bluuebunny/crossref_metadata_2025_split huggingface dataset:
Germline variants are associated with increased primary melanoma tumor thickness at diagnosis
Authors: Mangantig Ernest , MacGregor Stuart , Iles Mark M , Scolyer Richard A , Cust Anne E , Hayward Nicholas K , Montgomery Grant W , Duffy David L , Thompson John F , Henders Anjali , Bowdler Lisa , Rowe Casey , Cadby Gemma , Mann Graham J , Whiteman David C , Long Georgina V , Ward Sarah V , Khosrotehrani Kiarash , Barrett Jennifer H , Law Matthew H 
Published: October 2020

Abstract
Germline genetic variants have been identified, which predispose individuals and families to develop melanoma.
Tumor thickness is the strongest predictor of outcome for clinically localized primary melanoma patients. We sought to determine whether there is a heritable genetic contribution to variation in tumor thickness. If confirmed, this will justify the search for specific genetic variants influencing tumor thickness.
To address this, we estimated the proportion of variation in tumor thickness attributable to genome-wide genetic variation (variant-based heritability) using unrelated patients with measured primary cutaneous melanoma thickness. As a secondary analysis, we conducted a genome-wide association study (GWAS) of tumor thickness.
The analyses utilized 10 604 individuals with primary cutaneous melanoma drawn from nine GWAS datasets from eight cohorts recruited from the general population, primary care and melanoma treatment centers. Following quality control and filtering to unrelated individuals with study phenotypes, 8125 patients were used in the primary analysis to test whether tumor thickness is heritable. An expanded set of 8505 individuals (47.6% female) were analyzed for the secondary GWAS meta-analysis. Analyses were adjusted for participant age, sex, cohort and ancestry.
We found that 26.6% (SE 11.9%, P = 0.0128) of variation in tumor thickness is attributable to genome-wide genetic variation. While requiring replication, a chromosome 11 locus was associated (P &lt; 5 × 10−8) with tumor thickness. Our work indicates that sufficiently large datasets will enable the discovery of genetic variants associated with greater tumor thickness, and this will lead to the identification of host biological processes influencing melanoma growth and invasion.
Profound bilateral deafness complicating aortic arch surgery
Authors: Carré Fabienne , Mamelle Elisabeth , Ferrier Suzanne , Achouh Paul 
Published: October 2020

Abstract
Hearing loss is a rare complication of cardiac surgery; bilateral profound deafness has never been reported in this setting. A 45-year-old male presented with profound bilateral sudden deafness following arch surgery and frozen elephant trunk. Patient’s presentation, surgery details and aetiological mechanisms are discussed.
Development of the Diaphragmatic Paralysis Questionnaire: a simple tool for patient relevant outcome
Authors: Kosse Nils Jurriaan , Windisch Wolfram , Koryllos Aris , Lopez-Pastorini Alberto , Piras Denis , Schroiff Hans-Willi , Straßmann Stephan Eric , Stoelben Erich , Schwarz Sarah Bettina 
Published: October 2020

Abstract

OBJECTIVES
Measurement tools of health-related quality of life (HRQL) that are specific for the underlying disorder are inevitably needed to assess HRQL changes following specific treatment strategies. The aim of the current study was to develop a questionnaire assessing HRQL in patients with unilateral diaphragmatic paresis.

METHODS
Firstly, topics of health impairments covering physical, psychological, social and functional aspects were predefined by a physician expert panel to ensure face validity. Secondly, all predefined topics were rated by a patient group with unilateral diaphragmatic paresis (untreated: n = 11; postoperative: n = 9) using a 5-point Likert scale ranging from ‘not relevant at all’ (−2) to ‘absolutely relevant’ (+2) to guarantee content validity. Thirdly, only relevant topics (0 to +2) were used for item development, while non-relevant items (&lt;0) were not subject for item development.

RESULTS
In total, 20 patients rated a total of 43 topics covering a broad spectrum of health impairment. 21 were considered as relevant for item development. Items are answered on a 5-point Likert scale ranging from ‘completely untrue’ (−2) to ‘always true’ (+2). The Diaphragmatic Paralysis Questionnaire (DPQ) Summary Score ranges from 0 (worst HRQL) to 100 (best HRQL). Finally, the German DPQ was professionally translated and transculturally adapted into English, Italian, Dutch, French, Greek and Spanish, using translation/back-translation procedures.

