bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractThis 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.
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.
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.
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.
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.
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.
Employment impacts of the San Francisco sugar-sweetened beverage tax 2 years after implementation
Authors: Marinello Samantha , Leider Julien , Powell Lisa M. 
Published: June 2021

Introduction
Sugar-sweetened beverage (SSB) taxes have been implemented worldwide to raise revenue and reduce consumption of SSBs, which is associated with health harms. Empirical evaluations have found that these taxes are successful at reducing demand for SSBs; however, SSB taxes face opposition, in part because of claims that they will lead to substantial job losses. The purpose of this study is to examine the impact of the San Francisco SSB tax, implemented on January 1st, 2018, on employment.

Methods
Monthly employment counts were obtained from the Bureau of Labor Statistics from January 2013 (5-years pre-tax) through December 2019 (2-years post-tax) for the overall economy, private sector, supermarkets and other grocery stores, convenience stores, limited-service restaurants, and beverage manufacturing. A synthetic control analysis was conducted for each employment outcome. The synthetic controls (i.e., estimated counterfactuals) were generated from a pool of urban control counties using pre-tax labor market-related characteristics.

Results
The synthetic controls had similar labor market-related characteristics and employment outcomes to those in San Francisco in the pre-tax period. Up to 2 years post-tax, differences in employment between San Francisco and the synthetic controls were small and not “statistically significant” based on placebo tests for all employment outcomes.

Conclusions
Up to two years post-tax, we do not find evidence that the San Francisco SSB tax negatively impacted net employment, employment in the private sector, or employment in specific SSB-related industries.
Dynamic phospho-modification of viral proteins as a crucial regulatory layer of influenza A virus replication and innate immune responses
Authors: Boergeling Yvonne , Brunotte Linda , Ludwig Stephan 
Published: June 2021

Abstract
Influenza viruses are small RNA viruses with a genome of about 13 kb. Because of this limited coding capacity, viral proteins have evolved to fulfil multiple functions in the infected cell. This implies that there must be mechanisms allowing to dynamically direct protein action to a distinct activity in a spatio-temporal manner. Furthermore, viruses exploit many cellular processes, which also have to be dynamically regulated during the viral replication cycle. Phosphorylation and dephosphorylation of proteins are fundamental for the control of many cellular responses. There is accumulating evidence that this mechanism represents a so far underestimated level of regulation in influenza virus replication. Here, we focus on the current knowledge of dynamics of phospho-modifications in influenza virus replication and show recent examples of findings underlining the crucial role of phosphorylation in viral transport processes as well as activation and counteraction of the innate immune response.
Rye Island, 2010: Impact of the flooding on the groundwater level
Authors: Červeňanská Michaela , Baroková Dana , Šoltész Andrej 
Published: June 2021

Abstract
During the flood situations in May and June 2010, the culmination of the Váh River and the Danube River was accompanied by the groundwater level rising in the Rye Island, in some boreholes even to their maximum measured levels. The increased groundwater level caused major problems, e.g. flooded cellars and underground spaces, contaminated drinking water in wells, flooded railways and farmlands. As a part of the research concentrating on the groundwater flooding phenomena in the Rye Island, the flood situation from the year 2010 was reconstructed, establishing the basis for a construction of the flood hazard maps and flood risk management plans. The problem was solved with a MODFLOW numerical model using the Groundwater Modeling System.