bluuebunny/crossref_metadata_2025_split huggingface dataset:
Developing Transitional Justice for Youth: An Assessment of Youth Reintegration Programmes in Colombia
Authors: Mitra Arpita 
Published: January 2022

ABSTRACT∞
Young people, or ‘youth’ are one of the key groups affected by armed conflict as well as in the process of transitioning from it. This article explores what a youth-inclusive process of transitional justice may entail. It looks at the reintegration of youth, who were previously associated with armed groups, into civilian lives through Disarmament, Demobilisation and Reintegration (DDR) programmes and broader community-based initiatives with a prevention focus that lie outside a traditional transitional justice framework. The article scopes the study to the context in Colombia. A selection of programmes is assessed alongside international standards on youth reintegration, particularly the UN Integrated DDR Standards on Youth and complemented with empirical evidence that attests the ways in which youth experience these interventions. In doing so, the article analyzes potential ‘blueprints’ for the programmatic response to youth reintegration and contribute to an under-researched area that links youth, transitional justice and guarantees of non-recurrence.
SARS-CoV-2 Variant Exposures Elicit Antibody Responses With Differential Cross-Neutralization of Established and Emerging Strains Including Delta and Omicron
Authors: Laurie Matthew T , Liu Jamin , Sunshine Sara , Peng James , Black Douglas , Mitchell Anthea M , Mann Sabrina A , Pilarowski Genay , Zorn Kelsey C , Rubio Luis , Bravo Sara , Marquez Carina , Sabatino Joseph J , Mittl Kristen , Petersen Maya , Havlir Diane , DeRisi Joseph 
Published: January 2022

Abstract
The wide spectrum of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with phenotypes impacting transmission and antibody sensitivity necessitates investigation of immune responses to different spike protein versions. Here, we compare neutralization of variants of concern, including B.1.617.2 (delta) and B.1.1.529 (omicron), in sera from individuals exposed to variant infection, vaccination, or both. We demonstrate that neutralizing antibody responses are strongest against variants sharing certain spike mutations with the immunizing exposure, and exposure to multiple spike variants increases breadth of variant cross-neutralization. These findings contribute to understanding relationships between exposures and antibody responses and may inform booster vaccination strategies.
Proteus, Matrine, and Pyridalyl Toxicity and Their Sublethal Effects on Orius laevigatus (Hemiptera: Anthocoridae)
Authors: Kordestani Mona , Mahdian Kamran , Baniameri Valiollah , Garjan Aziz Sheikhi 
Published: January 2022

Abstract
Proteus, matrine, and pyridalyl were tested in the laboratory for their effects upon Orius laevigatus (Fieber), which is a polyphagous predator used for IPM programs of Frankliniella occidentalis (Pergande). Against female adults, the most toxic insecticide was Proteus (LC50 = 44.3 µl L–1), followed by pyridalyl (LC50 = 83.8 µl L–1) and matrine (LC50 = 102.7 µl L–1). The mortality of female adults was checked 24, 48, 72, and 96 h after exposure to 14-d residues of the treatments on strawberry leaves. The residual of Proteus was less toxic; the remaining products caused the lowest mortality at different times after exposure. Sublethal treatments (LC25) significantly prolonged the developmental duration of total immature stages from 17.6 d in control to 21.6 and 20.0 d in Proteus and pyridalyl treatments, respectively. Also, the fecundity of O. laevigatus treated with Proteus, pyridalyl, and matrine decreased to 58.8%, 75.6%, and 96.7%, respectively, in comparison to the control. Compared with the control population (0.118 d–1), the intrinsic rate of increase (r) of F1 generation decreased by 0.053, 0.095, and 0.110 d–1 in Proteus, pyridalyl, and matrine treatments, respectively. The consumption rate of control bugs reached 14.0 thrips during 24 h. The adults fed on Proteus treatment had the lowest consumption rate in this period (9.4 preys). Overall, matrine proved to be harmless with reproductive capacity and r similar to what was recorded in control bugs. We concluded that matrine can be used as an alternative for the synthetic insecticide to integrate with O. laevigatus.
Exploiting non-linear scales in galaxy–galaxy lensing and galaxy clustering: A forecast for the dark energy survey
Authors: Salcedo Andrés N , Weinberg David H , Wu Hao-Yi , Wibking Benjamin D 
Published: January 2022

