequent randomized, double-blind, placebo-controlled phase III clinical trial of the Ad26. COV2. S COVID-19 vaccine administered at a single dose of 5 Â 10 10 vps, the safety and efficacy was evaluated in 19,630 participants who received the vaccine and in 19,691 participants who received placebo (NCT04505722).
Safety of species C Ad5 vectors Vaccines to combat COVID-19 based on the common human adenovirus serotype, Ad5, were developed (CanSino Biologics) and evaluated for safety and efficacy in China (NCT04313127). 176 In a phase I doseescalation, open-label, non-randomized clinical trial, reactogenicity was evaluated in three cohorts of participants who received 5 Â 10 10 vps (low-dose cohort, 36 participants), 1 Â 10 11 vps (middle-dose cohort, 36 participants), and 1. 5 Â 10 11 vps (high-dose cohort, 36 participants). 176 Although the frequency of all reported AEs was similar in all cohorts, grade 3 AEs were more common in participants who received the highest vaccine dose. While pain at the injection site was the most frequent local AE, observed in 47% of participants in the low-dose, 56% of participants in the middle-dose, and 58% of participants in the high-dose cohorts, fever, followed by headache, fatigue, and muscle pain, was the most frequently recorded systemic AEs.
In this larger trial, the dose-dependent increase in the severity of AEs was documented and determined to be highly statistically significant (NCT04341389). 176 Specifically, while the majority of reported adverse reactions were mild to moderate in severity, grade 3 adverse reactions were noted in 9% of participants who received vaccine dose of 1 Â 10 11 vps, which was significantly higher than in participants who received 5 Â 10 10 vps of the vaccine (1% of participants; p = 0. 0011) or placebo (0% participants; p = 0. 0004). Similar to findings in the phase I trial described above (NCT04313127),  177  fever was the most frequently reported grade 3 adverse reaction, while fatigue was re-ported as the most frequent systemic adverse reaction: observed in 42% of participants who received 1 Â 10 11 vps vaccine dose and in 34% of participants who received 5 Â 10 10 vps dose of the vaccine.
In this study, it was noted that high levels of pre-existing anti-Ad5 immunity, older age, and male sex were associated with a significantly lower frequency of fever after vaccination. All grade 3 reactions resolved within 72-96 h without medical intervention. No differences in the occurrence of unsolicited AEs between vaccine and placebo groups were noted during the 14-day observation period post-immunization with either vaccine or placebo. No SAEs were observed within 28 days of vaccination in this trial. 176 Data from an ongoing placebo-controlled phase III clinical trial of this Ad5-based COVID-19 vaccine in 20,000 participants who will receive a single dose of vaccine or placebo are due for reporting in early 2022 (NCT04526990).
Safety of heterologous prime:boost with Ad26 and Ad5 vectors A heterologous Ad vaccine regimen for COVID-19, Gam-COVID-Vac (Sputnik V), was developed, tested, and approved for use in Russia. 178 Gam-COVID-Vac consists of a replication-deficient Ad26 vector, which is used for the prime, and an Ad5-based vector used for the boost. Gam-COVID-Vac is administered at a dose of 1 Â 10 11 vps for each vector component, and the prime and boost vaccine doses are administered 21 days apart. The largest datasets on the safety and efficacy of this vaccine were reported upon interim analysis of findings from a randomized, double-blind, placebo-controlled phase III clinical trial. In this study, 16,427 participants received one dose of the vaccine and were monitored for AEs and SAEs, with the nature and frequency of AEs and SAEs compared with 5,435 participants who received placebo (NCT04530396).
179 This observational study reported solicited AE data collected from vaccinated participants during the first 8 days post-administration of each of the vaccine doses, in which 3,236 out of 13,435 participants reported AEs post-vaccination. Pain at the injection site was the most frequently reported local AE, reported by 58. 2% of respondents after receiving the first dose of the vaccine and by 54. 1% of respondents after receiving the second vaccine dose. For vaccinees who reported systemic AEs, the most frequently reported were fatigue (reported by 54. 2% after the first and by 44% after the second vaccine doses), body pain (48. 6% after the first and 38% after the second vaccine www. moleculartherapy. org Review dose), weakness (46. 6% after the first and 38. 1% after the second vaccine doses), headache (38.
