bluuebunny/crossref_metadata_2025 huggingface dataset:
The Scottish Hepatology Access Research Partnership (SHARP) improving access to liver services throughout Scotland
Authors: Lynch Ruairi , Fallowfield Jonathan , Blane David , Swann Rachael , Mills Kirsty , Cordwell Amy , Forrest Ewan ,   Scottish Hepatology Access Research Partnership (SHARP)
Published: October 2024

Background and aims Scotland has the highest rate of deaths from chronic liver disease (CLD) in the UK. Socioeconomic and geographic isolation represent significant challenges to delivery of care. The multidisciplinary Scottish Hepatology Access Research Partnership (SHARP) aimed to identify and break down barriers to diagnosing and treating liver disease in Scotland. Methods SHARP comprised a core Partnership Management Group that developed projects and a Partnership Advisory Group which provided oversight. Results SHARP established workstreams to achieve its aims: Understanding current access to liver services To identify barriers to liver patient care in Scotland we audited liver services and surveyed the experience of patients (n=276); primary care physicians (n=199) and Gastroenterologists/Hepatologists (n=99). Technologies to monitor and diagnose CLD Liver disease is diagnosed and monitored using routine blood testing which disadvantages isolated patients. We plan to develop a point of use test to analyse ALT and AST to enable community-based identification and monitoring of liver disease. Identification of patients at risk of liver disease CLD is often diagnosed late. We propose developing an artificial intelligence tool to predict an individual's risk of an emergent admission to hospital due to CLD. This tool will be validated in a Welsh cohort. Barriers to engagement with care for liver disease Hepatology did-not-attend rates are the highest of any specialty. We propose research to co-design a suite of recommendations to improve engagement with care for CLD patients. We aim to achieve this by interviewing practitioners alongside patients who do and don’t engage with services. Conclusions Through a national survey SHARP has developed an understanding of the issues affecting access to hepatology services in Scotland. SHARP has developed projects that will help address the issues that socioeconomically and geographically isolated patients face when it comes to identifying and treating liver disease.
THE INTERSECTION OF TIME: THE IMAGINARY MEETING AMONG RONGGOWARSITO, MANGKUNEGORO IV AND RADEN SALEH
Authors: Subiyanto Subiyanto , Rustopo Rustopo , Kartika Dharsono Sony
Published: October 2024

The 19th century was a turbulent period for the island of Java, especially for its Javanese inhabitants, who had recently survived a devastating conflict known as the Java War. Prince Diponegoro became a symbol of Javanese resistance and a pivotal figure, signifying the inception of the high colonial era under the rule of Pax Nederlandica. Key historical figures like Raden Ngabehi Ronggowarsito, Mangkunegoro IV, and Raden Saleh Syarif Bustaman came of age in this epoch. The research project seeks to juxtapose the thoughts of these three key historical figures. A historical approach is used to analyze the available primary and secondary data and to constitute a metaphorical approach for reading art through the prism of these three exceptionally talented figures. The creative process of “The Intersection of Time” has been produced based on various considerations. Their interactions resulted in (1) heightened social awareness, which is evident in the way their thought processes responded to contemporary socio-economic, political, and cultural conditions during their respective lifetimes; (2) increased aesthetic awareness, allowing for creative responses to their environment and contemporary circumstances through their work; and (3) enhanced spiritual awareness, informing their individual and collective initiatives to protect Java’s circumstance. Drawing from a profound understanding of Javanese history, the history of the three selected individuals, and their artwork, the film “The Intersection of Time” will effectively encapsulate the distinct spirit and zeitgeist of the 19th century, setting it apart from conventional historical narratives.
Lille erasmus exchange
Authors: Dablouk Lena
Published: October 2024

Lille Erasmus Exchange
Different inflammatory, fibrotic, and immunologic signatures between pre-fibrotic and overt primary myelofibrosis
Authors: Jung Seung-Hyun , Lee Sung-Eun , Yun Sujin , Min Da-Eun , Shin Youngjin , Chung Yeun-Jun , Lee Sug Hyung
Published: October 2024

Primary myelofibrosis (PMF) is a myeloid proliferative neoplasm (MPN) characterized by bone marrow (BM) fibrosis. Pre-fibrotic PMF (pre-PMF) progresses to overt PMF. Megakaryocytes (MKs) play a primary role in PMF; however, the functions of MK subsets and those of other hematopoietic cells during PMF progression remain unclarified. Therefore, we analyzed BM aspirates in pre-PMFs, overt PMFs, and other MPNs using single-cell RNA sequencing (scRNA-seq). We identified 14 cell types with subsets, including hematopoietic stem and progenitor cells (HSPCs) and MKs. HSPCs in overt PMF were MK-biased and inflammation/fibrosis-enriched. Among MKs, the epithelial-mesenchymal transition (EMT)-enriched subset was abruptly increased in overt PMF. MKs in non-fibrotic/non-PMF MPN were MK differentiation-enriched, whereas those in fibrotic/non-PMF MPN were inflammation/fibrosis-enriched. Overall, the inflammation/fibrosis signatures of the HSPC, MK, and CD14+ monocyte subsets increased from pre-PMF to overt PMF. Cytotoxic and dysfunctional scores also increased in T and NK cells. Clinically, MK and HSPC subsets with high inflammation/fibrosis signatures were frequent in the patients with peripheral blood blasts ≥1%. scRNA-seq predicted higher cellular communications of MK differentiation, inflammation/fibrosis, immunologic effector/dysfunction, and tumor-associated signaling in overt PMF than pre-PMF. However, no decisive subset emerged during PMF progression. Our study demonstrated that HSPCs, monocytes, and lymphoid cells contribute to PMF progression, and subset specificity existed regarding inflammation/fibrosis and immunologic dysfunction. PMF progression may depend on multiple cell types’ alterations, and EMTenriched MKs may be potential targets for the diagnosis and therapy of the progression.
Expression levels of genes implicated in the working mechanism of lenalidomide predict treatment response in lower risk myelodysplastic syndrome patients
Authors: In’t Hout Florentien E.M. , Scheele Thessa N. , Westers Theresia M. , Alhan Canan , Duetz Carolien , Cremers Eline M.P. , Visser-Wisselaar Heleen A. , Verbrugge Annelies , Chitu Dana A. , Van der Reijden Bert A. , De Graaf Aniek O. , Van de Loosdrecht Arjan A. , Jansen Joop H.
Published: October 2024

