bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diagnosis and management of segmental volvulus of the jejunoileum in a first lactation Flekvieh heifer
Authors: Ridgway Rachel , Ghirello Gabriele , Gillespie Amy 
Published: April 2021

AbstractA three‐year‐old first lactation Flekvieh heifer was presented with sudden milk drop, anorexia and absence of faeces in the rectum after being perceived as fit and healthy the day before. Following medical treatment and close monitoring, an exploratory laparotomy was performed and a segmental volvulus of part of the small intestine was identified. Successful treatment involved relieving the intestinal distension and untwisting the intestine. This case was interesting as the cow showed minimal outward signs of discomfort and cardiovascular compromise with intestinal volvulus.
(Im)mobility Patterns among Polish Unemployed Migrants in Iceland Navigating Different Welfare Regimes
Authors: Wojtyńska Anna , Skaptadóttir Unnur Dís 
Published: April 2021

AbstractBased on fieldwork among unemployed Polish migrants in Iceland, this chapter examines how they negotiate and adapt to the social risks and changing circumstances encountered in the countries of emigration and immigration as well as how they navigate the available ‘resource environments’ emerging in conjunction with different welfare regimes. We particularly look at the European Union (EU) regulations for social-security protection vis-à-vis national welfare-protection policies on unemployment in Iceland and Poland and their possible ramifications for the mobility and immobility of Polish workers. Furthermore, we highlight some problematic interactions between the internationalisation of the labour market and concomitant transnational livelihoods, EU social policy and the welfare-assistance environment of member states. In so doing, we apply a critical approach to the commonly assumed high flexibility and extensive geographical mobility of migrant workers that tends to overlook counterfactors that influence different forms of immobility.
Teaching the World Court Makes a Bad Case: Revisiting the Relationship Between Domestic Courts and the ICJ
Authors: Kunz Raffaela 
Published: April 2021

AbstractSentenza238/2014 once more highlights the important role domestic courts play in international law. More than prior examples, it illustrates the ever more autonomous and self-confident stance of domestic courts on the international plane. But the ruling of the Italian Constitutional Court (ItCC) also shows that more engagement with international law does not necessarily mean that domestic courts enhance the effectiveness of international law and become ‘compliance partners’ of international courts.Sentenza238/2014 suggests that domestic courts, in times of global governance and increased activity of international courts, see the role they play at the intersection of legal orders also as ‘gate-keepers’, ready to cushion the domestic impact of international law if deemed necessary. The judgment of the ItCC thus offers a new opportunity to examine the multifaceted and complex role of these important actors that apply and shape international law, while always remaining bound by domestic (constitutional) law. This chapter does so by exploring how domestic courts deal with rulings of the World Court. It shows that despite the fact that in numerous situations domestic courts could act as compliance partners of the International Court of Justice, in reality, more often than not, they have refused to do so, arguing that its judgments are not self-executing and thus deferring the implementation to the political branches. Assessing this practice, the chapter argues that domestic courts should take a more active stance and overcome the purely interstate view that seems at odds with present-day international law. While it seems too far-reaching to expect domestic courts to follow international courts unconditionally, the chapter cautions that there is a considerable risk of setting dangerous precedents by openly defying international judgments. Domestic courts should carefully balance the different interests at stake, namely an effective system of international adjudication on the one hand and the protection of fundamental domestic principles on the other hand. The chapter finds that the ItCC’s attempt to reintroduce clear boundaries between legal orders lacks the openness and flexibility needed to effectively cope with today’s complex and plural legal reality.
Between a Rock and a Hard Place: Italian Concerns Between Constitutional Rights and International Law
Authors: Paulus Andreas L. 
Published: April 2021

