bluuebunny/crossref_metadata_2025 huggingface dataset:
Investment Tribunals’ Search for the Truth and Its Impact on the Arbitral Award
Authors: Blackaby Nigel , Julia Milesi Maria
Published: August 2024

Because of the international nature of investment arbitration, and the fact that arbitrators come from different cultures, tribunals often follow a ‘hybrid’ approach to the exercise of their fact-finding powers. That is, tribunals do not always rely exclusively on the parties’ presentation of the case and sometimes take an active fact-finding role by going beyond the parties’ submissions when deciding the cases in front of them. Through specific examples, this chapter explores the impact that the tribunals’ search for the ‘material truth’ has had on the resulting awards. In particular, this chapter highlights the importance of the tribunals’ exercise of their fact-finding powers in the field of investment arbitration where there may be policies and issues of public interest beyond the narrower interests of the disputing parties.
The Impact of Expert Legal Opinions
Authors: Lévesque Céline , Schmid Christian
Published: August 2024

The use of expert legal opinions is an understudied topic in international investment arbitration. Focusing on Chapter 11 of the North American Free Trade Agreement (NAFTA), the case study in this chapter examines the practice and impact of expert legal opinions in investor-state dispute settlement (ISDS). The chapter highlights and discusses three issues with the practice—independence from the disputing parties, delegation of decision-making powers from tribunals to experts, and due process—and provides examples of each. The case study confirms that more expert legal opinions on international law were submitted early under NAFTA while expert legal opinions on domestic law have been used more constantly throughout the years. The chapter’s findings have implications for the jura novit curia principle, double-hatting prohibitions, and transparency.
The Role of Tribunal Secretaries in the Drafting of Investment Awards
Authors: Frutos-Peterson Claudia , Umerov Marat , Ozolins Marija
Published: August 2024

According to the International Centre for Settlement of Investment Disputes (ICSID), the average duration of an international investment arbitration administered by ICSID is more than three years. Where these arbitrations involve voluminous party submissions, complex facts, and can result in 300-plus page awards, it is no wonder that busy tribunal members often need help managing case procedures. Tribunals often appoint a tribunal secretary for this very purpose, and some individual arbitrators seek additional support from assistants. The trouble lies at the heart of this method of dispute resolution: arbitration is always based on consent of the parties. Where parties appoint specific arbitrators to determine their dispute, there is understandable discomfort and alarm when the line between supporting a tribunal and contributing to decision-making can seem blurred. Concerns about the role of a tribunal secretary in drafting have led to challenges of awards, and could be seen as a factor undermining the legitimacy of investment arbitration. It is critical that arbitral institutions, tribunals, and parties openly discuss the duties and role of tribunal secretaries in order to achieve transparency and consensus on the permissible scope of their activities.
An Empirical Analysis of Legal Reasoning
Authors: Strong SI
Published: August 2024

Legal reasoning is at the heart of international arbitration, yet relatively little is known about how arbitrators go about determining the outcome of a particular dispute. This chapter—which is an offshoot of a larger mixed qualitative–quantitative study of legal reasoning in international commercial disputes—undertakes a novel empirical analysis of legal reasoning in international arbitration, using a quantitative analysis of original arbitral awards brought to the United States for recognition or enforcement under the Convention on the Recognition and Enforcement of Foreign Arbitral Awards (New York Convention). The study compares awards arising out of contract-based investment arbitration with awards generated by international commercial disputes, using an innovative methodology that captures entirely new data. In so doing, the analysis provides novel insights into a variety of matters, including the nature of legal authorities and factual authorities (evidence) cited by international arbitrators (thereby showing the types of materials arbitrators find most persuasive) as well as the relative rates of citation of legal and factual material.
Annulment and Set-Aside
Authors: Hindelang Steffen , Nassl Julia
Published: August 2024

This chapter reviews the basic principles of the mechanisms that govern the life of an award in investor-state dispute settlement (ISDS) after it was rendered, in particular annulment and set-aside. It analyses the similarities and differences between the two review procedures in terms of preserving the finality of an award as an essential feature of ISDS, while considering competing policy considerations. It first examines annulment according to Article 52 of the Convention on the Settlement of Investment Disputes between States and Nationals of Other States (ICSID Convention) and the performance of the ad hoc committees in their role as guardians of both the arbitral process and the finality of awards. It then briefly compares this ‘tailor-made’ review mechanism with the set-aside procedure for non-ICSID awards under domestic arbitration law at the seat of arbitration in domestic courts. Finally, the chapter reflects on the general increase in challenges to awards in recent years and the implications for ‘finality’ in ISDS.
Review beyond Annulment
Authors: Nowrot Karsten , Sipiorski Emily
Published: August 2024

The chapter introduces and assesses different types of so-called post-award remedies that are of practical relevance in international investment arbitration. In particular, it covers requests for correction and rectification, requests for additional awards and supplementary decisions, requests for interpretations, as well as requests for revision of the award. Moreover, adopting an overarching perspective, the chapter draws attention to and addresses a number of challenges that may arise in connection with recourse by parties to these post-award remedies in the practice of international investment arbitration.
A Sociology of Religious Freedom
Authors: Breskaya Olga , Giordan Giuseppe , Richardson James T
Published: August 2024