Not available.
Abdullah HAMIDADDIN (Editor), The Huthi Movement in Yemen: Ideology, Ambition, and Security in the Arab Gulf (London, Bloomsbury Publishing, 2023)
Authors: Doğan Akkaş Betül
Published: October 2024

Abdullah Hamidaddin edited a comprehensive study published by Bloomsbury in cooperation with King Faisal Research and Islamic Studies. The book provides outstanding research on the Huthi movement including sections on its ideology, belief system; and role in reconfiguring one of the oldest and strongest culture and history in the region. The current state of the Yemeni government, that is the divided and insecure rule of country since the Arab revolts in 2011 poses military and political threats to the Arab Gulf States and the Horn of Africa. Yemen hosts paramilitary groups like the Huthis and Al-Qaeda in the Arabian Peninsula along with unorganized groups belonging to Islamic State of Iraq and Syria (ISIS) as well as military groups with links to the Southern secessionists. Yemen is a failed state that poses serious insecurities for its citizens and for other states in the region. The underlining socio-economic problems of Yemen in terms of lack of economic activities, food insecurity, and the security of civilians are closely related with the ongoing proxy war between Saudi Arabia and Iran; the military intervention led by Saudi Arabia since 2015; the internal conflict among three major groups including Huthis, the Central government and the Southern secessionists. Amid all these overlapping elements of the conflict, the nature of the Huthi movement and how it has evolved to be major actor in Yemen require further attention.
Sergei I. ZHUK, KGB Operations against the USA and Canada in Soviet Ukraine, 1953-1991 (London and New York, Routledge, 2022)
Authors: Koç Mustafa
Published: October 2024

Professor Zhuk’s “KGB Operations against the USA and Canada in Soviet Ukraine, 1953- 1991” focuses on the post-Stalin Cold War period, when Soviet Ukraine was gradually opened to American and Canadian visitors and combines counter-intelligence documents in the 1st (and 16th) fund of Security Service of Ukraine (SBU) archive with the Committee for State Security’s (KGB) official correspondence and reports to the political leadership of Soviet Ukraine. The first and most important historical source of the book which follows a chronological and thematic sequence reflecting the story of special KGB operations is the reports of various KGB agents who participated in KGB counterintelligence operations. The second group of “unexpected” sources, as the author calls it, consists of interviews with retired KGB officials in Kyiv and Dnipro. In the first part of the book (pp. 1-94), it is emphasized that the most important target of the KGB in the geopolitical conflict was Ukrainian nationalism, which was linked to and financed by Americans, and from 1953 to 1991, almost 50% of all criminal cases were devoted to this “dangerous” issue of Ukrainian nationalism. The author states that the second target of Ukrainian KGB was Jewish nationalism, while the third target was religious sects and the fourth target was American espionage. The most interesting narrative of the first part is the “Yankees case” involving Valentina Fedorovna Safianova and seven so-called nationalist Jews. Professor Zhuk, who mentioned in his work that the KGB adopted an antiSemitic approach despite the Soviet Union’s (USSR) official distancing from anti-Semitism, states that the KGB used Ukrainians and Russians for the needs of Soviet intelligence. The Ukrainian diaspora in America in the 1960s became the “useful means” of the Soviet KGB and one demonstrative example used by the author, Zhuk, is Peter Krawchuk who visited Soviet Ukraine as a member of Canadian Ukrainian Communist Delegations almost every year starting from 1947. Zhuk wrote regarding Peter Krawchuk that “Their material wellbeing, even their Canadian businesses depended on those relations (p. 66)”.
Ben BUCHANAN, The Hacker and the State: Cyber Attacks and the New Normal of Geopolitics (Cambridge, Harvard University Press, 2020)
Authors: Lorci Enescan
Published: October 2024

