bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human Rights
Authors: Muchlinski Peter T 
Published: March 2021

Abstract
This chapter evaluates another element of corporate social responsibility (CSR) applicable to multinational enterprises (MNEs): human rights. Historically, human rights have been used by corporations to protect their vital interests against state action, leading to human/civil rights protections for corporations. The chapter focuses on how far MNEs, and other business actors, should be responsible for human rights violations. This has been significantly influenced by the UN Guiding Principles on Business and Human Rights (UNGPs), endorsed in June of 2011 by the UN Human Rights Council, which implement the UN ‘Protect, Respect and Remedy’ framework. The UNGPs have created a framework for business and human rights that covers three pillars: the state duty to protect human rights, the corporate responsibility to respect human rights and access to remedy. The chapter then traces the development of concern for business and human rights, and discusses the justifications for holding businesses accountable for human rights violations, the establishment of business and human rights on the agenda of the UN and the principal areas in which business violations of human rights arise.
Investor–State Dispute Settlement
Authors: Muchlinski Peter T 
Published: March 2021

Abstract
This chapter studies investor–state dispute settlement (ISDS) in International Investment Agreements (IIAs), the primary method of which is investor–state arbitration. It outlines the nature of investor–state disputes and the main types of dispute settlement techniques. The chapter also considers the principal characteristics of investor–state arbitration and examines arbitration under the Washington Convention on Settlement of Investment Disputes between States and Nationals of Other States 1965 (the ICSID Convention), which established the International Centre for Settlement of Investment Disputes (ICSID). Most Bilateral Investment Treaties (BITs) refer to ICSID arbitration as the sole, or optional, method of dispute settlement. ICSID Tribunals have acted in a wide range of disputes, adopting expansive interpretations of personal and subject-matter jurisdiction. This has led to criticism that investor–state arbitration has become too pervasive and a threat to the states’ ‘right to regulate’, given the risk of high procedural costs and compensation. ‘New-generation’ IIAs have responded by limiting the jurisdiction of tribunals over investment disputes. Moreover, recourse to alternative dispute resolution (ADR) and dispute avoidance techniques is being encouraged. The United Nations Commission on International Trade Law (UNCITRAL) has also taken up ISDS reform and is in the process of formulating a multilateral reform package.
Introduction
Authors: Fleck Dieter 
Published: March 2021

Abstract
This introductory chapter provides an overview of international humanitarian law. During the past decades, international humanitarian law has been subject to a progressive development which culminated in the four 1949 Geneva Conventions, the 1977 Protocols Additional to these Conventions, the 1980 Weapons Convention, the 1993 Chemical Weapons Convention, and the 1998 Rome Statute of the International Criminal Court. While many efforts have been made by states to implement their obligations under international humanitarian law, much work remains to be done at international and national levels. This task poses a challenge to political decision-makers and to their legal and military advisers, many of whom must shoulder this workload in addition to other duties and in spite of the pressure of other priorities. Recent achievements of worldwide co-operation in this field are manifold: The interrelationship between humanitarian law and the protection of human rights in armed conflicts is largely accepted and better understood today than ever before. A progressive development of international criminal law has led to increased jurisprudence on war crimes and crimes against humanity by national courts, international ad hoc tribunals, and finally to the establishment of the International Criminal Court (ICC).
Protection of Civilians
Authors: Fleck Dieter 
Published: March 2021

Abstract
This chapter assesses the provisions of international law concerning the protection of civilians in armed conflict. The rules applicable in international armed conflict are highly developed and extensively codified. Of course, their scope of application is limited to conflicts of an international character, in particular armed clashes between states. Situations of foreign occupation are also international armed conflicts. The four Geneva Conventions, supplemented by their first 1977 Additional Protocol, constitute the heart of protections granted to civilians in international armed conflicts. Meanwhile, the law protecting civilians in non-international armed conflicts has been codified by Article 3 common to the four Geneva Conventions and the second 1999 Additional Protocol. Although these provisions are more summary in nature than the law on international armed conflicts, they contain important rules on the protection of civilians in an internal conflict. The chapter then considers the provisions concerning situations in which a party to an armed conflict comes into contact with civilians of the opposing side, especially with aliens on its own territory and with inhabitants of occupied territories.
Implementation and Enforcement of International Humanitarian Law
Authors: Fleck Dieter 
Published: March 2021