Freedom of and from religion is a key concept to understand the place of religious and spiritual identities, beliefs, and practices in the contemporary world. Sociology can assist in explaining why and how religious freedom holds a variety of meanings in society and may be perceived differently by individuals, social groups, and institutions. This book addresses three major questions of a sociology of religious freedom. First, how to define religious freedom as a multidimensional concept considering its complex and controversial nature. Second, what are the recurrent sociological conditions and relevant social perceptions that will foster an understanding of religious freedom in varying political, legal, and socioreligious contexts. Third, what are the mechanisms of social implementation of religious freedom that contribute to making it a fundamental value of human rights culture in a society. The book suggests that a sociological definition of religious freedom requires taking into account historical, philosophical, legal, religious, and political considerations of a given society. By disclosing the interplay of structural conditions and individual and group perceptions, sociology develops an understanding of the normative and value-laden nature of religious freedom, as well as its societal functions. The book argues that the social mechanisms of incorporation of religious freedom principles into institutional culture are as important as its legal implementation.
Toward a Sociology of Religious Freedom
Authors: Breskaya Olga , Giordan Giuseppe , Richardson James T
Published: August 2024

This chapter highlights the importance of providing a comprehensive vision of religious freedom in modern societies. It develops a working definition of religious freedom as a multidimensional concept and emphasizes the value of a sociological approach when specifying its meaning and key elements. It proposes to consider religious freedom integrating theoretical perspectives within which it has been defined in four complementary ways by Berger, Finke, Richardson, and Fox. By illustrating these perspectives, it specifies their sociological aspects, putting at the center the following five dimensions for further analysis: (a) individual and groups’ autonomy; (b) the societal value of religious freedom; (c) the normative principle of state–religion governance; (d) international human rights standards; and (e) sociolegal impacts of the judicialization of religious freedom. It highlights that this concept involves a much broader understanding than the usual legal and political perspectives.
Elements of Sociology of Religious Freedom
Authors: Breskaya Olga , Giordan Giuseppe , Richardson James T
Published: August 2024

This chapter delves into recurrent structural conditions and social perceptions of religious freedom that represent central elements of a sociology of religious freedom. It argues that in establishing the norms of religious freedom within everyday interactions two overlapping processes must be considered. The first focuses on the effects produced by structural conditions inherent to legal and political institutions. The second process refers to how individuals or groups develop the meanings they attribute to specific practices and convictions such as religious garb, religious holidays, dietary restrictions, conversion, collective religious and secular experiences, and others. In this attempt to analyze structural conditions and everyday life issues connected to the norms of religious freedom, the chapter describes functions of this freedom. It scrutinizes the relationship between the legal and social implementation of religious freedom. Important legal cases from Turkey and Russia are examined.
Introduction
Authors: Hardy Jeffrey S
Published: August 2024

The introduction explores the background behind the Soviet Gulag, presenting it as a hybrid prison–concentration camp system that served several competing goals. One of those goals was to produce productive Soviet citizens who accepted Soviet ideology, including atheism, although this was often neglected as the Gulag became hyperfocused on maximizing production. This introduction also lays forth the place of religion, and especially Christianity, in the late Russian Empire and the early Soviet Union. Although Vladimir Lenin and his Bolsheviks were atheists, they at times suggested—including in the constitution itself—that the separation of church and state was sufficient in terms of official state policy. This meant that the USSR and its penal system were founded on a set of contradictions in terms of how hard to fight against religious believers. And this tension would ultimately provide space for the persistence of religion in the Gulag.
Separating Church and State in Bolshevik Prisons
Authors: Hardy Jeffrey S
Published: August 2024

This chapter focuses on the early Soviet period before Joseph Stalin seized the reins of power. Attempts to create a new penal system were challenged by scarce resources and conflicting ideas about the regime’s new values, including both atheism and the freedom of religion. This resulted in inmates not only being held in monasteries, surrounded by images of Christian belief, but in many cases being allowed to attend worship services (which some guards also attended). Antireligious propaganda, meanwhile, was scarce initially before becoming more pervasive as the 1920s went on. In the midst of this confusion, inmates were often able to continue their religious practices with relatively little interference from prison guards.
The War against Religion in the Gulag
Authors: Hardy Jeffrey S
Published: August 2024

This chapter investigates the creation of the Gulag, a hybrid prison-camp system in the 1930s, and a rise in antireligious propaganda and repression among prisoners. The imprisoned religious community at Solovki was broken up and dispersed to various other camps, and other inmates suffered greater abuse and more confiscations of religious books and symbols. And yet intense production demands placed on Gulag camps actually provided some space for religiosity. Propaganda focused so much on labor and production that other concerns, including the teaching of atheism, were neglected. And at least some camp overseers tasked with reaching quotas left religious inmates to quietly practice their faith in peace as long as they were hard workers.
Khrushchev’s Reforms and the Camp for Sectarians
Authors: Hardy Jeffrey S
Published: August 2024

