bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mapping the paleo-landscape features and middle or/and later Stone Age settlements of Tokar region, North-eastern Sudan using Radar Sentinel-1 (GRD) imagery
Authors: Elfiky Hend , Elfadaly Abdelaziz 
Published: June 2024

Abstract
Along the western coastal plain of the Red Sea, the discovery of lithic tools proved that the occurrence of archaeological remains belonged to the Stone Age era. Unfortunately, until recently, most of the Stone Age site plans in the western Red Sea periphery have been unknown because of change in climate in addition to covering these sites with a large layer of sand. Recently, remote sensing (RS) data have proven to be effective at identifying buried archaeological sites using radar satellite imagery due to their ability to penetrate the land surface. This paper aims to identify and reconstruct several potential Stone Age sites using radar satellite images in the Tokar region, North-Eastern Sudan, on the western plain of the Red Sea. Radar (Sentinel-1 SAR GRD: C-band) data were processed utilizing the advantages of the Google Earth Engine platform and Snap software. The results of this research showed that some potential settlements belonging to the Stone Age era (expectedly dating back to the end of the Pleistocene and/or the initial phase of the Holocene) have subcircular shapes with some interior subcircles. These results shed new light on the potential construction technique, size, and function of the settlement in the Stone Age era and can provide some initial insights into the ancient lifestyle in this region. Additionally, this study can aid in future archaeological surveys and excavation missions in this region.
Assessment of ecosystem health and driving forces in response to landscape pattern dynamics: the Shibing Karst world natural heritage site case study
Authors: He Lixiang , Zhang Juan , Yu Bin , Hu Mengshan , Zhang Zihao 
Published: June 2024

Abstract
The Shibing Karst constitutes a pivotal component of the "South China Karst," and its ecosystem health integrity crucially influences the Outstanding Universal Value (OUV) of the corresponding Natural World Heritage (NWH). Consequently, robust ecosystem health assessment (EHA) is imperative for the judicious conservation and management of this heritage, as well as for the sustainable progression of the region. This research assessed the health of the Shibing Karst ecosystem from 2004 to 2020 by employing changes in landscape patterns through the Vigor-Organization-Resilience-Ecosystem Services (VORS) model. Spatial autocorrelation was employed to discern the spatial coherence and evolutionary patterns of ecosystem health, whereas a geo-detector ascertained the pivotal determinants impacting regional ecosystem vitality. The findings revealed that: (1) The landscape patterns distribution in the study area exhibited considerable constancy, primarily comprising forest land, with a rising trajectory in construction land and water, juxtaposed with a recession in shrubland, grassland, paddy land, and dryland expanses. (2) From 2004 to 2020, the ecosystem of the study area maintained its health and remained stable, with mean values of 0.8303, 0.7689, 0.6976, and 0.7824, respectively, showing an evolutionary trend of an initial downtrend trend followed by an upswing, with 2016 marking a pivotal juncture. (3) Spatial clustering analysis highlighted significant clustering characteristics of ecosystem health, with a nominal decrease in the Global Moran's I index from 0.666 to 0.665, which is indicative of a subtle decrease in clustering over time. High-high clustering areas were predominantly located within the World Heritage Site (WHS), while low-low clustering areas were mainly distributed in the southeastern part of buffer zone. (4) Land use and cover change (LUCC) and Ecosystem Services (ESs) were identified as the primary indexes of EHA, with Ecosystem Resilience (ER), Ecosystem Vigor (EV), and Ecosystem Organization (EO) exerting relatively mild influences. This study provides a scientific framework for policymakers in local governance to devise strategies for ecosystem conservation and management, enhances the analytical perspective on the integrity and conservation of Karst Natural World Heritage (KNWH).
Diabetes mellitus and hard braking events in older adult drivers
Authors: Liu Difei , Chihuri Stanford , Andrews Howard F. , Betz Marian E. , DiGuiseppi Carolyn , Eby David W. , Hill Linda L. , Jones Vanya , Mielenz Thelma J. , Molnar Lisa J. , Strogatz David , Lang Barbara H. , Li Guohua 
Published: June 2024

Abstract
Background
Diabetes mellitus (DM) can impair driving safety due to hypoglycemia, hyperglycemia, diabetic peripheral neuropathy, and diabetic eye diseases. However, few studies have examined the association between DM and driving safety in older adults based on naturalistic driving data.