Abstract
This chapter deals with the most important and at the same time most challenging part of international humanitarian law, as it describes and evaluates national and international measures to ensure implementation and compliance with existing rules and to provide remedies for violations. One necessary condition for the effective implementation of humanitarian law is that its contents are known by persons involved in a conflict, especially the combatants, that those persons are aware that violations carry disciplinary or penal consequences, and that they realize that persistent breaches may lead to an escalation of the conflict. In this regard, compliance with humanitarian law is in the interest of every individual party to an armed conflict. Highlighting long-lasting legal developments which have eventually led to a strengthening of national and international criminal jurisdiction on war crimes and crimes against humanity, the chapter explores the legal obligations of states and international organizations and appropriate measures to implement existing obligations, to prevent any violations, and take effective action where breaches are committed. It also reflects on the continuing increase of relevant jurisprudence and policymaking by intergovernmental and other organizations in recent years.
Rights of the Reinsurer
Authors: Edelman Colin , Burns Andrew 
Published: March 2021

Abstract
This chapter details the rights of the reinsurer, one of which is the payment of premium. The premium is the consideration for the contract which proceeds from the reinsured to the reinsurer in return for coverage according to the policy terms. A reinsurer has the right to treat the contract of reinsurance as discharged upon non-payment of the premium if the contract contains an express right to cancel for non-payment of premium. In the absence of such an express clause, cancellation may be justified if it is an implied condition of the contract that the premium would be paid in advance or on the grounds that the reinsured has repudiated the contract by evincing an intention not to pay the premium. Meanwhile, a reinsurer can circumscribe the power of the reinsured to make settlements or other decisions which are binding on it by the use of a claims co-operation clause. A claims control clause gives a reinsurer even more influence in the handling of the original claim by the underlying insured. The chapter then looks at the right of the reinsurer to inspect the reinsured’s records; to declaratory relief; and to subrogation.
Structural phylogenetic analysis reveals lineage-specific RNA repetitive structural motifs in all coronaviruses and associated variations in SARS-CoV-2
Authors: Chen Shih-Cheng , Olsthoorn René C L , Yu Chien-Hung 
Published: March 2021

Abstract
In many single-stranded (ss) RNA viruses, the cis-acting packaging signal that confers selectivity genome packaging usually encompasses short structured RNA repeats. These structural units, termed repetitive structural motifs (RSMs), potentially mediate capsid assembly by specific RNA–protein interactions. However, general knowledge of the conservation and/or the diversity of RSMs in the positive-sense ssRNA coronaviruses (CoVs) is limited. By performing structural phylogenetic analysis, we identified a variety of RSMs in nearly all CoV genomic RNAs, which are exclusively located in the 5′-untranslated regions (UTRs) and/or in the inter-domain regions of poly-protein 1ab coding sequences in a lineage-specific manner. In all alpha- and beta-CoVs, except for Embecovirus spp, two to four copies of 5′-gUUYCGUc-3′ RSMs displaying conserved hexa-loop sequences were generally identified in Stem-loop 5 (SL5) located in the 5′-UTRs of genomic RNAs. In Embecovirus spp., however, two to eight copies of 5′-agc-3′/guAAu RSMs were found in the coding regions of non-structural protein (NSP) 3 and/or NSP15 in open reading frame (ORF) 1ab. In gamma- and delta-CoVs, other types of RSMs were found in several clustered structural elements in 5′-UTRs and/or ORF1ab. The identification of RSM-encompassing structural elements in all CoVs suggests that these RNA elements play fundamental roles in the life cycle of CoVs. In the recently emerged SARS-CoV-2, beta-CoV-specific RSMs are also found in its SL5, displaying two copies of 5′-gUUUCGUc-3′ motifs. However, multiple sequence alignment reveals that the majority of SARS-CoV-2 possesses a variant RSM harboring SL5b C241U, and intriguingly, several variations in the coding sequences of viral proteins, such as Nsp12 P323L, S protein D614G, and N protein R203K-G204R, are concurrently found with such variant RSM. In conclusion, the comprehensive exploration for RSMs reveals phylogenetic insights into the RNA structural elements in CoVs as a whole and provides a new perspective on variations currently found in SARS-CoV-2.
Illness Perceptions, Disabilities, and Quality of Life of Patients With Hand Injury: A Prospective Study
Authors: Chen Ying-Ying , Yang Cheng-San , Lee Bih-O 
Published: March 2021

Background:
Few studies have tracked hand injury patients past the acute care period. Postdischarge tracking of hand injury patients may identify time points most patients require assistance, which can help direct interventions to reduce post–hand injury sequelae.

