bluuebunny/crossref_metadata_2025_split huggingface dataset:
A randomized phase II trial of adjuvant pembrolizumab versus observation following curative resection for stage I non-small cell lung cancer (NSCLC) with primary tumors between 1-4 cm: Big Ten Cancer Research Consortium BTCRC-LUN18-153.
Authors: Durm Greg Andrew , Furqan Muhammad , Feldman Lawrence Eric , Patel Malini , Hall Richard Delmar , Jalal Shadia Ibrahim , Birdas Thomas J. , Kesler Kenneth , Rieger Karen Marie , Ceppa DuyKhanh , Hanna Nasser H. 
Published: June 2021

TPS8583 Background: There are approximately 35,000 cases of stage I lung cancer in the United States each year. While these patients have better 5-year overall survival (OS) rates than their counterparts with locally advanced and metastatic disease, there is still considerable room for improvement. Based on a recent publication validating the 8th edition of the TNM classification, the 5-year OS for node-negative pathologically-staged NSCLC between 1-4cm ranges from 73-86%, and recurrence rates for resected stage I NSCLC can range from 18-38%. Previous studies looking at adjuvant chemotherapy in this setting have shown no benefit for stage IA tumors, and the current standard of care is observation alone. Checkpoint blockade with PD-1/PD-L1 inhibitors has shown considerable activity in NSCLC including in metastatic disease, as consolidation in stage III disease after chemoradiation, and in studies evaluating neoadjuvant immunotherapy. Given this activity and their favorable safety profile, we designed a study of adjuvant PD-1 inhibition following resection in stage I NSCLC. Methods: This study is a randomized phase II multicenter trial of adjuvant Pembrolizumab versus observation alone following complete resection of stage I NSCLC with tumors between 1-4cm. The trial will enroll 368 patients randomized 1:1 to either Pembrolizumab 400mg IV every 6 weeks for up to 9 cycles or observation alone with scheduled CT scans and routine clinical follow-up. Stratification factors include PD-L1 ≥50% vs. < 50% and tumor size of 1-2cm vs. > 2-4cm. The lead site is Indiana University, and the trial will be conducted through the Big Ten Cancer Research Consortium. The primary endpoint is disease free survival (DFS), and secondary endpoints include OS, DFS at 1-, 2-, and 3-year time points, and toxicity. The trial opened to accrual at the lead site in May 2020, and there are currently 6 patients enrolled. Clinical trial information: NCT04317534.
Randomized phase III Trial of MEDI4736 (durvalumab) as concurrent and consolidative therapy or consolidative therapy alone for unresectable stage 3 NSCLC: A trial of the ECOG-ACRIN Cancer Research Group (EA5181).
Authors: Varlotto John M. , Sun Zhuoxin , Ramalingam Suresh S. , Wakelee Heather A. , Lovly Christine M. , Oettel Kurt R. , Masters Gregory A. , Pennell Nate 
Published: June 2021

TPS8584 Background: Platinum-based concurrent chemoradiation(CRT) followed by one year of the human immunoglobulin G1 kappa (IgG1κ) monoclonal antibody, durvalumab, which blocks the interaction of PD-L1 with its receptors PD-1 and CD80, is the standard of care for locally advanced, unresectable non-small cell lung cancer (NSCLC). Early studies have noted the feasibility of concomitant administration of radiotherapy and immune checkpoint inhibition in NSCLC. EA5181 will evaluate the use of concomitant durvalumab with chemo-radiotherapy for locally advanced NSCLC. Methods: EA5181 is a randomized, multi-center, phase III study for patients with unresectable Stage III NSCLC comparing the efficacy of CRT with concomitant durvalumab to CRT, followed by one year of durvalumab. Eligibility criteria include: an ECOG PS of 0-1, adequate pulmonary function (FEV1 and DLCO both > 40%), no history of auto-immune disease and no past chemotherapy or RT for this lung cancer. Stratification factors include age, sex, stage, and planned concurrent chemotherapy type. Eligible patients with be randomized 1:1 to receive 60Gy RT (2Gy fractions) CRT and durvalumab (Arm A) or 60Gy CRT (Arm B). Investigators will be allowed to choose from three different chemotherapy options: cisplatin/etoposide q 28 days, Pemetrexed/cisplatin q 21 days, and weekly paclitaxel/Carboplatin. Arm A will use 750mg fixed of durvalumab (considered equivalent to 10mg/kg) on days 1, 11, and 21 of RT. Assuming no disease progression, patients in both arms will be followed by monthly (q28 days) fixed dose of 1500mg durvalumab for one year which will be given optimally within 14 days of radiation or when (non)hematologic toxicity is < Grade 2. The primary endpoint is overall survival. Secondary endpoints include progression-free survival, incidence of local/distant progression and toxicity. The target sample size is 660 patients, anticipated to recruit over 55 months, with follow up for an additional 42 months. This provides approximately 82% power if the true hazard ratio for overall survival was 0.75 or less, with 2-sided alpha of 0.05, and assuming a median survival of 42.5 months in the control arm. The study was activated on 04/09/20 and has currently accrued 90 patients on 02/03/21. Clinical trial information: NCT04092283.
AdvanTIG-302: Anti-TIGIT monoclonal antibody (mAb) ociperlimab (OCI) plus tislelizumab (TIS) versus pembrolizumab (PEM) in programmed death ligand-1 (PD-L1) selected, previously untreated, locally advanced, unresectable or metastatic non-small cell lung cancer (NSCLC).
Authors: Socinski Mark A. , Spira Alexander I. , Paz-Ares Luis G. , Reck Martin , Lu Shun , Nishio Makoto , Li Jiang , Zhou Yunfei , Rhee Joon Whan , Chica Duque Sandra , Yu Xinmin 
Published: June 2021

