bluuebunny/crossref_metadata_2025_split huggingface dataset:
TORCHLIGHT: A randomized, double-blind, phase III trial of toripalimab versus placebo, in combination with nab-paclitaxel(nab-P) for patients with metastatic or recurrent triple-negative breast cancer (TNBC).
Authors: Jiang Zefei , Ouyang Quchang , Sun Tao , Zhang Qingyuan , Teng Yuee , Cui Jiuwei , Wang Haibo , Yin Yongmei , Wang Xiaojia , Zhou Xin , Wang Yongsheng , Sun Gang , Wang Jingfen , Zhang Lili , Yang Jin , Qian Jun , Yi Tienan , Yan Min , Liu Xinlan ,   Shanghai Junshi Biosciences
Published: June 2023

LBA1013 Background: Checkpoint blockade combined with taxanes based chemotherapy had generated mixed results as first line treatment for metastatic TNBC. Toripalimab, a humanized IgG4K monoclonal antibody specific for PD-1, provided significant clinical efficacy with a favorable safety profile in various solid tumors. The purpose of this study is to compare the efficacy and safety of toripalimab versus placebo, in combination with nab-P for metastatic or recurrent TNBC (NCT04085276). Methods: Patients with initially diagnosed metastatic or recurrent inoperable TNBC were randomized 2:1 to receive toripalimab (240mg, D1, q3w) or placebo along with nab-P on days1, 8 in 3-week cycles. Stratifications included PD-L1 expression, paclitaxel therapy history and line of prior therapy at enrollment. Primary endpoint was progression-free survival (PFS) assessed by a blinded independent central review (BICR) per RECIST v1.1, first in the PD-L1-positive population and then in the ITT population. Secondary endpoints included overall survival (OS) and safety. Results: 531 patients were randomized to toripalimab (n = 353) or placebo (n = 178); 200 and 100 patients, respectively had PD-L1 positive TNBC. At interim analysis, with the median follow-up of 14 months, a statistically significant improvement in PFS by BICR was demonstrated for the toripalimab arm in the PD-L1 positive subgroup (mPFS 8.4 vs 5.6 months; HR = 0.653, 95% CI 0.470-0.906, P = 0.0102). The PFS in the ITT population showed a similar trend (mPFS 8.4 vs 6.9 months, HR = 0.773, 95%CI 0.602-0.994). Descriptive analysis of OS showed a trend towards improved OS in the PD-L1 positive (mOS 32.8 vs 19.5 months; HR = 0.615, 95%CI 0.414-0.914) and the ITT population (mOS 33.1 vs 23.5 months; HR = 0.691, 95% CI 0.513-0.932). No new safety signals were identified. Grade≥3 adverse events (AEs) (56.4% vs 54.3%) and fatal AEs (0.6% vs 3.4%) were similar between arms, while AEs leading to discontinuation of toripalimab/placebo (8.5% vs. 3.4%) and immune-related (irAEs) (40.8% vs. 24.0%) were more frequent in the toripalimab arm. Conclusions: The addition of toripalimab to nab-P provided a significant improvement in PFS for PD-L1 positive metastatic or recurrent TNBC patients receiving first-line treatment with an acceptable safety profile. Patients will be followed for the final PFS and OS analysis. Clinical trial information: NCT04085276 .
Randomized phase II trial of cabozantinib combined with PD-1 and CTLA-4 inhibition versus cabozantinib in metastatic soft tissue sarcoma.
Authors: Van Tine Brian Andrew , Eulo Vanessa , Toeniskoetter Jacqui , Ruff Tyler , Luo Jingqin , Kemp Lindsey , Moreno Tellez Cristiam , Weiss Mia C. , Hirbe Angela C. , Meyer Christian Frederick , Elias Anthony D. , Diamond Mark , Hartner Lee P. , Bui Nam , Ganjoo Kristen N. , Maki Robert G. , Wilky Breelyn A. 
Published: June 2023