Objective:
To examine hand injury patients' experiences during early recovery to illness perceptions, disabilities, and quality of life and to identify predictors of quality of life at 1 month and 3 months after hospital discharge.

Methods:
This prospective observational study of hand injury patients was performed at a teaching hospital in Taiwan. Data were collected at patient discharge, 1 month, and 3 months after discharge, from January 2017 to October 2018. The variables measured included illness perceptions, disabilities, and quality of life.

Results:
A total of 117 patients participated in the study. The patients reported more positive illness perceptions at 3 months versus 1 month after discharge. The impact of disabilities on patient work was significantly greater at 1 month than at 3 months after discharge. Quality of life was better at 3 months than at 1 month after discharge. Predictors of quality of life after hospital discharge were demographic variables, clinical variables, and illness perceptions. Patients with lower education reported poorer psychological quality of life after discharge.

Conclusion:
Primary care providers should perform a comprehensive assessment of patients prior to their discharge. Patients should undergo regular follow-ups to reduce comorbidities and improve their outcomes.
The impact of paternal alcohol, tobacco, caffeine use and physical activity on offspring mental health: A systematic review and meta-analysis
Authors: Easey Kayleigh E , Sharp Gemma C 
Published: March 2021

AbstractBackgroundThere is some evidence that paternal health behaviours during and around pregnancy could be associated with offspring health outcomes. However, the impact that paternal health behaviours during pregnancy can have on offspring mental health is understudied and remains unclear.MethodsWe conducted a systematic review and meta-analysis of articles in PubMed describing studies of potentially modifiable paternal health behaviours (tobacco smoking, alcohol consumption, caffeine consumption and physical activity) in the prenatal period in relation to offspring mental health.ResultsTen studies were included and categorized by paternal health behaviour and offspring mental health outcome investigated. The narrative synthesis provided evidence of association between paternal health behaviours around pregnancy and offspring mental health problems, with the strongest evidence shown for tobacco use. Grouped by analysis type, two separate meta-analyses showed evidence of paternal smoking during pregnancy being associated with greater odds of ADHD in offspring (OR 1.42, 95% CI 1.02 to 1.99; HR 1.28, 95% CI 1.19 to 1.39).ConclusionsOur review suggests that paternal tobacco smoking and alcohol consumption in the prenatal period are associated with poorer offspring mental health, particularly hyperactivity/ADHD. Future investigation using methods that allow stronger causal inference is needed to further investigate if these associations are causal.
Maternal Levels of Acute Phase Proteins in Early Pregnancy and Risk of Autism Spectrum Disorders in Offspring
Authors: Brynge Martin , Gardner Renee M , Sjöqvist Hugo , Karlsson Håkan , Dalman Christina 
Published: March 2021

AbstractPrevious research supports a contribution of early-life immune disturbances in the etiology of autism spectrum disorders (ASD). Biomarker studies of the maternal innate (non-adaptive) immune status related to ASD risk have focused on one of the acute phase proteins (APP), C-reactive protein (CRP), with conflicting results. We evaluated levels of eight different APP in maternal serum samples drawn in first trimester, from 318 mothers to ASD-cases and 429 mothers to ASD-unaffected controls, nested within the register-based Stockholm Youth Cohort. Overall, we found no general trend of high levels of maternal APP being associated with increased risk of ASD. In contrast, maternal levels of CRP in the lowest compared to the middle tertile were associated with increased risk of ASD without ID or ADHD in offspring (OR = 2.15, 95 % CI 1.17-3.93). Further, levels of maternal ferritin in the lowest (OR = 1.82, 95 % CI 1.19-2.78) and highest (OR = 1.74, 95 % CI 1.16-2.60) tertiles were associated with increased risk of any ASD diagnosis in offspring, with stronger associations still between the lowest (OR = 3.58, 95 % CI 1.79-7.17) and highest (OR = 3.20, 95 % CI 1.62-6.29) tertiles of ferritin and risk of ASD with ID. The biological interpretation of lower CRP-levels among mothers to ASD-cases is not clear but might be related to the function of the maternal innate immune system. The finding of aberrant levels of ferritin conferring risk of ASD-phenotypes indicates a plausibly important role of iron during neurodevelopment.
Characterization of the neurogenic niche in the aging dentate gyrus using iterative immunofluorescence imaging
Authors: Cole John Darby , del Castillo Jacobo Sarabia , Gut Gabriele , Gonzalez-Bohorquez Daniel , Pelkmans Lucas , Jessberger Sebastian 
Published: March 2021

