bluuebunny/crossref_metadata_2025 huggingface dataset:
Retinal Organoids: A Next-Generation Platform for High-Throughput Drug Discovery
Authors: Zhao Hongkun , Yan Fei
Published: December 2023

Retinal diseases are leading causes of blindness globally. Developing new drugs is of great significance for preventing vision loss. Current drug discovery relies mainly on two-dimensional in vitro models and animal models, but translation to human efficacy and safety is biased. In recent years, the emergence of retinal organoid technology platforms, utilizing three-dimensional microenvironments to better mimic retinal structure and function, has provided new platforms for exploring pathogenic mechanisms and drug screening. This review summarizes the latest advances in retinal organoid technology, emphasizing its application advantages in high-throughput drug screening, efficacy and toxicity evaluation, and translational medicine research. The review also prospects the combination of emerging technologies such as organ-on-a-chip, 3D bioprinting, single cell sequencing, gene editing with retinal organoid technology, which is expected to further optimize retinal organoid models and advance the diagnosis and treatment of retinal diseases.
Fringing reef growth in the Mid-Devonian: An example from the southern Rhenish Massif, Germany
Authors: Königshof Peter , Flick Heiner
Published: December 2023

The Givetian Balduinstein Reef developed upon mixed felsic lavas and volcaniclastic tuffs. The Givetian age of the reef is proven by conodonts (Polygnathus rhenanus/varcus Zone to the Polygnathus ansatus Zone) and the occurrence of the brachiopod Stringocephalus burtini. Remains of land plants and subaerially ejected volcanic bombs in the vicinity of the outcrops document that the volcano was an emerged island surrounded by a fringing reef in an unstable tectonic environment. Reef development is characterised by a complex interaction of volcanism, erosion and the rate and pattern of sea-level change, which resulted in a variety of facies settings and rock-types. Microfacies analysis and rock-types prove that the fringing reef was backed by a shallow lagoon. A lime mudstone/alkali rhyolitic breccia represents a lava flow, or more probably a dome collapse breccia, which flowed into the lagoonal mud and confirms a contemporaneous occurrence of volcanism and reef growth. Reefs flourished during several episodes of inactivity of the volcano, particularly in the upper part of the sections, suggesting that the reef development kept up with sea-level changes and/or local events. Lithofacies of the upper part of the youngest section point to a regressive phase. The distinctive depositional architecture and evolution of the Balduinstein Reef are interpreted as having been controlled mainly by regional tectonics and volcanism with contributions from eustasy.
Early Cretaceous Equisetites from Slovakia
Authors: Kvaček Jiří , Čerňanský Andrej
Published: December 2023

A new find of terrestrial plant Equisetites cf. lyellii is reported from the Early Cretaceous of Slovakia. It comes from the Mráznica Formation of the Rajec Basin in Fatricum, Zbyňov locality, Rajecké Teplice (Žilina district). The presence of a 53 mm long horsetail axis provides good evidence of terrestrial environments during sedimentation of the studied strata. According to our interpretation, such a plant strongly indicates a moist to wet habitat (even swampy environments) on the presumed dryland from where it was transported. This dryland could represent an isolated unknown small island(s) in the vicinity, or the Vindelician-Bohemian Massif that was active as a dryland for the entire period of time from the Triassic through the Late Cretaceous. However, the exact palaeogeographic position of the Fatricum during the Mesozoic in relation to the Vindelician Landmass is not entirely clear, and such an interpretation needs a bit of caution.
Time Management, Fluid Intelligence and Academic Achievement
Authors: Romero Miriam , Casadevante Cristina , Santacreu José
Published: December 2023

Time management and fluid intelligence have been studied in relation to academic success. Traditionally, fluid intelligence has been measured using performance tests (also called objective tests) meanwhile time management has been measured using self-reports. However, self-reports can be affected by bias and sometimes participant’s responses are inaccurate. To address this limitation, we employed objective tests to measure both fluid intelligence (using the TRASI test) and time management (using the My Schedule test) to investigate their relation to academic grades. The sample consisted of 120 university students. Results indicate a positive relation between time management and fluid intelligence. Fluid intelligence is positively related to grades in mathematics. Time management is positively related to mathematics, physics and chemistry grades. While the present study does not establish causality, the results complement prior research and underscore the significance of time management and fluid intelligence in the academic context.
Is it possible to differentiate pulmonary sarcoidosis in tumor patients and pulmonary lymphangitic carcinomatosis caused by extrapulmonary tumors on 18F-FDG PET/CT images?
Authors: Ji Yu , Wang Yaru , Jiang Jie , Chen Min , Xiao Juan , Dai Zhengjun , Zheng Jingsong
Published: December 2023

Purpose

Pulmonary sarcoidosis (PS) and pulmonary lymphangitic carcinomatosis (PLC) can be complications in tumor patients, and both involve the pulmonary interstitium and have similar imaging findings. Our objective was to distinguish PS and PLC on 18F-FDG PET/CT images.

Material and methods

The authors reviewed 18F-FDG PET/CT data of PS and PLC, diagnosed based on histopathology and imaging, in patients with tumors from July 2015 to January 2023. Three independent readers performed a blinded comparative analysis of 18F-FDG PET/CT signs in all patients. A multivariate logistic regression model was used to establish a differential diagnosis model.