In “Hacker and the State: Cyber Attacks and the New Normal of Geopolitics,” a comprehensive work spanning three chapters, Ben Buchanan undertakes a significant exploration of the transformative effect that hackers have had on global affairs over the past two decades. Positioned at the intersection of cyberspace and international relations, Buchanan employs the established concepts of “signaling and shaping” from the field of International Relations (IR), which refer to the tactics and activities that governments or other players use to convey their intentions, sway public opinion, and mold geopolitical outcomes. In IR, signaling refers to deliberate acts or signals taken by states or other actors to tell others about their intentions or capacities, affecting perceptions and forming expectations in the process. Contrarily, shaping describes intentional attempts to alter the dynamics, norms, or structure of the international system to bring about outcomes that support one’s strategic goals or interests. For example, in the field of IR, nuclear capabilities are frequently analyzed as signaling mechanisms due to their potential for catastrophic destruction. Similarly, contemporary scholarship suggests that cyber capabilities have become increasingly instrumental for signaling purposes, reflecting the evolving dynamics of international security and diplomacy.
Dennis DIJKZEUL and Margit FAUSER (eds.), Diaspora Organisations in International Affairs (Oxon, Routledge, 2020)
Authors: Özdemir Oğuzhan
Published: October 2024

Diasporas and their organisations, which traditionally aimed to serve their interest in the homeland and abroad, have long been studied under several social science disciplines, such as anthropology, sociology, political science, and geography. At the beginning of the 2000s, for instance, human and political geographers started to focus on diaspora realizing that it is a geographical concept, which addresses various geographical themes such as dispersion, boundaries, territory (as homeland), and identity. The “geographical turn” contributed to the concept theoretically, and also to transnationalism and migration studies empirically by which cases were reconsidered through the lens of geographical concepts, such as space, place, and time. Similar to geographers’ arguments, diaspora organisations (DO) -as a distinct form of collectivity- and their activities are very relevant to what we study in International Relations (IR), especially when it comes to exploring DOs’ role that transcends state borders in development, human rights, conflict, and peace. In that regard, attempts to introduce novel contributions from various disciplines have the potential to significantly enhance our comprehension of the theory of diaspora and its associated organizations.
Dominique AREL and Jesse DRISCOLL, Ukraine’s Unnamed War: Before the Russian Invasion of 2022
Authors: Pala Burulkan , Çetin Nur
Published: October 2024

The 400-day-long occupation of Ukraine has cost thousands of lives and billions of dollars and continues to threaten global stability to this day. In the aftermath of Russia’s February
2022 attack on Ukraine, there has been an increasing number of studies, articles, books, and commentaries, including a book co-authored by Dominique Arel and Jesse Driscoll entitled
Ukraine’s Unnamed War: Before the Russian Invasion of 2022, which provides vital information to understand the context that preceded the 2022 invasion by focusing on the events between
Russia and Ukraine from 2013-2021.
Modeling Android Security Vulnerabilities: Insights from Statistical Distributions
Authors: Gencer Kerem , Basciftci Fatih
Published: October 2024

Android operating system is a mobile operating system that supports multimedia features. Android offers a wide range of applications and integrated features for playing, recording, editing and sharing audio, video, images and other multimedia content. Most Android devices include cameras, speakers, microphones, and other multimedia components. In software security, vulnerabilities are critical concerns that often emerge during software development. Predicting these vulnerabilities post-release is essential for risk assessment and mitigation. While various models have been explored, the Android operating system remains relatively uncharted. This study delves into modeling Android security vulnerabilities using different statistical distributions, comparing their suitability to the widely-used Alhazmi-Malaiya Logistic (AML) model. Data from the National Vulnerability Database (NVD) spanning 2016 to 2018, along with Common Vulnerability Scoring System (CVSS) scores, was analyzed. The study evaluates several distribution models, including Logistic, Weibull, Nakagami, Gamma, and Log-logistic, for monthly vulnerability counts and average monthly impact values. Goodness-of-fit tests and information criteria were applied for model robustness assessment. The findings offer valuable insights for researchers and Android software developers, aiding prediction, risk assessment, resource allocation, and research direction. Logistic and Nakagami distributions emerged as the best-fit models for average monthly impact values and monthly vulnerability counts, respectively. Finally, statistical methods perform better against known artificial intelligence methods for small data sets or more clearly defined data due to their flexible features such as comprehensibility, amount of data, need for calculation, and data independence.
Effect of climate change on ecosystem service trade-offs and synergies: a case study in Huai River Basin
Authors: Yu H , Zhang F , Ma H , Sun R , Xu X , Lu Y
Published: October 2024

Uncovering changes in ecosystem services (ESs) and their interactions, and exploring the effect of climate change, is fundamental to developing ecosystem management. In this study, carbon sequestration (CS), water yield (WY), and soil conservation (SC) in the Huai River Basin (HRB) from 2001 to 2020 were investigated using meteorological and remote sensing data. The results show that CS showed a significant increasing trend (p < 0.01), especially in the central region, while WY and SC showed a non-significant increasing trend (p > 0.05), especially in the southern and eastern regions. Synergistic relationships existed between all ESs, but shifted in specific regions. The CS-SC pair shifted from trade-off to synergistic in the northeast; the CS-WY pair shifted from synergistic to trade-off in the center, east, and west; and the SC-WY pair shifted in both trade-off and synergistic relationships in the east. The main drivers of changes in these relationships included vegetation cover, topography, climate change, and land use type. Specifically, the normalized difference vegetation index (NDVI) and digital elevation model (DEM) dominated changes in the CS-SC pair, air temperature, DEM, total solar radiation, and precipitation dominated changes in the CS-WY pair, and precipitation and DEM dominated changes in the SC-WY pair. These findings will help inform the development of refined ecological restoration efforts and management policies.
Land use and runoff effects on tidal creek ecosystem metabolism
Authors: Bickley S , Isik S , Anderson CJ , Kalin L
Published: October 2024