gov NCT02231866 (2017) PMID (year) Review www. moleculartherapy. org G2: $0. 2% versus <0. 01% IFN-g ELISpot SFU/10 6 Ebola EBO-Z GP (Zaire ebolavirus glycoprotein) ChAd3 (GSK) Healthy adults R18-50 (phase 1) 1. 0 Â 10 10 vps 2. 5 Â 10 10 vps 5. 0 Â 10 10 vps (i. m. ) +Boost MVA/3-10 weeks (1. 5 Â 10 8 PFUs 3 Â 10 8 PFUs) D14 versus D0 633 versus <50 Flow cytometry CD4 + : 0. 2% versus 0. 13% D14 versus D0 GMT (95% CI) rVSV-ZEBOV: 920. 7 D28 versus rVSV-ZEBOV ChAd3 prime: 752. 4 NCT02240875 (2016) CD8 + : 0. 004% versus ? GMT (95% CI), ELISA EC 90 Ebola (GP) Ad5 (CanSino Biologic) Healthy adults R18-60 years (phase 1) 4 Â 10 10 vps 1. 6 Â 10 11 vps (i. m. ) Single dose or homologous prime:boost IFN-g ELISpot SFU/10 6 Prime D28 versus D0: Low dose: 6,110 versus 197. 9 reported in PMID: 25817373 Prime:boost D196 versus D168: NCT02326194 NCT02533791 (2017) High dose: 11,825 versus 575.
5 IFN-g ELISpot SFU/10 6 Ebola (GP) Ad5 (CanSino Biologic) Healthy adults R18-60 years (phase 1) 4 Â 10 10 vps 1. 6 Â 10 11 vps (i. m. ) Single dose (median, D14) Low dose: 465 High dose: 765 CD4 + /CD8 + Flow ICS GMT (95% CI), ELISA EC 90 High dose: 1,305. 7 versus 5 Prime D28 versus placebo: Low dose: 682. 7 versus 5 NCT02326194 (2015) IFN-g, TNF, IL-2 increased FC, fold change; GMC, geometric mean concentration; GMT, geometric mean titer; ICS, intracellular cytokine staining; IL, interleukin; IUs, infectious units; SFUs, spot forming units; vps, viral particles.
5 Â 10 10 vps G3: 5 Â 10 10 vps (i. m. ) Single dose D14 versus D0 D14: 1,031 versus 180. 1 D28: 541. 1 versus 180. 1 D56: 398. 2 versus 180. 1 D182: 352. 8 versus 180. 1 G2: $64-384 versus <6 (D28 versus D0) G3: $64-384 versus <6 (D28 versus D0) Against Â4 CHIKV lineages GMT (95% CI), ELISA units G1: 80. 99 versus 4. 74 (D182 versus D1) NCT03590392 34330906 All groups combined G2: 205. 9 versus 4. 72 (D182 versus D1) G3: 169. 7 versus 3. 00 (D182 versus D1) Against E2 protein G1: 1 Â 10 10 vps Avian influenza (H5 HA) Replicating Ad4 (PaxVax) Healthy adults R18-40 years (phase 1) (oral, enteric) G3: 1 Â 10 3 vps-1 Â 10 8 G2: 1 Â 10 3 vps-1 Â 10 8 vps (tonsillar) Single dose Flow cytometry i. n. groups increases in IFN-g + CD69 + CD4 + /CD8 + in tonsillar and Pseudovirus IC 50 (median) G3: $320 versus $35 (W8 versus W0) G1: $170 versus $35 (W8 versus W0) G2: $800 versus $35 (W8 versus W0) NCT01806909 NCT01443936 33529172 vps (i.
n. ) G1: 1 Â 10 10 vps Avian influenza (H5 HA) Replicating Ad4 (PaxVax) Healthy adults R18-49 years (phase 1) (oral, enteric) G3: 1 Â 10 3 vps-1 Â 10 8 G2: 1 Â 10 3 vps-1 Â 10 8 vps (tonsillar) Single dose Not reported in this study Pseudovirus IC 50 (median) G3: $352 versus $? (W8 versus W0) G1: $210 versus $? (W8 versus W0) G2: $836 versus $? (W8 versus W0) NCT01443936 31004012 vps (i. n. ) ?, values not provided; HA, hemagglutinin; IC50, half-maximal inhibitory concentration; MN 50 , microneutralization titer-50; PRNT 50 , plaque reduction neutralization test-50.