Methods
Data for this study came from a multisite naturalistic driving study of drivers aged 65–79 years at baseline. Driving data for the study participants were recorded by in-vehicle recording devices for up to 44 months. We used multivariable negative binomial modeling to estimate adjusted incidence rate ratios (aIRRs) and 95% confidence intervals (CIs) of hard braking events (HBEs, defined as maneuvers with deceleration rates ≥ 0.4 g) associated with DM.

Results
Of the 2856 study participants eligible for this analysis, 482 (16.9%) reported having DM at baseline, including 354 (12.4%) insulin non-users and 128 (4.5%) insulin users. The incidence rates of HBEs per 1000 miles were 1.13 for drivers without DM, 1.15 for drivers with DM not using insulin, and 1.77 for drivers with DM using insulin. Compared to drivers without DM, the risk of HBEs was 48% higher for drivers with DM using insulin (aIRR 1.48; 95% CI: 1.43, 1.53).

Conclusion
Older adult drivers with DM using insulin appear to be at increased proneness to vehicular crashes. Driving safety should be taken into consideration in DM care and management.
Key ingredients for successful collaboration in health research: perspectives of patient research partners
Authors: Bruce Marcia , Yogaratnam Karthika , Suryaprakash Nitya , Barker Karis L. , Marshall Deborah A. 
Published: June 2024

Abstract
Background
There are increasing publications on meaningful collaboration between researchers and patient research partners (PRPs), but fewer publications of such work from the PRP perspective using an evaluation framework. Our aim is to present our own perspectives and reflections on meaningful collaboration as PRPs working on a qualitative research study.

Main body
We were part of a study team that comprised of PRPs, clinicians and academic researchers, and was led by a PRP. The team designed and conducted a qualitative study aimed at understanding how patients make decisions around tapering of biologics for inflammatory bowel disease. The study was conducted online. The PRP lead was trained in qualitative methodology through a one-year certificate program called Patient and Community Engagement Research offered through the University of Calgary Continuing Education. We had received patient-oriented research training and qualitative research training prior to this project. Team members were assigned tasks by our group lead based on member interests and willingness. Some group members were part of the Strategy for Patient-Oriented Research, Inflammation, Microbiome, and Alimentation: Gastro-Intestinal and Neuropsychiatric Effects Network, one of five chronic disease networks in the Strategy for Patient Oriented Research initiative of the Canadian Institutes of Health Research. We describe the five key ingredients to successful collaboration based on our experiences and reflections utilizing the Experience-Reflection-Action Cycle as our framework. The five key ingredients that we identified were: inclusiveness, goal and role clarity, multi-level training and capacity building, shared decision making, and a supportive team lead.

Conclusion
Overall, our experience was positive. With successful collaboration came an increased level of trust, commitment and performance. There is a need for more studies with diverse PRPs in different settings to validate and/or identify additional factors to improve collaboration in patient-oriented research.
Trastuzumab deruxtecan (T-DXd) vs physician’s choice of chemotherapy (TPC) in patients (pts) with hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-low or HER2-ultralow metastatic breast cancer (mBC) with prior endocrine therapy (ET): Primary results from DESTINY-Breast06 (DB-06).
Authors: Curigliano Giuseppe , Hu Xichun , Dent Rebecca Alexandra , Yonemori Kan , Barrios Carlos H. , O'Shaughnessy Joyce , Wildiers Hans , Zhang Qingyuan , Im Seock-Ah , Saura Cristina , Biganzoli Laura , Sohn Joohyuk , Levy Christelle , Jacot William , Begbie Natasha , Ke Jun , Patel Gargi Surendra , Bardia Aditya 
Published: June 2024