Tidal creeks connect coastal lands and estuaries and are important conduits of watershed runoff and pollutants. With expanding urban development in many coastal areas, increased stormwater runoff to tidal creeks has the potential to increase nutrient loading, shift salinity regimes, and change ecosystem functions. To better understand these linkages, we measured dissolved oxygen (DO), water levels, salinity, and temperature for over 1 yr at 6 tidal creeks in Alabama and western Florida, USA. We coupled these measures with watershed-model (Soil and Water Assessment Tool) estimates of nutrient (NO3-, NH4+, and mineralized P) loading, flow, and other available watershed data. We estimated gross primary productivity, ecosystem respiration (ER), and net ecosystem metabolism (NEM) and found that all creeks were heterotrophic throughout the study period and frequently experienced periods of low DO. Our results did not identify a direct relation between urban land use and metabolism measures. Stepwise regression models showed that temperature, salinity fluctuations, and nitrogen loading were associated with seasonal measures of ER and NEM, which may be related to agricultural land use in some watersheds. We also noted that severe declines in DO related to ER occurred in most creeks following rainfall events associated with tropical cyclones. While this study indicates that low- to moderate-density residential development in this region may not readily elicit a response in ecosystem metabolism, runoff factors associated with land use change and excessive precipitation were related to metabolism. Further research is needed to understand how these stressors may interact to influence tidal creeks and the larger estuary.
RENEWABLE ENERGY SOURCES FOR SUSTAINABLE OFF-GRID ELECTRIFICATION IN MOKWA LGA CASE STUDY OF EDAN RURAL COMMUNITY
Authors:   Electrical Maintenance department  Kanji hydro power plant, Niger State, Nigeria., Ademola Alabi , Gbenro Philip Oguntunde ,   Department of Agricultural Engineering  Federal university of technology Akure,  Nigeria., Adekunle Nicholas Adefela ,   Centre for renewable energy  Federal university of technology Akure,  Ondo State, Nigeria.
Published: October 2024

Utilizing renewable energy sources for off-grid electrification has emerged as a viable solution in the pursuit of sustainable development, particularly for rural communities where conventional grid extension is challenging. The focus of this research is Edan, an isolated community within Mokwa Local Government Area (LGA) that faces significant economic and technical hurdles with traditional power options. This study aims to assess whether solar or wind could supply consistent and steady electricity to meet their needs sustainably. The methodology involves assessing renewable resources available within Edan through feasibility analyses on several different off-grid systems. Taking into account the high levels of solar irradiance experienced in the region, photovoltaic (PV) systems appear promising due to suitability; however data surrounding wind speed yield results less favorable than PVs. Hybrid solutions combining both options may offer stability while remaining cost-effective when put forth accordingly. Successful implementation depend heavily upon involvement from local leaders capable of upholding ownership over system maintenance by equipping them with capacity building tools imperative project success at all stages until completion along continuing usage thereafter. By highlighting tailored strategies utilized during remote area electrification processes such as found here provides helpful insights useful applyable elsewhere even across Nigerian borders beyond set limitations encountered en route implementing grassroots endeavors towards cleaner sourced self-sustainable worldwide.
ENHANCED ENERGY EFFICIENCY OF WIRELESS SENSOR NETWORKS USING PROTOCOL BASED RESPONSE ROUTING (PBRR) IN OIL RIG
Authors:   Department of Electronic and Computer Engineering  Faculty of Engineering  Nnamdi Azikiwe University Awka  Anambra State Nigeria, Nneka Okeke , Victor N Okorogu , Scholastica U Nnebe , Ekene E Alagbu , Charles O Oranugo
Published: October 2024

A system called system-Based Response Routing (PBRR) was created to increase energy efficiency in wireless sensor networks (WSNs) installed on oil rigs. By optimizing routing choices in response to sensor responses, PBRR reduces energy usage and increases network lifetime. It ensures that vital information is transmitted on time while sparing less urgent data from energy use by prioritizing data transmission according to urgency. By using multi-hop routing techniques, PBRR saves energy costs and guarantees dependable monitoring under difficult circumstances. This method makes WSNs more practical for long-term deployment in difficult situations like oil rigs.
A hybrid mock circulatory loop integrated with a LED-PIV system for the investigation of AAA compliant phantoms
Authors: Bardi Francesco , Gasparotti Emanuele , Vignali Emanuele , Antonuccio Maria Nicole , Storto Eleonora , Avril Stéphane , Celi Simona
Published: October 2024

Background

Cardiovascular diseases remain a leading cause of morbidity and mortality worldwide and require extensive investigation through in-vitro studies. Mock Circulatory Loops (MCLs) are advanced in-vitro platforms that accurately replicate physiological and pathological hemodynamic conditions, while also allowing for precise and patient-specific data collection. Particle Image Velocimetry (PIV) is the standard flow visualization technique for in-vitro studies, but it is costly and requires strict safety measures. High-power Light Emitting Diode illuminated PIV (LED-PIV) offers a safer and cheaper alternative.

Methods

In this study, we aim to demonstrate the feasibility of a Hybrid-MCL integrated with a LED-PIV system for the investigation of Abdominal Aortic Aneurysm (AAA) compliant phantoms. We considered two distinct AAA models, namely, an idealized model and a patient-specific one under different physiological flow and pressure conditions.

Results

The efficacy of the proposed setup for the investigation of AAA hemodynamics was confirmed by observing velocity and vorticity fields across multiple flow rate scenarios and regions of interest.