AbstractAdvancing age causes reduced hippocampal neurogenesis, associated with age-related cognitive decline. The spatial relationship of age-induced alterations in neural stem cells (NSCs) and surrounding cells within the hippocampal niche remains poorly understood due to limitations of antibody-based cellular phenotyping. We established iterative indirect immunofluorescence imaging (4i) in tissue sections, allowing for simultaneous detection of 18 proteins to characterize NSCs and surrounding cells in young and aged mice. We show that reorganization of the DG niche already occurs in middle-aged mice, paralleling the decline in neurogenesis. Tissue 4i-based analysis of the DG identifies changes in cell-type contributions to the blood brain barrier and microenvironments surrounding NSCs to play a pivotal role to preserve neurogenic permissiveness. The data provided represent a resource to characterize the principles causing alterations of stem cell-associated plasticity within the aging DG and provide a blueprint to analyze somatic stem cell niches across lifespan in complex tissues.
Comparison of Chronic Wasting Disease Detection Methods and Procedures: Implications for Free-Ranging White-Tailed Deer (Odocoileus Virginianus) Surveillance and Management
Authors: Schwabenlander Marc D. , Rowden Gage R. , Li Manci , LaSharr Kelsie , Hildebrand Erik C. , Stone Suzanne , Seelig Davis M. , Jennelle Chris S. , Cornicelli Louis , Wolf Tiffany M. , Carstensen Michelle , Larsen Peter A. 
Published: March 2021

ABSTRACTThroughout North America, chronic wasting disease (CWD) has emerged as perhaps the greatest threat to wild cervid populations, including white-tailed deer (Odocoileus virginianus). White-tailed deer are the most sought after big game species across North America with populations of various subspecies in nearly all Canadian provinces, the contiguous USA, and Mexico. Documented CWD cases have dramatically increased across the white-tailed deer range since the mid-1990s, including in Minnesota. CWD surveillance in free-ranging white-tailed deer and other cervid populations mainly depends upon immunodetection methods (e.g., immunohistochemistry [IHC] and enzyme-linked immunosorbent assay [ELISA]) on medial retropharyngeal lymph nodes and obex. More recent technologies centered on prion protein amplification methods of detection have shown promise as more sensitive and rapid CWD diagnostic tools. Here, we used blinded samples to test the efficacy of real time quaking-induced conversion (RT-QuIC) in comparison to ELISA and IHC for screening tissues, blood, and feces collected in 2019 from white-tailed deer in southeastern Minnesota, where CWD has been routinely detected since 2016. Our results support previous findings that RT-QuIC is a more sensitive tool for CWD detection than current antibody-based methods. Additionally, a CWD testing protocol that includes multiple lymphoid tissues (medial retropharyngeal lymph node, parotid lymph node, and palatine tonsil) per animal may effectively identify a greater number of CWD detections in a white-tailed deer population than a single sample type (i.e., medial retropharyngeal lymph nodes). These results reveal that the variability of CWD pathogenesis, sampling protocol, and testing platform must be considered for the effective detection and management of CWD throughout North America.
Landscape connectivity alters the evolution of density-dependent dispersal during pushed range expansions
Authors: Dahirel Maxime , Bertin Aline , Calcagno Vincent , Duraj Camille , Fellous Simon , Groussier Géraldine , Lombaert Eric , Mailleret Ludovic , Marchand Anaël , Vercken Elodie 
Published: March 2021

