bluuebunny/crossref_metadata_2025 huggingface dataset:
A single-arm confirmatory study to evaluate the efficacy of nonsurgical therapy for HER2-positive early breast cancer with clinical complete response after primary systemic therapy (JCOG1806: AMATERAS-BC study).
Authors: Fujisawa Tomomi , Shien Tadahiko , Iwata Hiroji , Shigematsu Hideo , Shibata Taro , Sasaki Keita , Takahashi Yuko
Published: June 2021

TPS601

Background: The surgical treatment is a standard therapy for early breast cancer (EBC) after primary systemic therapy (PST). In more than half of HER2 positive (HER2(+)) breast cancer, pathological complete response (pCR) is achieved by PST with HER2 inhibitors and chemotherapy. In addition, hormone receptor (HR) negative HER2(+) (HR(-)HER2(+)) subtype has higher concordance between pCR and clinical complete response (cCR) before surgery than other subtypes, especially in EBC. However, non-surgical therapy is not an option for EBC with cCR after PST because of few evidence. We planned single arm confirmatory study to evaluate the efficacy and safety of the non-surgical therapy for HR(-)HER2(+) EBC with cCR after PST. Methods: The key eligibility criteria are as follows: 1) Histologically confirmed as invasive ductal carcinoma of breast, HR(-)HER2(+). 2) cT1-2, N0, M0 (UICC 8th). 3) No ipsilateral BC. 4) Women aged 20-74 years. 5) ECOG performance status 0 or 1. 6) Written informed consent. HER2 inhibitors (trastuzumab and pertuzumab) and cytotoxic drugs as PST are administered for all patients (pts). After completion of PST, cCR is diagnosed by breast imaging and physical examination. cCR is defined as 1) Not palpable breast mass by physical examination, 2) No enhanced breast mass by enhanced MRI, 3) No breast mass by sonography. After diagnosis of cCR, conventional radiotherapy for whole breast and boost radiation for tumor bed are mandatory, followed by pertuzumab and trastuzumab every 3 weeks during 9 months. In non-cCR cases, surgical resection is performed and adjuvant therapy are not specified. The primary endpoint is a distant metastasis-free survival (DMFS) at 3 year, the secondary endpoints are DFS, OS, RFS, proportion of local recurrence, and cosmetics outcome. Given that the threshold and expected of DMFS at 3-year is 93% and 98% with a significance level 2.5% (one sided) and 80% power, 170 cCR cases are required. Assuming half of HER2 pts reach to cCR, 350 pts are required as sample size started PST. Enrollment launched January, 2020 and 57 pts are enrolled as of January 12, 2021. Recent reports found that HR positive HER2(+) subtype has higher concordance between pCR and cCR by adding needle biopsy in the diagnosis, so we are planning to include HR positive subtype in this trial. This clinical trial has been registered at Japan Registry of Clinical Trials as jRCTs031190129 and conducted by the Japan Clinical Oncology Group (JCOG) Breast Cancer Study Group under public fund (National Cancer Center Research and Development Fund). Clinical trial information: jRCTs031190129.
Phase 3 trial (GCT3013-05) of epcoritamab versus standard of care in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).
Authors: Thieblemont Catherine , Clausen Michael Roost , Sureda Balari Anna , Zinzani Pier Luigi , Fox Christopher , Kim Su Young , Vindeloev Signe Diness , Lugtenburg Pieternella
Published: June 2021

TPS7569

Background: Patients (pts) with DLBCL who are refractory to/or have relapsed (R/R) after treatment with chemotherapy and anti-CD20 monoclonal antibody (mAb) have a poor prognosis. There is a need for new treatment options to improve outcomes. Epcoritamab, a novel subcutaneous (SC) bispecific antibody, binds to CD3 on T-lymphocytes and CD20 on B-cell non-Hodgkin lymphoma (NHL) cells to induce potent and selective killing of malignant CD20+ B-cells. In an ongoing phase 1/2 dose-escalation trial in heavily pretreated pts with B-cell NHL (N = 68), epcoritamab demonstrated a tolerable safety profile and substantial single-agent anti-tumor activity, with a complete response (CR) rate of 55% and an overall response rate (ORR) of 91% in pts with R/R DLBCL (at ≥48 mg doses; n = 12) (NCT04663347; Hutchings, ASH, 2020). Furthermore, all 4 evaluable R/R DLBCL pts previously treated with chimeric antigen receptor T-cell (CAR-T) therapy achieved an objective response with 2 achieving CR. These encouraging data support the potential for epcoritamab to improve clinical outcomes in pts with R/R DLBCL. Here we describe the phase 3 trial of epcoritamab versus standard of care (SOC) treatments in pts with R/R DLBCL (NCT04628494). Methods: GCT3013-05 is a randomized, open-label, worldwide, multicenter, phase 3 study designed to evaluate the efficacy of epcoritamab versus investigator’s choice of SOC with R-GemOx (rituximab, gemcitabine, oxaliplatin) or BR (bendamustine, rituximab) in adults with R/R disease of one the following CD20+ B-cell NHL histologies: I) DLBCL, not otherwise specified including de novo DLBCL or DLBCL histologically transformed from follicular lymphoma; II) “double-hit” or “triple-hit” DLBCL (high-grade B-cell lymphoma, with MYC and BCL2 and/or BCL6 translocations); or III) follicular lymphoma grade 3B. Other key eligibility criteria include: ≥1 line of prior chemotherapy that included treatment with an anti-CD20 mAb, Eastern Cooperative Oncology Group performance status 0–2, and prior failure of/ineligibility for autologous stem cell transplantation. Prior CAR-T therapy is allowed. A total of 480 pts will be randomized 1:1 to receive either SC epcoritamab at the recommended phase 2 dose (28-day cycles; weekly, biweekly, or monthly schedule depending on cycle number) until disease progression or unacceptable toxicity; or up to 4 cycles of biweekly treatment with intravenous (IV) R-GemOx (8 doses); or up to 6 cycles of IV BR (6 doses; dosing every 3 weeks). The primary endpoint is overall survival. Key secondary endpoints include progression-free survival, ORR, duration of response, time to response, and safety. The study is currently enrolling in Australia, Belgium, Denmark, France, Spain, and will open for enrollment in additional countries. Clinical trial information: NCT04628494.
Phase 3 study of pembrolizumab with concurrent chemoradiation therapy followed by pembrolizumab with or without olaparib versus concurrent chemoradiation therapy followed by durvalumab in unresectable, locally advanced, stage III non-small cell lung cancer: KEYLYNK-012.
Authors: Jabbour Salma K. , Cho Byoung Chul , Bria Emilio , Kato Terufumi , Bhosle Jaishree , Gainor Justin F. , Reguart Noemi , Wang Luhua , Morgensztern Daniel , Gurary Ellen , Ashraf Tanya B. , Lara-Guerra Humberto , Reck Martin
Published: June 2021