Results

A total of 114 patients were included in the study: 56 patients with PS (mean age, 56 ± 11 [SD] years; 10 men) and 58 patients with PLC caused by extrapulmonary tumors (mean age, 51 ± 11 [SD] years; 21 men). For PS, breast cancer and cervical cancer were the most common primary tumors. For PLC, breast cancer and gastric cancer were the most common extrapulmonary tumors. The model constructed using multivariate logistic regression consisted of five factors: area of lymph node involvement, bronchovascular bundle diffuse thickening, interlobular septal thickening, pleural effusion, and subpleural hypermetabolic activity. The area under the model characteristic curve was 0.973 (95% CI 0.925–0.994), with a sensitivity, specificity, and positive and negative likelihood ratios of 87.50%, 98.28%, 50.75 and 0.13 respectively.

Conclusion

There are detailed differences in 18F-FDG PET/CT manifestations of PS in tumor patients and PLC caused by extrapulmonary tumors, and the constructed diagnostic model has high clinical application value in differentiating the two.
In situ environmental conditions and molecular identification of the photosymbiotic marine worm Symsagittifera roscoffensis
Authors: Thomas Nathan J. , Tang Kam W. , Coates Christopher J.
Published: December 2023

Known as the Roscoff worm or mint-sauce worm, Symsagittifera roscoffensis is an Acoel distinguishable due to the presence of symbiotic alga Tetraselmis convolutae, held beneath the epidermis. Isolated populations of S. roscoffensis span a broad geographical range along the north-eastern Atlantic coast, from Wales to Portugal. The only known population of the worm in the United Kingdom was discovered in Wales decades ago, but very little research has been conducted since. For 13 months, we measured how environmental conditions such as temperature, salinity and light intensity coincided with population size at the Welsh field site. To establish phylogenetic relationships among the different populations and their algal symbionts, we designed new polymerase chain reaction (PCR) oligonucleotides to assess the nucleotide diversity of the mitochondrial cytochrome c oxidase I subunit (COI) gene in gDNA extracted from representative worms across their known range (Wales, France, Portugal, Spain, and Guernsey). We also targeted the 18S rRNA gene of their algal symbiont, Tetraselmis convolutae. We observed temporal shifts in environmental factors coinciding with fluctuating worm colony size, notably temperature. Based on the molecular data, the worm exhibited different ecotypes across locations, while the algal symbiont showed little genetic variation.
Kortere operatieduur ongeacht hardheid van de steen met thulium fiber laser versus Holmium:YAG-laser
Authors: Michiels Timo , Niemeijer Anuschka S. , Poerink Jaap G. H.
Published: December 2023

Samenvatting

Voor endoscopisch laseren van nier- en ureterstenen is de holmium:yttrium-aluminium-garnet (Ho:YAG) laser de gouden standaard, maar de thulium fiber laser (TFL) is in opkomst. Deze retrospectieve studie heeft als doel de effectiviteit van TFL te vergelijken met Ho:YAG. Bij 204 ureterorenoscopieën (URS) werden operatieduur, invloed van hardheid van stenen, peroperatief gebruik van een basket, postoperatief stenten en complicatierisico vergeleken. Uitkomsten werden univariaat en multivariaat geanalyseerd. De behandelde stenen in de TFL groep blijken significant harder dan in de Ho:YAG groep. Hiervoor werd gecorrigeerd en de operatieduur bij TFL blijkt 19 minuten korter (p = 0,033). Baskets waren significant minder vaak nodig in de TFL-groep dan in de Ho:YAG-groep. Operatieduur bij gebruik van TFL blijkt onafhankelijk van de hardheid van de steen; bij Ho:YAG neemt bij toename van de hardheid de operatieduur echter toe. Deze resultaten versterken de toenemende voorkeur voor endoscopische lithotripsie middels TFL, specifiek voor hardere stenen.
A meta-learning network method for few-shot multi-class classification problems with numerical data
Authors: Wu Lang
Published: December 2023

The support vector machine (SVM) method is an important basis of the current popular multi-class classification (MCC) methods and requires a sufficient number of samples. In the case of a limited number of samples, the problem of over-learning easily occurs, resulting in unsatisfactory classification. Therefore, this work investigates an MCC method that requires only a small number of samples. During model construction, raw data are converted into two-dimensional form via preprocessing. Via feature extraction, the learning network is measured and the loss function minimization principle is considered to better solve the problem of learning based on a small sample. Finally, three examples are provided to illustrate the feasibility and effectiveness of the proposed method.
Quantitative Modelling in Stem Cell Biology and Beyond: How to Make Best Use of It
Authors: Greulich Philip
Published: December 2023

Purpose of Review

This article gives a broad overview of quantitative modelling approaches in biology and provides guidance on how to employ them to boost stem cell research, by helping to answer biological questions and to predict the outcome of biological processes.

Recent Findings

The twenty-first century has seen a steady increase in the proportion of cell biology publications employing mathematical modelling to aid experimental research. However, quantitative modelling is often used as a rather decorative element to confirm experimental findings, an approach which often yields only marginal added value, and is in many cases scientifically questionable.