Conclusion

The findings of this study underscore the potential impact of Hybrid-MCL integrated with a LED-PIV system on enhancing the affordability, accessibility, and safety of in-vitro CVD investigations.
Mapping the landscape of PSC-CM research through bibliometric analysis
Authors: Li Jun , Han Shangting , Yu Fengxu , Li Tao , Liao Bin , Liu Feng
Published: October 2024

Objectives

The discovery of pluripotent stem cell-derived cardiomyocytes (PSC-CMs) has not only deepened our understanding of the pathogenesis and progression of heart disease, but also advanced the development of engineered cardiac tissues, cardiac regenerative therapy, drug discovery and the cardiotoxicity assessment of drugs. This study aims to visualize the developmental trajectory of PSC-CM research over the past 18 years to identify the emerging research frontiers and challenges.

Methods

The literature on PSC-CMs from 2007 to 2024 was retrieved from the Web of Science and PubMed databases. Bibliometrix, VOSviewer and CiteSpace software were used for statistical analysis and visualization of scientific literature. Previous clinical trials were summarized using data from the ClinicalTrials.gov database.

Results

A total of 29,660 authors from 81 countries and regions published 6,406 papers on PSC-CMs over the past 18 years. The annual output of PSC-CM research experienced a general upward trend from 2007 to 2021, reaching its peak in 2021, followed by a notable decline in 2022 and 2023. The United States has emerged as the most influential nation in this field, with Stanford University being the most prolific institution and Joseph C. Wu standing out as the most productive and highly cited scholar. Circulation Research, Circulation, and Nature have been identified as the most co-cited journals. Organ-on-a-chip, 3D bio-printing, cardiac microtissue, extracellular vesicle, inflammation, energy metabolism, atrial fibrillation, personalized medicine etc., with a longer burst period, and maturation of PSC-CMs, with the highest burst strength of 27.19, are the major research focuses for rigorous investigation in recent years. Cardiac organoid is emerging as a promising key research frontier. While the clinical trials of stem-cell-mediated treatment for heart diseases shows promise, significant challenges remain. Further research is imperative to optimize protocols, enhance cell delivery methods, and establish standardized practices to improve clinical outcomes.

Conclusions

In conclusion, several major research hotspots, including engineered cardiac tissue and maturation, exosome-based regenerative therapy, inflammation response, energy metabolism, atrial fibrillation, and personalized medicine etc. will continue to attract substantial interest from investigators worldwide. Cardiac organoids to in vitro recapitulate the intricate human heart is emerging as a promising key research frontier. Significant challenges persist in the clinical trials of stem-cell-mediated therapies for heart diseases.
AI security and cyber risk in IoT systems
Authors: Radanliev Petar , De Roure David , Maple Carsten , Nurse Jason R. C. , Nicolescu Razvan , Ani Uchenna
Published: October 2024

Internet-of-Things (IoT) refers to low-memory connected devices used in various new technologies, including drones, autonomous machines, and robotics. The article aims to understand better cyber risks in low-memory devices and the challenges in IoT risk management. The article includes a critical reflection on current risk methods and their level of appropriateness for IoT. We present a dependency model tailored in context toward current challenges in data strategies and make recommendations for the cybersecurity community. The model can be used for cyber risk estimation and assessment and generic risk impact assessment. The model is developed for cyber risk insurance for new technologies (e.g., drones, robots). Still, practitioners can apply it to estimate and assess cyber risks in organizations and enterprises. Furthermore, this paper critically discusses why risk assessment and management are crucial in this domain and what open questions on IoT risk assessment and risk management remain areas for further research. The paper then presents a more holistic understanding of cyber risks in the IoT. We explain how the industry can use new risk assessment, and management approaches to deal with the challenges posed by emerging IoT cyber risks. We explain how these approaches influence policy on cyber risk and data strategy. We also present a new approach for cyber risk assessment that incorporates IoT risks through dependency modeling. The paper describes why this approach is well suited to estimate IoT risks.
Rate of testicular histology failure in predicting successful testicular sperm extraction
Authors: Castellano Stefano , Tondo Francesca , Bulbul Ozgur , Aprea Sabrina , Monti Emanuela , Carnesi Edoardo , Levi Setti Paolo Emanuele , Albani Elena
Published: October 2024

Background

The management of Non-Obstructive (NOA) Azoospermia or Obstructive Azoospermia (OA) patients relies on testicular sperm extraction (TESE) followed by intracytoplasmic sperm injection (ICSI). In NOA patients the sperm recovery is successful in only 50% of cases and therefore the ability to predict those patients with a high probability of achieving a successful sperm retrieval would be a great value in counselling the patient and his partner. Several studies tried to suggest predictors of a positive TESE (e.g. FSH concentration), but most concluded that diagnostic testicular biopsy (histology) is best.

Methods

This is a retrospective analysis of 526 TESE patients. After the extraction of the testis, the resulting sample was immediately given to the embryologist, who examined the tubules for sperm cryopreservation. During the same procedure, a different specimen was destined to the histological analysis. The comparison between the two methodological approaches was carried out through a score.

Results

Concordance between TESE and testicular histology outcomes was found in 70,7% of patients; discordance was found in 29,3% of patients. Among the discordance outcomes, in approximately 95% we found at least 1 sperm in the TESE retrieval, while the histology report did not find any spermatozoa or found not enough compared to our evaluation; in only 5% of cases we did not find any spermatozoa or found not enough compared to what was detected in the testicular histology.