LBA11504 Background: Cabozantinib (C) has been combined successfully with either PD-1 or CTLA-4 inhibition in cancer clinical trials. The combination of nivolumab (N) and ipilimumab (I) previously was evaluated in soft tissue sarcoma (STS) and demonstrated activity as well as an acceptable safety profile. Given these data, we hypothesize that C in combination with both I and N is a therapeutic strategy that will be more effective than C alone in metastatic STS that lack translocations. Additionally, we hypothesized that C priming would enhance the efficacy of combination I and N at the time of crossover. Methods: This is a 2:1 randomized phase 2 clinical trial evaluating the overall response rate (RR) of C 40mg orally daily in combination with I (1mg/kg IV) / N (3mg/kg) for 4 doses Q3W and then maintenance N 480mg Q4W compared to C 60mg oral alone, with crossover. Secondary endpoints include progression free survival (PFS), disease control rate (DCR), RR in crossover, quality of life by FACT-G7, RR by iRECIST and safety. Correlative and biomarker analysis are preplanned. Key patient selection includes ECOG 0-1, 1-2 lines of prior therapy, and sarcomas that lack of translocations. The trial was balanced for leiomyosarcoma (LMS), liposarcoma and UPS. Results: 69 patients were randomized to C+I/N and 36 patients were randomized to C alone. 19 patients crossed over to C+I/N at progression. 54/105 patients had LMS. RR of C+I/N was 11% (5 PR and 2 CR), while the RR of C was 6% (2 PR and 0 CR) (p = NS). C+I/N responding histologies included LMS, angiosarcoma, epithelioid sarcoma, and myxofibrosarcoma. C responding histologies included 2 PRs in LMS. There were also 2 LMS PRs in crossover to C+I/N. The median PFS for C+I/N was 5.4 months and for C was 3.8 months (p = 0.016). The DCR for C+I/N was 80% (41 SD, 5 PR, 2 CR), and 42% for C (11 SD, 2 PR) (p = 0.0004). The most common grade 3-4 adverse events affecting > 10% of patients included hypothyroidism, diarrhea, mucositis, oral dysesthesia, nausea, vomiting, elevated AST and ALT, anorexia, dysgeusia, headache, pruritis, maculopapular rash, and hypertension for C+I/N and hypothyroidism, diarrhea, oral dysesthesia, fatigue, palmar-plantar erythrodysesthesia, and hypertension for C. Conclusions: The combination of C+I/N was superior to C for the treatment of non-translocation STS for DCR and PFS. Most frequent responding histology was LMS. Correlative work is ongoing. Clinical trial information: NCT04551430 .
PROSPECT: A randomized phase III trial of neoadjuvant chemoradiation versus neoadjuvant FOLFOX chemotherapy with selective use of chemoradiation, followed by total mesorectal excision (TME) for treatment of locally advanced rectal cancer (LARC) (Alliance N1048).
Authors: Schrag Deborah , Shi Qian , Weiser Martin R. , Gollub Marc J , Saltz Leonard B. , Musher Benjamin Leon , Goldberg Joel , Al Baghdadi Tareq , Goodman Karyn A. , McWilliams Robert R. , Farma Jeffrey M. , George Thomas J. , Kennecke Hagen Fritz , Venook Alan P. , O'Reilly Eileen Mary , Meyerhardt Jeffrey A. , Dueck Amylou C. , Basch Ethan , Chang George J. , Mamon Harvey J. ,   Alliance for Clinical Trials in Oncology
Published: June 2023

