bluuebunny/crossref_metadata_2025_split huggingface dataset:
Therapeutic Targeting of LIF Overcomes Macrophage-mediated Immunosuppression of the Local Tumor Microenvironment
Authors: Hallett Robin M. , Bonfill-Teixidor Ester , Iurlaro Raffaella , Arias Alexandra , Raman Swetha , Bayliss Peter , Egorova Olga , Neva-Alejo Almudena , McGray AJ Robert , Lau Esther , Bosch Alexandre , Beilschmidt Melissa , Maetzel Dorothea , Fransson Johan , Huber-Ruano Isabel , Anido Judit , Julien Jean-Philippe , Giblin Patricia , Seoane Joan 
Published: November 2022

AbstractPurpose:Leukemia inhibitory factor (LIF) is a multifunctional cytokine with numerous reported roles in cancer and is thought to drive tumor development and progression. Characterization of LIF and clinical-stage LIF inhibitors would increase our understanding of LIF as a therapeutic target.Experimental Design:We first tested the association of LIF expression with transcript signatures representing multiple processes regulating tumor development and progression. Next, we developed MSC-1, a high-affinity therapeutic antibody that potently inhibits LIF signaling and tested it in immune competent animal models of cancer.Results:LIF was associated with signatures of tumor-associated macrophages (TAM) across 7,769 tumor samples spanning 22 solid tumor indications. In human tumors, LIF receptor was highly expressed within the macrophage compartment and LIF treatment drove macrophages to acquire immunosuppressive capacity. MSC-1 potently inhibited LIF signaling by binding an epitope that overlaps with the gp130 receptor binding site on LIF. MSC-1 showed monotherapy efficacy in vivo and drove TAMs to acquire antitumor and proinflammatory function in syngeneic colon cancer mouse models. Combining MSC-1 with anti-PD1 leads to strong antitumor response and a long-term tumor-free survival in a significant proportion of treated mice.Conclusions:Overall, our findings highlight LIF as a therapeutic target for cancer immunotherapy.
Impact of RNA Signatures on pCR and Survival after 12-Week Neoadjuvant Pertuzumab plus Trastuzumab with or without Paclitaxel in the WSG-ADAPT HER2+/HR− Trial
Authors: Graeser Monika , Gluz Oleg , Biehl Claudia , Ulbrich-Gebauer Daniel , Christgen Matthias , Palatty Jenci , Kuemmel Sherko , Grischke Eva-Maria , Augustin Doris , Braun Michael , Potenberg Jochem , Wuerstlein Rachel , Krauss Katja , Schumacher Claudia , Forstbauer Helmut , Reimer Toralf , Stefek Andrea , Fischer Hans Holger , Pelz Enrico , zu Eulenburg Christine , Kates Ronald , Ni Hua , Kolberg-Liedtke Cornelia , Feuerhake Friedrich , Kreipe Hans Heinrich , Nitz Ulrike , Harbeck Nadia 
Published: November 2022

AbstractPurpose:To identify associations of biological signatures and stromal tumor-infiltrating lymphocytes (sTIL) with pathological complete response (pCR; ypT0 ypN0) and survival in the Phase II WSG-ADAPT HER2+/HR− trial (NCT01817452).Experimental Design:Patients with cT1-cT4c, cN0–3 HER2+/HR− early breast cancer (EBC) were randomized to pertuzumab+trastuzumab (P+T, n = 92) or P+T+paclitaxel (n = 42). Gene expression signatures were analyzed in baseline biopsies using NanoString Breast Cancer 360 panel (n = 117); baseline and on-treatment (week 3) sTIL levels were available in 119 and 76 patients, respectively. Impacts of standardized gene expression signatures on pCR and invasive disease-free survival (iDFS) were estimated by logistic and Cox regression.Results:In all patients, ERBB2 [OR, 1.70; 95% confidence interval (CI), 1.08–2.67] and estrogen receptor (ER) signaling (OR, 1.72; 95% CI, 1.13–2.61) were favorable, whereas PTEN (OR, 0.57; 95% CI, 0.38–0.87) was unfavorable for pCR. After 60 months median follow-up, 13 invasive events occurred (P+T: n = 11, P+T+paclitaxel: n = 2), none following pCR. Gene signatures related to immune response (IR) and ER signaling were favorable for iDFS, all with similar HR about 0.43–0.55. These patterns were even more prominent in the neoadjuvant chemotherapy-free group, where additionally BRCAness signature was unfavorable (HR, 2.00; 95% CI, 1.04–3.84). IR signatures were strongly intercorrelated. sTILs (baseline/week 3/change) were not associated with pCR or iDFS, though baseline sTILs correlated positively with IR signatures.Conclusions:Distinct gene signatures were associated with pCR versus iDFS in HER2+/HR− EBC. The potential role of IR in preventing recurrence suggests that patients with upregulated IR signatures could be candidates for de-escalation concepts in HER2+ EBC.
[18F]FluorThanatrace ([18F]FTT) PET Imaging of PARP-Inhibitor Drug-Target Engagement as a Biomarker of Response in Ovarian Cancer, a Pilot Study
Authors: Pantel Austin R. , Gitto Sarah B. , Makvandi Mehran , Kim Hyoung , Medvedv Sergey , Weeks Joanna K. , Torigian Drew A. , Hsieh Chia-Ju , Ferman Benjamin , Latif Nawar A. , Tanyi Janos L. , Martin Lainie P. , Lanzo Shannon M. , Liu Fang , Cao Quy , Mills Gordon B. , Doot Robert K. , Mankoff David A. , Mach Robert H. , Lin Lilie L. , Simpkins Fiona 
Published: November 2022