Quantitative modelling can boost biological research in manifold ways, but one has to take some careful considerations before embarking on a modelling campaign, in order to maximise its added value, to avoid pitfalls that may lead to wrong results, and to be aware of its fundamental limitations, imposed by the risks of over-fitting and “universality”.
Ecotoxicology of magnesium-based explosive: impact on animal and human food chain
Authors: Giri Arup , Bharti Vijay K. , Garai Purabi , Singh K. P.
Published: December 2023

The previous few decades have seen widespread environmental exposure to munitions and explosives systems in and around war and weapon testing ranges. Most contemporary warheads use explosives to launch metal shards and charge jets to destroy targets. Presently, Warheads with improved blast performance and shelf life are manufactured using technologies with improved blast performance; among them, plastic-bonded explosives (PBX) have emerged as one of the most promising high explosives for use in various ammunition warheads. The hydroxyl-terminated polybutadiene (HTPB) binder-based PBX has metals like aluminium (Al) and magnesium (Mg) to improve munitions performance by boosting blast pressure. Further, magnesium hydride and other derivatives are commonly added to energetic formulations to enhance the heat of explosion of aluminized explosives and to improve burn rate of certain propellants. So, explosions of these warheads and munitions leave thick fumes and residues in the battlefield soil, which release toxic chemicals, including magnesium, into the air, water, and soil. Later on, magnesium metal contamination negatively impacts the environment and food chain. Hence, magnesium toxicity in the environment, including soil, water, plants, and animals, is the subject of this research and a significant concern to animal and human health. Until now, enough literature has been unavailable; hence, this review brings knowledge on the ecotoxicology of magnesium-based explosives and their possible alarming effects on animal and human health by affecting the food chain.
Exploitation of tolerance to drought stress in carrot (Daucus carota L.): an overview
Authors: Junaid Muhammad Daniyal , Öztürk Zahide Neslihan , Gökçe Ali Fuat
Published: December 2023

Drought stress is a significant environmental factor that adversely affects the growth and development of carrot (Daucus carota L.), resulting in reduced crop yields and quality. Drought stress induces a range of physiological and biochemical changes in carrots, including reduced germination, hindered cell elongation, wilting, and disrupted photosynthetic efficiency, ultimately leading to stunted growth and decreased root development. Recent research has focused on understanding the molecular mechanisms underlying carrot's response to drought stress, identifying key genes and transcription factors involved in drought tolerance. Transcriptomic and proteomic analyses have provided insights into the regulatory networks and signaling pathways involved in drought stress adaptation. Among biochemical processes, water scarcity alters carrot antioxidant levels, osmolytes, and hormones. This review provides an overview of the effects of drought stress on carrots and highlights recent advances in drought stress-related studies on this crop. Some recent advances in understanding the effects of drought stress on carrots and developing strategies for drought stress mitigation are crucial for ensuring sustainable carrot production in the face of changing climate conditions. However, understanding the mechanisms underlying the plant's response to drought stress is essential for developing strategies to improve its tolerance to water scarcity and ensure food security in regions affected by drought.
Liquid-liquid phase separation as a major mechanism of plant abiotic stress sensing and responses
Authors: Liu Xin , Zhu Jian-Kang , Zhao Chunzhao
Published: December 2023

Identification of environmental stress sensors is one of the most important research topics in plant abiotic stress research. Traditional strategies to identify stress sensors or early signaling components based on the cell membrane as a primary site of sensing and calcium signal as a second messenger have had only limited successes. Therefore, the current theoretical framework underlying stress sensing in plants should be reconsidered and additional mechanisms need to be introduced. Recently, accumulating evidence has emerged to suggest that liquid-liquid phase separation (LLPS) is a major mechanism for environmental stress sensing and response in plants. In this review, we briefly introduce LLPS regarding its concept, compositions, and dynamics, and then summarize recent progress of LLPS research in plants, emphasizing the contribution of LLPS to the sensing of various environmental stresses, such as dehydration, osmotic stress, and low and high temperatures. Finally, we propose strategies to identify key proteins that sense and respond to environmental stimuli on the basis of LLPS, and discuss the research directions of LLPS in plant abiotic stress responses and its potential application in enhancing stress tolerance in crops.
Prevalence of Undiagnosed Attention Deficit Hyperactivity Disorder (ADHD) Symptoms in the Young Adult Population of the United Arab Emirates: A National Cross-Sectional Study
Authors: Al-Yateem Nabeel , Slewa-Younan Shameran , Halimi Aram , Saeed Sara Aideed , Tliti Daniah , Mohammad Muna , Ridwan Mada , Zeidan Razan , Hammash Muna Hasan , Ahmed Fatma Refaat , Dias Jacqueline Maria , Rahman Syed Azizur , Subu Muhammad Arsyad , Hijazi Heba , Yeganeh Fatemeh , Momani Aaliyah , Zandi Mitra , Mottershead Richard
Published: December 2023

Background

Attention deficit hyperactivity disorder (ADHD), a globally prevalent behavioural disorder, remains underdiagnosed, particularly among adults. This issue is exacerbated in the Arab region due to stigma and insufficient healthcare facilities and professionals. Despite the United Arab Emirates (UAE) efforts to improve mental healthcare, shortcomings persist. No studies in the UAE currently assesses the appropriateness of the screening system for ADHD and other behavioural issues. Furthermore, prevalence rates of ADHD, particularly within the young adult population, are absent.