CONCLUSIONS
The DPQ is the first diseases-specific HRQL measure developed for patients with diaphragmatic paresis. In addition, the DPQ is available in 7 languages free of charge for non-profit purposes.

Clinical trial registration
German clinical trials register: DRKS00017056
Prevalence and clinicopathological/molecular characteristics of mismatch repair protein-deficient tumours among surgically treated patients with prostate cancer in a Japanese hospital-based population
Authors: Kagawa Makoto , Kawakami Satoru , Yamamoto Azusa , Suzuki Okihide , Eguchi Hidetaka , Okazaki Yasushi , Akagi Kiwamu , Tamaru Jun-ichi , Arai Tomio , Yamaguchi Tatsuro , Ishida Hideyuki 
Published: October 2020

Abstract

Background
The prevalence and molecular characteristics of deficient mismatch repair prostate cancer in the Japanese population have scarcely been investigated.

Methods
Immunohistochemistry for mismatch repair proteins (MLH1, MSH2, MSH6 and PMS2) was performed in formalin-fixed paraffin-embedded sections prepared from resected primary prostate cancers in patients who underwent prostatectomy at our institution between January 2001 and May 2016. Genetic and/or epigenetic alterations of mismatch repair genes were investigated in patients with any loss of mismatch repair protein expression in the tumour.

Results
Of the 337 patients, four (1.2%) showed loss of mismatch repair protein expression on immunohistochemistry. All four patients showed loss of both MSH2 and MSH6 protein expression. Genetic testing was performed in two of the four patients, demonstrating no pathogenic germline alterations were present. In each of these two patients, at least one somatic alteration inactivating MSH2 without MSH2 hypermethylation was identified, leading to the diagnosis of supposed ‘Lynch-like syndrome’. Patients with deficient mismatch repair prostate cancer were at a significantly higher stage (pT2pN0 vs. pT3-4pN0/pTanypN1, P = 0.02) and had a greater Gleason score (&lt;8 vs. ≥8, P &lt; 0.01) than those with proficient mismatch repair prostate cancer.

Conclusions
The prevalence of deficient mismatch repair prostate cancer in the Japanese hospital-based prostatectomized population was extremely low. To improve screening efficacy for deficient mismatch repair prostate cancer, screening candidates can be limited to patients with locally advanced, node-positive and/or Gleason score of 8 or greater prostate cancer. Universal tumour screening for Lynch syndrome seems ineffective in patients with prostate cancer.
Phenotypic Insecticide Resistance in Anopheles gambiae (Diptera: Culicidae): Specific Characterization of Underlying Resistance Mechanisms Still Matters
Authors: Medjigbodo Adandé A , Djogbenou Luc S , Koumba Aubin A , Djossou Laurette , Badolo Athanase , Adoha Constantin J , Ketoh Guillaume K , Mavoungou Jacques F 
Published: October 2020