AbstractPurpose:PARP inhibitors have become the standard-of-care treatment for homologous recombination deficient (HRD) high-grade serous ovarian cancer (HGSOC). However, not all HRD tumors respond to PARPi. Biomarkers to predict response are needed. [18F]FluorThanatrace ([18F]FTT) is a PARPi-analog PET radiotracer that noninvasively measures PARP-1 expression. Herein, we evaluate [18F]FTT as a biomarker to predict response to PARPi in patient-derived xenograft (PDX) models and subjects with HRD HGSOC.Experimental Design:In PDX models, [18F]FTT-PET was performed before and after PARPi (olaparib), ataxia-telangiectasia inhibitor (ATRi), or both (PARPi-ATRi). Changes in [18F]FTT were correlated with tumor volume changes. Subjects were imaged with [18F]FTT-PET at baseline and after ∼1 week of PARPi. Changes in [18F]FTT-PET uptake were compared with changes in tumor size (RECISTv1.1), CA-125, and progression-free survival (PFS).Results:A decrease in [18F]FTT tumor uptake after PARPi correlated with response to PARPi, or PARPi-ATRi treatment in PARPi-resistant PDX models (r = 0.77–0.81). In subjects (n = 11), percent difference in [18F]FTT-PET after ∼7 days of PARPi compared with baseline correlated with best RECIST response (P = 0.01), best CA-125 response (P = 0.033), and PFS (P = 0.027). All subjects with &gt;50% reduction in [18F]FTT uptake had &gt;6-month PFS and &gt;50% reduction in CA-125. Utilizing only baseline [18F]FTT uptake did not predict such responses.Conclusions:The decline in [18F]FTT uptake shortly after PARPi initiation provides a measure of drug-target engagement and shows promise as a biomarker to guide PARPi therapies in this pilot study. These results support additional preclinical mechanistic and clinical studies in subjects receiving PARPi ± combination therapy.See related commentary by Liu and Zamarin, p. 1384
Host-parasite relationship between Aphelenchoides besseyi and soybean
Authors: Calandrelli Angélica , Silva Monique T.R. , Miamoto Angélica , Rinaldi Luanna K. , Favoreto Luciany , Meyer Maurício C. , Machado Andressa C.Z. , Silva Santino A. , Dias-Arieira Cláudia R. 
Published: November 2022