LBA2 Background: Radiation with sensitizing fluoropyrimidine (5FUCRT) is a standard curative intent treatment for LARC. It improves disease-free survival (DFS) by decreasing pelvic recurrence but has short- and long-term toxicity. The PROSPECT trial compares FOLFOX chemotherapy with selective use of 5FUCRT (intervention) to 5FUCRT (control) for neoadjuvant treatment prior to TME for LARC. Methods: Eligible patients (pts) had cT2N+, cT3N-, cT3N+ rectal cancers deemed appropriate for neoadjuvant therapy prior to low anterior resection with TME. Pts with distal, T4 tumors, threatened radial margins or > 4 enlarged lymph nodes were ineligible. Pts were randomized 1:1 without blinding. Pts in the control group received 5FUCRT with 5040 cGy over 5.5 weeks with either capecitabine or 5FU. Pts in the intervention group had 6 cycles of mFOLFOX6 followed by restaging. If tumor regression was > 20%, then TME was performed without radiation; if < 20%, 5FUCRT was given before TME. DFS was the 1°outcome, defined as time from randomization to any recurrence or death, analyzed in the per-protocol population. One interim analysis was conducted with α spending = 0.001. Noninferiority (NI) of the intervention could be claimed if the upper limit of the 2-sided 90.2% confidence interval (CI) of the DFS hazard ratio did not exceed 1.29 (NI margin). Secondary endpoints included overall survival (OS), local recurrence free survival, R0 resection, pathologic complete response (CR), and toxicity. Results: From June 2012 to December 2018, 1194, pts were randomized and 1128 initiated protocol-assigned treatment. Median age was 57, 34.5% were women and 61.9% had clinically positive nodes. 53 of 585 pts in the intervention group (9%) received preop 5FUCRT. DFS was analyzed after 227 events and median follow-up of 58 months. Conclusions: FOLFOX chemotherapy with selective use of 5FUCRT is non-inferior to 5FUCRT for neoadjuvant treatment of LARC prior to low anterior resection with TME. Patients and physicians have alternative strategies for management of LARC. Clinical trial information: NCT01515787 . [Table: see text]
PD-1 blockade with sintilimab plus induction chemotherapy and concurrent chemoradiotherapy (IC-CCRT) versus IC-CCRT in locoregionally-advanced nasopharyngeal carcinoma (LANPC): A multicenter, phase 3, randomized controlled trial (CONTINUUM).
Authors: Ma Jun , Sun Ying , Liu Xu , Yang Kun-Yu , Zhang Ning , Jin Feng , Zou Guorong , Zhu Xiaodong , Xie Fangyun , He Zhenyu , Chen Nian-Yong , Mao Yan-Ping , Shen Liangfang , Shi Mei , Hong Shu-Bin , Zhao Hongyun , Li Ji-Bin , Tang Ling-Long , Liu Na , Chen Yu-Pei 
Published: June 2023

LBA6002 Background: Despite the success of PD-1 blockade plus chemotherapy in recurrent/metastatic NPC, its role in LANPC is unproven. This trial evaluated the efficacy and safety of adding sintilimab (a PD-1 inhibitor) to IC-CCRT in LANPC. Methods: Patients with non-metastatic high-risk LANPC (stage III-IVA, excluding T3-4N0/T3N1) were enrolled at 9 centers in China, and randomized (1:1; stratified by center and stage with block size four) to the Standard Arm (gemcitabine and cisplatin IC plus cisplatin CCRT), or Sintilimab Arm (sintilimab plus IC-CCRT). Sintilimab 200mg was given intravenously once every 3 weeks for up to 12 cycles (3 induction, 3 concurrent, and 6 adjuvant). The primary endpoint was event-free survival (EFS) (i.e. freedom from local/regional/distant failure or death). It is estimated that approximately 417 patients would provide 80% power to detect a hazard ratio (HR) of 0.52 with a two-sided type 1 error of 0.05. Quality of life (QoL) was assessed by EORTC-C30. Biomarkers including tertiary lymphoid structure (TLS), PD-L1, and gene expression were also analyzed. Results: Between December 2018, and March 2020, 425 patients were randomized to the Sintilimab Arm (n = 210) and Standard Arm (n = 215). After a median follow-up of 42 months (94% alive patients ≥36 months), the intention-to-treat analysis showed that 3-year EFS was 86.1% in the Sintilimab Arm and 76.0% in the Standard Arm (stratified HR, 0.59; 95% confidence interval [CI], 0.38-0.92; stratified log-rank p = 0.019). Grade 3-4 adverse events (AEs) occurred in 155 (74.2%) and 140 (65.4%) patients, including immune-related AEs in 20 (9.6%) and 2 (0.9%) patients and grade 5 AEs in 2 (0.95%) and 1 (0.5%) patients in the Sintilimab and Standard Arm, respectively (Table). No minimum clinically important differences in QoL were observed. The benefit of the addition of sintilimab was observed in patients with TLS (HR 0.18; 95% CI, 0.04-0.81; p = 0.011) but not in patients without TLS (HR 0.94; 95% CI, 0.50-1.76; p = 0.85). Conclusions: The addition of sintilimab to standard IC-CCRT results in significant improvement of EFS, manageable safety profile, and comparable QoL in high-risk LANPC. TLS appears to be a predictive biomarker for benefit of sintilimab. Clinical trial information: NCT03700476 . [Table: see text]
Distinguishing Renal Cell Carcinoma From Normal Kidney Tissue Using Mass Spectrometry Imaging Combined With Machine Learning
Authors: Shankar Vishnu , Vijayalakshmi Kanchustambham , Nolley Rosalie , Sonn Geoffrey A. , Kao Chia-Sui , Zhao Hongjuan , Wen Ru , Eberlin Livia S. , Tibshirani Robert , Zare Richard N. , Brooks James D. 
Published: June 2023