TPS8580

Background: Pembrolizumab, an anti‒PD-1 antibody is standard of care therapy for metastatic non‒small-cell lung cancer (NSCLC) as monotherapy and in combination with chemotherapy. Durvalumab, an anti–PD-L1 antibody, is approved for unresectable, stage III NSCLC without disease progression following concurrent chemoradiation therapy (CCRT). Early trials of pembrolizumab in combination with chemoradiotherapy, either concurrently or as consolidation, showed acceptable tolerability and promising PFS in patients with unresectable stage III NSCLC. Early data suggest the combination of poly(ADP-ribose) polymerase (PARP) plus anti–PD-(L)1 inhibition can enhance treatment effects. KEYLYNK-012 (NCT04380636) is evaluating pembrolizumab plus CCRT followed by pembrolizumab with/without the PARP inhibitor olaparib vs CCRT followed by durvalumab in patients with unresectable, locally advanced, stage III NSCLC. Methods: This global phase 3, randomized, placebo- and active-controlled, double-blind study is enrolling patients aged ≥18 y with previously untreated, pathologically confirmed, stage IIIA–C NSCLC, an ECOG PS of 0 or 1, and a tumor sample available for PD-L1 evaluation. Patients are randomized 1:1:1 to CCRT (platinum-doublet chemotherapy [cisplatin plus pemetrexed or etoposide; or carboplatin plus paclitaxel] plus radiotherapy 60 Gy over 6 wks [cycles 2–3]) with pembrolizumab 200 mg Q3W (groups A and B) or CCRT alone (group C) for 3 cycles. This is followed by pembrolizumab 200 mg Q3W for 17 cycles plus placebo (group A) or olaparib 300 mg BID (group B); or durvalumab 10 mg/kg Q2W for 26 cycles (group C). Randomization is stratified by disease stage (IIIA vs IIIB/IIIC), tumor histology (squamous vs nonsquamous), PD-L1 tumor proportion score (≥50% vs < 50%) and region (East Asia vs North America/Western Europe/UK vs other). PFS (RECIST v1.1 by blinded independent central review [BICR]) and OS are dual primary endpoints. Secondary endpoints include ORR, duration of response, safety and tolerability, and quality-of-life outcomes. Tumor response will be evaluated per RECIST v1.1 by BICR after CCRT and at regular intervals throughout the study until disease progression, new cancer therapy, study withdrawal, or death. AEs will be graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0. Enrollment began July 6, 2020 and is ongoing at 204 sites in 24 countries. Clinical trial information: NCT04380636.
Trial in progress: A multicenter phase Ib/II study of pelcitoclax (APG-1252) in combination with paclitaxel in patients with relapsed/refractory small-cell lung cancer (R/R SCLC).
Authors: Qin Angel , Kalemkerian Gregory Peter , Patel Jyoti D. , Mohindra Nisha Anjali , Carlisle Jennifer W , Sands Jacob , He Zhicong , Winkler Robert , Liang Zhiyan , Hammock Vakessa , Bombelli Riccardo , Lu Ming , Xu Yang , Fu Tommy , Wang Cunlin , Yang Dajun , Zhai Yifan
Published: June 2021