Conclusion

Based on our experience, to increase diagnostic accuracy, a larger biopsy should be sent to the histopathology laboratory; another option may be to use TESE cell suspension (the same embryologists employ for cryopreservation) for cytological evaluation of spermatogenesis.
Modified Dendritic cell-based T-cell expansion protocol and single-cell multi-omics allow for the selection of the most expanded and in vitro-effective clonotype via profiling of thousands of MAGE-A3-specific T-cells
Authors: Sennikov Sergey , Volynets Marina , Alrhmoun Saleh , Perik-Zavodskii Roman , Perik-Zavodskaia Olga , Fisher Marina , Lopatnikova Julia , Shevchenko Julia , Nazarov Kirill , Philippova Julia , Alsalloum Alaa , Kurilin Vasily , Silkov Alexander
Published: October 2024

Introduction

Adoptive cell therapy using TCR-engineered T-cells is one of the most effective strategies against tumor cells. The TCR T-cell approach has been well tested against a variety of blood neoplasms but is yet to be deeply tested against solid tumors. Among solid tumors, cancer-testis antigens are the most prominent targets for tumor-specific therapy, as they are usually found on cells that lie behind blood-tissue barriers.

Methods

We have employed a novel efficient protocol for MAGE-A3-specific T-cell clonal expansion, performed single-cell multi-omic analysis of the expanded T-cells via BD Rhapsody, engineered a selected T-cell receptor into a lentiviral construct, and tested it in an in vitro LDH-cytotoxicity test.

Results and discussion

We have observed a 191-fold increase in the MAGE-A3-specific T-cell abundance, obtained a dominant T-cell receptor via single-cell multi-omic BD Rhapsody data analysis in the TCRscape bioinformatics tool, and observed potent cytotoxicity of the dominant-clonotype transduced TCR T-cells against a MAGE-A3-positive tumor. We have demonstrated the efficiency of our T-cell enrichment protocol in obtaining potent anti-tumor T-cells and their T-cell receptors, especially when paired with the modern single-cell analysis methods.
Binding to the neonatal Fc receptor enhances the pathogenicity of anti-desmoglein-3 antibodies in keratinocytes
Authors: Zakrzewicz Anna , Vanderheyden Katrien , Galaly Yad , Feldhoff Simon , Sips Magdalena , Brinkhaus Maximilian , Tikkanen Ritva
Published: October 2024

The neonatal Fc receptor (FcRn) is important for numerous cellular processes that involve antibody recycling and trafficking. A major function of FcRn is IgG recycling and half-life prolongation, and FcRn blockade results in a reduction of autoantibodies in IgG-mediated autoimmune diseases. In epithelial cells, FcRn functions in processes different from IgG recycling, such as antibody transcytosis in intestinal cells. In pemphigus vulgaris, an autoimmune disease of the epidermis, IgG autoantibodies directed against desmosomal adhesion proteins, especially desmoglein-3 and -1, cause loss of keratinocyte adhesion. We have previously demonstrated that FcRn blockade with efgartigimod, a human Fc fragment with enhanced FcRn binding, significantly reduces the keratinocyte monolayer fragmentation caused by anti-desmoglein-3 antibodies. This points to a direct function of FcRn in keratinocytes, beyond IgG recycling, but the mechanisms have not yet been elucidated in detail. Here, we show that FcRn binding is required for the full pathogenicity of recombinant anti-desmoglein-3 antibodies in keratinocytes, and that antibodies that exhibit enhanced or reduced FcRn affinity due to targeted substitutions in their Fc region, as well as F(ab’)2 fragments not binding to FcRn display different degrees of pathogenicity. Blockade of FcRn by efgartigimod only shows a protective effect on keratinocyte adhesion against antibodies capable of binding to FcRn. Furthermore, antibody-induced degradation of desmoglein-3 in keratinocytes does not depend on FcRn, demonstrating that desmoglein-3 degradation and acantholysis are functionally disconnected processes. Our data suggest that the role of FcRn in autoimmune diseases is likely to be versatile and cell-type dependent, thus stressing the importance of further studies on FcRn function in autoimmune diseases.
Revolutionizing the treatment for nasopharyngeal cancer: the impact, challenges and strategies of stem cell and genetically engineered cell therapies
Authors: Looi Chin-King , Loo Ee-Mun , Lim Heng-Chee , Chew Yik-Ling , Chin Kok-Yong , Cheah Shiau-Chuen , Goh Bey Hing , Mai Chun-Wai
Published: October 2024

Nasopharyngeal carcinoma (NPC) is a distinct malignancy of the nasopharynx and is consistently associated with the Epstein-Barr virus (EBV) infection. Its unique anatomical location and complex aetiology often result in advanced-stage disease at first diagnosis. While radiotherapy (RT) and chemotherapy have been the mainstays of treatment, they often fail to prevent tumour recurrence and metastasis, leading to high rates of treatment failure and mortality. Recent advancement in cell-based therapies, such as chimeric antigen receptor (CAR)-T cell therapy, have shown great promise in hematological malignancies and are now being investigated for NPC. However, challenges such as targeting specific tumour antigens, limited T cell persistence and proliferation, and managing treatment-related toxicities must be addressed. Extensive research is needed to enhance the effectiveness and safety of these therapies, paving the way for their integration into standard clinical practice for better management of NPC and a better quality of life for human health.
Assessment of nutrient amendments on stony coral tissue loss disease in Southeast Florida
Authors: Carreiro Ashley M. , Eckert Ryan J. , Sturm Alexis B. , Ingalls Thomas C. , Combs Ian R. , Walker Brian K. , Voss Joshua D.
Published: October 2024