Aim

To estimate the prevalence of ADHD amongst young adults attending university in UAE and examine its relationship with gender and academic outcomes.

Methods

A cross-sectional, correlational design was used. Young adults in their first year at university were recruited from different academic institutions across the UAE. The study utilized the Adult ADHD Self-Report Scale (ASRS) for data collection.

Results

A sample of 406 young adults, aged between 18 and 20 years of age were recruited. Approximately, 34.7% (n = 141) reported symptoms suggestive of probable ADHD. Significantly lower grade point average marks were observed in participants with ADHD symptoms (M = 3.15) compared to those without (M = 3.35). Females reported symptoms of probable ADHD at higher rates than males, indicating possibly a potential screening deficiency and a potential stigma consequence.

Conclusions

The study demonstrates a high prevalence of probable ADHD in young adults, particularly among females attending university in the United Arab Emirates. Implications for early screening, service provision, and greater professional health training on this disorder are required.
Operational demonstration and experimental characterisation of a central cathode electrostatic thruster equipped with a high temperature superconducting magnet
Authors: Acheson Chris R. , Glowacki Jakub , Nakano Ryota , Maeshima Daiki , Saile Dominik , Pavri Betina , Takagi Ryohei , Mori Ryoyu , Pollock Randy , Olatunji Jamal R. , Goddard-Winchester Max , Strickland Nicholas M. , Ichihara Daisuke , Wimbush Stuart C. , Kinefuchi Kiyoshi
Published: December 2023

Interplanetary transport of payloads of unprecedented mass, as envisaged beyond the lunar gateway, will require thrusters with high specific impulse as well as high thrust. To achieve this, innovations in propulsion are critical. Many classes of electric thruster utilise a magnetic applied field module to accelerate charged particles. Magnetoplasmadynamic thrusters exhibit improved performance with increasing field, at least up to the limit of around 0.5 T able to be provided by permanent magnets or copper electromagnets. However, superconducting magnets can generate much stronger magnetic fields. In this study, we utilised a space-relevant cryocooled high temperature superconducting magnet as the applied field module for a central cathode electrostatic thruster (CC-EST). A convex anode enabled ignition at high magnetic fields, and in this configuration the thruster’s performance was characterised in the power range of 1 kW to 2.5 kW and at steady applied fields ranging from 0.6 T to 0.8 T, representing a significant advance in achievable field strength. In combination, these operating parameters enabled the achievement of a magnet-inclusive thruster efficiency of 19%, while the cryocooled magnet was demonstrated to be thermally stable in the presence of the kW-scale plasma, demonstrating the viability of such a design for space flight applications.
CAGSI: A Classification Approach towards Gait Speed Identification
Authors: Chakraborty Amartya , Chattaraj Suvendu
Published: December 2023

The last few decades have witnessed a remarkable amount of research addressing numerous challenges in the domain of human activity recognition. One popular problem in this domain has been that of gait analysis. A subproblem in this domain is to identify the speed of a mobile object through gait analysis. Apart from clinical diagnostic applications, the detection of the speed of a person is also important in remote health monitoring, tracking of the mentally incompetent, and determining proper ambulatory assistive devices for the orthopaedically impaired. Gait analysis-related problems commonly deal with large volumes of interrelated data for which machine-learning techniques have been proven effective. However, the size of the feature set used in such problems is a crucial factor. The choice of a large feature set may complicate the approach for long-term analysis. The present work addresses the problem of human walking speed classification through the machine learning approach. Data was experimentally collected with the mobile phone sensors carried by volunteers of different physiques. Only the acceleration readings along the three axes of the accelerometer are considered for further experimentation. Although walking speed is a personal trait, four classes of data have been curated, namely, slow walking, moderate walking, fast walking, and sitting. The speeds of the walks were not pre-defined so the volunteers performed the walks as per their own comfort, which enhances the challenge of distinguishing between sensor signals of varying speed. Experiments have been performed using different supervised learning algorithms with only acceleration data. The performance of the learning models has been analyzed with the help of accuracy, precision, recall, f1-score, and the ROC curve in a One-vs-Rest approach. The results demonstrate that the performance of this system for walking speed identification is comparable to state-of-the-art works. Our work has a unique perspective as it uses a primary dataset comprising only three features.
Assessing landscape fragmentation and its implications for biodiversity conservation in the Greater Accra Metropolitan Area (GAMA) of Ghana
Authors: Bonsu Kofi , Bonin Olivier
Published: December 2023