TPS8589

Background: Increased expression of BCL-2, BCL-xL, and MCL-1 allows certain tumors to evade apoptosis. Pelcitoclax is a novel, dual BCL-2/BCL-xL inhibitor with strong single-agent antitumor activity against tumor cells addicted to BCL-2, BCL-xL, and BCL-w, and exhibits even broader antitumor activity when administered with chemotherapy. Pelcitoclax reduces tumor growth in SCLC and other human cancer xenograft models, with manageable effects on platelet counts. Preliminary findings from the first-in-human study suggested promising antitumor activity and a favorable safety profile. Methods: This open-label study is evaluating the safety and preliminary efficacy of pelcitoclax combined with paclitaxel in adults with R/R SCLC that has progressed on or after initial treatment. Prior treatments may include platinum-based therapy (± thoracic radiation), immunotherapy, or chemotherapeutic agents other than paclitaxel. Eligible patients have an ECOG performance status of 0-2; adequate organ function; no known bleeding diathesis, immune thrombocytopenic purpura, autoimmune hemolytic anemia, serious gastrointestinal bleeding, or concomitant use of most anticoagulants; and no residual grade ≥ 2 adverse events from previous treatment. In the phase Ib study, the pelcitoclax maximum tolerated dose is being determined using a time-to-event continual reassessment method. In this phase, pelcitoclax is administered by IV infusion over 30 minutes on Days 1, 8, and 15 at dose levels of 80, 160, and 240 mg per week, with fixed-dose paclitaxel 80 mg/m2 on Days 1 and 8 of a 21-day cycle. In addition to a baseline scan within 4 weeks before study entry, computed tomography will be performed every two cycles to evaluate antitumor response. Treatment will continue until disease progression, unacceptable toxicity, consent withdrawal, or administrative discontinuation. The primary endpoint of this phase includes dose-limiting toxicity by NCI CTCAE v5.0 over 21 days. After determination of the recommended phase II dose of pelcitoclax in the phase Ib study, the efficacy of pelcitoclax with paclitaxel will be determined in the phase II study using a Simon two-stage design, with overall response rate as the primary endpoint. Other study endpoints in the phase II study include pharmacokinetics of pelcitoclax with paclitaxel, as well as progression-free and overall survival. As of February 8, 2021, 15 of 58 patients had been enrolled. Internal study identifier APG1252SU101. Clinical trial information: NCT04210037.
A randomized, phase 3 study of datopotamab deruxtecan (Dato-DXd; DS-1062) versus docetaxel in previously treated advanced or metastatic non-small cell lung cancer (NSCLC) without actionable genomic alterations (TROPION-Lung01).
Authors: Yoh Kiyotaka , Goto Yasushi , Thomas Michael , Spira Alexander I. , Sands Jacob , Johnson Melissa Lynne , Greenberg Jonathan , Petrich Adam Matthew , Guevara Ferdinand M. , Phillips Penny , Alexandris Ekaterine , Gu Jessie , Zhang Yong , Shuster Dale Edward , Lisberg Aaron Elliott
Published: June 2021

TPS9127

Background: Treatment options are limited for patients with advanced/metastatic NSCLC without driver genomic alterations after failure of a platinum-based chemotherapy and immunotherapy; median survival is < 1 year. Datopotamab deruxtecan (Dato-DXd; DS-1062) is an antibody-drug conjugate consisting of a humanized anti-TROP2 IgG1 monoclonal antibody attached to a topoisomerase I inhibitor payload via a tetrapeptide-based cleavable linker. Results from the ongoing phase 1 study (TROPION-PanTumor01; Spira, WCLC 2020) demonstrated an overall response rate (ORR) of 21%, a disease control rate (DCR) of 67%, and a preliminary median progression-free survival (PFS) of 8.2 months (all by blinded independent central review [BICR]), with a manageable safety profile, in patients with NSCLC who were treated with 6 mg/kg of Dato-DXd. This phase 3 study (NCT04656652) will compare the efficacy of Dato-DXd with that of docetaxel as 2/3L therapy in patients with advanced/metastatic NSCLC. Methods: TROPION-Lung01 is an open-label, phase 3, randomized study of Dato-DXd vs docetaxel in patients with advanced/metastatic NSCLC without EGFR, ALK, or other actionable genomic alterations. Patients must have been previously treated with platinum-based chemotherapy and a PD-(L)1 monoclonal antibody in combination or sequentially and have radiographic disease progression on or after the most recent therapy. Those with asymptomatic and stable/treated brain metastases are eligible. A tumor specimen is required for biomarker analyses. Patients (N = 590) are randomized 1:1 to either Dato-DXd 6 mg/kg or docetaxel 75 mg/m2 given intravenously on day 1 of each 3-week cycle. Randomization is stratified by histology (squamous vs nonsquamous), immunotherapy in last regimen (yes vs no), and region (US/Japan/Western Europe vs rest of world). Treatment continues until disease progression or intolerance or other discontinuation criteria are met. The study will be conducted globally at approximately 184 study sites. Dual primary endpoints are PFS by BICR and overall survival. Secondary outcome measures include PFS by investigator, ORR, duration of response, DCR, and time to response (all assessed by BICR and by investigator per RECIST version1.1), patient-reported outcomes, safety, pharmacokinetics, and proportion of patients who develop antidrug antibodies. Biomarkers will be evaluated for potential associations with efficacy. Clinical trial information: NCT04656652.
KRYSTAL-12: A randomized phase 3 study of adagrasib (MRTX849) versus docetaxel in patients (pts) with previously treated non-small-cell lung cancer (NSCLC) with KRASG12C mutation.
Authors: Mok Tony S. K. , Lawler William E. , Shum Merrill Kingman , Dakhil Shaker R. , Spira Alexander I. , Barlesi Fabrice , Reck Martin , Garassino Marina Chiara , Spigel David R. , Alvarez Delia , Kheoh Thian , Paxton William , Chao Richard C. , Felip Enriqueta
Published: June 2021

