bluuebunny/crossref_metadata_2025_split huggingface dataset:
The
Neosartorya (Aspergillus) fischeri
antifungal protein NFAP2 has low potential to trigger resistance development in
Candida albicans in vitro
Authors: Bende Gábor , Zsindely Nóra , Laczi Krisztián , Kristóffy Zsolt , Papp Csaba , Farkas Attila , Tóth Liliána , Sáringer Szabolcs , Bodai László , Rákhely Gábor , Marx Florentine , Galgóczy László 
Published: November 2024

ABSTRACT

Due to the increase in the number of drug-resistant
Candida albicans
strains, new antifungal compounds with limited potential for the development of resistance are urgently needed. NFAP2, an antifungal protein (AFP) secreted by
Neosartorya
(
Aspergillus
)
fischeri
, is a promising candidate. We investigated the ability of
C. albicans
to develop resistance to NFAP2 in a microevolution experiment compared with generic fluconazole (FLC).
C. albicans
adapted to only 1× minimum inhibitory concentration (MIC) of NFAP2, which can be considered tolerance rather than resistance, compared with 32× MIC of FLC. Genome analysis revealed non-silent mutations in only two genes in NFAP2-tolerant strains and in several genes in FLC-resistant strains. Tolerance development to NFAP2 did not influence cell morphology. The susceptibility of NFAP2-tolerant strains did not change to FLC, amphotericin B, micafungin, and terbinafine. These strains did not show altered susceptibility to AFPs from
Penicillium chrysogenum
, except one which had less susceptibility to
Penicillium chrysogenum
antifungal protein B. FLC-resistant strains had decreased susceptibility to terbinafine and NFAP2, but not to other drugs and AFPs from
P. chrysogenum
. NFAP2-tolerant and FLC-resistant strains showed decreased and increased NFAP2 binding and uptake, respectively. The development of tolerance to NFAP2 decreased tolerance to cell wall, heat, and UV stresses. The development of FLC resistance increased tolerance to cell wall stress and decreased tolerance to heat and UV stresses. Tolerance to NFAP2 did not have significant metabolic fitness cost and could not increase virulence, compared with resistance to FLC.

IMPORTANCE

Due to the increasing number of (multi)drug-resistant strains, only a few effective antifungal drugs are available to treat infections caused by opportunistic
Candida
species. Therefore, the incidence of hard-to-treat candidiasis has increased dramatically in the past decade, and the demand to identify antifungal compounds with minimal potential to trigger resistance is substantial. The features of NFAP2 make it a promising candidate for the topical treatment of
Candida
infection. Data on the development of resistance to antifungal proteins in
Candida albicans
are lacking. In this study, we provide evidence that NFAP2 has a low potential to trigger resistance in
C. albicans in vitro
, and the developed tolerance to NFAP2 is not associated with severe phenotypic changes compared with development of resistance to generic fluconazole. These results suggest the slow emergence of NFAP2-resistant
Candida
strains, and NFAP2 can reliably be used long-term in the clinic.
Lack of activity of HIV-1 integrase strand-transfer inhibitors on recombinase activating gene (RAG) activity at clinically relevant concentrations
Authors: Demirdjian Sally , Duong Vincent N. , Byrum Jennifer N. , Nayak Arabinda , McKinney Cooper B. , Perry Jason K. , Callebaut Christian , Rodgers Karla K. , Falkard Brie , Feng Joy Y. 
Published: November 2024

ABSTRACT

Human immunodeficiency virus 1 (HIV-1) infection remains a global health concern, with nearly 30 million people on antiretroviral (ARV) treatment. Integrase strand-transfer inhibitors (INSTIs) that block HIV-1 integrase are crucial components of first-line combination ARV therapies recommended in most international guidelines and have significantly improved HIV-1 treatment due to their efficacy and safety. This study evaluates potential off-target effects of INSTIs on recombinase activating genes (RAG1 and RAG2), which are essential for adaptive immune system function. We performed a comprehensive assessment of the off-target effects of clinically approved INSTIs on RAG activity, utilizing both biochemical and cellular assays. We purified the first catalytically active recombinant human core RAG1–RAG2 complex and tested it in the presence of the co-factor human HMGB1 protein for the gel-based biochemical RAG DNA cleavage assay. Additionally, we optimized an extrachromosomal V(D)J recombination cellular assay using murine mCherry-core RAG1, full-length murine mCherry-RAG2, and a plasmid substrate green fluorescent protein (GFP) reporter system, transfecting them into cells in the absence or presence of inhibitors. This setup enabled high-throughput analysis of V(D)J recombination for multiple compounds in a dose–response manner via flow cytometry. Physiologically relevant concentrations of INSTIs were examined for their potential impact on RAG activity and V(D)J recombination, with approved INSTIs showing minimal to no effects on recombinase activity. Consequently, the findings support the continued use of INSTIs in HIV-1 treatment without substantial concern for adverse effects on V(D)J recombination and immune system function.