Context

This paper discusses the impact of urban expansion on the environment, including its effects on biodiversity conservation. As urban areas develop, natural habitats such as forests and agricultural lands are transformed into industrial, commercial, and residential uses, which alters landscape patterns and can lead to fragmentation. Fragmentation can have negative impacts on biodiversity, such as deforestation, alteration of watercourses leading to flooding, reduced availability of food, and increased pollution. The objective of this paper is to provide a comprehensive and data-driven analysis of the urban expansion of Greater Accra Metropolitan Area (GAMA) over time, and its effects on biodiversity. The idea is to capture the changes in land cover and landscape patterns in GAMA from 1991 to 2022 and predict the region’s landscape patterns for 2030. This was achieved by performing a land cover change analysis of GAMA from 1991 to 2022; capturing the evolution of landscape patterns by calculating landscape metrics; and using multiradial fractal dimension as a transition variable to model and predict the land cover and landscape pattern of GAMA for 2030. The landscape metrics revealed extensive fragmentation of the Vegetation land cover type of GAMA, indicating a negative impact on biodiversity conservation, species movements, ecosystem functioning, and long-term ecological resilience. The trends highlight the importance of considering landscape connectivity, habitat fragmentation and spatial arrangement of land cover types for assessing ecological processes and urban development impacts on the environment. Additionally, multiradial fractal dimension of built-up areas is recommended as an explanatory variable for urban growth modelling.
Beyond 'push–pull': unraveling the ecological pleiotropy of plant volatile organic compounds for sustainable crop pest management
Authors: Munawar Asim , Zhu Zengrong , Machado Ricardo A. R. , Zhou Wenwu
Published: December 2023

Plants produce an array of different volatile organic compounds (VOCs) that have diverse eco-physiological functions and agricultural applications. Hence, the potential of VOCs as a natural and eco-friendly solution to increase crop productivity has garnered substantial attention. In particular, VOC-based pest management measures, such as Push–Pull, have been widely investigated in different cropping systems. However, our understanding of how the release and use of these VOCs impact agro-ecosystems beyond the targeted effects is still very limited. Therefore, studying the functions of plant VOCs from the perspective of pleiotropy may offer insights into optimizing and improving the effectiveness of VOC-based agronomic practices. Here, we discuss the current literature on the pleiotropic functions of plant VOCs, illustrate the underlying mechanism for their production and propose a systematic perspective for the usage of plant VOCs to enhance the sustainable management of crop health.
Logical Empiricism as Scientific Philosophy
Authors: Richardson Alan
Published: December 2023

This Element offers a new account of the philosophical significance of logical empiricism that relies on the past forty years of literature reassessing the project. It argues that while logical empiricism was committed to empiricism and did become tied to the trajectory of analytic philosophy, neither empiricism nor logical analysis per se was the deepest philosophical commitment of logical empiricism. That commitment was, rather, securing the scientific status of philosophy, bringing philosophy into a scientific conception of the world.
Where Worlds Collide: Late Woodland Potting Practice and Social Interaction in Upstate South Carolina
Authors: Duke C. Trevor , Markus David M. , Catalano Joshua Casmir
Published: December 2023

Many anthropologists have now adopted a relational view of the culture concept. Much research has shown that, far from being bounded or self-replicating, cultures emerge through interactions between social Others. These findings are particularly important to research on borderlands and peripheries, where communities routinely encounter wide-ranging social and political diversity. We present ceramic frequencies alongside petrographic analysis from the Late Woodland component at Esseneca (38OC20) to illustrate two main points: (1) pottery types previously understood as culture historical isolates co-occur in parts of Upstate South Carolina, and (2) potters collected clays from two main geologic formations near the site. This research shows that communities in the region traveled freely, crossing cultural boundaries while acquiring potting clays. We suggest that this level of interaction between disparate social groups laid the foundation for some aspects of Mississippianization in the region.
Random and mean Lyapunov exponents for
Authors: ARMENTANO DIEGO , CHINTA GAUTAM , SAHI SIDDHARTHA , SHUB MICHAEL
Published: December 2023

We consider orthogonally invariant probability measures on
$\operatorname {\mathrm {GL}}_n(\mathbb {R})$
and compare the mean of the logs of the moduli of eigenvalues of the matrices with the Lyapunov exponents of random matrix products independently drawn with respect to the measure. We give a lower bound for the former in terms of the latter. The results are motivated by Dedieu and Shub [On random and mean exponents for unitarily invariant probability measures on
$\operatorname {\mathrm {GL}}_n(\mathbb {C})$
. Astérisque287 (2003), xvii, 1–18]. A novel feature of our treatment is the use of the theory of spherical polynomials in the proof of our main result.
Equilibrium states for non-uniformly expanding skew products
Authors: HEMENWAY GREGORY
Published: December 2023

We study equilibrium states for a class of non-uniformly expanding skew products, and show how a family of fiberwise transfer operators can be used to define the conditional measures along fibers of the product. We prove that the pushforward of the equilibrium state onto the base of the product is itself an equilibrium state for a Hölder potential defined via these fiberwise transfer operators.
An updated checklist of Stomiiformes from Indian waters with nine new records
Authors: Rajakrishnan Rajeev , Rajeeshkumar Meleppura , Cubelio Sherine Sonia , Saravanane Narayanane
Published: December 2023

Over the years as a part of many fishery surveys, considerable number of stomiiform fishes were collected by the Centre for Marine Living Resources and Ecology (CMLRE) Research Vessel ‘Sagar Sampada’. The collection came from throughout the Indian EEZ and some from the western Indian Ocean. However, a systematic identification of these fishes had never been carried out prior to this paper. Thirty-four species were identified and it was found that eight species were new records to India and one to peninsular India. Among the records, two species, Photonectes paxtoni Flynn and Klepadlo, 2012 and Photonectes barnetti Klepadlo, 2011, are collected from the Indian Ocean for the first time. The paper provides a detailed report on all the new records and a list of stomiiform species collected during these surveys. Differences in barbel morphology observed for many of the stomiids are discussed.
Farming out judicial offices in the Ottoman Empire, c. 1750–1839
Authors: Akiba Jun
Published: December 2023