Florida’s coral reefs are facing a multi-year outbreak of stony coral tissue loss disease (SCTLD) with dramatic consequences for coral communities. However, potential anthropogenic and environmental drivers of SCTLD progression and severity remain poorly understood. This study was designed to determine the potential impacts of nutrient amendments on the progression and spread of SCTLD on reefs in Southeast Florida. In situ fertilizer amendments with 30 g of Osmocote™ slow-release fertilizer were used to mimic the effects of agricultural and urban runoff. Fifteen healthy and thirty SCTLD-affected Montastraea cavernosa coral colonies were tagged and divided into three experimental groups: apparently healthy colonies, SCTLD-affected nutrient-amended colonies, and SCTLD-affected control colonies. SCTLD lesion progression, coral tissue loss, and disease prevalence were tracked over a 30-day nutrient amendment period and for an additional 40 days after nutrient amendment removal to determine if there were any latent or recovery effects. Coral tissue loss was tracked over time using Structure-from-Motion photogrammetry and disease prevalence was recorded from diver surveys within a 3-m radius surrounding five centroid colonies from each experimental group. Throughout the experiment, temperature, nutrient concentrations, and SCTLD status of the coral colonies were also monitored. Ultimately, we observed no significant differences in SCTLD progression or surrounding SCTLD prevalence between the nutrient-amended and control groups, suggesting that nutrient amendment had no effect on SCTLD severity during this experiment in Southeast Florida.
Long-term sheep grazing reduces fungal necromass carbon contribution to soil organic carbon in the desert steppe
Authors: Zhao Tianqi , Lu Naijing , Guo Jianying , Zhang Xin , Liu Jing , Zhao Mengli
Published: October 2024

Grazing has been shown to impact the soil environment and microbial necromass carbon (MNC), which in turn regulates soil organic carbon (SOC). However, the carbon sequestration potential of fungi and bacteria under different stocking rates remains unclear, limiting our understanding of soil carbon sequestration in grazing management. In 2004, we established grazing experiments in the desert steppe of northern China with four stocking rates. Our findings indicate that MNC decreased under moderate and heavy grazing, while light grazing did not significantly differ from no grazing. Notably, the reduction in fungal necromass carbon, rather than bacterial necromass carbon, was primarily responsible for the decreased contribution of MNC to SOC. This difference is attributed to the varying effects of sheep grazing on fungal and bacterial community characteristics, including richness, diversity, and composition. Thus, to accurately predict carbon dynamics in grassland ecosystems, it is essential to consider that the ecological impacts and carbon sequestration potential of microbial communities may vary with different grazing management practices.
On preserving anatomical detail in statistical shape analysis for clustering: focus on left atrial appendage morphology
Authors: Lee Matthew T. , Martorana Vincenzo , Md Rafizul Islam , Sivera Raphael , Cook Andrew C. , Menezes Leon , Burriesci Gaetano , Torii Ryo , Bosi Giorgia M.
Published: October 2024

Introduction

Statistical shape analysis (SSA) with clustering is often used to objectively define and categorise anatomical shape variations. However, studies until now have often focused on simplified anatomical reconstructions, despite the complexity of studied anatomies. This work aims to provide insights on the anatomical detail preservation required for SSA of highly diverse and complex anatomies, with particular focus on the left atrial appendage (LAA). This anatomical region is clinically relevant as the location of almost all left atrial thrombi forming during atrial fibrillation (AF). Moreover, its highly patient-specific complex architecture makes its clinical classification especially subjective.

Methods

Preliminary LAA meshes were automatically detected after robust image selection and wider left atrial segmentation. Following registration, four additional LAA mesh datasets were created as reductions of the preliminary dataset, with surface reconstruction based on reduced sample point densities. Utilising SSA model parameters determined to optimally represent the preliminary dataset, SSA model performance for the four simplified datasets was calculated. A representative simplified dataset was selected, and clustering analysis and performance were evaluated (compared to clinical labels) between the original trabeculated LAA anatomy and the representative simplification.

Results

As expected, simplified anatomies have better SSA evaluation scores (compactness, specificity and generalisation), corresponding to simpler LAA shape representation. However, oversimplification of shapes may noticeably affect 3D model output due to differences in geometric correspondence. Furthermore, even minor simplification may affect LAA shape clustering, where the adjusted mutual information (AMI) score of the clustered trabeculated dataset was 0.67, in comparison to 0.12 for the simplified dataset.