Data and discussion of variables The firm level data used in this study are taken from the Flash Eurobarometer 421 survey conducted in June 2015 in 34 European countries. 1 All firms are small and medium sized enterprises (SMEs) with 1 to 249 employees. In the survey firms were asked in question Q11_1 "Is it possible to look at a website presenting your products and/or services?" Firms that answered "yes" are classified as firm with a web presence. Descriptive evidence on the share of firms with a web presence in the total sample and by country is reported inTable 1. While the overall share of firms with a website in the sample is 75. 75 percent, figures differ widely between the 34 countries. Web presence is only 49. 00 percent in Albania and 49. 64 percent in Bulgaria while 88. 98 percent of all firms in the sample have a website in Sweden and 92.
A soft lockdown aims at reducing the number of contacts but not stopping then, while a hard lockdown aims at minimizing them fully and can therefore be a proxy for full lockdown with most of the societal infrastructure closed. During the study period, any patients suffering from typical COVID-19 symptoms, and those testing LFT reactive, were categorised as suspected COVID-19 cases and recommended immediate self-isolation (Fig. 1B ). We used three different datasets for each of the 94 Austrian districts for the period between October 01 to December 31, 2020. Firstly, we used the reimbursement data of the largest Austrian health insurance provider (Österreichische Gesundheitskasse, Austrian Health Insurance Fund, https:// www. gesun dheit skasse. at) covering the monthly sum of reimbursed LFTs per district conducted by contracted general practitioners, and pediatric and internist practices.
Through these practices, the Austrian Health Insurance Fund is the sole provider of free symptomatic POC-LFT in the country; and the dataset is a good representation of the level of LFT use across the 94 districts. Secondly, we used the publicly available district-level data of people testing SARS-CoV2 PCR positive and deaths (available at https:// covid 19dashb oard. ages. at/). The third dataset used were daily COVID-19-related hospital admissions for each district provided by the Austrian National Public Health Institute (Gesundheit Österreich GmbH, https:// goeg. at/ engli sh). All data on PCR, hospital admissions and deaths were stratified per age group and sex.
impacted measures of the productive HIV reservoir using the VIP-SPOT assay. Methods: eCLEAR trial (NCT03041012) is a phase 1b/2a, open-label, multicenter, randomized controlled trial among people starting ART randomly allocated to one of 4 treatment groups: ART alone, ART+3BNC117, ART+romidepsin, ART +3BNC117+romidepsin (3BNC117 on days 7+21 followed by romidepsin on days 10+17+24 after ART initiation). eCLEAR assessed whether administration of the bNAb 3BNC117, with or without the latency-reversing agent romidepsin, could potentially enhance clearance of HIV-infected cells. Cryopreserved PBMCs from 50/60 study participants were used to evaluate the productive viral reservoir 1 year after ART initiation using the novel VIP-SPOT assay. We compared raw VIP-SPOT data with plasma viremia, HIV viral clade from sequencing, proviral HIV DNA, and intact provirus measured by an IPDA-like duplexed ddPCR (3dPCR) assay.
Background: Blockade of the programmed cell death protein-1 (PD-1) pathway can reverse HIV latency, potentiate virus-specific CD8 T-cell responses, and has been associated with favorable outcome in some cases of central nervous system (CNS) infection. The effects of PD-1 blockade on CNS reservoirs for HIV are under study in clinical trial NCT03239899. We evaluated HIV reservoirs in blood in participants from this trial. Methods: People with HIV on ART and CD4 counts >350 cells/µL received one infusion of 200 mg pembrolizumab. PBMC were collected at baseline, week 3 and 24 post-infusion. CD4 Tcells were FACS-sorted into naïve, central/transitional memory, and effector memory (EM) subsets. HIV DNA was quantified by limiting dilution PCR of env and Sanger sequencing. HIV RNAs were quantified by ddPCR.