PURPOSE Accurately distinguishing renal cell carcinoma (RCC) from normal kidney tissue is critical for identifying positive surgical margins (PSMs) during partial and radical nephrectomy, which remains the primary intervention for localized RCC. Techniques that detect PSM with higher accuracy and faster turnaround time than intraoperative frozen section (IFS) analysis can help decrease reoperation rates, relieve patient anxiety and costs, and potentially improve patient outcomes. MATERIALS AND METHODS Here, we extended our combined desorption electrospray ionization mass spectrometry imaging (DESI-MSI) and machine learning methodology to identify metabolite and lipid species from tissue surfaces that can distinguish normal tissues from clear cell RCC (ccRCC), papillary RCC (pRCC), and chromophobe RCC (chRCC) tissues. RESULTS From 24 normal and 40 renal cancer (23 ccRCC, 13 pRCC, and 4 chRCC) tissues, we developed a multinomial lasso classifier that selects 281 total analytes from over 27,000 detected molecular species that distinguishes all histological subtypes of RCC from normal kidney tissues with 84.5% accuracy. On the basis of independent test data reflecting distinct patient populations, the classifier achieves 85.4% and 91.2% accuracy on a Stanford test set (20 normal and 28 RCC) and a Baylor-UT Austin test set (16 normal and 41 RCC), respectively. The majority of the model's selected features show consistent trends across data sets affirming its stable performance, where the suppression of arachidonic acid metabolism is identified as a shared molecular feature of ccRCC and pRCC. CONCLUSION Together, these results indicate that signatures derived from DESI-MSI combined with machine learning may be used to rapidly determine surgical margin status with accuracies that meet or exceed those reported for IFS.
Age and Gender Adjusted FT3 Levels as Novel Predictors of Survival
Authors: Strich David , Israel Ariel , Edri Shalom , Gillis David 
Published: June 2023

Abstract

Context
Lower levels of free T3 (FT3) occur during acute illness, as part of “euthyroid sick syndrome.” A chronic form of this syndrome also exists.

Objective
To determine whether thyroid hormone levels predict long-term survival.

Design and Setting
This was a “big-data” study of thyroid function tests from samples taken between 2008 and 2014. Data were crossed with electronic health records for morbidity and mortality. Test results were converted to age- and gender-adjusted percentiles (AGAPs). The hazard ratio for death was crossed with ranges of initial AGAPs and change in AGAPs for 2 subgroups: “not healthy” (subjects with at least 1 of 5 chronic conditions registered in their electronic health chart) and “healthy” (all others).