IMPORTANCE
INSTIs are a crucial component of antiretroviral treatments for HIV-1 infection. This study provides a careful and thorough analysis of the impact of approved INSTIs on recombinase activating gene (RAG1 and RAG2) activity, which plays a pivotal role in the adaptive immune system. The concentrations tested were derived from several clinical studies and accounted for the maximum free fraction of the drug available in patients. This approach ensures that our findings are directly applicable to clinical scenarios by providing meaningful insights into the potential drug side effects in patients. We developed biochemical and cellular assays to measure the impact of INSTIs on RAG activity. All tested INSTIs did not inhibit RAG at supratherapeutic concentrations in the RAG1/RAG2 biochemical cleavage and cellular V(D)J recombination assays. Our assessment supports the continued use of INSTIs in HIV-1 treatments without concern for adverse effects.
Appearance Modeling of Iridescent Feathers with Diverse Nanostructures
Authors: Yu Yunchen , Weidlich Andrea , Walter Bruce , d'Eon Eugene , Marschner Steve 
Published: November 2024

Many animals exhibit structural colors, which are often iridescent, meaning that the perceived colors change with illumination conditions and viewing perspectives. Biological iridescence is usually caused by multilayers or other periodic structures in animal tissues, which selectively reflect light of certain wavelengths and often result in a shiny appearance---which almost always comes with spatially varying highlights, thanks to randomness and irregularities in the structures. Previous models for biological iridescence tend to each target one specific structure, and most models only compute large-area averages, overlooking spatial variation in iridescent appearance.
In this work, we build appearance models for biological iridescence using bird feathers as our case study, investigating different types of feathers with a variety of structural coloration mechanisms. We propose an approximate wave simulation method that takes advantage of quasi-regular structures while efficiently modeling the effects of natural structural irregularities. We further propose a method to distill our simulation results into distributions of BRDFs, generated using noise functions, that preserve relevant statistical properties of the simulated BRDFs. This allows us to model the spatially varying, glittery appearance commonly seen on feathers. Our BRDFs are practical and efficient, and we present renderings of multiple types of iridescent feathers with comparisons to photographic images.
On an Euler–Abel Type Transform of Trigonometric Series
Authors: Berisha N. Sh. , Berisha F. M. , Sadiku M. 
Published: November 2024

In the paper, we give several limit case Euler–Abel type transforms for alternating cosine and sine series. Making use of a property of the operator of generalized difference, applied in the transforms, we give transforms for nonalternating series, which are stronger than similar transforms for alternating series given earlier.MSC2020 Classification: Primary 65B10, Secondary 42A38, 40A25, 40A05
Characteristics of a CCL21 Gene–Modified Dendritic Cell Vaccine Utilized for a Clinical Trial in Non–Small Cell Lung Cancer
Authors: Oh Michael S. , Dumitras Camelia , Salehi-Rad Ramin , Tran Linh M. , Krysan Kostyantyn , Lim Raymond J. , Jing Zhe , Tappuni Shahed , Lisberg Aaron , Garon Edward B. , Dubinett Steven M. , Liu Bin 
Published: November 2024