This article focuses on the widespread practice of appointing deputy judges, called naibs, in the Ottoman Empire from the mid-eighteenth to the early nineteenth centuries. Based on extensive archival research, it analyses how the judiciary turned into a system of allocating revenue sources. An increasing number of offices of kadı (judge) were assigned as a source of income to higher-ranking ulema, who, through intermediaries, in turn farmed out their judicial offices to naibs in return for a fixed sum of money. Importantly, the apportionment fees for taxes collected from local taxpayers constituted a significant part of naibs’ incomes. The practice of deputizing in the Ottoman judiciary thus shows a close parallel with tax farming. Because the naibs transferred their revenues to the higher-ranking ulema, farming out judicial offices became a major economic basis for maintaining the Ottoman ulema hierarchy.
The impact of COVID-19 pandemic on the incidence of acute gastroenteritis outbreaks in Catalonia (Spain)
Authors: Parrón Ignasi , Carol Mònica , Bes Núria , Izquierdo Conchita , Godoy Pere , Barrabeig Irene , Sala M. Rosa , Minguell Sofía , Ferras Joaquin , Rius Cristina , Martínez Ana I. , Domínguez Àngela ,   Working Group for the Study of Outbreaks of Acute Gastroenteritis in Catalonia
Published: December 2023

We carried out a retrospective study of acute gastroenteritis (AGE) outbreaks reported between 1 January 2015 and 31 December 2021 in Catalonia (Spain) to compare the incidence from 2015 to 2019 with that observed from 2020 to 2021. We observed a higher incidence rate of outbreaks during the prepandemic period (16.89 outbreaks/1,000,000 person-years) than during the pandemic period (6.96 outbreaks/1,000,000 person-years) (rate ratio (RR) 0.41; 95% confidence interval (CI) 0.34 to 0.51). According to the aetiology of the outbreak, those of viral aetiology decreased from 7.82 to 3.38 outbreaks/1,000,000 person-years (RR 2.31; 95% CI 1.72 to 3.12), and those of bacterial aetiology decreased from 5.01 to 2.78 outbreaks/1,000,000 person-years (RR 1.80; 95% CI 1.29 to 2.52). There was a great reduction in AGE outbreaks in Catalonia. This reduction may have been due to the effect of the nonpharmaceutical measures applied to reduce the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the collapse of the healthcare system and epidemiological surveillance services may also have had a strong influence.
The effect of electro-anatomical mapping on the success rate and fluoroscopy time in supra-ventricular tachycardia ablation in children: single centre retrospective study
Authors: Bertels Robin A. , Françoijs Maud W. , Averdieck Catharina W. , Kammeraad Janneke A.E. , Filippini Luc H. , de Kezel Charlotte C.A. , Frerich Stefan , Fejzic Zina , du Plessis Frederik A. , Rammeloo Lucas A.J. , Kuipers Irene M. , Blom Nico A.
Published: December 2023

Aims:

To evaluate the effect of electro-anatomical mapping on success rate and fluoroscopy time in ablation of supraventricular tachycardia substrates in a large group of children.

Methods:

Patients referred from multiple centres in the Netherlands and who received a first ablation for supraventricular tachycardia substrates in the Leiden University Medical Center between 2014 and 2020 were included in this retrospective cohort study. They were divided in procedures in patients with fluoroscopy and procedures in patients using electro-anatomical mapping.

Results:

Outcomes of ablation of 373 electro-anatomical substrates were analysed. Acute success rate in the fluoro-group (n = 170) was 95.9% compared to 94.5% in the electro-anatomical mapping group (n = 181) (p = 0.539); recurrence rate was 6.1% in the fluoro-group and 6.4% in the electro-anatomical mapping group (p = 0.911) after a 12-months follow-up. Redo-ablations were performed in 12 cases in the fluoro-group and 10 cases in the electro-anatomical mapping group, with a success rate of 83.3% versus 80.0%, resulting in an overall success rate of 95.9% in the fluoro-group and 92.8% in the electro-anatomical mapping group (p = 0.216) after 12 months. Fluoroscopy time and dose area product decreased significantly from 16.00 ± 17.75 minutes (median ± interquartile range) to 2.00 ± 3.00 minutes (p = 0.000) and 210.5 µGym2 ± 249.3 to 32.9 µGym2 ± 78.6 (p = 0.000), respectively. In the fluoro-group, four complications occurred (2.0%) and in the electro-anatomical mapping group no complications occurred.