TPS9129

Background: Despite significant advances in chemotherapy and immunotherapy for advanced NSCLC, the majority of pts ultimately develop progressive disease associated with poor outcomes. KRAS is a key mediator of the RAS/MAPK signaling cascade that promotes cell growth and proliferation. KRASG12C mutations occur in 14% of NSCLC (adenocarcinoma), and mutations in KRAS are associated with a poor prognosis. Although KRAS has historically been undruggable, recent research into the development of agents that specifically bind mutant KRAS has led to the development of direct inhibitors of KRASG12C. Adagrasib, an investigational agent, is a potent, covalent inhibitor of KRASG12C that irreversibly and selectively binds to and locks KRASG12C in its inactive state. Adagrasib was optimized for favorable pharmacokinetic (PK) properties, including oral bioavailability, long half-life (̃24 h), and extensive tissue distribution. Initial results have demonstrated encouraging antitumor activity and tolerability of adagrasib monotherapy in pts with NSCLC harboring a KRASG12C mutation. Methods: KRYSTAL-12 is a multicenter, randomized Phase 3 study evaluating the efficacy of adagrasib (600 mg BID) vs docetaxel in pts with advanced NSCLC harboring a KRASG12C mutation who have progressed during or after treatment with a platinum-based regimen and an immune checkpoint inhibitor. The study is designed to demonstrate improvement in the dual primary endpoints of progression-free survival (PFS) and overall survival (OS). Secondary endpoints include safety, objective response rate (ORR) per RECIST 1.1, duration of response (DOR), plasma PK parameters of adagrasib, and patient-reported outcomes (PROs). The study will also explore correlations between gene alterations (at baseline and upon development of treatment resistance) and efficacy. Approximately 450 patients will be randomized in a 2:1 ratio to receive adagrasib or docetaxel and will be stratified by region (United States/Canada vs other countries) and sequential vs concurrent administration of prior platinum-based chemotherapy and anti–PD-1/PD-L1 antibody. The planned sample size is sufficiently powered for the hypothesized treatment effect of the endpoints. Pts will receive study treatment until disease progression, unacceptable adverse events, investigator decision to terminate treatment, or patient withdrawal. This study is currently enrolling and will be open at sites in the United States, Europe, and Asia. Clinical trial information: NCT04685135.
Camrelizumab monotherapy or in combination with apatinib for PD-L1-positive advanced pulmonary sarcomatoid carcinoma: A multicenter, open-label, single-arm, phase II study.
Authors: Zhao Mingfang , Han Tao
Published: June 2021

TPS9130

Background: Pulmonary sarcomatoid carcinoma (PSC) is a rare subtype of non-small cell lung cancer (NSCLC) with a fairly poor prognosis. As a highly aggressive malignancy, PSC is insensitive to conventional chemotherapy or radiotherapy and no optimal treatment for PSC has been established yet. Immune checkpoint inhibitors (ICIs) were documented to possess encouraging therapeutic efficacy in PSC patients, which is demonstrated to be associated with high expression of programmed death-ligand 1 (PD-L1) in PSC. However, because of the rarity of PSC, most of the existed data were derived from case repots which could not reflect the true clinical efficacy of ICIs for PSC treatment. This clinical trial was designed to investigate the clinical outcomes of camrelizumab in treating PD-1-positive PSC. Apatinib may be used simultaneously based on the expression level of PD-L1 in PSC as the combination of camrelizumab and apatinib exhibited treatment potential in NSCLC in previous researches. Methods: In this multicenter, open-label, single-arm, phase II study conducted in 44 sites in China, 30 patients with an age of 18-80 years old, an Eastern Cooperative Oncology Group (ECOG) performance score of 0–2, positive PD-L1 expression, no EGFR, ALK, ROS1, and MET gene mutations, and histologically or cytologically confirmed stage IIIB-IV PSC regardless of prior lines of standard therapy will be enrolled. Patients with PD-L1 expression 1-49% will receive Camre (200 mg, IV, Q3W) and Apa (250mg, QD). Patients with PD-L1 expression≥50% receive Camre (200 mg IV Q3W) alone. The treatment will continue until a maximum treatment duration of 36 months, disease progression, intolerable toxicity, death or consent withdrawal. The primary endpoint is objective response rate (ORR). The secondary endpoints are progression-free survival (PFS), overall survival (OS), disease control rate (DCR), time to objective response (TTR), duration of response (DOR) and safety. This study is ongoing. Clinical trial information: ChiCTR2000032649, China.
Improved Decision-Making Confidence Using Item-Based Pharmacometric Model: Illustration with a Phase II Placebo-Controlled Trial
Authors: Llanos-Paez Carolina , Ambery Claire , Yang Shuying , Tabberer Maggie , Beerahee Misba , Plan Elodie L. , Karlsson Mats O.
Published: June 2021

This study aimed to illustrate how a new methodology to assess clinical trial outcome measures using a longitudinal item response theory–based model (IRM) could serve as an alternative to mixed model repeated measures (MMRM). Data from the EXACT (Exacerbation of chronic pulmonary disease tool) which is used to capture frequency, severity, and duration of exacerbations in COPD were analyzed using an IRM. The IRM included a graded response model characterizing item parameters and functions describing symptom-time course. Total scores were simulated (month 12) using uncertainty in parameter estimates. The 50th (2.5th, 97.5th) percentiles of the resulting simulated differences in average total score (drug minus placebo) represented the estimated drug effect (95%CI), which was compared with published MMRM results. Furthermore, differences in sample size, sensitivity, specificity, and type I and II errors between approaches were explored. Patients received either oral danirixin 75 mg twice daily (n = 45) or placebo (n = 48) on top of standard of care over 52 weeks. A step function best described the COPD symptoms-time course in both trial arms. The IRM improved precision of the estimated drug effect compared to MMRM, resulting in a sample size of 2.5 times larger for the MMRM analysis to achieve the IRM precision. The IRM showed a higher probability of a positive predictive value (34%) than MMRM (22%). An item model–based analysis data gave more precise estimates of drug effect than MMRM analysis for the same endpoint in this one case study.
Association between convalescent plasma and the risk of mortality among patients with COVID-19: a meta-analysis
Authors: Wardhani Shinta Oktya , Fajar Jonny Karunia , Wulandari Laksmi , Soegiarto Gatot , Purnamasari Yeni , Asmiragani Anisa , Maliga Helnida Anggun , Ilmawan Muhammad , Seran Gloriana , Iskandar Dheka Sapti , Ndapa Conchita Emiliana , Hamat Viviana , Wahyuni Rafika Ajeng , Cyntia Linda Oktaviana Suci , Maarang Feronika Maryanti , Beo Yosef Andrian , Adar Olivera Agnes , Rakhmadhan Iraky Mardya , Shantikaratri Emilia Tiara , Putri Ayu Sekarani Damana , Wahdini Rizqa , Broto Endang Pati , Suwanto Agnes Wanda , Tamara Fredo , Mahendra Aditya Indra , Winoto Eden Suryoiman , Krisna Pratista Adi , Harapan Harapan
Published: June 2021