This chapter explores religion in the Gulag during the reign of Nikita Khrushchev (1953–1964). Although the “Thaw,” as this period is often called, featured a relaxation of repression in many aspects of Soviet life, Khrushchev renewed the assault against religion in the early 1960s. This was reflected to some extent in the reformed penal system, which became much smaller after Stalin’s death but continued to persecute devout Christians for their beliefs. One of the more fascinating aspects of this period is the creation of a few isolated zones for Christian “sectarians” in the Dubravny Camp. Separated from other inmates to prevent them from proselytizing, these prisoners enjoyed a vibrant and to some extent competitive environment of religious worship barely encumbered by the guards.
The Significance of Insignificance
Authors: Glasgow Joshua
Published: August 2024

If we are cosmically insignificant, how should we feel about that fact? Many, such as Pascal, feel a kind of fear or terror. This chapter argues that such fear is misplaced. In addition to the fact that being significant is not in our interests, so also being insignificant is in our interests. In particular, it can liberate us from the pressure and anxiety we feel when trying to optimize our choices. Once we appreciates that our choices do not matter so much, this “tyranny of value” becomes less tyrannical. Our choices still do matter; but if we are relatively insignificant, then they do not matter as much as they might have, and this is a good thing for us.
Escalation process of critical values when these cannot be communicated on first attempt: A hospital-wide process improvement project
Authors: Guarner Jeannette , Osoria Zully , Barker Debra , Stigaard Leslie C
Published: August 2024

Objectives

Since laboratory critical values reflect such an abnormal pathologic state that there is imminent danger to the patient, it is crucial to deliver the result upon initial call with an escalation process when the initial call cannot occur. In our 8-hospital system, one of the hospitals used the escalation procedure twice as frequently compared with the other hospitals. This work presents hospital-wide quality improvement processes that decreased escalation of critical value calls so as to reach the same proportion of escalated calls compared to other hospitals in the system.

Methods

The laboratory met weekly with leaders of different hospital areas and quality management; they presented the interventions they implemented, and the laboratory monitored their progress.

Results

Monitoring and reviewing with providers the importance of critical values decreased temporarily escalated calls from 25% to 18%. Having a dedicated phone to call critical values in each hospital area decreased the calls in a sustained fashion, which now fluctuate between 9% and 14%. Other interventions, including having a dedicated person receiving critical value results, did not decrease escalated critical value calls.

Conclusions

Having a dedicated phone in each hospital area that receives the initial critical value call simplifies and standardizes the process.
The KCa3.1 Channel Blocker TRAM-34 and Minocycline Prevent Fructose-Induced Hypertension in Rats
Authors: Hamad Abdelrahman , Ozkan Melike Hacer
Published: August 2024

BACKGROUND

High fructose consumption increases blood pressure through microglia-related neuroinflammation in rats. Since intermediate-conductance calcium-activated potassium channels (KCa3.1) potentiates microglial reactivity, we examined whether the pretreatment with the KCa3.1 channel blocker TRAM-34 or minocycline prevents hypertension development in fructose-fed rats.

METHODS

The study involved male Wistar rats that were given either high fructose (10% in drinking water) or tap water for 21 days. Fructose groups also received minocycline or TRAM-34 systemically for 21 days. We measured systolic and diastolic blood pressure (SBP and DBP), heart rate (HR) periodically with tail-cuff; proinflammatory cytokines, and insulin levels in plasma via Enzyme-linked immunosorbent assay (ELISA), and neuroinflammatory markers in the nucleus tractus solitarii (NTS) by qPCR at the end of 21 days. We also examined endothelium-dependent hyperpolarization (EDH)-type vasorelaxations in isolated mesenteric arteries of the rats ex vivo.

RESULTS

SBP, DBP, and HR increased in the fructose group. Both minocycline and TRAM-34 significantly prevented these increases. Fructose intake also increased plasma interleukin-6, interleukin-1β, tumor necrosis factor-α, and insulin levels, whereas pretreatment with TRAM-34 prevented these increases as well. Iba-1, but not cluster of differentiation-86 levels were significantly higher in the NTS samples of fructose-fed hypertensive rats which implied microglial proliferation. EDH-type vasorelaxations mediated by endothelial KCa3.1 attenuated in the fructose group; however, TRAM-34 did not cause further deterioration in the relaxations.

CONCLUSIONS

TRAM-34 is as effective as minocycline in preventing fructose-induced hypertension without interfering with EDH-type vasodilation. Furthermore, TRAM-34 relieves high fructose-associated systemic inflammation.
Oral Administration of Lutein Improves Fat Graft Survival by Alleviating Oxidative Stress in Mice
Authors: Chen Zhiyou , Liu Tong , Luan Jie
Published: August 2024

Background

Oxidative stress induced by ischemia and hypoxia in fat transplantation is a major obstacle to graft retention. Previous studies have shown that lutein has excellent adipose tissue affinity and antioxidative stress ability, however, the effects of oral lutein on fat transplantation have not yet been studied.

Objectives

We aimed to investigate whether oral lutein could improve fat transplantation retention by regulating oxidative stress, apoptosis, and inflammatory cytokine levels in graft tissues.

Methods

Nude mice were assigned to the control group (normal saline), low-dose lutein group (10 mg/kg/day), and high-dose lutein group (20 mg/kg/day) randomly. All mice received treatment by gavage 1 week before fat grafting and continued for 2 weeks. The grafts were collected 1, 2, and 12 weeks after treatment. By conducting histological analyses, Western blotting, quantitative polymerase chain reaction and cell metabolic function detection, the regulatory effects of lutein on apoptosis and oxidative stress in grafts were demonstrated. Additionally, RNA sequencing was conducted to further clarify the efficacy of lutein on fat grafting.