TPS9128 Background: Monotherapy with programmed death 1 (PD-1)/PD-L1 antibodies has improved clinical outcomes for patients (pts) with non-oncogenic driven NSCLC but clinical responses are limited by primary and secondary resistance, and improvements in durability of response are required. T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domain (TIGIT) is a co-inhibitory, immune checkpoint receptor upregulated on T-cells and natural killer cells in multiple solid tumors, which can inhibit anticancer immune responses. OCI (BGB-A1217) is a novel, humanized mAb that binds to TIGIT with high affinity and specificity, which has demonstrated competent binding with C1q and all Fcγ receptors while inducing antibody-dependent cellular cytotoxicity. Preclinical and clinical studies suggest that dual targeting with anti-TIGIT and anti-PD-1 antibodies produces synergistic immune cell activation and enhanced antitumor activity. Methods: AdvanTIG-302 is a Phase 3, multicenter, international, randomized, double-blind study (NCT04746924) investigating OCI in combination with TIS compared with PEM in adult pts (≥ 18 years of age) with PD-L1 selected, previously untreated, locally advanced, unresectable or metastatic NSCLC without oncogenic EGFR or ALK mutation. Approximately 605 pts will be randomized 5:5:1 to receive: OCI 900 mg intravenously (IV) plus TIS 200 mg IV every three weeks (Q3W; Arm A), PEM 200 mg IV plus placebo IV Q3W (Arm B) or TIS 200 mg IV plus placebo IV Q3W (Arm C). Pts will be treated until disease progression, loss of clinical benefit, intolerable toxicity or withdrawal of consent. Stratification factors include histology (squamous vs non-squamous) and region (Asian vs non-Asian). Cross-over is not permitted. Key eligibility criteria include histologically confirmed disease, PD-L1 expression ≥ 50%, no known EGFR or ALK mutations and no prior checkpoint inhibitor therapy. Dual primary endpoints are investigator-assessed progression-free survival (PFS; RECIST v1.1) and overall survival (Arms A and B) in the Intention-to-Treat population. Secondary endpoints include PFS (assessed by Blinded Independent Review Committee), investigator-assessed overall response rate and duration of response, safety and tolerability, and patient-reported health-related quality of life (EORTC-QLQ-C30, QLQ-LC13 and EQ-5D-5L; Arms A and B). Exploratory endpoints include disease control rate, clinical benefit rate and time to response. This study will also evaluate the association between biomarkers and response or resistance. Study enrollment has begun and recruitment is ongoing. Clinical trial information: NCT04746924.
A multicenter, randomized, double-blind study of gefitinib in combination with anlotinib or placebo in previously untreated patients with EGFR mutation-positive advanced non-small cell lung cancer (FL-ALTER).
Authors: Zhang Li , Fang Wenfeng , Yang Yunpeng , Yu Qitao , Wu Di , Lin Yingcheng , Zhang Hua , Zhu Junfei , Wu Guowu , Lan Bin , Zhou Zeqiang , WANG Zibing , Lei Xiaolin , Lin Haifeng , HU Xiaohua , Pan Suming 
Published: June 2021