Summary
Aphelenchoides besseyi is a concern to Brazilian agriculture, since the losses caused by the green stem and foliar retention syndrome in soybean, especially in hot and humid climates, could reach high levels. However, limited information is available regarding the host-parasite relationship. The objective of this study was to evaluate the capacity of A. besseyi to penetrate soybean roots and its movement in soybean tissues until reaching the top parts. Plants inoculated with 1000 A. besseyi were evaluated for root penetration from 1-28 days after inoculation (DAI), and post-penetration and movement inside tissues by staining them with acid fuchsin. Plant development, chronology of the symptoms and the number of pods were also evaluated at 60 DAI. Aphelenchoides besseyi was found in the cortex and xylem vessels of roots from 1 DAI. During the experimental period, the number of nematodes from roots to shoots increased more than 123, 330 and 430%, respectively, for roots, stems + petioles + inflorescences, and leaves, demonstrating the ascendent movement of A. besseyi. Necrotic lesions in young leaves and apical tissues were observed from 8 DAI; the typical symptom of ‘amachamiento’ was observed from 10 DAI, with enlargement of nodes and lesions in inflorescences and, at 30 DAI, stunted plants were detected. At 60 DAI, inoculated plants had lower numbers of pods and exhibited severe symptoms including abortion of flowers and tissue splitting and cortical lesions in a few pods and roots. These observations emphasise the importance of A. besseyi for Brazilian soybean production.
Host plant status and damage threshold of spinach (Spinacia oleracea) for the temperate root-knot nematode Meloidogyne chitwoodi
Authors: Taning Lirette M. , Chann Leakena , Fleerakkers Sander , Cap Nathalie , Formesyn Ellen , Tirry Luc , Wesemael Wim M.L. 
Published: November 2022

Summary
Problems with plant-parasitic nematodes remain a major challenge in most field vegetable crops worldwide. In agricultural fields in Belgium, these problems have increased in recent years. A major problem is the quarantine root-knot nematode Meloidogyne chitwoodi. The host plant status of the most commonly grown cultivars of spinach (Spinacia oleracea) and the damage threshold for M. chitwoodi were determined in a climate-controlled glasshouse and in a naturally infested field. The yield data with the final population densities were fitted to Seinhorst’s yield and population dynamic models, respectively. The damage threshold values (T) for the relative fresh weight yield were 0.14, 1.08, 11.53 J2 (100 cm3 soil)−1, minimum yield (m) of 0.84, 0.64, 0.52 and maximum yield () of 12.51, 12.44 and 9.60 for ‘Gnu’, ‘Meerkat’ and ‘Whale’ spinach cultivars, respectively. The maximum multiplication rates (a) were 3.81, 2.38 and 2.72, whilst the maximum population densities (M) were 563, 916, and 922 J2 (100 cm3 soil)−1 for ‘Gnu’, ‘Meerkat’ and ‘Whale’, respectively. Meloidogyne chitwoodi had an impact on the spinach yield. The higher the nematode density the lower the yield and vice versa. The tested cultivars were all hosts for M. chitwoodi but differences between cultivars occurred. ‘Kolibri’ and ‘Rhino’ were tested as the least sensitive cultivars for M. chitwoodi during the host screening test and bring opportunities for resistance breeding. This is the first report of spinach as a host for M. chitwoodi.
Unduly Indicated? Provisional Measures and Subsequent Adverse Findings at the International Court of Justice
Authors: Merlin Jean-Baptiste 
Published: November 2022

Abstract
The method currently applied by the International Court of Justice for the purpose of indicating provisional measures does not fully preclude the risk that provisional measures might prove in retrospect to have been unjustified in specific circumstances. The question arises whether a litigating State might be entitled to reparation for the prejudice incurred from complying with onerous provisional measures in such cases. While the Court has only exceptionally come close to such a situation, it has not been faced with reparation claims yet. However, developments since LaGrand should prompt an examination of how the Court’s judicial practice may address the risk of problematic discrepancy between provisional measures and the Court’s final decision.
Will the ICJ Objectively Assess the Statehood of Palestine? A Brief Reflection
Authors: Ahmed Kawser 
Published: November 2022

Abstract
Is Palestine a state? The International Court of Justice (ICJ) is expected to address this question in the Case concerning Relocation of the United States Embassy to Jerusalem (Palestine v. United States of America) during the preliminary objections stage. In the meanwhile, scholars have discussed possible options that international law can offer to deal with the question of Palestine’s statehood. The suggestions include, for example, state recognition, the Vienna formula, etc. This article, however, envisages that in determining Palestine’s statehood the ICJ is likely to adopt an objective assessment test on the basis of international legal criteria of statehood.
Proliferation of Standards of Proof in International Administrative Tribunals
Authors: Tavadian Alexandre , Ducamin Clément 
Published: November 2022