Results

Lutein induced superior graft retention, histological structures, and more viable adipocytes than the control group. It relieved tissue oxidative stress and lipid oxidative damage by decreasing reactive oxygen species and significantly reduced inflammation and apoptosis of grafts. RNA sequencing analysis confirmed that lutein could downregulate the gene expression of oxidative stress and related inflammation and apoptosis.

Conclusions

Our study suggests that oral administration of lutein can improve fat graft survival by reducing the levels of oxidative stress, inflammation, and apoptosis in grafted fat.
Resolution of Vascular Compromise From Liquid Rhinoplasty Using Hirudo medicinalis Therapy
Authors: Rivkin Alexander , Chepka Solomiia
Published: August 2024

Hyaluronic acid (HA) fillers are a relatively safe and effective means of cosmetic treatment for the face; however, as the numbers of both patients and injectors continue to rise, reports of adverse events (AEs) and ischemia are increasing. Although visual complications and stroke are the most-feared AEs, skin and underlying tissue necrosis is far more common and can be catastrophic. HA can be dissolved with hyaluronidase, but this does not always resolve ischemia. In some instances, including the case presented here, conventional interventions are inadequate to reverse the progression of ischemia and restore blood flow. In this case study, HA injection of the nasal sidewall resulted in ischemia and impending necrosis of the nasal tip. Following failure of standard-of-care measures to reverse the progression of ischemia and restore blood flow, Hirudo medicinalis therapy was successfully used as an adjuvant treatment. To our knowledge, this is the first report of H. medicinalis therapy for treatment of ischemia and necrosis from aesthetic filler injection. Based on experience here, this approach should be considered for patients who are out of therapeutic options, or as a helpful adjunct to speed resolution of vascular occlusion. In addition, the success of H. medicinalis therapy, which acts locally on the microvasculature, may inform our understanding of the mechanism of vascular occlusion with fillers.

Level of Evidence: 5 (Therapeutic)
PLM_Sol: predicting protein solubility by benchmarking multiple protein language models with the updated Escherichia coli protein solubility dataset
Authors: Zhang Xuechun , Hu Xiaoxuan , Zhang Tongtong , Yang Ling , Liu Chunhong , Xu Ning , Wang Haoyi , Sun Wen
Published: August 2024

Protein solubility plays a crucial role in various biotechnological, industrial, and biomedical applications. With the reduction in sequencing and gene synthesis costs, the adoption of high-throughput experimental screening coupled with tailored bioinformatic prediction has witnessed a rapidly growing trend for the development of novel functional enzymes of interest (EOI). High protein solubility rates are essential in this process and accurate prediction of solubility is a challenging task. As deep learning technology continues to evolve, attention-based protein language models (PLMs) can extract intrinsic information from protein sequences to a greater extent. Leveraging these models along with the increasing availability of protein solubility data inferred from structural database like the Protein Data Bank holds great potential to enhance the prediction of protein solubility. In this study, we curated an Updated Escherichia coli protein Solubility DataSet (UESolDS) and employed a combination of multiple PLMs and classification layers to predict protein solubility. The resulting best-performing model, named Protein Language Model-based protein Solubility prediction model (PLM_Sol), demonstrated significant improvements over previous reported models, achieving a notable 6.4% increase in accuracy, 9.0% increase in F1_score, and 11.1% increase in Matthews correlation coefficient score on the independent test set. Moreover, additional evaluation utilizing our in-house synthesized protein resource as test data, encompassing diverse types of enzymes, also showcased the good performance of PLM_Sol. Overall, PLM_Sol exhibited consistent and promising performance across both independent test set and experimental set, thereby making it well suited for facilitating large-scale EOI studies. PLM_Sol is available as a standalone program and as an easy-to-use model at https://zenodo.org/doi/10.5281/zenodo.10675340.
An extension of latent unknown clustering integrating multi-omics data (LUCID) incorporating incomplete omics data
Authors: Zhao Yinqi , Jia Qiran , Goodrich Jesse , Darst Burcu , Conti David V
Published: August 2024

Motivation

Latent unknown clustering integrating multi-omics data is a novel statistical model designed for multi-omics data analysis. It integrates omics data with exposures and an outcome through a latent cluster, elucidating how exposures influence processes reflected in multi-omics measurements, ultimately affecting an outcome. A significant challenge in multi-omics analysis is the issue of list-wise missingness. To address this, we extend the model to incorporate list-wise missingness within an integrated imputation framework, which can also handle sporadic missingness when necessary.

Results

Simulation studies demonstrate that our integrated imputation approach produces consistent and less biased estimates, closely reflecting true underlying values. We applied this model to data from the ISGlobal/ATHLETE “Exposome Data Challenge Event” to explore the association between maternal exposure to hexachlorobenzene and childhood body mass index by integrating incomplete proteomics data from 1301 children. The model successfully estimated proteomics profiles for two clusters representing higher and lower body mass index, characterizing the potential profiles linking prenatal hexachlorobenzene levels and childhood body mass index.