Abstract
The treatment of non–small cell lung cancer has made major strides with the use of immune checkpoint inhibitors; however, there remains a significant need for therapies that can overcome immunotherapy resistance. Dendritic cell (DC) vaccines have been proposed as a therapy that can potentially enhance the antitumor immune response. We have embarked on a phase I clinical trial of a vaccine consisting of monocyte-derived DCs (moDC) modified to express the chemokine C–C motif chemokine ligand 21 (CCL21-DC) given in combination with pembrolizumab. In this study, we report a comprehensive characterization of this CCL21-DC vaccine and interrogate the effects of multiple factors in the manufacturing process. We show that the cellular makeup of the CCL21-DC vaccine is heterogeneous because of the presence of passenger lymphocytes at a proportion that is highly variable among patients. Single-cell RNA sequencing of vaccines revealed further heterogeneity within the moDC compartment, with cells spanning a spectrum of DC phenotypes. Transduction with a CCL21-containing adenoviral vector augmented CCL21 secretion by moDCs, but otherwise had a minimal effect on vaccine characteristics. A single freeze–thaw cycle for stored vaccines was associated with minor alterations to the DC phenotype, as was the use of healthy donors rather than patient autologous blood. Our results highlight important considerations for the production of DC vaccines and identify underexplored factors that may affect their efficacy and immunologic impact.
NSAID Allergy Labels Associated With Mortality and Cardiovascular Outcomes in Stroke
Authors: Tsui Cheryl C.W. , Mak Hugo W.F. , Leung William C.Y. , Teo Kay Cheong , Wong Yuen Kwun , Chiang Valerie , Lau Gary K.K. , Li Philip H. 
Published: November 2024

BACKGROUND:
Mislabeled drug allergy can restrict future prescriptions and medication use, but its prevalence and impact among patients with stroke remain unknown. This study investigated the prevalence of the most commonly labeled drug allergies, their accuracy, and their impact among patients with stroke.

METHODS:
In this combined longitudinal and cross-sectional study, we compared the prevalence of allergy labels among the general population and patients with ischemic stroke between 2008 and 2014 from electronic health care records in Hong Kong. Outcomes between patients with stroke with or without the most prevalent labels (ie, NSAID) were compared. Rate of mislabeled NSAID allergy was confirmed by provocation testing.

RESULTS:

Compared with the general population (n=702 966), patients with stroke had more labels (n=235) to cardiovascular and hematopoietic system (prevalence, 19.5% versus 9.2%; odds ratio [OR], 2.4 [95% CI, 1.74–3.32];
P
<0.001) and radiographic and diagnostic agents (prevalence, 4.2% versus 0.9%; OR, 4.82 [95% CI, 2.56–9.08];
P
<0.001). The most common labels were to NSAID (prevalence, 1.8%). Patients with NSAID allergy labels were significantly less likely to be prescribed aspirin after acute stroke (OR, 0.24 [95% CI, 0.09–0.60];
P
=0.003) and on follow-up (OR, 0.22 [95% CI, 0.08–0.56];
P
=0.002). The median duration of follow-up was 6.7 years (6499±2.49 patient-years). Patients with stroke with NSAID allergy labels also experienced significantly higher mortality (OR, 7.44 [95% CI, 2.44–23.18];
P
<0.001), peripheral vascular disease (OR, 9.35 [95% CI, 1.95–44.86];
P
=0.005), and major adverse cardiovascular events (OR, 6.09 [95% CI, 2.00–18.58];
P
=0.001) in the poststroke period. Patients with NSAID allergy labels (who remained alive and could consent) were referred for allergist assessment and offered drug provocation testing. The majority (80%; 4/5) had negative provocation tests and were delabeled.

CONCLUSIONS:
NSAID allergy labels were significantly more prevalent among patients with stroke, associated with excessive mortality, peripheral vascular disease, and major adverse cardiovascular events. Given the high rate of mislabeled allergies, multidisciplinary neuro-allergy interventions could have the potential to improve patient outcomes.
Chapter 1: On the Dismissal of the MSPI Action by the General Court of the EU (Case T-158/21)
Authors: Malkmus Moritz 
Published: November 2024

Abstract
In its judgment of 9 November 2022, the General Court (GC) of the European Union fully upheld the European Commission’s Communication setting out the reasons for not adopting any of the (legislative) proposals put forward by the Minority SafePack Initiative (MSPI). This paper argues that several MSPI proposals do indeed tie in with existing EU competences and would lead to a significant extension of the protection of persons belonging to minorities within the Union. However, given the Commission’s wide discretion in responding to European Citizens’ Initiatives (ECI) and the limited standard of judicial review in this regard, it will be difficult to challenge the Commission’s dismissive response even on appeal. This does not necessarily mean the end of the initiative. The validity of its proposals under EU law is visibly consolidating and even the outcome of the appeal proceedings would not prejudice seeking to implement them by other (political) means. This paper provides a legal assessment of the above-mentioned first instance decision.
Chapter 2: Twenty-Five Years of Minority Rights Monitoring in Ukraine
Authors: Craig Elizabeth 
Published: November 2024