Abstract
All international organizations have or ought to have a code of conduct. When international civil servants breach their basic obligations and engage in misconduct, they may face disciplinary proceedings and be subject to a wide range of sanctions, including dismissal and other forms of separation from service. However, different international organizations apply dissimilar standards of proof for establishing the alleged facts that constitute misconduct. For instance, in some institutions, the applicable standard of proof is “beyond a reasonable doubt”, while in others, it is a balance of probabilities. The lack of consistency is attributable to the jurisprudence of various international administrative tribunals. This article compares how six international administrative tribunals interpret and apply the evidential threshold to disciplinary cases. It identifies practical difficulties caused by a lack of a uniform approach and recommends remedial measures for international organizations and international administrative tribunals.
Chinese international lawyer and British doctoral supervisor
Authors: Chen Li 
Published: November 2022

Summary
This article draws upon multi-archival research to rediscover Hwang King Hung, a forgotten Chinese international lawyer who was the first ethnic Chinese person to receive a PhD in Law from Cambridge University. Specifically, it aims to shed light on how Hwang was trained by Hersch Lauterpacht, Hwang’s doctoral supervisor, and how Lauterpacht played a crucial role in training eminent Chinese international lawyers in the first part of the 20th century. It further aims to challenge the traditional Eurocentrism of international legal history and inspire further research into the lived experiences of the pioneer generation of international lawyers from China.
Mobilising, Politicising and Serving: The Ambivalence of the ‘Revitalisation’ of Argentine Trade Unionism
Authors: Rouxel Pierre 
Published: November 2022

Abstract
Since the beginning of the 2000s, a significant literature has developed around the study of the “revitalisation” of trade unionism. These contributions often take up typologies that oppose the ‘old’ and the ‘new’ and thus tend to harden the contours of what would constitute a ‘trade union renewal’. From this perspective, this article re-examines the nature and limits of this process, in the light of the Argentine case. It is based on a field survey of two comisiones internas that are emblematic of the ‘bottom-up revitalisation’ of Argentinean trade unionism since the 2000s. The localized and in-depth study of these two collectives makes it possible to document the concrete conditions of trade union work, by relating them to the socialization trajectories of the delegates and the social contexts in which they evolve. In this way, the article shows the constraints that lead delegates to internalise a ‘sense of limits’ in their work of politicising trade union action, thus highlighting the articulations between militant practices and service practices that characterise their modes of action.
The prevalence of depression, anxiety, stress and their relationship to length of service in the UK police force
Authors: Gullon-Scott Paul , Longstaff Laura 
Published: November 2022

Policing is considered a highly stressful role, and police officers are at risk of mental health issues during their service. This is an area which has gained increasing attention in recent years, but further research, using validated measures, is needed to help identify other factors that are important and ensure further development as well as evidence-based, bespoke intervention. The current study sought to explore the general prevalence of stress, depression and anxiety in a UK sample of police officers, to examine whether length of service moderates the effects of stress, depression and anxiety, and whether certain personality traits protect against these. A self-report questionnaire was completed by 177 serving UK police officers from 10 different regions. Results revealed clinical levels of anxiety and depression, and comorbid presentations of major depression and anxiety, at rates significantly higher than reported in the general population. Results indicated officers are most at risk of experiencing stress during the first 15 years of their service, and that officers’ stress was organisational rather than trauma related. Additionally, officers higher in traits of extraversion and lower in neuroticism reported lower anxiety. The results of these findings are discussed, and suggestions have been made based on the current findings.
Modifications to Risk Aversion in High Gain Situations
Authors: MacKay J.A. , Lerche I. , Rose P.R. 
Published: November 2022

The classical Cozzolino formula for risk aversion, which determines the optimum working interest that should be taken in an exploration opportunity, suffers from the disadvantage that the predicted optimum working interest decreases for opportunities which have increasing high gain potential, independently of the success chance, while the predicted risk adjusted value tends towards a constant limit, which is independent of anticipated costs and depends only on the corporate risk tolerance and the success probability. For low gain opportunities the classical risk formula does an adequate job of assessing optimum working interest. Modifications are given to the method which, for low gain opportunities, reduce to the classical risk adjusted behaviors but which, for high gain opportunities, provides a predicted optimum working interest which increases with increasing gain. A practical procedure is provided for using these modifications in a simple manner to differentiate between high gain (good-risk) opportunities versus low gain (bad-risk) opportunities. Numerical illustrations indicate graphically the changes in risk aversion brought about by the required modifications.
Establishment of a Quantitative Index for Evaluation of Caprock Sealing, and Application to the SHONGLIAO Basin, China
Authors: Pang X. , Fu G. , Jiang Z. , Lerche I. 
Published: November 2022