Discussion

This study suggests that greater anatomical preservation for complex and diverse LAA morphologies, currently neglected, may be more useful for shape categorisation via clustering analyses.
Dynamic micro-optical coherence tomography enables structural and metabolic imaging of the mammalian cochlea
Authors: Schulz-Hildebrandt Hinnerk , Spasic Svetolik , Hou Fang , Ting Kuan-Chung , Batts Shelley , Tearney Guillermo , Stankovic Konstantina M.
Published: October 2024

Sensorineural hearing loss (SNHL) is caused by damage to the mechanosensory hair cells and auditory neurons of the cochlea. The development of imaging tools that can directly visualize or provide functional information about a patient’s cochlear cells is critical to identify the pathobiological defect and determine the cells’ receptiveness to emerging SNHL treatments. However, the cochlea’s small size, embedded location within dense bone, and sensitivity to perturbation have historically precluded high-resolution clinical imaging. Previously, we developed micro-optical coherence tomography (μOCT) as a platform for otologic imaging in animal models and human cochleae. Here we report on advancing μOCT technology to obtain simultaneously acquired and co-localized images of cell viability/metabolic activity through dynamic μOCT (DμOCT) imaging of intracellular motion. DμOCT obtains cross-sectional images of ATP-dependent movement of intracellular organelles and cytoskeletal polymerization by acquiring sequential μOCT images and computing intensity fluctuation frequency metrics on a pixel-wise basis. Using a customized benchtop DμOCT system, we demonstrate the detailed resolution of anatomical and metabolic features of cells within the organ of Corti, via an apical cochleostomy, in freshly-excised adult mouse cochleae. Further, we show that DμOCT is capable of capturing rapid changes in cochlear cell metabolism following an ototoxic insult to induce cell death and actin stabilization. Notably, as few as 6 frames can be used to reconstruct cochlear DμOCT images with sufficient detail to discern individual cells and their metabolic state. Taken together, these results motivate future development of a DμOCT imaging probe for cellular and metabolic diagnosis of SNHL in humans.
Chronic exposure to inhaled vaporized cannabis high in Δ9-THC suppresses Adderall-induced brain activity
Authors: Ognibene Jack M. , Desai Rajeev I. , Kulkarni Praveen P. , Ferris Craig F.
Published: October 2024

Background

There are increasing reports of the misuse of prescription psychostimulants for cognitive enhancement together with recreational cannabis. This raises a concern that chronic use of cannabis high in Δ9-THC may alter the sensitivity to amphetamines. In this exploratory study we hypothesized chronic exposure to Δ9-THC through vaporized cannabis would diminish the central nervous system (CNS) activity of Adderall.

Methods

To address this issue we exposed male and female mice to inhaled vaporized cannabis (10.3% Δ9-THC) or placebo for 30 min each day for ten consecutive days. After 24 h, mice were imaged fully awake for changes in BOLD signal following an IP injection of Adderall (60 µg) during the scanning session. After a 2-week washout, without any cannabis or placebo exposure, mice were again imaged and challenged with Adderall during the scanning session. The data were registered to a mouse 3D MRI atlas with 134 brain regions providing site-specific increases and decreases in global brain activity.

Results

Mice exposed to cannabis when compared to placebo showed a decrease in brain activation to Adderall. The blunted Adderall response was characterized by a decrease in positive BOLD signal and increase in negative BOLD. The prefrontal cortex, accumbens, ventral pallidum, caudate/putamen, and thalamus were most affected. After a 2-week wash out there were no significant differences between the cannabis and placebo groups when challenged with Adderall.

This exploratory study shows that short, daily exposures to inhaled cannabis, something equivalent to recreational use, affects the sensitivity to the psychostimulant Adderall. The reduced Adderall effect on brain activity, particularly circuitry associated with dopaminergic signaling raises concerns about escalation in psychostimulant use.
Fei-Yan-Qing-Hua decoction attenuates influenza virus infection by enhancing host antiviral response through microbiota-derived acetate
Authors: Dou Biao , Wu Xiao , He Yurong , Xu Guihua , Zhang Huan , Huang Qilin , Chen Xuan , Duan Naifan , Zhou Linqiong , Zhang Wei , An Huazhang , Zheng Yuejuan
Published: October 2024

Background

Fei-Yan-Qing-Hua decoction (FYQHD) is derived from the well-known Ma Xing Shi Gan decoction, which was documented in Zhang Zhong Jing’s “Treatise on Exogenous Febrile Disease” during the Han Dynasty. Although FYQHD has been used in the treatment of pneumonia and has demonstrated clinical efficacy for decades, the underlying mechanism by which FYQHD protects against influenza virus infection through modulation of gut flora remains unclear. Here, we examined the regulatory impacts of FYQHD on an influenza virus-infected mouse model and explored the mechanisms involved.

Methods

An infectious mouse model was created by intranasal instillation of influenza A virus (IAV). The effectiveness of FYQHD was assessed through various measures, including weight loss, lung wet/dry ratio, oxidative stress levels, viral load in lung tissues, and intestinal injuries. Changes in gut microbiota and SCFA production were also examined.

Results

The results showed that FYQHD significantly reduced viral load, increased the production of type I interferon (IFN-I), and restored the integrity of the intestinal barrier following IAV challenge. Additionally, FYQHD significantly corrected the dysbiosis of gut microbiota induced by influenza virus infection, enhancing the abundance of SCFA-producing bacteria and acetate production. However, the depletion of gut microbiota significantly attenuated the protective effects of FYQHD against influenza virus infection. In vitro, the antiviral effect of acetate was demonstrated through the upregulation of concentrations of IFN-β.

Conclusion

FYQHD attenuates influenza virus-induced lung and intestinal injuries by boosting the host antiviral response through increasing the abundance of Lachnospiraceae_NK4A136 and Roseburia, along with elevated acetate levels. The study advances our understanding of the therapeutic mechanisms of FYQHD and provides a theoretical basis for the application of FYQHD in the treatment of influenza.