Participants
2 453 091 sets of thyroid function tests from 365 965 distinct patients were evaluated. 258 695 sets remained after excluding patients registered as taking thyroid preparations or anti-thyroid drugs.

Main Outcome Measure
Hazard ratio for death, planned before data collection.

Results
The cohort included 151 868 not healthy and 106 827 healthy people. After a median of 6.8 years, 5865/151 868 (10.4%) of the not healthy had died and 2504/106 827 (2.3%) of healthy participants. Low initial FT3 AGAPs were predictive of poor survival. The hazard ratio for survival compared between the lowest 5 and highest 50 percentiles of initial FT3 AGAPs for not healthy participants was 5.71 [confidence interval (CI) 5.23-6.26, P &lt; .001] and for healthy was 3.92 (CI 3.06-5.02, P &lt; .001).

Conclusion
Low FT3 AGAPs predicted poor survival, most strongly among not healthy people.
Nontruthful Position Auctions Are More Robust to Misspecification
Authors: Dütting Paul , Fischer Felix , Parkes David C. 
Published: June 2023

We consider the classical model of sponsored search due to Edelman et al. and Varian and examine how robust standard position auctions are to a misspecification of the position-dependent quality factors used by this model. We show that under both complete and incomplete information a nontruthful position auction admits an efficient equilibrium for a strictly broader range of parameter values than the Vickrey-Clarke-Groves (VCG) mechanism, which would be truthful if the parameters were specified correctly. Our result for complete information concerns the generalized second-price (GSP) mechanism and is driven by a detailed understanding of the Nash equilibrium polytopes of the VCG mechanism and the GSP mechanism. Our result for incomplete information concerns the generalized first-price (GFP) mechanism and uses a surprising connection between the unique candidate equilibrium bidding functions of the VCG mechanism and the GFP mechanism. Funding: F. Fischer was supported by the Engineering and Physical Sciences Research Council [Grant EP/T015187/1] and Einstein Stiftung Berlin.
NOMA security scheme based on constellation camouflage and selective mapping
Authors: Ma Yiming , Ren Jianxin , Liu Bo , Ma Yilan , Ullah Rahat , Wu Xiangyu , Mao Yaya , Chen Shuaidong , Wan Yibin , Zhong Qing , Xia Wenchao , Wu Yongfeng , Zhao Lilong 
Published: June 2023

This study aims to present a non-orthogonal multiple access (NOMA) security scheme based on constellation camouflage and selective mapping. To improve the security of the system, we use a four-dimensional chaos model to camouflage high-power signals at the transmitter. The constellation diagram of high power is disguised from binary phase-shift keying (BPSK) form to quadrature phase-shift keying (QPSK) form, and after power multiplexing, further camouflaged from 8 points to 16 points. To improve the transmission performance of the designed system as much as possible and not increase the computational complexity, we use the selective mapping method in the process of power multiplexing and use the region decision method for demodulation at the receiving end. The proposed scheme is verified by experiments on a 2-km 7-core optical fiber, and achieves the safety transmission of a power division multiplexing–orthogonal frequency-division multiplexing (PDM-OFDM) signal with a net rate of 97.38 Gb/s without signal damage. The maximum achievable key space of the proposed scheme is 10135. Hence, it is a feasible and secure non-orthogonal multiple access-passive optical network scheme.
Temporal patterns, spatial risks, and characteristics of tegumentary leishmaniasis in Brazil in the first twenty years of the 21st Century
Authors: Belo Vinícius Silva , Bruhn Fábio Raphael Pascoti , Barbosa David Soeiro , Câmara Daniel Cardoso Portela , Simões Taynãna César , Buzanovsky Lia Puppim , Duarte Anna Gabryela Sousa , de Melo Saulo Nascimento , Cardoso Diogo Tavares , Donato Lucas Edel , Maia-Elkhoury Ana Nilce Silveira , Werneck Guilherme Loureiro 
Published: June 2023