Background: Convalescent plasma (CCP) has been used for treating some infectious diseases; however, the efficacy of CCP in coronavirus disease 2019 (COVID-19) remains controversial. The aim of this research was to assess the efficacy of CCP as an adjunctive treatment in COVID-19 patients.

Methods: Embase, PubMed, Web of Science, Cochrane and MedRix were searched for potentially relevant articles. All included papers were assessed for the quality using modified Jadad scale and Newcastle-Ottawa scale for randomized controlled trial (RCT) and non – RCT, respectively. We used a Q test and Egger test to assess the heterogeneity and publication bias among studies, respectively. Mortality rates between patients treated with standard treatment and standard treatment with CCP were compared using a Z test.

Results: A total of 12 papers consisting of three cross-sectional studies, one prospective study, five retrospective studies, and three RCT studies were included in our analysis. Of them, a total of 1,937 patients treated with CCP and 3,405 patients without CCP were included. The risk of mortality was 1.92-fold higher in patients without CCP compared to patients treated with CCP (OR: 1.92; 95%CI: 1.33, 2.77; p=0.0005). In severe COVID-19 sub-group analysis, we found that patients without CCP had a 1.32 times higher risk of mortality than those treated with CCP (OR: 1.32; 95%CI: 1.09, 1.60; p=0.0040).

Conclusions: CCP, as adjunctive therapy, could reduce the mortality rate among COVID-19 patients.
Is Tourette syndrome a rare disease?
Authors: Hartmann Andreas , Szejko Natalia , Mol Debes Nanette , Cavanna Andrea E. , Müller-Vahl Kirsten
Published: June 2021

Based on its prevalence, Tourette syndrome cannot be considered a rare disease. However, in this opinion article, we make the claim that it should nonetheless be considered as an orphan or neglected disease.
Can Market Participants Report Their Preferences Accurately (Enough)?
Authors: Budish Eric , Kessler Judd B.
Published: June 2021

In mechanism design theory it is common to assume that agents can perfectly report their preferences, even in complex settings in which this assumption strains reality. We experimentally test whether real market participants can report their real preferences for course schedules “accurately enough” for a novel course allocation mechanism, approximate competitive equilibrium from equal incomes (A-CEEI), to realize its theoretical benefits. To use market participants’ real preferences (i.e., rather than artificial “induced preferences” as is typical in market design experiments), we develop a new experimental method. Our method, the “elicited preferences” approach, generates preference data from subjects through a series of binary choices. These binary choices reveal that subjects prefer their schedules constructed under A-CEEI to their schedules constructed under the incumbent mechanism, a bidding points auction, and that A-CEEI reduces envy, suggesting subjects are able to report their preferences accurately enough to realize the efficiency and fairness benefits of A-CEEI. However, preference-reporting mistakes do meaningfully harm mechanism performance. One identifiable pattern of mistakes was that subjects had relatively more difficulty reporting cardinal as opposed to ordinal preference information. The experiment helped to persuade the Wharton School to adopt the new mechanism and helped guide aspects of its practical implementation, especially around preference reporting.

This paper was accepted by Yan Chen, decision analysis.
Is there still a role for the oesophageal Doppler in cardiac output monitoring?
Authors: Harris Joseph , Jones Conor
Published: June 2021

The oesophageal Doppler monitor received early endorsement as an effective emerging medical technology, although numerous alternatives have since been widely adopted. This article examines the evidence supporting the continued use of the oesophageal Doppler.
Managing the side effects of contraception
Authors: Boog Katie
Published: June 2021

Side effects are the most common reason for the discontinuation of contraceptive methods. Dr Katie Boog summarises the available evidence on how to manage them

Although often transient, side effects are the most common reason for individuals to discontinue contraception. The evidence to prove causality is limited, as is evidence-based guidance on how to manage these side effects. This article summarises the available evidence. For individuals who have new or worsening acne on progestogen-only contraception (POC), switching to combined hormonal contraception (CHC) is likely to improve their skin. Continuous or extended CHC use may be beneficial for individuals with premenstrual mood change, and for those who experience headaches in the hormone-free interval. Unpredictable bleeding patterns on POC are common. Injectable users can try reducing the interval between injections to 10 weeks. Implant, injectable or intrauterine system users can be offered a 3-month trial of a combined oral contraceptive pill (COC). CHC and POP users with unpredictable bleeding may benefit from switching to an alternative preparation.
Real-Time Performance and Security of IEC 61850 Process Bus Communications
Authors: Mocanu Stéphane , Thiriet Jean-Marc
Published: June 2021