Using basin modelling principles and methods, this paper puts forward a quantitative and comprehensive index (comprising the influence of a series of geological factors) to evaluate the sealing ability of a caprock, to establish the index with a computer modelling system, and to illustrate its value by application to the Shongliao Basin. The advantage of the Cap Rock Index (CRI) is that it can be used to calculate the oil and gas columns that could be sealed by a caprock, to identify and grade caprocks, to recover sealing changes, and to evaluate the critical points at which caprocks start to seal oil and also gas in the geohistory evolution of a basin.
Sedimentary Shattering as Hydrocarbon Migration Avenues in Salt-floored Basins: A New Migration Paradigm
Authors: Lowrie A. , MacKenzie M.G. , Guderion E. , Talbert F.E. 
Published: November 2022

The salt-floored basin concept as applied to the Louisiana offshore, with its total dependence on laterally migrating salt, provides a dynamic view of geologic evolution. Salt domes, ridges, and massifs move basinward at rates of one to ten cm/yr, causing extensive fracturing, thermal anomalies, and under- and over-pressured horizons. The ever-enlarging sedimentary wedge contains its own tectonics; principally basin-spanning shelf-edge growth faults that sole out in shale layers. Advancing salt tongues can create counter-regional and local growth faults that terminate in the semi-plastic salt. Additional stresses, some by basement faulting, are also active within the salt-floored passive margin. A geologically reasonable conclusion, derived from the abundance of tectonics, is that the sediments may be thought of as shattered. Porous flowage would be reminiscent of that through a colander, not a sieve. Given the possibility of such massive shattering, it is obligatory to prepare a different paradigm relative to hydrocarbon migration. The now decades old notion that most, if not all, hydrocarbons migrate along regional faults must be modified. The shattered sedimentary wedge becomes a conduit for hydrocarbon migration with some concentration of hydrocarbon flow along regional faults, however intermittent that may be. The sedimentary shattering may be so extensive that a new paradigm need be applied to hydrocarbon migration.
The risk of harm whilst waiting for varicose veins procedure
Authors: Bootun Roshan , Burrows Mandy , Chowdhury Mohammed M , Stather Philip W , Al-Jundi Wissam 
Published: November 2022

Introduction Varicose veins (VV) negatively impact quality of life (QoL) and have risks of major complications including bleeding, ulceration and phlebitis. During the COVID-19 pandemic, the VSGBI (Vascular Society of Great Britain and Ireland) and GIRFT (Get It Right First Time) classified VVs as lowest priority for intervention. Objective This study aims to determine harm caused and the impact on the QoL on patients waiting for their VVs procedures for more than 1 year. Methods This was a prospective study conducted at the Norfolk and Norwich University Hospital (NNUH). Patients with VVs awaiting intervention for >1 year were included in the study. Patients with CEAP C6 disease were considered to be too high risk to be invited for treatment during the Covid-19 pandemic. Patients were sent QoL questionnaires and underwent a telephone consultation to assess harm. Both generic (EQ-VAS and EQ-5D) and disease-specific (AVVQ and CIVIQ-14) instruments were utilised. There were no control groups available for comparison. Results 275 patients were identified (37.1% male) with median time on waiting list of 60 weeks (IQR 56–65). 19 patients (6.9%) came to major harm, including phlebitis (3.6%), bleeding (1.8%) and ulceration (1.8%). Fifty-two patients (18.9%) had minor harm, including worsening pain (12.7%) and swelling (6.2%). 6.9% reported psychological harm. Rising CEAP stage was also associated with worsening level of harm in patients with C5-6 disease ( p < 0.0001). Only 8.7% stated they would decline surgery during the pandemic. 104 QoL questionnaires were returned. Median EQ-VAS and EQ-5D was 75 (IQR: 60–85) and 0.685 (0.566–0.761), respectively. Median AVVQ score was 23.2 (14.9–31.0) and CIVIQ-14 score was 33 (21–44). ConclusionsThis study highlights the impact of delaying VVs surgery during a pandemic. A significant rate of both major and minor as well as psychological harm was reported. In addition, VVs had a significant detriment to quality of life.