Abstract
The war in Ukraine is the most high-profile war in Europe since the adoption and subsequent consolidation of European minority rights standards developed in the 1990s. Using a chronological approach, this contribution uses the case study of Ukraine to illustrate significant ongoing challenges to the realisation of minority rights and to the monitoring work under the Framework Convention for the Protection of National Minorities, as well as ongoing contestation and debate over its interpretation and application in specific contexts. It thereby clearly demonstrates the problems of seeing minority rights protection as a linear process of progression and socialisation rather than an ongoing process of negotiation that constantly needs to be adapted to current political realities. This is crucial to discussions not just over the future of minority rights in Ukraine but also to the future work of the Framework Convention Advisory Committee.
Chapter 3: National Minority Civil Society Organizations in Wartime
Authors: Haertel Kateryna 
Published: November 2024

Abstract
This article examines how the war in Ukraine has impacted the work of the civil society organizations of national minorities (hereinafter CSOs). The author looks into the operational specifics of three such CSOs during the first year of the war. Each organization represents a different ethnic group (i.e. Bulgarians, Hungarians, and Romanians), and is located in multi-ethnic regions of Ukraine, i.e. Odesa, Zakarpattia (or Transcarpathia, which is an alternative name for the region), and Chernivtsi respectively. Before the war, the CSOs focused on the preservation and promotion of ethnic cultures. Through desk research and interviews with the organizations’ representatives, the author attempts to answer the following sub-questions: have the organizations managed to continue working? What were their activities? Was it at all possible to promote ethnic cultures in wartime? Which risks and opportunities for their operation resulted from the war? The key finding is that the CSOs did shift their focus from the traditional realm of cultural affairs to humanitarian work. With the former activities not interrupted fully, the organizations have combined the implementation of duties from both realms, de facto operating on a wider mandate. Being a consequence of the CSOs’ ad hoc work in times of crisis, such extended engagement inter alia posed some additional opportunities for amplifying minorities’ influence in decision-making. A wider mandate is, therefore, examined by the author through the lens of its added value for improving the situation of minorities’ effective participation in public and political life in Ukraine. Inter alia, the study aims at documenting the contribution made by national minority CSOs in resisting Russia’s war of aggression.
Chapter 9: Advancing Social and Economic Rights of European Minorities from the Perspective of International Law—International Developments in 2022
Authors: Berdiqulov Aziz 
Published: November 2024

Abstract
In 2022, the reports by UN bodies and the Framework Convention for the Protection of National Minorities and the European Charter for Regional or Minority Languages monitoring findings indicated that the social and economic rights of national minorities were not yet fully implemented. The impact of the COVID-19 pandemic was featured in several reports and strategy documents since experts were still tracing the disproportionate effects of the disease on minority communities. The invasion of Ukraine by Russia sparked high-level discussions about the intersection of ethnic conflict and inequality, while several initiatives at the EU level were developed to accommodate Ukrainian refugees.
Chapter 10: Cultural Activities and Facilities, Including the Media, in the Context of the Rights of European Minorities—International Developments in 2022
Authors: Riekkinen Mariya 
Published: November 2024

Abstract
This report overviews the central 2022 international developments related to cultural activities and facilities as well as the media, or more broadly implementing the freedom of expression, in the context of the rights of European minorities. The ECtHR cases of Basu v. Germany and Muhammad v. Spain are among the highlights, since they elaborate on ethnic profiling during identity checks by the police. The adoption of General Comment No. 26 (2022) on Land and Economic, Social and Cultural Rights by the UN CESCR Committee and the General Recommendation No. 39 (2022) on the rights of Indigenous Women and Girls by the CEDAW Committee is also commented on as among the most significant advancements in 2022.
Freedom of Association in South Africa
Authors: Nankan Sahara 
Published: November 2024