LBA1000 Background: T-DXd is approved for HER2-low (IHC 1+ or 2+/ISH-negative) mBC after ≥1 line of chemotherapy (CT). DB-06 (NCT04494425) evaluated T-DXd in pts with HER2-low or -ultralow (IHC 0 with membrane staining), HR+ mBC after disease progression (PD) on endocrine-based therapy and no prior CT for mBC. Methods: Pts with HER2-low or -ultralow, HR+ mBC were randomized 1:1 to T-DXd 5.4 mg/kg or TPC. Pts had no prior CT for mBC, with ≥2 lines of ET for mBC, or 1 line of ET for mBC if PD occurred ≤24 months (mo) of adjuvant ET or ≤6 mo of ET+CDK4/6i for mBC. Primary endpoint was progression-free survival (PFS) by blinded independent central review (BICR) in HER2-low. Key secondary endpoints were PFS in intent-to-treat (ITT = HER2-low and -ultralow) and overall survival (OS). Other endpoints included objective response rate (ORR) and safety. Results: As of Mar 18, 2024, 866 pts (HER2-low, n=713; HER2-ultralow, n=153) were randomized; 90.4% had prior CDK4/6i. TPC group pts were selected for capecitabine (59.8%), nab-paclitaxel (24.4%) or paclitaxel (15.8%). T-DXd significantly improved PFS vs TPC in HER2-low (HR, 0.62 [95% CI 0.51, 0.74], P<0.0001; median, 13.2 vs 8.1 mo). ITT and HER2-ultralow results were consistent with HER2-low (Table). Median treatment duration was 11.0 mo (T-DXd) vs 5.6 mo (TPC). OS was immature at first interim analysis (HER2-low HR, 0.83 [95% CI 0.66, 1.05], P=0.1181; median follow up, 18.6 mo). Grade (Gr) ≥3 drug-related adverse events occurred in 40.6% (T-DXd) vs 31.4% (TPC). Adjudicated interstitial lung disease / pneumonitis occurred in 49 (11.3%; 0.7% Gr 3/4, 0.7% Gr 5) vs 1 (0.2% Gr 2) pts receiving T-DXd vs TPC. Conclusions: T-DXd showed a statistically significant and clinically meaningful PFS benefit vs TPC (CT) in HER2-low mBC. HER2-ultralow results were consistent with HER2-low. Safety was in line with known profiles. DB-06 establishes T-DXd as a standard of care following ≥1 endocrine-based therapy for pts with HER2-low and -ultralow, HR+ mBC. Clinical trial information: NCT04494425 .[Table: see text]
Preventive effect of naldemedine for opioid-induced constipation in patients with cancer starting opioids: A multicenter, double-blinded, randomized, placebo-controlled, phase 3 trial.
Authors: Hamano Jun , Higashibata Takahiro , Kessoku Takaomi , Kajiura Shinya , Hirakawa Mami , Ariyoshi Keisuke , Oyamada Shunsuke 
Published: June 2024

LBA12014 Background: A peripherally acting μ-opioid receptor antagonist (PAMORA), such as naldemedine, could alleviate OIC in cancer patients. However, the evidence of PAMORA on OIC prevention in cancer patients starting opioid analgesia is limited. This clinical trial aimed to confirm the preventive effect of naldemedine for OIC in cancer patients who start daily strong opioid administration compared with placebo. Methods: We conducted a multicenter, double-blinded, randomized, placebo-controlled trial between July 2021 and May 2023 with four academic hospital in Japan (jRCTs031200397). Patients with cancer starting regular strong opioid for the first time for cancer pain, and age 20 years or older were included. The eligible patient was randomly assigned to the naldemedine (Symproic 0.2 mg) or placebo group in a 1:1 ratio. The protocol treatment period was 14 days after the start of naldemedine (or placebo) and the naldemedine group had Symproic at 0.2 mg once a day after breakfast for 14 days. The placebo group had the placebo once a day after breakfast for 14 days. The primary endpoint was the proportion of patients with a Bowel Function Index (BFI) of less than 28.8 on Day 14. We conducted the safety assessments with the number of all adverse events occurring during the protocol treatment period using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 Japanese translation of Japan Clinical Oncology Group. Results: Of the 103 patients were assessed for eligibility, 99 patients were randomly assigned on a 1:1 basis to receive naldemedine (n = 49) or placebo (n = 50). The BFI score at Day 1 was 18.3±19.8 with naldemedine group and 18.2±20.0 with placebo. The proportion of patients with a BFI of less than 28.8 on Day 14 was significantly greater with naldemedine group (64.6% [31 of 48 patients]; 95% CI, 51.1% to 78.1%) than with placebo (17.0% [8 of 47 patients]; 95% CI, 6.3% to 27.8%) with a difference of 47.6% (95% CI, 30.3% to 64.8%, p< 0.0001). There was no statistical difference in the proportion of adverse events; abdominal distention, abdominal pain, diarrhea, bowel obstruction, and nausea. However, there was a significantly lower proportion of vomiting in patients treated with naldemedine. During the treatment period, none of patients treated with naldemedine had diarrhea, nausea, or vomiting as adverse events causally related to protocol treatment (0.0% [0 of 48 patients] v.s 34.0% [16 of 47 patients]. Conclusions: Naldemedine is a valuable option with proven efficacy in preventing OIC in cancer patients starting regular strong opioids. Clinical trial information: 031200397 .
Longitudinal circulating tumor DNA monitoring in predicting response to short-course neoadjuvant radiotherapy in locally advanced rectal cancer: Data from a phase III clinical trial (UNION).
Authors: Lin Zhenyu , Zhai Menglan , Yan Linghua , Zhang Tao 
Published: June 2024