Modern power-network communications are based on the IEC 61850 series standards. In this paper, we investigate the real-time performance and the vulnerabilities and attack scenarios at the sensor level communication networks more precisely on Sampled Measured Value protocol. The approach jointly evaluates the communication protocol, network topology and impact on electrical protection functions. We test the practical feasibility of the attacks on an experimental workbench using real devices in a hardware-in-the-loop setup. The tests are conducted on the two high-availability automation networks currently used in IEC 61850 process bus communications: Parallel Redundancy Protocol (PRP) and High-availability Seamless Redundancy (HSR)
Database Security Enhancement by Eliminating the Redundant and Incorrect Spelled Data Entries
Authors: Chopade Rupali , Pachghare Vinod
Published: June 2021

Database is used for storing the data in an easy and efficient format. In recent days large size of data has been generated through number of applications and same has been stored in the database. Considering the importance of data in every sector of digitized world, it is foremost important to secure the data. Hence, database security has been given a prime importance in every organization. Redundant data entries may stop the functioning of the database. Redundant data entries may be inserted in the database because of the absence of primary key or due to incorrect spelled data. This article addresses the solution for database security by protecting the database from redundant data entries based on the concept of Bloom filter. This database security has been obtained by correcting the incorrect spelled data from query values with the help of edit distance algorithm followed by the data redundancy check. This article also presents the performance comparison between proposed technique and MongoDB database for document search functionality.
Consistency of data collected through online life history calendars
Authors: Berchtold André , Wicht Bertil , Surís Joan-Carles , Morselli Davide
Published: June 2021

The collection of longitudinal data is crucial in some domains such as life course studies. However, prospective studies are considerably costly, and thus retrospective data are an appealing alternative. A life history calendar is a tool specifically conceived to collect retrospective data. However, although it is designed to enhance the recall process of the respondents, the accuracy of the data collected through this approach remains unknown, particularly when data is collected online. In this study, we conducted a secondary analysis of data collected from n = 5,181 respondents through an online survey regarding their sexual health. Because we inquired about the occurrence of certain events twice during the survey, once using a life calendar and once through a traditional questionnaire, we were able to perform three types of consistency checks: (1) reporting of single events, (2) age when the events occurred and (3) correct timing between two events. The main results indicated that it is generally more difficult to remember the exact age of occurrence of an event than the event itself, that the report of related events is generally coherent, and that women are generally more accurate in their answers than men. Based on our results, it is therefore possible to identify a subset of persons whose answers are more consistent throughout the survey. This study also shows that data obtained through an online life history calendar can be of a quality similar to that obtained through a traditional online questionnaire.
Efficient second-harmonic and terahertz generation from single BiB3O6crystal using nanosecond and femtosecond lasers
Authors: Ghorui Chandan , Rudra A. M. , Chatterjee Udit , Chaudhary A. K. , Ganesh D.
Published: June 2021

The paper reports the efficient UV and terahertz generation from a 1.29 mm thick and Type I,

θ
=

28.9

∘

cut

B
i
B

3

O

6

(bismuth triborate, BIBO) crystal using femtosecond and nanoseconds laser pulses. We have employed 800 nm wavelength pulses of 50 and 140 fs obtained from a Ti:sapphire laser amplifier and oscillators at 1 kHz and 80 MHz repetition rates, respectively. The conversion efficiency of second-harmonic generation (SHG) was

∼

50

%

while that obtained for terahertz (THz) generations was of the order of

1.85

×

10

−
5

%

. In addition, LDS-698 dye laser radiation tunable between 650–700 nm was also used as a source for SHG between the 325–350 nm range. The dye laser was pumped by SHG (532 nm) radiation from an electro-optically

Q

-switched Nd:YAG laser having a pulse repetition rate of 10 Hz and a pulse width of 10 ns. A conversion efficiency of 4.01% was obtained for generation of UV at 343.5 nm. Finally, we have measured the transmission, refractive index, absorbance, and conductivity properties of BIBO crystal in the THz domain. We also ascertained the coherence length, relative permittivity and reflectivity of the crystal.
Panoramic annular SLAM with loop closure and global optimization
Authors: Chen Hao , Hu Weijian , Yang Kailun , Bai Jian , Wang Kaiwei
Published: June 2021

In this paper, we propose panoramic annular simultaneous localization and mapping (PA-SLAM), a visual SLAM system based on a panoramic annular lens. A hybrid point selection strategy is put forward in the tracking front end, which ensures repeatability of key points and enables loop closure detection based on the bag-of-words approach. Every detected loop candidate is verified geometrically, and the

S
i
m

(
3
)

relative pose constraint is estimated to perform pose graph optimization and global bundle adjustment in the back end. A comprehensive set of experiments on real-world data sets demonstrates that the hybrid point selection strategy allows reliable loop closure detection, and the accumulated error and scale drift have been significantly reduced via global optimization, enabling PA-SLAM to reach state-of-the-art accuracy while maintaining high robustness and efficiency.
Performance analysis of an all-optical double-hop free-space optical communication system considering fiber coupling
Authors: Chang Yidi , Liu Zhi , Ni Xiaolong , Yao Haifeng , Gao Shiming , Gao Siyuan , Tong Xin
Published: June 2021

In an all-optical double-hop free-space optical communication system, the outage probability and bit error rate are analyzed using a composite channel. The model involves atmospheric attenuation, atmospheric turbulence, pointing error, and fiber coupling efficiency. Based on analysis of the channel model and amplifier spontaneous emission noise, the outage probability and bit error rate are obtained. For an all-optical double-hop link, fiber coupling efficiency has an important impact on outage probability, especially at relatively short total link length. By compensating for three terms of wavefront distortions, the system outage probability significantly decreases. The communication performance is further improved by optimizing the receiving aperture diameter and beam width.
Improved resolution in x-ray tomography by super-resolution
Authors: Dreier Till , Peruzzi Niccolò , Lundström Ulf , Bech Martin
Published: June 2021