AbstractSentenza 238/2014 has led to a sharp dissonance between the international law of state immunity as interpreted by the International Court of Justice (ICJ) and Italian constitutional law as understood and applied by the Corte Costituzionale. While the interpretation and application by the Italian Constitutional Court (ItCC) of the access-to-courts provision in the Italian Constitution may not have been inevitable, this does not remove the need for finding a solution to the stalemate between international and domestic law. On the one hand, the easy solution, namely that the rejection of German state immunity from jurisdiction does not necessarily remove immunity from execution into German property, appears unlikely to be accepted by the ItCC because it would give stones rather than bread to the complainants and render court access a futile exercise. On the other hand, bringing Sentenza to its logical conclusion would result in Italy having to return to Germany what Italian courts took from her by requiring compensation—either by way of the general international law of restitutio in integrum, which the Corte Costituzionale has neither contemplated nor contradicted, or by way of the 1961 Treaty between Germany and Italy in which Italy promises to indemnify Germany against any further claims. Thus, a compromise would have to distinguish between full access to the Italian courts notwithstanding international immunity—as required by the ItCC—and substantive law, which could accept a more symbolical recognition of the suffering of the victims. That recognition could stem from a direct source other than the two states involved, such as a common fund, and address only the small group of immediate victims who were unjustly, if arguably legally, excluded from the previous compensation scheme of the 1960s. It is by no means certain, however, whether such an outcome would be acceptable to all sides—including the Corte itself. Thus, legal certainty would have to be established as quickly as possible so that the victims can still receive at least symbolic compensation.
Overcoming the Judicial Conundrum: The Road to a Diplomatic Solution
Authors: Francioni Francesco 
Published: April 2021

AbstractThe role of international law and of international lawyers is at its best when it results in a ‘work of reconciliation and realistic construction’ (Dag Hammarskjöld, 1953). Unfortunately, it is difficult to find much of this spirit in the unfolding, regrettable and never-ending saga of Germany versus Italy. In answering the basic question of whether Germany is obliged to negotiate a settlement with Italy, this chapter argues that even if there is no hard and fast legal obligation, there is a political and moral obligation to negotiate a settlement, as indicated by paragraph 104 of the Jurisdictional Immunities Judgment of the International Court of Justice (ICJ); the same obligation is incumbent upon Italy. The current legal ‘black hole’ cannot be filled by further proceedings before the ICJ because immunity serves the value of the equality of states, yet equality is not a value in its own sake but is functional to the preservation of peaceful and orderly international relations and to the ‘realistic construction’ of conditions for the fulfilment of human rights. Negotiations in view of the creation of a joint German–Italian fund for the reparation of victims is the appropriate way to overcome the present impasse and to do justice to a whole class of victims who so far have fallen into oblivion.
State Immunity, Individual Compensation for Victims of Human Rights Crimes, and Future Prospects
Authors: Kadelbach Stefan 
Published: April 2021

AbstractThis chapter first recapitulates the state of affairs as to the principle of state immunity and why exceptions from jurisdictional immunity for gross violations of human rights and humanitarian law are not recognized. It explores customary law and the global compensation treaty between Germany and Italy. Both indicate that Italy would be obligated to indemnify Germany from individual claims raised before Italian courts.In a second step, the development towards individual rights in public international law will be taken up. It appears that human beings are increasingly recognized as holders of individual claims but, apart from human rights treaty systems, lack the capacity under international law to invoke their rights before courts. Instead, they depend on their home states, which have standing but are not entitled to waive the individual rights of their citizens.In order to reconcile the seemingly antagonistic regimes of state immunity and claim settlement, prospects for a friendly solution of the present dilemma will be assessed. Against the background of cases pending before Italian courts, it will be examined whether the distinction between jurisdictional immunity and immunity from execution opens up a way out of the impasse, which the two states and private capital could pursue, and whether this solution would create a precedent for other similar constellations.Lastly, some concluding remarks will address lessons to be learnt for future conflicts. They will deal with elements of a general regime of compensation, drawing from the experience of both past reparation schemes and the experience of reconciliation in post-totalitarian societies. Such elements could be a duty to seek bona fide settlements, possible consequences of violations for domestic court proceedings, methods of assessing damages inspired by mass claim processing, the categorization of claims according to the gravity of violations, rules on evaluating evidence, procedures to give victims a say, and appropriate forms of monetary and non-pecuniary compensation including the necessary institutional framework.
On rational points in CFT moduli spaces
Authors: Benjamin Nathan , Keller Christoph A. , Ooguri Hirosi , Zadeh Ida G. 
Published: April 2021