LBA3606 Background: The data presented here is from a multicenter, randomized, open-label, controlled Phase III clinical study evaluating the feasibility of short-course radiotherapy (shortRT) sequentially combined with camrelizumab and chemotherapy as neoadjuvant therapy (NAT) for locally advanced rectal cancer (LARC)(UNION). Our aim is to explore the value of circulating tumor DNA (ctDNA)-based minimal residual disease (MRD) in assessing the comparative efficacy of short-course and long-course chemoradiotherapy (CRT). Methods: A total of 244 plasma samples from 79 LARC patients, who underwent NAT prior to curative surgery, were collected at baseline (C1), on-NAT (C2), post-NAT (C3), and post-surgery (C4). Deep targeted panel sequencing of 556 cancer-related genes was performed. The changes in genomic features and ctDNA-MRD status during treatment were monitored, and the relationship between these changes and treatment response were explored. Results: During NAT, the ctDNA-MRD positivity rate showed significant declining trends. Patients with high baseline TMB tend to show a significant inclination towards major pathological response and tumor regression grade 0/1 after NAT, while there is no significant correlation observed between baseline ctDNA-MRD status and treatment response. Interestingly, compared to long-course radiotherapy, microsatellite instability is more pronounced after shortRT ( P=0.042), and ctDNA negativity is significantly associated with pathological complete response (pCR) ( P=0.022). Furthermore, both ctDNA clearance ( P=0.049) and MRD clearance ( P=0.015) after shortRT are significantly correlated with pCR. A risk scoring predictive model based on ctDNA-MRD was established, with achieving the highest C-index at the C2 time point. This model, combining MRD clearance and CEA, outperforms models using only MRD clearance (AUC=0.917, 95% CI=0.753 to 1.000) or only CEA (AUC=0.733, 95% CI=0.449 to 1.000), demonstrating superior performance in predicting pCR/non-pCR (AUC=0.983, 95% CI=0.937 to 1.000). Conclusions: These findings offers valuable insights into the dynamic landscape of NAT for LARC management and emphasize the potential of ctDNA-based MRD assessment as a valuable tool for tailoring treatment strategies. The differences observed between shortCRT and longCRT regimens underscore the need for personalized treatment approaches. Overall, our study contributes valuable insights into optimizing treatment decision-making and predicting treatment response in LARC patients, ultimately advancing the field of rectal cancer management.
Nivolumab (NIVO) plus ipilimumab (IPI) vs lenvatinib (LEN) or sorafenib (SOR) as first-line treatment for unresectable hepatocellular carcinoma (uHCC): First results from CheckMate 9DW.
Authors: Galle Peter Robert , Decaens Thomas , Kudo Masatoshi , Qin Shukui , Fonseca Leonardo , Sangro Bruno , Karachiwala Hatim , Park Joong-Won , Gane Edward , Pinter Matthias , Tai David , Santoro Armando , Pizarro Gonzalo , Chiu Chang-Fang , Schenker Michael , He Aiwu Ruth , Wang Qi , Stromko Caitlyn , Hreiki Joseph , Yau Thomas 
Published: June 2024