TPS9131 Background: Preclinical and clinical evidence has demonstrated that the dual blockade of the EGFR and VEGF pathways is a viable strategy in the EGFR-mutated advanced NSCLC population. Anlotinib is an oral multi-targeted tyrosine kinase inhibitor (TKI) that effectively inhibits VEGFRs, FGFRs, PDGFRs, c-kit and MET. It has been proved to be safe and effective in advanced lung cancer after second-line standard chemotherapy failure. A cohort study of Anlotinib plus Erlotinib has shown a favorable safety profile and promising antitumor activity with an objective response rate (ORR)92.6%. This phase III study aims to evaluate the efficacy and safety of Anlotinib or placebo plus Gefitinib in patients(pts) with untreated EGFR-mutated metastatic NSCLC. Methods: Eligible pts were aged 18̃75 years old, had stage IIIB or IV NSCLC, with an EGFR 19del or 21L858R mutation, an ECOG PS of 0 or 1, measurable lesion according to RECIST v1.1 and adequate organ function. We randomly assigned eligible pts in a 1:1 ratio to receive oral Gefitinib (250 mg QD) plus either Anlotinib (12 mg QD from day 1 to 14 of a 21-day cycle) or matching placebo until progressive disease or unacceptable toxicity. Randomization was done by an interactive web response system with a computer-generated sequence and stratified by EGFR mutation status, gender, ECOG PS and pathological type. The primary endpoint is progression-free survival(PFS). Secondary endpoints include overall survival, ORR, disease control rate, time to progression, duration of response, quality of life and the safety profile. The peripheral blood of the pts will be detected three times by polygenic detection to monitor the resistance mechanism (before treatment, during the first evaluation, during tumor progression, each time 10ml peripheral blood). Independent Data Monitoring Committee and Independent Review Committee will be used in this study. According to previous report (Erlotinib plus Bevacizumab vs. Erlotinib alone: 16.0 vs. 9.7 mos, HR 0.54, Lancet Oncol, 15(11):1236-1244), the sample size was determined based on a median PFS of 15 months for the Anlotinib + Gefitinib group and median PFS of 10 months for the Placebo + Gefitinib group. To achieve 80% power at a two-sided α = 0.05 and an anticipated dropout rate of 20%, 310 patients (with 192 events required for the analyses) were needed. In total, 310 patients will be enrolled in this trial at 16 sites in China. From April 2019, 224 patients have been enrolled. Clinical trial information: NCT04028778.
Multicenter phase I/II trial of encorafenib with and without binimetinib in combination with nivolumab and low-dose ipilimumab in metastatic BRAF-mutant melanoma.
Authors: Jameson-Lee Max , Ott Patrick Alexander , Luke Jason J. , Postow Michael A. , Poklepovic Andrew Stewart 
Published: June 2021

TPS9596 Background: Targeted therapy (BRAF + MEK inhibitors) and immunotherapy (anti-PD1 + anti-CTLA4) have improved overall survival for metastatic or unresectable BRAFV600E/Kmutant melanoma. Whereas targeted therapy has a high response rate, immunotherapy may deliver longer term disease control for a larger number of patients. Despite these treatments, patients with high risk metastatic melanoma such as those with brain or liver metastases, elevated lactate dehydrogenase (LDH) and bulky disease have inferior treatment outcomes with current therapies. A BRAF+MEK+PDL1 regimen has recently emerged however the role for this treatment remains unclear. Several recent trials combining MEK inhibition and immunotherapy have failed possibly because MEK inhibition can compromise T cell activation. Meanwhile the addition of CTLA4 blockade to PD1 inhibition appears to disproportionately benefit patients with non-T cell-inflamed tumors and potentially high-risk disease. For patients with high risk BRAF-mutant metastatic melanoma, further investigation of BRAF/MEK targeted and PD-1/CTLA-4 directed immunotherapy combination strategies remains a priority. Methods: This is an open label, multi-site, Phase 1/2 study of encorafenib (Enco) +/- binimetinib (Bini) + nivolumab (Nivo) + ipilimumab (Ipi) for the treatment of patients with unresectable or metastatic BRAF-mutated melanoma in high-risk cohorts (NCT04655157). An initial regimen confirming Phase I approach will be pursued on two schedules concurrently, with patients accruing equally to each group. Group 1 will receive 3mg/kg Nivo, and 1 mg/kg Ipi and 300mg Enco (12 participants, triple therapy) and Group 2 will receive 3mg/kg Nivo and 1mg/kg Ipi and 450mg Enco and 45mg Bini, (12 participants, quadruple therapy). Dose limiting toxicity (DLT) will be evaluated weeks 1-6. A recommended Phase II regimen (RP2R) [either triple or quadruple therapy] will be carried forward into two high risk metastatic disease cohort expansions of 30 participants each. Cohort 1 will include patients with symptomatic brain metastases, while cohort 2 will include patients with elevated LDH as well as either liver metastases OR bulky visceral disease (sum of longest diameters > 44mm). Patients meeting criteria for cohorts 1 and 2 will be placed in cohort 1. Patients with symptomatic brain metastases will be included with an ECOG up to 2 and on ≤ 4mg of dexamethasone or equivalent. Continuous Bayesian toxicity monitoring will be used throughout to monitor DLT. Pre and on-treatment tumor biopsies will assess changes in the tumor microenvironment while peripheral blood ctDNA and T cell Ki67% changes will assess early response and immune activation during triplet and quadruplet therapy. Clinical trial information: NCT04655157.
Physical and Reported Subjective Health Status in 222 Individuals with XY Disorder of Sex Development
Authors: Gong Xin Li , Raile Klemens , Slowikowska-Hilczer Jolanta , Pienkowski Catherine , Quinkler Marcus , Roehle Robert , Nordenström Anna , Neumann Uta 
Published: June 2021