In this paper, super-resolution imaging is described and evaluated for
x-ray tomography and is compared with standard tomography and
upscaling during reconstruction. Blurring is minimized due to the
negligible point spread of photon counting detectors and an
electromagnetically movable micro-focus x-ray spot. Scans are acquired
in high and low magnification geometry, where the latter is used to
minimize penumbral blurring from the x-ray source. Sharpness and level
of detail can be significantly increased in reconstructed slices to
the point where the source size becomes the limiting factor. The
achieved resolution of the different methods is quantified and
compared using biological samples via the edge spread function,
modulation transfer function, and Fourier ring
correlation.
One-shot dual-projection topography enhanced by phase-shifting logical moiré
Authors: Jiang Jiajia , Guo Hongwei
Published: June 2021

In conventional dual-projection moiré topography, the additive-type moiré pattern has an amplitude modulated form, and therefore poor visibility, unable to be improved through low-pass filtering. To overcome this difficulty, this paper presents an enhanced dual-projection moiré topography by means of logical moiré. In its implementation, a couple of projectors project two fringe patterns of different colors onto the object simultaneously and then a color camera captures the deformed fringe pattern. Instead of directly processing the additive-type moiré fringes, we separate the deformed fringes of two chromatic channels, binarize them, and then calculate their exclusive OR (XOR) moiré pattern. By differentiating one of the two deformed fringe patterns, a second XOR moiré pattern having exactly a

π

/

2

-rad phase shift can also be generated, so that the phases are simply calculated by using an arctangent function after low-pass filtering to the XOR moiré patterns. By doing so, we can measure the three-dimensional shape of an object in an efficient way requiring a single-shot implementation. The validity of this method has been demonstrated through simulation and experimental results.
Dual-modality optical coherence tomography and fluorescence tethered capsule endomicroscopy
Authors: Wartak Andreas , Kelada Alfred K. , Leon Alarcon Paola A. , Bablouzian Ara L. , Ahsen Osman O. , Gregg Abigail L. , Wei Yuxiao , Bollavaram Keval , Sheil Conor J. , Farewell Edward , VanTol Schuyler , Smith Rachel , Grahmann Patricia , Baillargeon Aaron R. , Gardecki Joseph A. , Tearney Guillermo J.
Published: June 2021

OCT tethered capsule endomicroscopy (TCE) is an emerging noninvasive diagnostic imaging technology for gastrointestinal (GI) tract disorders. OCT measures tissue reflectivity that provides morphologic image contrast, and thus is incapable of ascertaining molecular information that can be useful for improving diagnostic accuracy. Here, we introduce an extension to OCT TCE that includes a fluorescence (FL) imaging channel for attaining complementary, co-registered molecular contrast. We present the development of an OCT-FL TCE capsule and a portable, plug-and-play OCT-FL imaging system. The technology is validated in phantom experiments and feasibility is demonstrated in a methylene blue (MB)-stained swine esophageal injury model, ex vivo and in vivo.
SOA-MZI photonic sampler with a post-distortion linearization technique
Authors: Kastritsis Dimitrios , Rampone Thierry , Franco Maeva , Zoiros Kyriakos E. , Sharaiha Ammar
Published: June 2021

We present a post-distortion linearization technique for a semiconductor optical amplifier Mach-Zehnder interferometer (SOA-MZI) photonic sampler. The sampling source is an active mode-locked laser producing 12.6 ps-width pulses with a repetition frequency of 10 GHz. The mathematical model for the linearization technique is presented and then evaluated for the quasi-static regime, i.e. sampling continuous-wave signals, and for the dynamic regime, i.e. sampling sinusoidal signals. A significant improvement in terms of total harmonic distortion (THD) equal to 23.4 dB is observed for a modulation index equal to 80% in the quasi-static regime, matching the highest observed THD improvement in the dynamic regime.
Force sensing in a dual-mode optomechanical system with linear–quadratic coupling and modulated photon hopping
Authors: Chao Shi-Lei , Yang Zhen , Zhao Cheng-Song , Peng Rui , Zhou Ling
Published: June 2021

A weak force sensor scheme is presented in an optomechanical system, in which the two cavity modes couple to a mechanical mode with linear and quadratic coupling. Due to introducing time-dependent hopping, the linear and quadratic coupling terms coexist under the rotating-wave approximation in the interaction picture. Compared with the quantum non-demolition measurement (ignoring the quadratic optomechanical coupling), the current scheme can decrease the additional noise to a lower level. Our proposal provides a promising platform for improving the detection of a weak force.
Heterojunction interface-induced enhancement of position-sensitive photodetection in the nano-film of Ti/SrTiO3 based on the p-type silicon
Authors: Liu Shuai , Dong Anhua , Dong Xinyuan , Niu Yiru , Zheng Diyuan , Wang Hui
Published: June 2021

Complex oxide perovskites exhibit a range of novel, to the best of our knowledge, physical phenomena and have gained popularity as a material system in the past decades. Strontium titanate (

S
r
T
i
O

3

) is an iconic material among oxide perovskite due to its unusual electronic transport behavior and has been investigated in many electronic devices. In this Letter, a type of

S
r
T
i
O

3

nano-film-induced enhancement of lateral photovoltaic effect (LPE) is observed in the heterojunction of Ti/

S
r
T
i
O

3

/p-type Si. Optimizing the thickness of

S
r
T
i
O

3

, the LPE sensitivity can reach 123.2 mV/mm, which is much higher than the sensitivity in the control samples of Ti/Si (55.3 mV/mm) and