LBA4008 Background: First-line therapies based on programmed death ligand 1 (PD-L1) inhibitors are standard of care (SOC) in uHCC and demonstrate improved outcomes over SOR; however, prognosis remains poor and there is an unmet need for alternative therapies with long-term benefits. Second-line NIVO + IPI demonstrated clinically meaningful efficacy and manageable safety in SOR-treated patients (pts) with HCC in CheckMate 040, leading to its accelerated approval in the United States. We report first results from the preplanned interim analysis of the phase 3, open-label, randomized CheckMate 9DW trial evaluating the efficacy and safety of NIVO + IPI vs LEN or SOR as first-line therapy for pts with uHCC (NCT04039607). Methods: Adult pts with previously untreated HCC not eligible for curative surgical or locoregional therapies, Child-Pugh score 5–6, and ECOG performance status 0–1 were included. Pts were randomly assigned 1:1 to receive NIVO 1 mg/kg + IPI 3 mg/kg Q3W (up to 4 cycles) followed by NIVO 480 mg Q4W or investigator’s choice of LEN 8 mg or 12 mg QD or SOR 400 mg BID until disease progression or unacceptable toxicity. NIVO was given for a maximum of 2 years. The primary endpoint was overall survival (OS). Secondary endpoints included objective response rate (ORR) and duration of response (DOR) per blinded independent central review (BICR) using RECIST v1.1. Results: In total, 668 pts were randomized to NIVO + IPI (n = 335) or LEN/SOR (n = 333); among 325 pts treated in the LEN/SOR arm, 275 (85%) received LEN. After a median (range) follow-up of 35.2 (26.8–48.9) months (mo), median OS was 23.7 mo with NIVO + IPI vs 20.6 mo with LEN/SOR (HR, 0.79; 95% CI, 0.65–0.96; P = 0.0180) (Table), with respective 24-mo OS rates (95% CI) of 49% (44–55) vs 39% (34–45). ORR was higher with NIVO + IPI (36%) vs LEN/SOR (13%; P < 0.0001); complete response was observed in 7% of pts with NIVO + IPI vs 2% with LEN/SOR. Median DOR was 30.4 mo with NIVO + IPI vs 12.9 mo with LEN/SOR (Table). A summary of treatment-related adverse events (TRAEs) is shown in the Table. Conclusions: NIVO + IPI demonstrated statistically significant OS benefit vs LEN/SOR in pts with previously untreated uHCC, as well as higher ORR and durable responses with a manageable safety profile. These results support this combination as a potential new first-line SOC for uHCC. Clinical trial information: NCT04039607 . [Table: see text]
Rates of pathologic complete response (pCR)after neoadjuvant datopotamab deruxtecan (Dato): Results from the I-SPY2.2 trial.
Authors: Meisel Jane Lowe , Khoury Katia , Chien Amy Jo , Wallace Anne M. , Arora Mili , Rozenblit Mariya , Williams Nicole Olivia , Nanda Rita , Borges Virginia F. , Stringer-Reasor Erica Michelle , Boughey Judy Caroline , Nangia Chaitali , Vaklavas Christos , van 't Veer Laura , DeMichele Angela , Hylton Nola , Yee Douglas , Yau Christina , Esserman Laura ,   ISPY2 Investigators
Published: June 2024

LBA509 Background: I-SPY2.2 is a multicenter phase 2 platform sequential multiple assignment randomized trial (SMART) evaluating novel experimental regimens in the neoadjuvant breast cancer setting. The novel therapy is given as first in a sequence (Block A), followed by standard chemo/targeted therapies (Block B/C) if indicated. The goal is to identify agents that lead to pCR after novel targeted agents alone, or in sequence with optimal therapy assigned based on the tumor response predictive subtype (RPS). RPS incorporates expression-based immune, DNA repair deficiency (DRD), and luminal signatures with hormone receptor (HR) and HER2 status to classify patients by subtype: S1: HR+HER2-Immune-DRD-; S2: HR-HER2-Immune-DRD-; S3: HER2-Immune+; S4: HER2-Immune-DRD+; S5: HER2+/non-Luminal; S6: HER2+/Luminal. Methods: RPS S1, S2, S3 and S4 were eligible for assignment to Dato in Block A. Patients (pts) were followed by MRI during treatment (at 3, 6 and 12 weeks after start of Blocks A and B). Predicted responders by MRI and biopsy at the end of Block A or B have the option of going to surgery early, otherwise they proceed to next treatment Block (B +/- C). Randomization to Block B includes a taxane-based regimen specific to the RPS, and options include S1: paclitaxel; S2 and S3: paclitaxel + carboplatin + pembrolizumab; S4: paclitaxel + carboplatin vs. paclitaxel + carboplatin + pembrolizumab. Patients who did not go to surgery after Block B proceeded to Block C (AC or AC + Pembrolizumab if HR-HER2-). The primary endpoint is pCR. Efficacy is evaluated within each RPS and HR+HER2- and HR-HER2- signatures. To estimate the arm's efficacy as a stand-alone therapy, we use a Bayesian covariate-adjusted model to estimate the pCR rate and compare the posterior distribution to a subtype-specific fixed threshold. This model uses pCR data when available and MRI data when pCR is not. To estimate pCR rate in the context of a multi-decision treatment regimen, we use a Bayesian model based on if and when a pCR occurred in the trial. The posterior is compared to a subtype-specific dynamic control generated from historical I-SPY data. Results: 103 pts were randomly assigned to the Dato arm between August 2022 and August 2023. All patients have proceeded beyond Block A; 33 went to surgery after Dato alone. The efficacy results for Dato as a stand-alone therapy are summarized in Table. Conclusions: Dato monotherapy was active, particularly in the HR-HER2- signature, but did not meet the pre-specified threshold for graduation in I-SPY 2.2. Clinical trial information: NCT01042379 . [Table: see text]