Abstract
This article examines, as a foundational touchstone, the ways in which the South African Constitutional Court has interpreted the nature, scope and rationales that undergird the right to freedom of association enshrined under Section 18 of the Constitution. It is divided into two inter-linked thematic parts. Part i. outlines the socio-legal and historical development of the right, its nature and scope understood within a unique constitutional framing: its positive and negative elements, applicability of international law, comparative case law, and justifiable limitations. Part ii. then highlights some of the key rationales for respecting, protecting and promoting freedom of association, in particular, on the interplay between collective interests, group rights and individual liberty within the wider purposes of ensuring harmonious and coherent democratic pluralism. It seeks to inform, demystify and map the common threads and key underpinnings of the Court’s highly interpretative approach and provides plenty of room for further exploration, reflection and analysis.
A rare case of late-onset spondyloenchondrodysplasia with immune dysregulation presenting as adult-onset monogenic lupus
Authors: Firat Senturk Esra , Ayvaz Bilal Berke , Firtina Sinem , Ugurlu Serdal 
Published: November 2024

Background Spondyloenchondrodysplasia is classified as an interferonopathy resulting from recessive mutations in the ACP5 gene and manifests with various clinical features, including distinctive skeletal dysplasia, neurological abnormalities, immune dysfunction resembling systemic lupus erythematosus (SLE) and Sjogren’s syndrome. While SLE is typically considered multifactorial and more prevalent in adulthood, a subset of approximately 10%–25% of childhood cases arise from monogenic form. Among these, spondyloenchondrodysplasia accounts for only a rare fraction of monogenic lupus cases, with only 22 reported instances in the literature. Case Report This paper presents a new case of spondyloenchondrodysplasia-immune dysregulation (SPENCDI) in an adult patient born to nonconsanguineous parents. The patient was diagnosed with SPENCDI and exhibited immune neutropenia, anti-dsDNA positivity, platyspondyly, immune deficiency, and a homozygous variant (c.155 A > C, p. Lys52Thr) in the ACP5 gene, previously classified as pathogenic. Notably, the patient achieved successful clinical management through the initiation of baricitinib treatment, a Janus kinase inhibitor. Conclusion SPENCDI represents an uncommon cause of SLE in adulthood. Clinicians should be vigilant of underlying Mendelian inheritance when encountering patients with associated features. While treatments for both Mendelian and non-Mendelian SLE are similar, Janus kinase inhibitors like baricitinib show potential for managing interferon-signature monogenic SLE cases.
Factors Associated With Quality of Life Among Colorectal Cancer Patients: Cross-Sectional Study
Authors: Flórez Jorge Emilio Salazar , Zapata Juanita Lozano , Duarte María Camila Pérez , Acevedo Valentina Valencia , Calle José Alejandro Zapata , Montoya Alejandra Rendón , Cardona Luz Stella Giraldo 
Published: November 2024

Introduction Colorectal cancer is a chronic condition that affects a substantial proportion of the global population. Ensuring a satisfactory quality of life (QoL) for these patients is, therefore, of critical importance. Objective To examine the relationship between sociodemographic, economic, lifestyle, and health-related variables and quality of life in patients with colorectal cancer receiving treatment at a leading health institution in Medellín, Colombia. Methods This cross-sectional study included all patients aged 18 years and older who were diagnosed with colorectal cancer and treated at the VIDA Clinic Foundation in 2022. Descriptive and bivariate analyses were conducted to characterize the population and explore factors associated with QoL, as assessed using the Functional Assessment of Cancer Therapy-Colorectal (FACT-C) scale. The Mann-Whitney U and Kruskal-Wallis tests were applied to compare median values across variables. A Generalized Linear Model (GLM) with a Gamma family distribution and identity link function was used to identify explanatory variables influencing QoL. Regression coefficients and 95% confidence intervals were calculated. Results A total of 126 patients with colorectal cancer were evaluated, of whom 60.3% were women, with a median age of 61.5 years. The regression model identified poor sleep quality, lack of financial support, dissatisfaction with income, and unemployment as significant factors negatively associated with QoL, after adjusting for sociodemographic variables. Conclusion This study provides an initial exploration of health-related QoL in a Colombian population diagnosed with colorectal cancer. The findings highlight the critical influence of both health-related and socioeconomic factors on patients' QoL. A holistic approach to addressing these dimensions could enhance patient care and inform more effective support strategies.