AbstractAs human influence reshapes communities worldwide, many species expand or shift their ranges as a result, with extensive consequences across levels of biological organization. Range expansions can be ranked on a continuum going from pulled dynamics, in which low-density edge populations provide the “fuel” for the advance, to pushed dynamics in which high-density rear populations “push” the expansion forward. While theory suggests that evolution during range expansions could lead pushed expansions to become pulled with time, empirical comparisons of phenotypic divergence in pushed vs. pulled contexts are lacking. In a previous experiment usingTrichogramma brassicaewasps as a model, we showed that expansions were more pushed when connectivity was lower. Here we used descendants from these experimental landscapes to look at how the range expansion process and connectivity interact to shape phenotypic evolution. Interestingly, we found no clear and consistent phenotypic shifts, whether along expansion gradients or between reference and low connectivity replicates, when we focused on low-density trait expression. However, we found evidence of changes in density-dependence, in particular regarding dispersal: populations went from positive to negative density-dependent dispersal at the expansion edge, but only when connectivity was high. As positive density-dependent dispersal leads to pushed expansions, our results confirm predictions that evolution during range expansions may lead pushed expansions to become pulled, but add nuance by showing landscape conditions may slow down or cancel this process. This shows we need to jointly consider evolution and landscape context to accurately predict range expansion dynamics and their consequences.
Cooperative regulation of coupled oncoprotein translation and stability in triple-negative breast cancer by EGFR and CDK12
Authors: Ang Hazel X. , Sutiman Natalia , Deng Xinyue L. , Bartelt Luke C. , Chen Qiang , Barrera Alejandro , Lin Jiaxing , Sheng Jeff , McDowell Ian C. , Reddy Timothy E. , Nicchitta Christopher V. , Wood Kris C. 
Published: March 2021

SUMMARYEvidence has long suggested that epidermal growth factor receptor (EGFR) may play a prominent role in triple-negative breast cancer (TNBC) pathogenesis, but clinical trials of EGFR inhibitors have yielded disappointing results. Using a candidate drug screen, we discovered that inhibition of CDK12 dramatically sensitizes diverse models of TNBC to EGFR blockade. Instead of functioning through CDK12’s well-established roles proximal to transcription, this combination therapy drives cell death through the 4E-BP1-dependent suppression of the translation and consequent stability of driver oncoproteins, including MYC. A genome-wide CRISPR/Cas9 screen identified the CCR4-NOT complex as a major determinant of sensitivity to the combination therapy whose loss renders 4E-BP1 unresponsive to drug-induced dephosphorylation, rescuing MYC translational suppression and stability. The central roles of CCR4-NOT and 4E-BP1 in response to the combination therapy were further underscored by the observation of CNOT1 loss and rescue of 4E-BP1 phosphorylation in TNBC cells that naturally evolved therapy resistance. Thus, pharmacological inhibition of CDK12 reveals a long proposed EGFR dependence in TNBC that functions through the cooperative regulation of translation-coupled oncoprotein stability.
Spt4 Facilitates the Movement of RNA Polymerase II through the +2 Nucleosomal Barrier
Authors: Uzun Ülkü , Brown Thomas , Fischl Harry , Angel Andrew , Mellor Jane 
Published: March 2021

AbstractSpt4 is a transcription elongation factor, with homologues in organisms with nucleosomes. Structural andin vitrostudies implicate Spt4 in transcription through nucleosomes, yet thein vivofunction of Spt4 is unclear. Here we assessed the precise position of Spt4 during transcription and the consequences of loss of Spt4 on RNA polymerase II (RNAPII) dynamics and nucleosome positioning inSaccharomyces cerevisiae. In the absence of Spt4, the spacing between gene-body nucleosomes increases and RNAPII accumulates upstream of the nucleosomal dyad, most dramatically at nucleosome +2. Spt4 associates with elongating RNAPII early in transcription and its association dynamically changes depending on nucleosome positions. Together, our data show that Spt4 regulates early elongation dynamics, participates in co-transcriptional nucleosome positioning, and promotes RNAPII movement through the gene-body nucleosomes, especially the +2 nucleosome.