Abstract

Context
Little is known about the physical health of individuals with 46,XY disorders of sex development (DSD).

Objective
To assess physical and reported subjective health of individuals with XY DSD.

Methods
As part of the dsd-LIFE study, patients with an XY DSD condition were analyzed in different diagnosis groups for metabolic parameters, comorbidities, metabolic syndrome, bone outcomes, and reported subjective health. Findings were evaluated by descriptive statistics.

Results
A total of 222 patients with XY DSD were included with a mean age of 28.8 ± 12.2 years, mean height of 175.3 ± 7.7 cm, mean weight of 74.3 ± 20.0 kg, and mean body mass index of 24.1 ± 6.0 kg/m2. Obesity rate was not increased when descriptively compared with Eurostat data. Fourteen patients had metabolic syndrome (14/175; 8.0%). In descriptive comparison with data from the DECODE study and World Health Organization, subjects fared better in the categories waist circumference, glucose, triglyceride, cholesterol, and high-density lipoprotein. Of participants with available bone health data, 19/122 (15.6%) patients had a Z-score ≤ –2.0 at lumbar spine indicating lowered bone mineral density (BMD). Mostly gonadectomized individuals with complete androgen insensitivity syndrome (CAIS) and no estrogen therapy had lowered BMD at lumbar spine. Individuals with XY DSD performed poorly in the category subjective health in descriptive comparison with Eurostat data.

Conclusion
Participants reported a lower subjective health status than Eurostat data but their overall metabolic health status was good. Decreased BMD at lumbar spine was especially present in gonadectomized individuals with CAIS and no estrogen therapy.
Technically Accessible, Practically Ineligible: The Effects of Medicaid Expansion Implementation on Chronic Homelessness
Authors: Willison Charley E. , Lillvis Denise , Mauri Amanda , Singer Phillip M. 
Published: June 2021

Abstract
Context: Homeless policy advocates viewed Medicaid expansion as an opportunity to enhance health care access for this vulnerable population. We studied Medicaid expansion implementation to assess the extent to which broadening insurance eligibility affected the functioning of municipal homelessness programs targeting chronic homelessness in the context of two separate governance systems.
Methods: We employed a comparative case study of San Francisco, California, and Shreveport, Louisiana, which were selected as exemplar cases from a national sample of cities across the United States. We conducted elite interviews with a range of local-level stakeholders and combined this data with primary-source documentation.
Findings: Medicaid expansion did not substantially enhance the functioning of homelessness programs and policies because of Medicaid access challenges and governance conflicts. Administrative burden and funding limitations contributed to limited provider networks, inadequate service coverage, and lack of linkages between Medicaid enrollment and homelessness programming. Governance conflicts reinforced these functional challenges, with homelessness under the administration of local municipalities and nongovernmental organizations while states administer Medicaid.
Conclusions: Improving access to health care services for persons experiencing homelessness cannot occur without intentional coordination between sectors and levels of government and thus necessitates the development of targeted policies and programs to overcome these challenges.
Wavelength-tunable narrow-linewidth gaseous Raman laser
Authors: Shen Chencheng , Cai Xianglong , Su Xinjun , Zheng Tiancheng , Liu Jinbo , Chen Ying , Jia Yuxi , Liu Dong , Guo Jingwei 
Published: June 2021

Gaseous Raman lasers cover a range of wavelengths but lack wavelength tunability. Here, a

1

c

m

−
1

linewidth 532 nm laser was used as a pump laser, and with a narrow-linewidth seed laser injection, a narrow-linewidth first Stokes (S1) Raman laser was achieved. By tuning the wavelength of the seed laser, a tuning range of S1 up to