Conclusion:

These results demonstrate that ablations of supraventricular tachycardia substrates in children remain a highly effective and safe treatment after the introduction of electro-anatomical mapping as a standard of care, while significantly reducing fluoroscopy time and dose area product.
Location choice and Indian outward foreign direct investment: institutional thresholds and differentiating between institutional quality and institutional distance
Authors: Nayyar Rishika , Luiz John M.
Published: December 2023

Institutions matter as regards foreign location investment decisions, but how they matter and in what ways, is still unsettled. We differentiate between absolute and relative institutional effects on both location choice and on the size of the FDI and do so by examining India's outward FDI flows between 2008 and 2020. We find that absolute and relative institutional measures have different effects, and these are noticeable at different stages. We show that the quality of institutions affects location choice, but once they have made that decision then the scale of the investment is impacted by institutional threshold effects and institutional distance, and we explain why this could be the case. We provide further nuance to studies on the asymmetrical effects of institutions on outward FDI. We provide empirical evidence that the effects of absolute institutions matter more where host countries lie at the lower end of the institutional profile distribution. Likewise with institutional distance—it might not be the direction of the difference that matters so much as where the host country is located along the institutional profile distribution. This has substantial consequences from both a managerial and a policy perspective.
Upregulation of miR-21-5p rescues the inhibition of cardiomyocyte proliferation induced by high glucose through negative regulation of Rhob
Authors: Wu Fang , Wang Feng , Yang Qian , Zhang Yawen , Cai Ke , Zhang Jialing , Xia Min , Wang Youhua , Wang Xu , Gui Yonghao , Li Qiang
Published: December 2023

Increasing evidence shows that maternal hyperglycemia inhibits cardiomyocyte (CM) proliferation and promotes cell apoptosis during fetal heart development, which leads to cardiac dysplasia. Accumulating evidence suggests that the overexpression of miR-21 in CMs has a protective role in cardiac function. Therefore, we investigated whether miR-21 can rescue CM injury caused by high glucose. First, we performed biological function analysis of miR-21-5p overexpression in H9c2 cells treated with high glucose. We found that the proliferation of H9c2 cells treated with high glucose decreased significantly and was rescued after overexpression of miR-21-5p. CCK-8 and EdU incorporation assays were performed to assess cell proliferation. The cell proliferation of the miR-21-5p mimic transfection group was improved compared with that of the NC mimic group (*p < 0.05, miR-21-5p mimics vs. NC mimics) when the proliferation of H9c2 cells was reduced by high glucose (****p < 0.0001, high glucose (HG) vs. normal glucose (NG)). Then, we verified the targeted and negative regulation of miR-21-5p on Rhob using a dual-luciferase activity assay and RT-qPCR, respectively. We further demonstrated that miR-21-5p regulates Rhob to rescue the inhibition of CM proliferation induced by high glucose. The CCK-8 results showed that the cell proliferation of the siRNA-Rhob group was higher than that of the NC mimic group (***p < 0.001) and that of the cotransfection group with Up-Rhob plasmids and miR-21-5p mimics was lower than that of the miR-21-5p mimic group (*p < 0.05). Conclusion: Overexpression of miR-21-5p rescues the inhibition of high glucose-induced CM proliferation through regulation of Rhob.
BCMA-targeted bortezomib nanotherapy improves therapeutic efficacy, overcomes resistance, and modulates the immune microenvironment in multiple myeloma
Authors: Dutta Debasmita , Liu Jiye , Wen Kenneth , Kurata Keiji , Fulciniti Mariateresa , Gulla Annamaria , Hideshima Teru , Anderson Kenneth C.
Published: December 2023

Bortezomib (BTZ) is a standard-of-care treatment in multiple myeloma (MM); however, adverse side effects and development of resistance limit its long term benefit. To improve target specificity, therapeutic efficacy, and overcome resistance, we designed nanoparticles that encapsulate BTZ and are surface-functionalized with BCMA antibodies (BCMA-BTZ-NPs). We confirmed efficient cellular internalization of the BCMA-BTZ-NPs only in BCMA-expressing MM cells, but not in BCMA-knockout (KO) cells. In addition, BCMA-BTZ-NPs showed target-specific cytotoxicity against MM cell lines and primary tumor cells from MM patients. The BCMA-BTZ-NPs entered the cell through receptor-mediated uptake, which escapes a mechanism of BTZ resistance based on upregulating P-glycoprotein. Furthermore, BCMA-BTZ-NPs induced cell death more efficiently than non-targeted nanoparticles or free BTZ, triggering potent mitochondrial depolarization followed by apoptosis. In BTZ-resistant cells, BCMA-BTZ-NPs inhibited proteasome activity more effectively than free BTZ or non-targeted nanoparticles. Additionally, BCMA-BTZ-NPs enhanced immunogenic cell death and activated the autophagic pathway more than free BTZ. Finally, we found that BCMA-BTZ-NPs selectively accumulated at the tumor site in a murine xenograft model, enhanced tumor reduction, and prolonged host survival. These results suggest BCMA-BTZ-NPs provide a promising therapeutic strategy for enhancing the efficacy of BTZ and establish a framework for their evaluation in a clinical setting.
Deep learning of cell spatial organizations identifies clinically relevant insights in tissue images
Authors: Wang Shidan , Rong Ruichen , Zhou Qin , Yang Donghan M. , Zhang Xinyi , Zhan Xiaowei , Bishop Justin , Chi Zhikai , Wilhelm Clare J. , Zhang Siyuan , Pickering Curtis R. , Kris Mark G. , Minna John , Xie Yang , Xiao Guanghua
Published: December 2023