Abstract
Motivated by the search for rational points in moduli spaces of two-dimensional conformal field theories, we investigate how points with enhanced symmetry algebras are distributed there. We first study the bosonic sigma-model with S1 target space in detail and uncover hitherto unknown features. We find for instance that the vanishing of the twist gap, though true for the S1 example, does not automatically follow from enhanced symmetry points being dense in the moduli space. We then explore the supersymmetric sigma-model on K3 by perturbing away from the torus orbifold locus. Though we do not reach a definite conclusion on the distribution of enhanced symmetry points in the K3 moduli space, we make several observations on how chiral currents can emerge and disappear under conformal perturbation theory.
Neugeborenenscreening auf spinale Muskelatrophie
Authors: Müller-Felber W. , Vill K. , Schwartz O. , Blaschek A. , Nennstiel U. , Schara U. , Hoffmann G. F. , Gläser D. , Becker M. , Röschinger W. , Bernert G. , Klein A. , Kölbel H. 
Published: April 2021

ZusammenfassungIm Dezember 2020 hat der Gemeinsame Bundesausschuss beschlossen, dass das Screening auf spinale Muskelatrophie (SMA) in das allgemeine Neugeborenenscreening aufgenommen werden soll. Grundlage dieser Entscheidung war die Tatsache, dass inzwischen gezielte Behandlungsmöglichkeiten für die Patienten mit SMA zur Verfügung stehen und der Zeitpunkt, zu dem die Behandlung begonnen wird, entscheidend für den Erfolg der Therapie ist.Das Neugeborenenscreening auf eine SMA basiert auf dem Nachweis einer homozygoten Deletion von Exon 7 im SMN1-Gen durch eine molekulargenetische Analyse aus der Trockenblutkarte. In allen Fällen muss eine Bestätigungsdiagnostik aus einer zweiten Blutprobe im Rahmen der Konfirmationsdiagnostik mit Bestimmung der SMN2-Kopien-Zahl durchgeführt werden. Die weitere Beratung und Therapie sollten in einer neuropädiatrischen Ambulanz mit Erfahrung in der Betreuung von Kindern mit SMA erfolgen.
Analysis of overlapping genetic association in type 1 and type 2 diabetes
Authors: Inshaw Jamie R. J. , Sidore Carlo , Cucca Francesco , Stefana M. Irina , Crouch Daniel J. M. , McCarthy Mark I. , Mahajan Anubha , Todd John A. 
Published: April 2021

Abstract
Aims/hypothesis
Given the potential shared aetiology between type 1 and type 2 diabetes, we aimed to identify any genetic regions associated with both diseases. For associations where there is a shared signal and the allele that increases risk to one disease also increases risk to the other, inference about shared aetiology could be made, with the potential to develop therapeutic strategies to treat or prevent both diseases simultaneously. Alternatively, if a genetic signal co-localises with divergent effect directions, it could provide valuable biological insight into how the association affects the two diseases differently.

Methods
Using publicly available type 2 diabetes summary statistics from a genome-wide association study (GWAS) meta-analysis of European ancestry individuals (74,124 cases and 824,006 controls) and type 1 diabetes GWAS summary statistics from a meta-analysis of studies on individuals from the UK and Sardinia (7467 cases and 10,218 controls), we identified all regions of 0.5 Mb that contained variants associated with both diseases (false discovery rate <0.01). In each region, we performed forward stepwise logistic regression to identify independent association signals, then examined co-localisation of each type 1 diabetes signal with each type 2 diabetes signal using coloc. Any association with a co-localisation posterior probability of ≥0.9 was considered a genuine shared association with both diseases.