ABSTRACT
The combination of galaxy–galaxy lensing (GGL) and galaxy clustering is a powerful probe of low-redshift matter clustering, especially if it is extended to the non-linear regime. To this end, we use an N-body and halo occupation distribution (HOD) emulator method to model the redMaGiC sample of colour-selected passive galaxies in the Dark Energy Survey (DES), adding parameters that describe central galaxy incompleteness, galaxy assembly bias, and a scale-independent multiplicative lensing bias Alens. We use this emulator to forecast cosmological constraints attainable from the GGL surface density profile ΔΣ(rp) and the projected galaxy correlation function wp, gg(rp) in the final (Year 6) DES data set over scales $r_p=0.3\!-\!30.0\, h^{-1} \, \mathrm{Mpc}$. For a $3{{\ \rm per\ cent}}$ prior on Alens we forecast precisions of $1.9{{\ \rm per\ cent}}$, $2.0{{\ \rm per\ cent}}$, and $1.9{{\ \rm per\ cent}}$ on Ωm, σ8, and $S_8 \equiv \sigma _8\Omega _m^{0.5}$, marginalized over all halo occupation distribution (HOD) parameters as well as Alens. Adding scales $r_p=0.3\!-\!3.0\, h^{-1} \, \mathrm{Mpc}$ improves the S8 precision by a factor of ∼1.6 relative to a large scale ($3.0\!-\!30.0\, h^{-1} \, \mathrm{Mpc}$) analysis, equivalent to increasing the survey area by a factor of ∼2.6. Sharpening the Alens prior to $1{{\ \rm per\ cent}}$ further improves the S8 precision to $1.1{{\ \rm per\ cent}}$, and it amplifies the gain from including non-linear scales. Our emulator achieves per cent-level accuracy similar to the projected DES statistical uncertainties, demonstrating the feasibility of a fully non-linear analysis. Obtaining precise parameter constraints from multiple galaxy types and from measurements that span linear and non-linear clustering offers many opportunities for internal cross-checks, which can diagnose systematics and demonstrate the robustness of cosmological results.
Translating the Biology of Diffuse Large B-cell Lymphoma Into Treatment
Authors: Danilov Alexey V , Magagnoli Massimo , Matasar Matthew J 
Published: January 2022

Abstract
Diffuse large B-cell lymphoma (DLBCL) is characterized by clinical and molecular heterogeneity; however, this heterogeneity is rarely taken into account by standard-of-care treatment approaches. While the disease was traditionally classified based on transcriptome signatures purporting the tumor cell of origin, recent classification systems have further differentiated these subtypes into clusters based on molecular and genetic features. Alongside a better understanding of the biology of the disease and the signaling pathways involved, emerging therapeutic agents may be better aimed at attacking distinct disease subsets. It is hoped that molecular subtyping at diagnosis will allow patients to be allocated to the appropriate treatment that targets their specific disease subtype, thus advancing the promise of precision medicine in lymphoma, an approach that is most needed. For high-risk disease subsets, this is particularly important, and much research is still needed to develop agents effective in this population. Here, we review recent advances in DLBCL biology and how they can be translated into clinical care.
Definitive Intensity-Modulated Chemoradiation for Anal Squamous Cell Carcinoma: Outcomes and Toxicity of 428 Patients Treated at a Single Institution
Authors: Holliday Emma B , Morris Van K , Johnson Benny , Eng Cathy , Ludmir Ethan B , Das Prajnan , Minsky Bruce D , Taniguchi Cullen , Smith Grace L , Koay Eugene J , Koong Albert C , Delclos Marc E , Skibber John M , Rodriguez-Bigas Miguel A , You Y Nancy , Bednarski Brian K , Tillman Mathew M , Chang George J , Jennings Kristofer , Messick Craig A 
Published: January 2022

Abstract

Background
Although intensity-modulated radiation therapy (IMRT) is considered the standard of care for the treatment of squamous cell carcinoma of the anus (SCCA), few large series have reported oncologic outcomes and toxicities. In this retrospective report, we aim to describe outcomes and toxicities after IMRT-based chemoradiation (CRT) for the treatment of SCCA, evaluate the impact of dose escalation (&gt;54 Gy), and compare concurrent fluoropyrimidine in combination with either mitomycin or with cisplatin as chemosensitizers.

Methods
Patients treated at The University of Texas MD Anderson Cancer Center between January 1, 2003 and December 31, 2018 with IMRT-based CRT were included. Median time to locoregional recurrence, time to colostomy, and overall survival were estimated using the Kaplan–Meier method.