Clinical study design The details of SIMPLIFY-1 (NCT01969838) and SIMPLIFY-2 (NCT02101268) study designs have been previously published  [23, 24]. SIMPLIFY-1 was a randomized, double-blind, phase 3 study conducted in JAK inhibitor-naïve intermediate-and high-risk patients with PMF, post-PV MF, or post-ET MF (n = 432) designed to test the non-inferiority of outcomes for subjects randomized 1:1 to receive MMB or RUX over a 24-week treatment period, at which time patients originally randomized to MMB were able to continue receiving the compound for an extended treatment period, while RUX-randomized patients were eligible to cross over to MMB therapy. In total, 430 subjects received at least one dose of study treatment, and 197/ 216 (91. 2%) of RUX-randomized patients crossed over to MMB treatment at week 24.
SIMPLIFY-2 was a 2:1 randomized, multinational, open-label phase 3 study testing the superiority of MMB compared to best available therapy (BAT, which included RUX in 88. 5% of patients) in patients with PMF, post-PV MF, or post-ET MF who experienced hematologic toxicity when previously treated with RUX (n = 156). All 156 subjects received study treatment, and 40/52 (76. 9%) of BAT/RUX-randomized patients crossed over to MMB treatment at week 24. In both trials, the primary endpoint was spleen volume reduction (SVR) ≥ 35% from baseline at 24 weeks. Secondary endpoints included total symptom score (TSS) response rate and red blood cell transfusion independence (TI) rate at 24 weeks and overall and leukemia-free survival (OS and LFS). Patients whose disease did not progress and who tolerated MMB treatment while enrolled in SIMPLIFY-1 or SIMPLIFY-2 were eligible to enroll in an ongoing open-label, extended access protocol (NCT03441113) at the completion of these phase 3 studies.
Statistical analyses OS and LFS were analyzed for the enrolled populations from SIMPLIFY-1 and SIMPLIFY-2, inclusive of data for those who continued MMB treatment beyond study through the extended access protocol, using Kaplan-Meier analyses and compared between groups with stratified log-rank tests and proportional hazard Cox regression models stratified by randomization stratification factors. OS was calculated as time from first dose of study drug to death of any cause, and LFS was calculated as time from randomization to leukemic transformation or death from any cause, whichever earlier. Subjects who did not die or transform were censored at the last date known to be alive. No adjustments were made for the crossover of active control patients at week 24 in either study in the analyses because limited information is available for the minority of patients who did not cross over to MMB.
There was no prespecified test for the difference between MMB and control arms for OS and LFS in the studies because it was recognized that the analyses would be confounded by the fact that all control patients were to cross over to MMB at week 24. Duration of follow up for OS and LFS was analyzed using the reverse Kaplan-Meier method. Long-term safety data was analyzed from SIMPLIFY-1 and SIMPLIFY-2 studies and included patients who continued to receive MMB through the extended access protocol. Treatment emergent adverse events (TEAE) were documented for patients who received MMB, RUX or BAT/RUX in the 24-week randomization treatment periods and those who received MMB from crossover at week 24 throughout extended treatment and long-term follow up. The incidences of any grade TEAEs, and grade 3/4 TEAEs, by patient were calculated for each trial with a final data cut of September 2021.
Moreover, the design of SIMPLIFY-2 did not allow for a washout period of prior JAKi therapy, which may have influenced the specificity of MMB effects and impacted the non-significance of association between week 24 clinical endpoints and OS in this study. Future studies are needed to uncover potential factors beyond baseline hemoglobin and transfusion requirements that may predict which MMB-treated patients are likely to become TI responders versus TI non-responders. Momelotinib's anemia benefits are currently being further characterized in MOMENTUM (NCT04173494), a global phase 3 clinical trial in symptomatic and anemic patients previously treated with an approved JAKi, intended to support potential registration of momelotinib for the treatment of MF  [31]. In addition to assessments of transfusion independence, symptoms, and splenomegaly, MOMENTUM will provide an opportunity to evaluate associations between MMB anemia benefit, transfusion burden and patient-reported measures of clinical benefit as well as survival.