Results
Of the 81 association signals from 42 genetic regions that showed association with both type 1 and type 2 diabetes, four association signals co-localised between both diseases (posterior probability ≥0.9): (1) chromosome 16q23.1, near CTRB1/BCAR1, which has been previously identified; (2) chromosome 11p15.5, near the INS gene; (3) chromosome 4p16.3, near TMEM129 and (4) chromosome 1p31.3, near PGM1. In each of these regions, the effect of genetic variants on type 1 diabetes was in the opposite direction to the effect on type 2 diabetes. Use of additional datasets also supported the previously identified co-localisation on chromosome 9p24.2, near the GLIS3 gene, in this case with a concordant direction of effect.

Conclusions/interpretation
Four of five association signals that co-localise between type 1 diabetes and type 2 diabetes are in opposite directions, suggesting a complex genetic relationship between the two diseases.

Graphical abstract
Modeling human tumor-immune environments in vivo for the preclinical assessment of immunotherapies
Authors: Bareham Bethany , Georgakopoulos Nikitas , Matas-Céspedes Alba , Curran Michelle , Saeb-Parsy Kourosh 
Published: April 2021

AbstractDespite the significant contributions of immunocompetent mouse models to the development and assessment of cancer immunotherapies, they inadequately represent the genetic and biological complexity of corresponding human cancers. Immunocompromised mice reconstituted with a human immune system (HIS) and engrafted with patient-derived tumor xenografts are a promising novel preclinical model for the study of human tumor-immune interactions. Whilst overcoming limitations of immunocompetent models, HIS-tumor models often rely on reconstitution with allogeneic immune cells, making it difficult to distinguish between anti-tumor and alloantigen responses. Models that comprise of autologous human tumor and human immune cells provide a platform that is more representative of the patient immune-tumor interaction. However, limited access to autologous tissues, short experimental windows, and poor retention of tumor microenvironment and tumor infiltrating lymphocyte components are major challenges affecting the establishment and application of autologous models. This review outlines existing preclinical murine models for the study of immuno-oncology, and highlights innovations that can be applied to improve the feasibility and efficacy of autologous models.
Crustal variability along the rifted/sheared East African margin: a review
Authors: Vormann Maren , Jokat Wilfried 
Published: April 2021

AbstractThe East African margin between the Somali Basin in the north and the Natal Basin in the south formed as a result of the Jurassic/Cretaceous dispersal of Gondwana. While the initial movements between East and West Gondwana left (oblique) rifted margins behind, the subsequent southward drift of East Gondwana from 157 Ma onwards created a major shear zone, the Davie Fracture Zone (DFZ), along East Africa. To document the structural variability of the DFZ, several deep seismic lines were acquired off northern Mozambique. The profiles clearly indicate the structural changes along the shear zone from an elevated continental block in the south (14°–20°S) to non-elevated basement covered by up to 6-km-thick sediments in the north (9°–13°S). Here, we compile the geological/geophysical knowledge of five profiles along East Africa and interpret them in the context of one of the latest kinematic reconstructions. A pre-rift position of the detached continental sliver of the Davie Ridge between Tanzania/Kenya and southeastern Madagascar fits to this kinematic reconstruction without general changes of the rotation poles.
Unusual mechanical failures of intrathecal baclofen pump systems: symptoms, signs, and trouble shooting
Authors: Gburek-Augustat Janina , Krause Matthias , Bernhard Matthias , Sorge Ina , Gräfe Daniel , Siekmeyer Manuela , Nestler Ulf , Merkenschlager Andreas 
Published: April 2021

Abstract
Introduction
Although intrathecal baclofen (ITB) therapy is an effective treatment for spasticity, it has several disadvantages and a risk of complications.