Results
A total of 428 patients were included; median follow-up was 4.4 years. Three hundred and thirty-four patients (78.0%) were treated with concurrent cisplatin and fluoropyrimidine, and 160 (37.4%) with &gt;54 Gy. Two- and 5-year freedom from locoregional failure, freedom from colostomy failure, and overall survival were 86.5% and 81.2%, respectively, 90.0% and 88.3%, respectively, and 93.6% and 85.8%, respectively. Neither dose escalation nor mitomycin-based concurrent chemotherapy resulted in improved outcomes. Mitomycin-based concurrent chemotherapy was associated with in approximately 2.5 times increased grade 3 or greater acute toxicity. Radiation dose &gt;54 Gy was associated with approximately 2.6 times increased Grade 3 or greater chronic toxicity.

Conclusions
Our results suggest IMRT-based CRT with concurrent fluoropyrimidine and cisplatin is a safe and feasible option for patient with SCCA and may cause less acute toxicity. The role for radiation dose escalation is unclear and requires further study.
Phase I Trial of a Third Generation EGFR Mutant-Selective Inhibitor (D-0316) in Patients with Advanced Non-Small Cell Lung Cancer
Authors: Jian Hong , Wang Kai , Cheng Ying , Ding Lieming , Wang Yang , Shi Zhe , Zhang Ling , Wang Yaolin , Lu Shun 
Published: January 2022

Abstract

Background
D-0316 is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) developed for patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with EGFR T790M mutation that progressed after prior treatment with the first- or second-generation EGFR-TKI.

Methods
This phase I, open-label, multicenter clinical trial evaluated daily oral D-0316 administration in dose-escalation (25 to 150 mg; 17 patients) and dose-expansion (50, 100 mg; 67 patients) cohorts for safety, tolerability, anti-tumor activity, and pharmacokinetics.

Results
D-0316 was well tolerated at daily doses of 25 to 150 mg and the maximum tolerated dose (MTD) was not reached. The most common treatment-related adverse events (AEs) were platelet count decreased, electrocardiogram QT corrected interval prolonged, anemia, rash, low white blood cell count, hypertriglyceridemia, high cholesterol, headache, pruritus, cough, and aspartate transaminase (AST) or alanine transaminase (ALT) increased. Most of AEs were grade 1 or 2. In the 50 and 100 mg group, the overall response rate (ORR) was 33.3% and 45.5%, the disease control rate (DCR) was 86.7% and 93.9%, and the median PFS was 8.3 and 9.6 months, respectively. D-0316 exposure increased in proportion to dose from 25 to 150 mg. The recommended phase II dose (RP2D) was 100 mg.

Conclusion
D-0316 is safe, tolerable, and effective for patients with locally advanced/metastatic NSCLC with the EGFR T790M mutation who previously received EGFR-TKI.

ClinicalTrials.gov Identifier
NCT03452150.
Cetuximab and Irinotecan With or Without Bevacizumab in Refractory Metastatic Colorectal Cancer: BOND-3, an ACCRU Network Randomized Clinical Trial
Authors: Lipsyc-Sharf Marla , Ou Fang-Shu , Yurgelun Matthew B , Rubinson Douglas A , Schrag Deborah , Dakhil Shaker R , Stella Philip J , Weckstein Douglas J , Wender Donald B , Faggen Meredith , Zemla Tyler J , Heying Erica N , Schuetz Samantha R , Noble Stephanie , Meyerhardt Jeffrey A , Bekaii-Saab Tanios , Fuchs Charles S , Ng Kimmie 
Published: January 2022

Abstract

Background
Combination irinotecan and cetuximab is approved for irinotecan-refractory metastatic colorectal cancer (mCRC). It is unknown if adding bevacizumab improves outcomes.

Patients and Methods
In this multicenter, randomized, double-blind, placebo-controlled phase II trial, patients with irinotecan-refractory RAS-wildtype mCRC and no prior anti-EGFR therapy were randomized to cetuximab 500 mg/m2, bevacizumab 5 mg/kg, and irinotecan 180 mg/m2 (or previously tolerated dose) (CBI) versus cetuximab, irinotecan, and placebo (CI) every 2 weeks until disease progression or intolerable toxicity. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), and adverse events (AEs).

Results
The study closed early after the accrual of 36 out of a planned 120 patients due to changes in funding. Nineteen patients were randomized to CBI and 17 to CI. Baseline characteristics were similar between arms. Median PFS was 9.7 versus 5.5 months for CBI and CI, respectively (1-sided log-rank P = .38; adjusted hazard ratio [HR] = 0.64; 95% confidence interval [CI], 0.25-1.66). Median OS was 19.7 versus 10.2 months for CBI and CI (1-sided log-rank P = .02; adjusted HR = 0.41; 95% CI, 0.15-1.09). ORR was 36.8% for CBI versus 11.8% for CI (P = .13). Grade 3 or higher AEs occurred in 47% of patients receiving CBI versus 35% for CI (P = .46).