Abstract
An effective control of malaria vectors requires an extensive knowledge of mechanisms underlying the resistance-phenotypes developed by these vectors against insecticides. We investigated Anopheles gambiae mosquitoes from Benin and Togo for their intensity of insecticide resistance and we discussed the involvement of genotyped mechanisms in the resistance-phenotypes observed. Three- to five-day-old adult mosquitoes emerged from field and laboratory An. gambiae larvae were assayed using WHO tube intensity tests against various doses of deltamethrin: 1× (0.05%); 2× (0.1%); 5× (0.25%); 7.5× (0.375%) and those of pirimiphos-methyl: 0.5× (0.125%); 1× (0.25%). Members of An. gambiae complex were screened in field populations using polymerase chain reaction (PCR) assays. The presence of kdrR(1014F/1014S) and ace-1R(119S) mutations was also investigated using TaqMan and PCR-RFLP techniques, respectively. Anopheles gambiae from field were very resistant to deltamethrin, whereas KisKdr and AcerKdrKis strains displayed 100% mortality rates at 2× the diagnostic dose. In contrast, the field mosquitoes displayed a low resistance-intensity against 1× the diagnostic dose of pirimiphos-methyl, whereas AcerKis and AcerKdrKis strains showed susceptibility at 0.5× the diagnostic dose. Anopheles gambiae s.s., Anopheles coluzzii, and Anopheles arabiensis were identified. Allelic frequencies of kdrR (1014F) and ace-1R (119S) mutations in the field populations varied from 0.65 to 1 and 0 to 0.84, respectively. The field An. gambiae displayed high-resistance levels against deltamethrin and pirimiphos-methyl when compared with those of the laboratory An. gambiae-resistant strains. These results exhibit the complexity of underlying insecticide resistance mechanisms in these field malaria vectors.
The interaction between wheat roots and soil pores in structured field soil
Authors: Zhou Hu , Whalley William R , Hawkesford Malcolm J , Ashton Rhys W , Atkinson Brian , Atkinson Jonathan A , Sturrock Craig J , Bennett Malcolm J , Mooney Sacha J 
Published: October 2020

Abstract
Wheat (Triticum aestivum L.) root growth in the subsoil is usually constrained by soil strength, although roots can use macropores to elongate to deeper layers. The quantitative relationship between the elongation of wheat roots and the soil pore system, however, is still to be determined. We studied the depth distribution of roots of six wheat varieties and explored their relationship with soil macroporosity from samples with the field structure preserved. Undisturbed soil cores (to a depth of 100 cm) were collected from the field and then non-destructively imaged using X-ray computed tomography (at a spatial resolution of 90 µm) to quantify soil macropore structure and root number density (the number of roots cm–2 within a horizontal cross-section of a soil core). Soil macroporosity changed significantly with depth but not between the different wheat lines. There was no significant difference in root number density between wheat varieties. In the subsoil, wheat roots used macropores, especially biopores (i.e. former root or earthworm channels) to grow into deeper layers. Soil macroporosity explained 59% of the variance in root number density. Our data suggested that the development of the wheat root system in the field was more affected by the soil macropore system than by genotype. On this basis, management practices which enhance the porosity of the subsoil may therefore be an effective strategy to improve deep rooting of wheat.
On the Application of International Law to Palestinian Refugees
Authors: Albanese Francesca P , Takkenberg Lex 
Published: October 2020

Abstract
This chapter explores the legal foundations of the Palestinian refugee question, reviewing their status under various branches of international law – as refugees, stateless persons, civilians protected under international humanitarian law, internally displaced persons, or, simply, as human beings entitled to human rights. International law as it stood in the early twentieth century, is relevant to the Palestinian refugee question. Since 1948, the evolution of its various branches – notably international humanitarian law (IHL), international human rights law (IHRL), international refugee law (IRL), and the frameworks to address statelessness and prevent internal displacement – have consolidated and evolved in ways that should benefit Palestinian refugees. IRL determines the foundation of the legal status of Palestinians as refugees and the standards of treatment specific to that status. IHRL, as the body of international law with the widest application, has the potential to improve significantly the status and conditions of Palestinian refugees. Meanwhile, IHL remains an important, composite protection framework whenever humanity fails. Thus, the failure to bring a just resolution to the plight of Palestinian refugees is ultimately attributable to the protracted lack of political will, rather than inadequacy of the legal framework and the persistence to treat their plight in political terms, as an outcome of war, a humanitarian crisis, and an issue for negotiation.
The Quest for Durable Solutions
Authors: Albanese Francesca P , Takkenberg Lex 
Published: October 2020