S
r
T
i
O

3

/

S
i

(

∼

0

m
V

/

m
m

). These findings offer an effective way to improve the sensitivity and will be helpful in the development of oxide-based photodetection devices.
Optimal elliptical retarder in rotating compensator imaging polarimetry
Authors: Gottlieb Dale , Arteaga Oriol
Published: June 2021

In this Letter, we present a new, to the best of our knowledge, design for elliptical retarders based on two quarter-wave retarders with an angle offset, which is particularly well suited for polarimetric measurements based on rotating compensator systems. We show that this simple elliptical retarder design offers the minimum condition number achieved by traditionally optimal polarimeter setups and can be used to further improve the accuracy of polarimetric imaging measurements in the presence of error sources, with the advantage that it only requires common quarter-wave retarders.
Interference effects in harmonic generation induced by focal phase distribution
Authors: Reiff R. , Venzke J. , Jaron-Becker A. , Becker A.
Published: June 2021

We have performed macroscopic calculations for the thin medium or low gas density regime and a central gas jet using microscopic numerical solutions of the time-dependent Schrödinger equation. In the case of a spatial phase distribution for broadband Gaussian pulses with a negative Porras factor, our theoretical results show an interference pattern in the angular distribution of below- and near-threshold harmonics, which is not present for the monochromatic Gouy phase distribution. The interference pattern is due to off-center contributions that are in-phase with those at the central points in the focus. The location of the maxima in the interference pattern can be estimated using the well-known double-slit formula with an effective slit separation.
Laplace metasurfaces for optical analog computing based on quasi-bound states in the continuum
Authors: Pan Danping , Wan Lei , Ouyang Min , Zhang Wei , Potapov Alexander A. , Liu Weiping , Liang Zixian , Feng Tianhua , Li Zhaohui
Published: June 2021

Laplace operation, the isotropic second-order differentiation, on spatial functions is an essential mathematical calculation in most physical equations and signal processing. Realizing the Laplace operation in a manner of optical analog computing has recently attracted attention, but a compact device with a high spatial resolution is still elusive. Here, we introduce a Laplace metasurface that can perform the Laplace operation for incident light-field patterns. By exciting the quasi-bound state in the continuum, an optical transfer function for nearly perfect isotropic second-order differentiation has been obtained with a spatial resolution of wavelength scale. Such a Laplace metasurface has been numerically validated with both 1D and 2D spatial functions, and the results agree well with that of the ideal Laplace operation. In addition, the edge detection of a concerned object in an image has been demonstrated with the Laplace metasurface. Our results pave the way to the applications of metasurfaces in optical analog computing and image processing.
A novel substrate for arrhythmias in Chagas disease
Authors: Santos-Miranda Artur , Joviano-Santos Julliane V. , Sarmento Jaqueline O. , Costa Alexandre D. , Soares Allysson T. C. , Machado Fabiana S. , Cruz Jader S. , Roman-Campos Danilo
Published: June 2021

Background

Chagas disease (CD) is a neglected disease that induces heart failure and arrhythmias in approximately 30% of patients during the chronic phase of the disease. Despite major efforts to understand the cellular pathophysiology of CD there are still relevant open questions to be addressed. In the present investigation we aimed to evaluate the contribution of the Na+/Ca2+ exchanger (NCX) in the electrical remodeling of isolated cardiomyocytes from an experimental murine model of chronic CD.

Methodology/Principal findings

Male C57BL/6 mice were infected with Colombian strain of Trypanosoma cruzi. Experiments were conducted in isolated left ventricular cardiomyocytes from mice 180–200 days post-infection and with age-matched controls. Whole-cell patch-clamp technique was used to measure cellular excitability and Real-time PCR for parasite detection. In current-clamp experiments, we found that action potential (AP) repolarization was prolonged in cardiomyocytes from chagasic mice paced at 0.2 and 1 Hz. After-depolarizations, both subthreshold and with spontaneous APs events, were more evident in the chronic phase of experimental CD. In voltage-clamp experiments, pause-induced spontaneous activity with the presence of diastolic transient inward current was enhanced in chagasic cardiomyocytes. AP waveform disturbances and diastolic transient inward current were largely attenuated in chagasic cardiomyocytes exposed to Ni2+ or SEA0400.

Conclusions/Significance

The present study is the first to describe NCX as a cellular arrhythmogenic substrate in chagasic cardiomyocytes. Our data suggest that NCX could be relevant to further understanding of arrhythmogenesis in the chronic phase of experimental CD and blocking NCX may be a new therapeutic strategy to treat arrhythmias in this condition.
Modelling urban vibrancy with mobile phone and OpenStreetMap data
Authors: Botta Federico , Gutiérrez-Roig Mario
Published: June 2021

The concept of urban vibrancy has become increasingly important in the study of cities. A vibrant urban environment is an area of a city with high levels of human activity and interactions. Traditionally, studying our cities and what makes them vibrant has been very difficult, due to challenges in data collection on urban environments and people’s location and interactions. Here, we rely on novel sources of data to investigate how different features of our cities may relate to urban vibrancy. In particular, we explore whether there are any differences in which urban features make an environment vibrant for different age groups. We perform this quantitative analysis by extracting urban features fromOpenStreetMapand the Italian census, and using them in spatial models to describe urban vibrancy. Our analysis shows a strong relationship between urban features and urban vibrancy, and particularly highlights the importance ofthird places, which are urban places offering opportunities for social interactions. Our findings provide evidence that a combination of mobile phone data with crowdsourced urban features can be used to better understand urban vibrancy.