Methods
We present six pediatric patients who suffered from unusual mechanical failures of intrathecal baclofen pump systems.

Results
With these case-vignettes, we provide a systematic approach on how to interpret the symptoms of ITB complications and an advice which further diagnostic and therapeutic steps to follow. We underline the seriousness of baclofen overdose, underdosing or withdrawal.
Tau strains shape disease
Authors: Vaquer-Alicea Jaime , Diamond Marc I. , Joachimiak Lukasz A. 
Published: April 2021

AbstractTauopathies consist of over 25 different neurodegenerative diseases that include argyrophilic grain disease (AGD), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and Pick’s disease (PiD). Tauopathies are defined by brain accumulation of microtubule-associated protein tau in fibrillar aggregates, whose prevalence strongly correlates with dementia. Dominant mutations in tau cause neurodegenerative diseases, and most increase its aggregation propensity. Pathogenesis of tauopathies may involve pathological tau conformers that serve as templates to recruit native protein into growing assemblies and also move between brain cells to cause disease progression, similar to prions. Prions adopt pathological conformations, termed “strains,” that stably propagate in living systems, and create unique patterns of neuropathology. Data from multiple laboratories now suggest that tau acts as a prion. It propagates unique strains indefinitely in cultured cells, and when these are inoculated into mouse models, they create defined neuropathological patterns, which establish a direct link between conformation and disease. In humans, distinct fibril structures are associated with different diseases, but causality has not been established as in mice. Cryo-EM structures of tau fibrils isolated from tauopathy brains reveal distinct fibril cores across disease. Interestingly, the conformation of the tau monomer unit within different fibril subtypes from the same patient appears relatively preserved. This is consistent with data that the tau monomer samples an ensemble of conformations that act as distinct pathologic templates in the formation of restricted numbers of strains. The propensity of a tau monomer to adopt distinct conformations appears to be linked to defined local motifs that expose different patterns of amyloidogenic amino acid sequences. The prion hypothesis, which predicts that protein structure dictates resultant disease, has proved particularly useful to understand the diversity of human tauopathies. The challenge now is to develop methods to rapidly classify patients according to the structure of the underlying pathological protein assemblies to achieve more accurate diagnosis and effective therapy.
Importance of evaluating protein glycosylation in pluripotent stem cell-derived cardiomyocytes for research and clinical applications
Authors: Kelly Maia I. , Albahrani Mustafa , Castro Chase , Poon Ellen , Yan Bin , Littrell Jack , Waas Matthew , Boheler Kenneth R. , Gundry Rebekah L. 
Published: April 2021

AbstractProper protein glycosylation is critical to normal cardiomyocyte physiology. Aberrant glycosylation can alter protein localization, structure, drug interactions, and cellular function. The in vitro differentiation of human pluripotent stem cells into cardiomyocytes (hPSC-CM) has become increasingly important to the study of protein function and to the fields of cardiac disease modeling, drug testing, drug discovery, and regenerative medicine. Here, we offer our perspective on the importance of protein glycosylation in hPSC-CM. Protein glycosylation is dynamic in hPSC-CM, but the timing and extent of glycosylation are still poorly defined. We provide new data highlighting how observed changes in hPSC-CM glycosylation may be caused by underlying differences in the protein or transcript abundance of enzymes involved in building and trimming the glycan structures or glycoprotein gene products. We also provide evidence that alternative splicing results in altered sites of glycosylation within the protein sequence. Our findings suggest the need to precisely define protein glycosylation events that may have a critical impact on the function and maturation state of hPSC-CM. Finally, we provide an overview of analytical strategies available for studying protein glycosylation and identify opportunities for the development of new bioinformatic approaches to integrate diverse protein glycosylation data types. We predict that these tools will promote the accurate assessment of protein glycosylation in future studies of hPSC-CM that will ultimately be of significant experimental and clinical benefit.