Abstract
This concluding chapter focuses on the quest for just and durable solutions, exploring the challenges and opportunities that have emerged through the various attempts at resolving the Palestinian refugee question. Solutions for Palestinian refugees have been sought since May of 1948. The work of the General Assembly; the UN Mediator for Palestine; the United Nations Conciliation Commission for Palestine (UNCCP); the Security Council in the aftermath of the Six Day War; the various peace initiatives and negotiations since the Madrid peace conference in 1991, have all included attempts to find solutions to the plight of the refugees. However, decades of Arab–Israel and Israeli–Palestinian peace efforts have not succeeded in bringing a resolution of the Palestinian refugee issue within reach. The chapter argues that a fundamental paradigm shift is necessary to advance solutions for Palestinian refugees. Moving the question from the essentially bilateral approach of the last decades back to the multilateral arena of the United Nations; ensuring respect for the international law governing the resolution of refugee problems, as informed by international practice; and moving beyond the ‘politics of suffering’ that dominate the Palestinian refugee discourse are key elements to progress towards just and durable solutions for Palestinian refugees. The New York Declaration on Refugees and Migrants, which called for the development of a Global Compact on Refugees, offers an opportunity to pursue solutions for Palestinian refugees.
Classification of Armed Conflicts
Authors: Akande Dapo 
Published: October 2020

Abstract
This chapter provides an overview of the rules by which situations of violence are classified as international armed conflicts (IACs) or non-international armed conflicts (NIACs) for the purposes of international humanitarian law. The chapter commences with an examination of the history of the distinction between these two types of conflict. It then considers the consequences of the distinction and whether it still has validity. The chapter then discusses legal concepts relevant to the two categories, and examines the criteria for the existence of IACs and NIACs. The final sections of the chapter turn to the situations where it is most difficult to classify situations of violence: cases of foreign intervention in internal conflicts; conflicts in which multinational forces are engaged; and transnational conflicts between a state and a non-state armed group.
Persons Covered by International Humanitarian Law: Main Categories
Authors: Hill-Cawthorne Lawrence 
Published: October 2020

Abstract
This chapter identifies the main categories of persons deemed to be in need of protection in situations of armed conflict, according to which the rules of international humanitarian law (IHL) are structured. The two principal categories of persons under the law of international armed conflict (IAC) are combatants/prisoners of war (POWs) and civilians. This categorization lies at the heart of one of the key principles of IHL, that of the distinction between combatants (being, generally, lawful targets) and civilians (being, generally, not lawful targets). These two principal categories are then further divided, with special (additional) rules applying to certain persons falling within each sub-category—including the wounded, sick, and shipwrecked; women; children; the elderly, disabled, and infirm; refugees and internally displaced persons (IDPs); mercenaries and spies; journalists; and the missing and the dead. For some of these categories of persons, such as women and displaced persons, the rules remain very basic and inadequate for the contemporary challenges faced in armed conflicts. What is more, many of these categories are even less clearly defined under the law of non-international armed conflict (NIAC).
Protection of the Natural Environment
Authors: Payne Cymie R 
Published: October 2020

Abstract
This chapter focuses on international humanitarian law’s (IHL) limitations on warfare to protect the natural environment from extremely serious damage and to prevent unnecessary or wanton harm. IHL protection of the environment developed from the principle of protection of civilians, and it has similar motives and goals. The chapter then describes a legal regime that is undergoing development. The International Law Commission (ILC) termed the overall topic ‘Protection of the Environment in Relation to Armed Conflict’ (PERAC). The central rules of IHL that are well accepted as customary law provide protection to aspects of the environment that can be considered public or private property, or that are essential to human survival. These aspects of PERAC are firmly rooted in the earliest law of war protections for drinking water, crops, and cultural elements, and in modern domestic environmental law and social norms. Yet protection of the environment during armed conflict as a specific legal obligation is a sufficiently recent international norm that its status as binding law has been more contested than early humanitarian commitments like neutrality of medical personnel. This reflects the tension between recognition of the importance of ecological integrity to peace and the interests of states in retaining freedom in their conduct of military operations.
Occupation
Authors: Vité Sylvain 
Published: October 2020

Abstract
This chapter discusses the phenomenon of ‘occupation’. Occupation refers to this particular phase in international armed conflict (IAC) where a belligerent has overpowered the adverse party and taken control of enemy territories, but the final outcome of the war has not yet been decided. Occupation is thus a transition phase between the end of active hostilities and formal conclusion of the conflict. It is a period where foreign armed forces are responsible for the administration of territories belonging to the defeated state. During this transitory period towards peace, international law seeks to ensure that the rights of the territorial state are not infringed and that local populations are protected against any risk of abuse by potentially hostile authorities. The chapter then looks at the sources, scope, and substance of the law of occupation. While relevant rules mainly fall under international humanitarian law (IHL), it is recognized today that human rights law is also applicable during occupation.
Humanitarian Relief Operations
Authors: Massingham Eve , Thynne Kelisiana 
Published: October 2020