BackgroundTegumentary leishmaniasis (TL) is a significant public health issue in Brazil. The present ecological study describes the clinical and epidemiological characteristics of TL cases reported in the country, and analyzes the spatial and temporal patterns of the incidences and risks of occurrence across the five geopolitical regions and 27 federative units.Methodology/Principal findingsData regarding new cases of TL notified between 2001 and 2020 were obtained from the Information System for Notifiable Diseases of the Brazilian Ministry of Health. Joinpoint and spatial and temporal generalized additive models were used to establish trends in the evolution of TL during the target period. The incidence rate for the entire period was 226.41 cases/100,000 inhabitants. All regions of Brazil showed trends of decreasing incidence rates, albeit with fluctuations at specific times, with the exception of the Southeast where rates have increased since 2014, most particularly in Minas Gerais state. The disease was concentrated predominantly in the North region, with Acre state leading the incidence rank in the whole country, followed by Mato Grosso (Midwest), Maranhão and Bahia (Northeast) states. The spatial distribution of the risk of TL occurrence in relation to the annual averages was relatively stable throughout the period. The cutaneous form of TL was predominant and cases most frequently occurred in rural areas and among men of working age. The ages of individuals contracting TL tended to increase during the time series. Finally, the proportion of confirmations by laboratory tests was lower in the Northeast.Conclusion/SignificanceTL shows a declining trend in Brazil, but its widespread occurrence and the presence of areas with increasing incidence rates demonstrate the persistent relevance of this disease and the need for constant monitoring. Our findings reinforce the importance of temporal and spatial tools in epidemiologic surveillance routines and are valuable for targeting preventive and control actions.
A Rare Cause of Abdominal Pain: Erdheim-Chester Disease
Authors: Chatterjee Arjun , de la Fuente Jaime , Rech Karen L. , Takahashi Naoki , Majumder Shounak 
Published: June 2023

ABSTRACT
A 65-year-old man presented with hematuria, night sweats, nausea, intermittent nonbloody diarrhea, and abdominal pain. Computed tomography angiogram with enterography showed retroperitoneal fibrosis surrounding both kidneys and ureters without any evidence of vascular obstruction or hydronephrosis. Laparoscopic biopsy demonstrated fibroadipose tissue involved by a subtle histiocytic infiltrate in a background of marked fibrosis, scattered lymphocytes, and plasma cells. The histiocytes strongly expressed CD163, Factor XIIIa, and BRAF V600E. He was diagnosed with Erdheim-Chester disease, a rare histiocytic neoplasm uncommonly presenting with gastroenterological manifestations.
Teachers’ Qualitatively Different Ways of Experiencing Assessment Feedback: Implications for Teacher Assessment Literacy
Authors: Goh Rachel , Kiat Tan Kelvin Heng 
Published: June 2023

Abstract
Assessment feedback is an important aspect of teacher assessment literacy which can be understood along three interrelated dimensions: 　conceptual in terms of conceptions teachers have of feedback, praxeological regarding feedback practice, and socio-emotional which relates to how teachers attend to the emotional dynamics of assessment from the students’ perspective (Pastore & Andrade, 2019). This paper presents the findings of a phenomenographic study involving 15 teachers in Singapore schools that explored their qualitatively different ways of experiencing assessment feedback. Drawing on the variation theory perspective, the analysis of interview data resulted in five teachers’ conceptions of assessment feedback that shed light on the non-static nature of feedback engagement. These conceptions represent the variation in teachers’ qualitatively different ways of experiencing assessment feedback, and ranged from feedback as inspection of students (emphasizing mistakes) to feedback as introspection for students (emphasizing reflection on feedback). The findings show the potential that teachers can aspire to move from level to level, depending on contexts and students. Insights on the continuum of teacher assessment feedback literacy are drawn. Implications for developing teacher assessment literacy are discussed to assist teachers in reviewing their conceptions of assessment feedback beliefs and enhancing assessment feedback practices beyond improving academic learning.