Conclusion
In this prematurely discontinued trial, there was no significant difference in the primary endpoint of PFS between CBI and CI. There was a statistically significant improvement in OS in favor of CBI compared with CI. Further investigation of CBI for the treatment of irinotecan-refractory mCRC is warranted.
Clinical Trial Registration: NCT02292758
FDA Approval Summary: Revised Indication and Dosing Regimen for Ponatinib Based on the Results of the OPTIC Trial
Authors: Pulte E Dianne , Chen Haiyan , Price Lauren S L , Gudi Ramadevi , Li Hongshan , Okusanya Olanrewaju O , Ma Lian , Rodriguez Lisa , Vallejo Jonathon , Norsworthy Kelly J , de Claro R Angelo , Theoret Marc R , Pazdur Richard 
Published: January 2022

Abstract
On December 18, 2020, US Food and Drug Administration (FDA) approved a supplemental application for ponatinib extending the indication in patients with chronic-phase chronic myeloid leukemia (CP-CML) to patients with resistance or intolerance of at least 2 prior kinase inhibitors. Ponatinib was initially approved in December 2012 but was briefly voluntarily withdrawn due to serious safety concerns including the risk of arterial occlusive events (AOE). It returned to the market in December 2013 with an indication limited to patients with T315I mutation or for whom no other tyrosine kinase inhibitor (TKI) therapy was indicated with revised warnings and precautions. A post-marketing requirement was issued to identify the optimal safe and effective dose for CP-CML. Thus, the OPTIC trial was performed, which randomized patients to 1 of 3 doses, 45 mg, 30 mg, or 15 mg, with a dose reduction to 15 mg on achievement of MR2 (BCR-ABLIS ≤1%). Patients enrolled were treated with at least 2 prior TKIs or had a T315I mutation. Patients with a history of clinically significant, uncontrolled, or active cardiovascular disease were excluded. Efficacy was established on an interim analysis based on the rate of MR2 at 12 months in the modified intent-to-treat population of 261 patients, with 88, 86, and 87 patients in the 45, 30, and 15 mg cohorts, respectively. With a median follow-up of 28 months, the rate of achievement of MR2 at 12 months was 42%, 28%, and 24% in the respective cohorts. The safety profile was consistent with that observed in prior evaluations of ponatinib with notable adverse reactions including pancreatitis, hypertension, hyperlipidemia, liver dysfunction, and AOE. Of patients treated at the 45/15 mg dose, AOEs were seen in 13%, with a higher rate being observed in patients age 65 or older compared to younger patients. A readjudication of AOEs seen on the prior pivotal phase 2 study resulted in a rate of 26%. Overall, the results supported a modification of the recommended dose for patients with CP-CML to 45 mg until the achievement of MR2 followed by a reduction to 15 mg. The expansion of the indication to patients with exposure to 2 prior TKIs was approved given data showing that ponatinib could be successfully used for the treatment of this population with appropriate monitoring and screening for risk factors.
Rational Second-Generation Antiandrogen Use in Prostate Cancer
Authors: Orme Jacob J , Pagliaro Lance C , Quevedo J Fernando , Park Sean S , Costello Brian A 
Published: January 2022

Abstract
The second-generation antiandrogens have achieved an ever-growing list of approvals and indications in subsets of prostate cancer. Here, we provide an overview of second-generation antiandrogen trials and FDA approvals and outline a rational sequencing approach for the use of these agents as they relate to chemotherapy and other available treatment modalities in advanced prostate cancer. All published phase II-III randomized controlled trials reporting outcomes with the use of second-generation antiandrogens in prostate cancer are included as well as all published trials and retrospective studies of second-generation antiandrogen sequencing and/or combinations. Complete tabular and graphical representation of all available evidence is provided regarding the use and sequencing of second-generation antiandrogens in prostate cancer. In metastatic castration-resistant prostate cancer, evidence suggests prioritization of abiraterone before chemotherapy, chemotherapy after second-generation antiandrogen failure, and postchemotherapy enzalutamide in select patients to maximize agent efficacy and tolerability. We conclude that a rational, optimized sequencing of second-generation antiandrogens with other treatment options is feasible with present data.
Phase II Study of Continued Trastuzumab Plus Irinotecan in Patients with HER2-positive Gastric Cancer Previously Treated with Trastuzumab (HGCSG 1201)
Authors: Kawamoto Yasuyuki , Yuki Satoshi , Meguro Takashi , Hatanaka Kazuteru , Uebayashi Minoru , Nakamura Michio , Okuda Hiroyuki , Iwanaga Ichiro , Kato Takashi , Nakano Shintaro , Sato Atsushi , Harada Kazuaki , Oba Koji , Sakata Yuh , Sakamoto Naoya , Komatsu Yoshito 
Published: January 2022