Abstract
This chapter examines humanitarian relief operations in armed conflict. The main tenet of international humanitarian law (IHL) is that human suffering should be limited, even in an environment where causing death and injury is, to a certain extent, legitimate. In amongst the violence and death that characterizes armed conflict in all its forms, humanitarian relief operations seek to assuage the suffering by providing protection and assistance to persons who are affected by the armed conflict. Humanitarian relief actors not only promote IHL to the parties to a conflict, but they also provide protection and assistance to victims of a conflict. States have the primary responsibility to provide humanitarian assistance to their citizens, to provide them with protection, and to respect and ensure respect for IHL. Non-state armed groups engaged in armed conflict also have a responsibility to uphold IHL and provide assistance to people in the territory which they control. However, where the state or armed group is not able to provide such assistance, humanitarian relief actors and organizations can fill the gap. Therefore, like combatants, civilians, and other protected persons, humanitarian relief personnel have specific protections, obligations, and requirements under IHL.
Terrorism, Counter-Terrorism, and International Humanitarian Law
Authors: Saul Ben 
Published: October 2020

Abstract
This concluding chapter addresses the debate about the coverage, adequacy, and effectiveness of international humanitarian law (IHL) in regulating ‘terrorism’. IHL does not recognize any specific legal categories for, or special regime governing, terrorists and terrorist groups. Rather, the general norms of IHL apply to terrorists according to their conduct. IHL was precisely developed as a kind of exceptional or emergency law comprehensively addressing all forms of violence in armed conflict, including that which is labelled ‘terrorist’ in other areas of law. Particularly relevant to terrorism are the general IHL rules on the classification of violence as armed conflict, the categorization of persons during conflict, targeting, detention, criminal liability, and fair trial. Thus, terrorist and counter-terrorist violence may constitute a non-international armed conflict (NIAC) to which IHL applies if the violence is sufficiently intense and organized. The chapter then considers three key legal issues of particular relevance and specificity to terrorism in armed conflict.
Effect of comorbidities on survival in patients &gt;80 years of age at onset of renal replacement therapy: data from the ERA-EDTA Registry
Authors: Helve Jaakko , Kramer Anneke , Abad Diez Jose Maria , Aresté-Fosalba Nuria , Arici Mustafa , Cases Aleix , Collart Frederic , Heaf James , De Meester Johan , Nordio Maurizio , Palsson Runolfur , Pobes Alfonso , Rydell Helena , Reisæter Anna Varberg , Massy Ziad A , Jager Kitty J , Finne Patrik 
Published: October 2020

Abstract

Background
The number of elderly patients on renal replacement therapy (RRT) is increasing. The survival and quality of life of these patients may be lower if they have multiple comorbidities at the onset of RRT. The aim of this study was to explore whether the effect of comorbidities on survival is similar in elderly RRT patients compared with younger ones.

Methods
Included were 9333 patients ≥80 years of age and 48 352 patients 20–79 years of age starting RRT between 2010 and 2015 from 15 national or regional registries submitting data to the European Renal Association–European Dialysis and Transplantation Association Registry. Patients were followed until death or the end of 2016. Survival was assessed by Kaplan–Meier curves and the relative risk of death associated with comorbidities was assessed by Cox regression analysis.

Results
Patients ≥80 years of age had a greater comorbidity burden than younger patients. However, relative risks of death associated with all studied comorbidities (diabetes, ischaemic heart disease, chronic heart failure, cerebrovascular disease, peripheral vascular disease and malignancy) were significantly lower in elderly patients compared with younger patients. Also, the increase in absolute mortality rates associated with an increasing number of comorbidities was smaller in elderly patients.

Conclusions
Comorbidities are common in elderly patients who enter RRT, but the risk of death associated with comorbidities is less than in younger patients. This should be taken into account when assessing the prognosis of elderly RRT patients.