Availability and implementation

The proposed methods have been implemented in the R package LUCIDus. The source code is available at https://github.com/USCbiostats/LUCIDus.
Adamts9 is required for the development of primary ovarian follicles and maintenance of female sex in zebrafish
Authors: Carver Jonathan J , Amato Ciro M , Hung-Chang Yao Humphrey , Zhu Yong
Published: August 2024

Previous studies have suggested that adamts9 (a disintegrin and metalloprotease with thrombospondin type-1 motifs, member 9), an extracellular matrix (ECM) metalloprotease, participates in primordial germ cell (PGC) migration and is necessary for female fertility. In this study, we found that adamts9 knockout (KO) led to reduced body size, and female-to-male sex conversion in late juvenile or adult zebrafish; however, primary sex determination was not affected in early juveniles of adamts9 KO. Overfeeding and lowering the rearing density rescued growth defects in female adamts9 KO fish but did not rescue defects in ovarian development in adamts9 KO. Delayed PGC proliferation, significantly reduced number and size of Stage IB follicles (equivalent to primary follicles) in early juveniles of adamts9 KO, and arrested development at Stage IB follicles in mid- or late-juveniles of adamts9 KO are likely causes of female infertility and sex conversion. Via RNAseq, we found significant enrichment of differentially expressed genes involved in ECM organization during sexual maturation in ovaries of wildtype fish; and significant dysregulation of these genes in adamts9 KO ovaries. RNAseq analysis also showed enrichment of inflammatory transcriptomic signatures in adult ovaries of these adamts9 KO. Taken together, our results indicate that adamts9 is critical for development of primary ovarian follicles and maintenance of female sex, and loss of adamts9 leads to defects in ovarian follicle development, female infertility, and sex conversion in late juveniles and mature adults. These results show that the ECM and extracellular metalloproteases play major roles in maintaining ovarian follicle development in zebrafish.
A dual-center study: can ultrasound radiomics differentiate type I and type II epithelial ovarian cancer patients with normal CA125 levels?
Authors: Chen Lixuan , Jin Chenyang , Chen Bo , Debora Asta , Su Weizeng , Zhou Qingwen , Zhou Shuai , Bian Jinyan , Yang Yunjun , Lan Li
Published: August 2024

Objective

CA125 is recommended by many countries as the primary screening test for ovarian cancer. But there are patients with ovarian cancer having normal CA125. We hope to identify the types of EOC with normal CA125 levels better by building a refined model based on the ultrasound radiomics, thus providing precise medical treatment for patients.

Methods

We included 58 patients with EOC with normal CA125 from 2 centres, who were confirmed by preoperative ultrasound and pathology. We extracted 1130 radiomics features based on the tumour’s region of interest from the most typical ultrasound image of each patient. We selected radiomics and clinical features by LASSO and logistic regression to construct Rad-score and clinical models, respectively. Receiver operating characteristic curves judged their test efficacy. On the basis of the combined model, we developed a nomogram.

Results

Area under the curves (AUCs) of 0.93 and 0.83 were achieved in both the training and test groups for the combined model. There were similar AUCs between the Rad-score and clinical models of 0.82 and 0.80, respectively. By analysing the calibration curves, it was determined that the nomogram matched actual observations in the training cohort.

Conclusion

Ultrasound radiomics can differentiate type I and type II EOC with normal CA125 levels.

Advances in knowledge

This study is the first to focus on EOC cases with normal level of CA125. The subset of patients constituting 20% of the disease population may require more refined radiomics models.
Diffusion tensor imaging in Behcet’s disease with and without neurological involvement patients: evaluation of microstructural white matter abnormality with a tract-based spatial statistical analysis
Authors: Aslan Kerim , Genç Barış , Bolat Necdet , Incesu Lutfi
Published: August 2024

Objective

This study aims to assess the microstructural abnormalities in white matter (WM) among Behcet’s disease (BD) patients, both with and without neurological involvement, utilising tract-based spatial statistics (TBSS) to elucidate the underlying causes of WM microstructural changes.

Methods

This prospective study comprised 43 BD patients without neurological involvement, 15 neuro-Behcet’s disease (NBD) patients with normal conventional MRI, and 54 healthy controls matched for age and sex. TBSS was applied in this diffusion tensor imaging study to conduct a whole-brain voxel-wise analysis of fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) of WM.

Results

Compared to the control group, BD patients exhibited decreased FA and increased MD and RD in nearly all WM tracts, along with increased AD in the left corticospinal tract (CST), left inferior longitudinal fasciculus (ILF), and left superior longitudinal fasciculus (SLF). NBD patients also showed a widespread decrease in FA and increased MD and RD, similar to BD patients without neurological involvement. Additionally, NBD patients had increased AD in the left CST, left ILF, left SLF, left inferior fronto-occipital fasciculus (IFOF), and right CST. Compared to BD patients without neurological involvement, NBD patients exhibited a greater reduction in FA and an increase in MD and RD in WM tracts, with no significant differences in AD.

Conclusion

These results suggest that the main mechanism of microstructural changes in the WM of BD patients may be related to impaired fibre integrity, demyelination, and decreased myelin sheath integrity.