1

c

m

−
1

was obtained. The wavelengths of the first anti-Stokes and second Stokes lasers could also be tuned. A theoretical model was developed, and spectral profiles of Raman lasers from experiments and simulations agreed well; further simulation predicted that the linewidth of S1 could be compressed to as narrow as

0.01

c

m

−
1

under optimal conditions. A universal method of fine-tunable Raman lasers is presented that can be utilized in several important applications.
Direct observation Brownian motion of individual nanoparticles in water using microsphere-assisted microscopy
Authors: Yang Songlin , Ye Yong-Hong , Zang Jiaojiao , Pei Yong , Xia Yang , Zhang Jiayu 
Published: June 2021

Observing Brownian motion of nanoscale objects through a traditional optical microscope is still a challenge. Here, we present a method to overcome this challenge by using a traditional optical microscope assisted with a removable microsphere-embedded thin film. The diffusion coefficient of individual unconstrained polystyrene (PS) nanoparticles with a diameter of 300 nm in water is calculated from their respective mean-square displacement versus time curves, and the measured diffusion coefficient shows good agreement with the theoretical Stokes–Einstein one, proving the feasibility of our method. In addition, the experimental results show that the movement of the PS nanoparticles is slowed down near a plane wall, and the diffusion coefficient is consistent with the theoretical constrained diffusion coefficient, which shows that our method can also study the constrained Brownian motion of nanoparticles constrained near a plane wall. Our research results are helpful for the application of microsphere-assisted microscopy in new fields and also provide a new method for nanoparticle tracking.
Multispectral small-angle light scattering from particles
Authors: Ceolato Romain , Aleau Killian , Paulien Lucas , Reynoso-Lara Edmundo , Berg Matthew J. 
Published: June 2021

Using a supercontinuum laser, reflective optics, and a spatial filter, we measure two-dimensional small-angle light-scattering patterns for a variety of microparticles including spheres, salt, sand, and volcanic dust. The measurements are done at 13 wavelengths from 450–850 nm, where the absence of refractive optical elements minimizes the effects of chromatic aberration. Qualitative particle-material sensitivity is demonstrated by layering differently colored patterns. Last, the multispectral capability of our device demonstrates a new possibility to probe different

q

-space regimes for a given particle in a single measurement.
Experimental realization of wavelength multiplexed nonlinear upconversion in cesium atoms
Authors: Wu Jinze , Xu Yuhui , Dong Ruige , Zhang Junxiang 
Published: June 2021

Blue-violet wavelength multiplexing offers the capability to enhance the operational capacity and efficiency in optical information processing, underwater communications, biology, and medicine. Here we present a specially designed atomic scheme of cesium for simultaneously generating two blue-violet lasers at 456 and 459 nm via four-wave-mixing (FWM)-based upconversion processes. We experimentally and theoretically show that a double-diamond-type coherent system pumped with 852 and 921 nm lasers is responsible for the efficient generation of the two blue-violet lasers. In this system, the large population inversions lead to self-amplified spontaneous emissions at 15.6 and

12.1

µ

m

, which, in turn, serve as the seeds for enhanced double FWM processes with dual-wavelength upconversions.
Considerations on the Castrop formula for calculation of intraocular lens power
Authors: Langenbucher Achim , Szentmáry Nóra , Cayless Alan , Weisensee Johannes , Fabian Ekkehard , Wendelstein Jascha , Hoffmann Peter 
Published: June 2021

Background
To explain the concept of the Castrop lens power calculation formula and show the application and results from a large dataset compared to classical formulae.

Methods
The Castrop vergence formula is based on a pseudophakic model eye with 4 refractive surfaces. This was compared against the SRKT, Hoffer-Q, Holladay1, simplified Haigis with 1 optimized constant and Haigis formula with 3 optimized constants. A large dataset of preoperative biometric values, lens power data and postoperative refraction data was split into training and test sets. The training data were used for formula constant optimization, and the test data for cross-validation. Constant optimization was performed for all formulae using nonlinear optimization, minimising root mean squared prediction error.

Results
The constants for all formulae were derived with the Levenberg-Marquardt algorithm. Applying these constants to the test data, the Castrop formula showed a slightly better performance compared to the classical formulae in terms of prediction error and absolute prediction error. Using the Castrop formula, the standard deviation of the prediction error was lowest at 0.45 dpt, and 95% of all eyes in the test data were within the limit of 0.9 dpt of prediction error.

Conclusion
The calculation concept of the Castrop formula and one potential option for optimization of the 3 Castrop formula constants (C, H, and R) are presented. In a large dataset of 1452 data points the performance of the Castrop formula was slightly superior to the respective results of the classical formulae such as SRKT, Hoffer-Q, Holladay1 or Haigis.