DATA AVAILABILITY Sierra Oncology commits to share clinical study data with qualified researchers to enable enhancement of public health. As such, Sierra will share anonymized patientlevel data on request or if required by law or regulation. Qualified scientific and medical researchers can request patient-level data for studies of Sierra pharmaceutical substances listed on ClinicalTrials. gov and approved by health authorities in the United States and the EU. Patient-level data for studies of newly approved pharmaceutical substances or indications can be requested 9 months after US Food and Drug Administration and European Medicines Agency approvals. Such requests are assessed at Sierra's discretion, and the decisions depend on the scientific merit of the proposed request, data availability, and the purpose of the proposal.
If Sierra agrees to share clinical data for research purposes, the applicant is required to sign an agreement for data sharing before data release, to ensure that the patient data are de-identified. In case of any risk of re-identification on anonymized data despite measures to protect patient confidentiality, the data will not be shared. The patients' informed consent will always be respected. If the anonymization process will provide futile data, Sierra will have the right to refuse the request. Sierra will provide access to patient-level clinical trial analysis datasets in a secured environment upon execution of the data sharing agreement. Sierra will also provide the protocol, statistical analysis plan, and the clinical study report synopsis if needed. For additional information or requests for access to Sierra clinical trial data for research purposes, please contact us at Medinfo@sierraoncology.
Patient population We performed a retrospective cohort study including patients from the HIBISCUS-STROKE cohort (CoHort of Patients to Identify Biological and Imaging markerS of CardiovascUlar Outcomes in Stroke; NCT03149705). This cohort is an ongoing observational cohort conducted since October 2016 that includes patients referred to our stroke center for LVO-AIS of the anterior circulation and candidates for MT  [9]. Patients were included in this study if they underwent an initial MRI with TOF-MRA and CE-MRA followed by a brain DSA performed during MT. We excluded patients with posterior circulation AIS and those for whom one of the angiographic modalities was not available. Baseline data on demographics characteristics were collected at hospital admission. In line with international guidelines, patients were additionally treated with intravenous thrombolysis immediately after brain MRI  [14].
Image analysis MRA images were reviewed, in random order, independently by two neuroradiologists blinded from clinical data, other MR sequences, and DSA. In case of discrepancy, a third neuroradiologist evaluated the images. Brain DSAs were also evaluated by two operators blinded from clinical data and MRIs, and a consensus was reached in case of discrepancy between them. All readings assessed the presence of an occlusion and its location according to the following classification: common carotid artery (CCA), internal carotid artery (ICA) including proximal ICA and distal ICA, proximal middle cerebral artery (MCA) including proximal M1 segment and distal M1 segment, and proximal M2 segment of MCA. In case of tandem occlusions, both levels were reported. Image quality was assessed using a three-point subjective score: 0 = poor quality resulting in impossible interpretation; 1 = moderate (OR = 1.
Acknowledgement This work was supported by the  RHU MARVELOUS  ( ANR-16-RHUS-0009 ) of  Universitede Lyon , within the program Fig. 2 -An example of tandem occlusion. In this example,  TOF-MRA (Fig. 2A ) revealed a signal void in the right proximal ICA (white arrow) and,  CE-MRA  (Fig. 2B) demonstrated a tandem occlusion including the proximal ICA and the proximal M1 segment of the MCA (white arrows). Brain DSA (Figs. 2C and D) confirms tandem occlusion by visualizing opacification defects at the original of the right proximal ICA and the proximal M1 segment of the MCA (black arrows). TOF-MRA: time-offlight magnetic resonance imaging; CE-MRA: contrast-enhanced magnetic resonance imaging; MCA: middle cerebral artery.
In this study, we characterized variations in dry season length (DSL), dry season arrival (DSA) date, and dry season end (DSE) date, as well as the severity of water deficit (WD) over the global tropics (23. 5°S-23. 5°N) during the period of 1983-2016, among different definitions of the dry season, using multiple combinations of observational and reanalysis datasets (see Methods). In particular, we considered three widely used definitions of "dry season": (i) P < Ep, a comparison of water supply vs. atmospheric water demand, (ii) P < E, a comparison of water supply vs. actual ecosystem water consumption, and (iii) P < P; a comparison of water supply vs. the long-term mean water supply. Our objective was to understand how the length and timing of the dry season have been changing over the tropics and whether definitions of the dry season that account for atmospheric water demand or actual ecosystem water loss indicate similar or different changes in the length and timing of the tropical dry season, compared to definitions based merely on precipitation.