Advances in knowledge

This study demonstrated BD patients without neurological involvement and NBD patients a decrease in FA and an increase in MD and RD were observed in larger areas of major WM tracts, while an increase in AD values was observed in fewer tracts. Our findings may be useful in understanding the pathophysiology underlying subclinical parenchymal involvement and neurological dysfunction in BD patients and the management of BD patients.
Optical manipulation of graphene oxide nanosheets toward arbitrary hetero-stacking of graphene and niobate and titanate nanosheets
Authors: Suzuki Yasutaka , Ikeda Akira , Nakao Shuji , Nakato Teruyuki , Saito Kanji , Kawamata Jun
Published: August 2024

The study explores a novel method for constructing hetero-stacked bilayers of graphene and various inorganic oxide nanosheets by utilizing optical manipulation technique. A graphene oxide (GO) is trapped by a laser beam, and the GO nanosheet is converted to reduced graphene oxide (rGO). The rGO pressed against the substrate, forming a hetero-stacked rGO–GO bilayer. Precise control over the relative location of the nanosheets is achieved by optically manipulating the rGO nanosheet. The technique is demonstrated with rGO-niobate and rGO-titanate bilayers, highlighting its simplicity and versatility.
“We are just with each other, everything is going to be okay”—BlackQueer rural–urban migration, danger and digital sexual desires
Authors: Lupindo Esihle
Published: August 2024

Much research looking at Queer migration focuses on the movement of people between countries and continents, where countries of origin are deemed unsafe. However, literature shows that in South Africa there are more people migrating internally than those migrating into South Africa from other countries. In this article, I draw on 15 interviews with BlackQueers who moved from rural to urban areas in South Africa to explain their Queer-centric motivations for migrating internally, which enabled them to “confront what it means to be Queer” through physical and digital interactions. The digital world is important because it surpasses fixed geographies. Digital spaces offer a refuge that may not be available in offline spaces even when there are legal protections that state that this should not be the case. This article provokes transnational scholarship to pay equal attention to movements within countries and digital spaces as it does to cross-country flows.
Atypical naevi in dermoscopy and reflectance confocal microscopy: correlation between immunohistochemistry and diagnostic patterns of atypia
Authors: Alma Antonio , Beretti Francesca , Bonilauri Cecilia , Chester Johanna , Kaleci Shaniko , Ciardo Silvana , Bertoni Laura , Pellacani Giovanni , Farnetani Francesca
Published: August 2024

Equivocal cutaneous melanocytic lesions can sometimes be diagnosed as naevi at histopathology, despite positive melanoma-associated features being observed at dermoscopy and/or reflectance confocal microscopy (RCM). We prospectively identified equivocal lesions with histopathological diagnosis of naevus and at least one criterion of melanoma on dermoscopy and/or RCM (Prot.# 289\13).
Cutaneous ulcers following high-dose prednisone
Authors: Liakos William , Abdelmoity Leena , Fields-Meehan January , Tonkovic-Capin Viseslav , Fite Elizabeth
Published: August 2024

A 60-year-old man presented to the dermatology clinic with longstanding nonhealing ulcers to the lower legs.
A GC–MS Method for Determination of β-Propiolactone Residues in Inactivated Covid-19 Vaccines
Authors: Mirjalili Seyedeh Zohreh , Tamiji Zahra , Shirangi Mehrnoosh , Amini Mohsen
Published: August 2024

β-propiolactone is a common inactivator agent used in vaccines. Due to β-propiolactone carcinogenicity, complete hydrolysis of it is necessary to prevent cytotoxicity in mammalian cells. As a result, more attention should be paid to it at the clinic, and it is important to measure its trace amounts. β-propiolactone analysis is challenging due to its instability. A simple and fast gas chromatography–mass spectrometry method was developed for quantitation of residual β-propiolactone in inactivated coronavirus disease 2019 (Covid-19) vaccines. Caprolactone was used as an internal standard in sample solutions; the analysis was performed after extraction of analyte from vaccine media by ethyl acetate. The validity of the method was studied with a linearity of r2 > 0.99 over the concentration range of 0.2–20 μg/mL with the limit of detection and the limit of quantification of 0.07 and 0.20 μg/mL, respectively. The target analyte β-propiolactone was not detected in the samples, demonstrating the test samples were qualified. The established method can be used for quality control of inactivated Covid-19 vaccines.
CLOVER (CLOstridium difficile Vaccine Efficacy tRial) Study: A Phase 3, Randomized Trial Investigating the Efficacy and Safety of a Detoxified Toxin A/B Vaccine in Adults 50 Years and Older at Increased Risk of Clostridioides difficile Infection
Authors: Donskey Curtis J , Dubberke Erik R , Klein Nicola P , Liles Elizabeth G , Szymkowiak Katarzyna , Wilcox Mark H , Lawrence Jody , Bouguermouh Salim , Zhang Haiying , Koury Kenneth , Bailey Ruth , Smith Helen M , Lockhart Stephen , Lamberth Erik , Kalina Warren V , Pride Michael W , Webber Chris , Anderson Annaliesa S , Jansen Kathrin U , Gruber William C , Kitchin Nicholas
Published: August 2024

Background

Clostridioides difficile infection (CDI) causes substantial mortality and healthcare burden. We assessed the detoxified toxin-A/B PF-06425090 vaccine for primary CDI prevention.