Recent advancements in tissue imaging techniques have facilitated the visualization and identification of various cell types within physiological and pathological contexts. Despite the emergence of cell-cell interaction studies, there is a lack of methods for evaluating individual spatial interactions. In this study, we introduce Ceograph, a cell spatial organization-based graph convolutional network designed to analyze cell spatial organization (for example,. the cell spatial distribution, morphology, proximity, and interactions) derived from pathology images. Ceograph identifies key cell spatial organization features by accurately predicting their influence on patient clinical outcomes. In patients with oral potentially malignant disorders, our model highlights reduced structural concordance and increased closeness in epithelial substrata as driving features for an elevated risk of malignant transformation. In lung cancer patients, Ceograph detects elongated tumor nuclei and diminished stroma-stroma closeness as biomarkers for insensitivity to EGFR tyrosine kinase inhibitors. With its potential to predict various clinical outcomes, Ceograph offers a deeper understanding of biological processes and supports the development of personalized therapeutic strategies.
Modeling cardiac fibroblast heterogeneity from human pluripotent stem cell-derived epicardial cells
Authors: Fernandes Ian , Funakoshi Shunsuke , Hamidzada Homaira , Epelman Slava , Keller Gordon
Published: December 2023

Cardiac fibroblasts play an essential role in the development of the heart and are implicated in disease progression in the context of fibrosis and regeneration. Here, we establish a simple organoid culture platform using human pluripotent stem cell-derived epicardial cells and ventricular cardiomyocytes to study the development, maturation, and heterogeneity of cardiac fibroblasts under normal conditions and following treatment with pathological stimuli. We demonstrate that this system models the early interactions between epicardial cells and cardiomyocytes to generate a population of fibroblasts that recapitulates many aspects of fibroblast behavior in vivo, including changes associated with maturation and in response to pathological stimuli associated with cardiac injury. Using single cell transcriptomics, we show that the hPSC-derived organoid fibroblast population displays a high degree of heterogeneity that approximates the heterogeneity of populations in both the normal and diseased human heart. Additionally, we identify a unique subpopulation of fibroblasts possessing reparative features previously characterized in the hearts of model organisms. Taken together, our system recapitulates many aspects of human cardiac fibroblast specification, development, and maturation, providing a platform to investigate the role of these cells in human cardiovascular development and disease.
Epilepsy-linked kinase CDKL5 phosphorylates voltage-gated calcium channel Cav2.3, altering inactivation kinetics and neuronal excitability
Authors: Sampedro-Castañeda Marisol , Baltussen Lucas L. , Lopes André T. , Qiu Yichen , Sirvio Liina , Mihaylov Simeon R. , Claxton Suzanne , Richardson Jill C. , Lignani Gabriele , Ultanir Sila K.
Published: December 2023

Developmental and epileptic encephalopathies (DEEs) are a group of rare childhood disorders characterized by severe epilepsy and cognitive deficits. Numerous DEE genes have been discovered thanks to advances in genomic diagnosis, yet putative molecular links between these disorders are unknown. CDKL5 deficiency disorder (CDD, DEE2), one of the most common genetic epilepsies, is caused by loss-of-function mutations in the brain-enriched kinase CDKL5. To elucidate CDKL5 function, we looked for CDKL5 substrates using a SILAC-based phosphoproteomic screen. We identified the voltage-gated Ca2+ channel Cav2.3 (encoded by CACNA1E) as a physiological target of CDKL5 in mice and humans. Recombinant channel electrophysiology and interdisciplinary characterization of Cav2.3 phosphomutant mice revealed that loss of Cav2.3 phosphorylation leads to channel gain-of-function via slower inactivation and enhanced cholinergic stimulation, resulting in increased neuronal excitability. Our results thus show that CDD is partly a channelopathy. The properties of unphosphorylated Cav2.3 closely resemble those described for CACNA1E gain-of-function mutations causing DEE69, a disorder sharing clinical features with CDD. We show that these two single-gene diseases are mechanistically related and could be ameliorated with Cav2.3 inhibitors.
Phase-separated CCER1 coordinates the histone-to-protamine transition and male fertility
Authors: Qin Dongdong , Gu Yayun , Zhang Yu , Wang Shu , Jiang Tao , Wang Yao , Wang Cheng , Chen Chang , Zhang Tao , Xu Weiya , Wang Hanben , Zhang Ke , Hu Liangjun , Li Lufan , Xie Wei , Wu Xin , Hu Zhibin
Published: December 2023

Idiopathic fertility disorders are associated with mutations in various genes. Here, we report that coiled-coil glutamate-rich protein 1 (CCER1), a germline-specific and intrinsically disordered protein (IDP), mediates postmeiotic spermatid differentiation. In contrast, CCER1 deficiency results in defective sperm chromatin compaction and infertility in mice. CCER1 increases transition protein (Tnp1/2) and protamine (Prm1/2) transcription and mediates multiple histone epigenetic modifications during the histone-to-protamine (HTP) transition. Immiscible with heterochromatin in the nucleus, CCER1 self-assembles into a polymer droplet and forms a liquid-liquid phase-separated condensate in the nucleus. Notably, we identified loss-of-function (LoF) variants of human CCER1 (hCCER1) in five patients with nonobstructive azoospermia (NOA) that were absent in 2713 fertile controls. The mutants led to premature termination or frameshift in CCER1 translation, and disrupted condensates in vitro. In conclusion, we propose that nuclear CCER1 is a phase-separated condensate that links histone epigenetic modifications, HTP transitions, chromatin condensation, and male fertility.