Abstract

Background
The efficacy of irinotecan plus continuous trastuzumab beyond progression in patients with gastric cancer previously treated with trastuzumab plus standard first-line chemotherapy has not been reported.

Methods
Patients with human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer who were previously treated with trastuzumab received trastuzumab every 3 weeks and irinotecan every 2 weeks. The primary endpoint was the overall response rate (ORR), and the secondary endpoints included progression-free survival (PFS), 6-month survival rates, safety, and subgroup analysis by HER2 status.

Results
Sixteen patients were enrolled in a 3-year pre-planned registration period. This study was prematurely closed due to poor patient accrual. The ORR and disease control rate were 6.7% (95% CI, 0.2-32.0) and 53.3% (95% CI, 26.6-78.7). The median PFS and overall survival (OS) were 2.4 months (95% CI, 0.0-5.2) and 9.7 months (95% CI, 8.2-11.2), respectively. The most frequently reported grades 3-4 adverse events were neutropenia (40%), anemia (27%), anorexia (33%), and fatigue (33%).

Conclusion
With only 16 patients enrolled, the present study has very low power to detect any clinical benefit of trastuzumab plus irinotecan beyond disease progression in patients with HER2-positive advanced gastric cancer who previously received trastuzumab.
Trial Identifier: UMIN000007636.
Combining Analysis of Tumor-infiltrating Lymphocytes (TIL) and PD-L1 Refined the Prognostication of Breast Cancer Subtypes
Authors: Ni Yunbi , Tsang Julia Y , Shao Yan , Poon Ivan K , Tam Fiona , Shea Ka-Ho , Tse Gary M 
Published: January 2022

Abstract

Background
PD-L1 has been used as a biomarker to select patients for treatment of PD-1/PD-L1 inhibitors.

Materials and Methods
In this study, we assessed the clinicopathological features of breast cancers that are associated with PD-L1 expression, as well as its relationship with other immune components and its prognostic significance.

Results
Totally 1752 cases were included in this cohort. PD-L1 expression in tumor-infiltrating immune cells (PD-L1-IC) expression and in tumor cells (PD-L1-TC) expression were identified in 34.2% and 10.1% of cases, respectively, and they showed a positive correlation with higher tumor grade, morphological apocrine features, presence of necrosis, and higher stromal tumor-infiltrating lymphocytes (sTIL). PD-L1-IC and PD-L1-TC expression correlated positively with each other, and both of them were negatively associated with estrogen receptor and progesterone receptor and positively associated with Ki67, HER2, EGFR, p63, and p-cadherin. In survival analysis, PD-L1-IC expression was associated with better disease-free survival (DFS) and breast cancer-specific survival (BCSS) in HER2-overexpressed (HER2-OE) cancers and high–grade luminal B cancers. In triple–negative breast cancers (TNBC) and HER2–OE cancers, compared with sTIL low PD-L1-IC negative cases, sTIL high cases showed significantly better DFS independent of PD-L1-IC status. sTIL low PD-L1-IC positive cases also demonstrated a better DFS in HER2–OE cancers. In high–grade luminal B cancers, sTIL high PD-L1-IC positive cases showed the best BCSS.

Conclusion
The data suggested that the combining analysis of sTIL and PD-L1-IC expression refined the prognostication of breast cancer subtypes. Cases with high TIL and PD-LI-IC expression appear to be more immune active.
Inventory-Constrained Underwriters and Corporate Bond Offerings
Authors: Nagler Florian , Ottonello Giorgio 
Published: January 2022

Abstract
We empirically study how inventory constraints of underwriters affect corporate bond offerings. Using underwriter-insurer-level transaction data, we find that a more constrained underwriter is more likely to place a bond and increases the allocation in the primary market to an insurer with a stronger preexisting relationship. The same underwriter is also more likely to buy back part of an allocation from the same insurer within 6 to 12 months after an offering. Overall, by “parking” inventory to relationship investors in the primary market, underwriters mitigate the effect of their inventory constraints on firms’ bond financing costs. (JEL G12, G32)