Methods

This phase 3 observer-blinded study randomized (1:1) ≥50-year-olds at increased CDI risk (N = 17 535) to receive 3 PF-06425090 or placebo doses (0, 1, and 6 months). Primary end points were first CDI episode (≥3 unformed stools within 24 hours; central laboratory-confirmed toxin A/B positive) ≥14 days post-dose 3 (PD3; first primary) and post-dose 2 (PD2; second primary). CDI duration, need for CDI-related medical attention (secondary end points), and antibiotic use (post hoc analysis) PD3 were evaluated. Tolerability and safety were assessed.

Results

The primary end point was not met (17 PF-06425090 and 25 placebo recipients had first CDI episode ≥14 days PD3 [vaccine efficacy (VE) = 31.0% (96.4% confidence interval [CI], −38.7% to 66.6%)]; 24 PF-06425090 and 34 placebo recipients had first CDI episode ≥14 days PD2 [VE = 28.6% (96.4% CI, −28.4% to 61.0%)]. Median CDI duration was lower with PF-06425090 (1 day) versus placebo (4 days; 2-sided nominal P = .02). Of participants with first CDI episode, 0 PF-06425090 and 11 placebo recipients sought CDI-related medical attention (post hoc analysis estimated VE = 100%; 95% CI, 59.6% to 100.0%) and 0 PF-06425090 and 10 placebo recipients required antibiotic treatment (VE = 100%; 95% CI, 54.8% to 100.0%). Local reactions were more frequent in PF-06425090 recipients, and systemic events were generally similar between groups; most were mild to moderate. Adverse event rates were similar between groups.

Conclusions

Three PF-06425090 doses were safe and well tolerated. Although the primary end point was not met, PF-06425090 reduced symptom duration, CDI that required medical attention, and CDI-directed antibiotic treatment, highlighting its potential to reduce CDI-associated healthcare burden.

Clinical Trials Registration

NCT03090191.
Implementation of Single High-dose Liposomal Amphotericin B Based Induction Therapy for Treatment of HIV-associated Cryptococcal Meningitis in Uganda: A Comparative Prospective Cohort Study
Authors: Gakuru Jane , Kagimu Enock , Dai Biyue , Okurut Samuel , Nsangi Laura , Bahr Nathan C , Okirwoth Michael , Namuju Olivie C , Jarvis Joseph N , Lawrence David S , Ahimbisibwe Cynthia , Ellis Jayne , Tadeo Kizza Kandole , Boulware David R , Meya David B , Tugume Lillian
Published: August 2024

Background

In 2022, the World Health Organization (WHO) recommended a single 10 mg/kg dose of liposomal amphotericin B in combination with 14 days of flucytosine and fluconazole (AMBITION-cm regimen) for induction therapy of human immunodeficiency virus (HIV)-associated cryptococcal meningitis, based on the results of the multisite AMBITION-cm trial. We evaluated outcomes after real-world implementation of this novel regimen in Uganda.

Methods

We enrolled Ugandan adults with cryptococcal meningitis into an observational cohort receiving the AMBITION-cm regimen with therapeutic lumbar punctures in routine care during 2022–2023. We compared 10-week survival and CSF early fungicidal activity with the outcomes observed in the AMBITION-cm clinical trial conducted at the same sites.

Results

During 2022–2023, 179 adults were treated with the AMBITION-cm regimen via routine care and compared to the 171 adults randomized to the AMBITION-cm trial interventional arm in Uganda from 2018 to 2021. No significant difference in 10-week survival occurred between the observational cohort (68.6%; 95% confidence interval [CI]: 61.6%–76.3%) and AMBITION-cm trial participants in the intervention arm (71.7%; 95% CI: 65.2%–78.8%; absolute risk difference = −3.1%; 95% CI: −13.1% to 6.9%; P = .61). Early fungicidal activity did not differ (0.42 vs 0.39 log10CFU/mL/day; P = .80) between groups. Among observational cohort participants discharged alive initially and for whom follow-up data were available, the incidence of re-hospitalizations due to persistently elevated intracranial pressure was 2.8% (4/144).

Conclusions

The AMBITION-cm regimen for cryptococcal meningitis resulted in similar outcomes as observed in the AMBITION-cm clinical trial when implemented in routine care. Intracranial pressure management during hospitalization and awareness after discharge are key components of optimizing outcomes.
Redundancy as a Legal Strategy to Combat Corruption: Exploring the Potential of Institutional Multiplicity to Create Fail-Safe Systems
Authors: Mota Prado Mariana
Published: August 2024

Engineering uses duplication to create fail-safe systems. The existence of two system components capable of performing the same function increases reliability, as the supposedly superfluous component can be turned on if the main one breaks down. Although redundancy ensures that many of our modern conveniences such as computers and planes do not crash, this solution has not been extensively explored in a legal context. This article will articulate some of the advantages of redundancy between different areas of the law (administrative, civil and criminal) and at an institutional level (among bodies performing monitoring, investigative, prosecutorial and adjudicative functions in the same and in distinct jurisdictions). Legal efforts to combat corruption around the world provide illustrative examples of the many advantages of this strategy, but also some of its risks and disadvantages. Far from providing a comprehensive empirical analysis of this subject, this article articulates hypotheses to be tested and proposes that the topic deserves more attention among legal scholars than it has received.
Heart–brain axis in health and disease: role of innate and adaptive immunity
Authors: Simats Alba , Sager Hendrik B , Liesz Arthur
Published: August 2024

The importance of the brain–heart interaction has been increasingly recognized as a critical physiological axis that is altered in disease. In this review, we explore the intricate relationship between the central nervous system and cardiovascular health, focusing particularly on immunological mechanisms that influence the course of both neurological and cardiovascular diseases. While previous studies have established a key role of the autonomic nervous system (ANS) in linking brain and the heart, more recent studies have expanded our understanding of the multifaceted inter-organ interactions. As such, circulating mediators include immune cells of the adaptive and innate immune system and their secreted immunogenic factors have come into the focus as mediators along this bidirectional communication. Hence, in this review we briefly discuss the contribution of the ANS and then focus on innate and adaptive immune mechanisms along the heart-to-brain and brain-to-heart axes, illustrating how cardiovascular diseases affect cognitive functions and how brain pathologies lead to cardiac complications.
Implementation of the kissing balloon technique using a perfusion balloon in acute myocardial infarction: a case report
Authors: Nakata Marohito , Tabata Tatsuya , Nago Chikashi , Abe Masami , Uehara Hiroki
Published: August 2024

Background

Prolonged antiplatelet-agent administration associated with stenting for acute myocardial infarction is not ideal in young patients. We successfully performed a perfusion balloon-based kissing balloon technique in the left anterior descending artery ostium in a young patient with acute myocardial infarction.

Case summary

A 34-year-old female presenting with recurrent chest pain was diagnosed with ST-segment elevation acute myocardial infarction. Emergency coronary angiography revealed 90% stenosis of the left anterior descending artery ostium. Considering her age, lesion dilation using a perfusion balloon was preferred. This inadvertently impinged the left circumflex artery, causing chest pain and ischaemia-related hypotension with only a 10 s perfusion dilation balloon. We transitioned to an alternative 7 Fr guiding catheter and performed the kissing balloon technique using a perfusion balloon. This allowed prolonged inflation for 120 s, without complications. Optical coherence tomography of the lesion revealed layered plaques. Based on the patient’s age and medical history, coronary spasm may be the aetiological factor underlying acute ST-segment elevation myocardial infarction. Coronary angiography 3 months post-discharge revealed no restenosis.

Discussion

Regarding acute myocardial infarction, prolonged inflation with a perfusion balloon had higher frequency of non-stent-related interventions than that of semi-compliant or non-compliant balloons. In this case, the perfusion balloon resulted in chest pain and hypotension. Perfusion balloon-based kissing balloon technique was useful in this setting. Optical coherence tomography revealing the responsible lesions can help determine the cause of acute myocardial infarction in young patients; in our case, a layered plaque was observed. Layered plaques are associated with coronary spasm; therefore, initiating treatment of coronary spasm was considered herein.
Late-onset left atrial appendage occlusion device–related thrombus attributed to mitral bioprosthetic stenosis: a case report
Authors: Rana Aakash , Xu Jack , Alturkmani Hani , Dhar Gaurav , Vallurupalli Srikanth
Published: August 2024

Background

Left atrial appendage occlusion (LAAO) is an alternative to anticoagulation for stroke prevention in select patients with atrial fibrillation (AF). In this study, we describe the case of a patient with delayed device-related thrombus (DRT) at 13 months post-LAAO in a setting of atrial stasis due to a worsening mitral bioprosthetic stenosis.

Case summary

A 69-year-old woman with a history of rheumatic mitral stenosis and regurgitation post-bioprosthetic mitral valve replacement (6 years prior) and paroxysmal AF was referred for percutaneous LAAO due to recurrent severe gastrointestinal bleeding while on anticoagulation. She underwent an uncomplicated LAAO, for which a 35 mm Watchman Flx device was used. Peri-procedural transoesophageal echocardiogram (TEE) at the time of implant showed thickened and calcified mitral bioprosthetic leaflets and a mild mitral stenosis. Her 45-day post-LAAO TEE showed a mild mitral stenosis and no peri-device leak or DRT. At 12 months, the patient had worsening exertional dyspnoea and pedal oedema. Her 12-month transthoracic echocardiogram (TTE) showed a moderate mitral stenosis and LAAO remained free of DRT. Her symptoms were deemed secondary from a worsening mitral valve stenosis. Mitral valve-in-valve (MViV) replacement was planned because the patient was deemed a prohibitive risk for a redo surgical replacement. Transthoracic echocardiogram on the day of MViV showed a large thrombus on the LAAO device. MViV was postponed. After the patient completed 45 days of anticoagulation with warfarin, a repeat TTE was performed, which showed a resolution of DRT. Transcatheter MViV was performed successfully.

Discussion

This case demonstrates that increased stasis and left atrial dysfunction from prosthetic mitral stenosis can be a risk factor for late DRT after successful LAAO. The use of a LAAO occlusion device in the presence of a mitral bioprosthesis requires more frequent echocardiographic monitoring to assess both the function of the prosthesis and a delayed formation of thrombus. More studies need to be conducted to assess the safety of percutaneous LAAO devices in those with mitral bioprosthesis.