bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel Long Noncoding RNA
HEAT4
Affects Monocyte Subtypes, Reducing Inflammation and Promoting Vascular Healing
Authors: Kneuer Jasmin M. , Grajek Ignacy A. , Winkler Melanie , Erbe Stephan , Meinecke Tim , Weiss Ronald , Garfias-Veitl Tania , Sheikh Bilal N. , König Ann-Christine , Möbius-Winkler Maximilian N. , Kogel Alexander , Kresoja Karl-Patrik , Rosch Sebastian , Kokot Karoline E. , Filipova Vanina , Gaul Susanne , Thiele Holger , Lurz Philipp , von Haehling Stephan , Speer Thimoteus , Laufs Ulrich , Boeckel Jes-Niels 
Published: July 2024

BACKGROUND:
Activation of the immune system contributes to cardiovascular diseases. The role of human-specific long noncoding RNAs in cardioimmunology is poorly understood.

METHODS:

Single-cell sequencing in peripheral blood mononuclear cells revealed a novel human-specific long noncoding RNA called
HEAT4
(heart failure–associated transcript 4).
HEAT4
expression was assessed in several in vitro and ex vivo models of immune cell activation, as well as in the blood of patients with heart failure (HF), acute myocardial infarction, or cardiogenic shock. The transcriptional regulation of
HEAT4
was verified through cytokine treatment and single-cell sequencing. Loss-of-function and gain-of-function studies and multiple RNA–protein interaction assays uncovered a mechanistic role of
HEAT4
in the monocyte anti-inflammatory gene program.
HEAT4
expression and function was characterized in a vascular injury model in NOD.CB17-Prkdc scid/Rj mice.

RESULTS:

HEAT4
expression was increased in the blood of patients with HF, acute myocardial infarction, or cardiogenic shock.
HEAT4
levels distinguished patients with HF from people without HF and predicted all-cause mortality in a cohort of patients with HF over 7 years of follow-up. Monocytes, particularly anti-inflammatory CD16
+
monocytes, which are increased in patients with HF, are the primary source of
HEAT4
expression in the blood.
HEAT4
is transcriptionally activated by treatment with anti-inflammatory interleukin-10.
HEAT4
activates anti-inflammatory and inhibits proinflammatory gene expression. Increased
HEAT4
levels result in a shift toward more CD16
+
monocytes.
HEAT4
binds to S100A9, causing a monocyte subtype switch, thereby reducing inflammation. As a result,
HEAT4
improves endothelial barrier integrity during inflammation and promotes vascular healing after injury in mice.

CONCLUSIONS:

These results characterize a novel endogenous anti-inflammatory pathway that involves the conversion of monocyte subtypes into anti-inflammatory CD16
+
monocytes. The data identify a novel function for the class of long noncoding RNAs by preventing protein secretion and suggest long noncoding RNAs as potential targets for interventions in the field of cardioimmunology.
Progressive Kidney Failure by Angiotensinogen Inactivation in the Germline
Authors: Wopperer Florian J. , Olinger Eric , Wiesener Antje , Broeker Katharina A.E. , Knaup Karl X. , Schaefer Jan T. , Galiano Matthias , Schneider Karen , Schiffer Mario ,   Genomics England Research Consortium, Büttner-Herold Maike , Reis André , Schmieder Roland , Pasutto Francesca , Hilgers Karl F. , Poglitsch Marko , Ziegler Christine , Shoemaker Robin , Sayer John A. , Wiesener Michael S. 
Published: July 2024

BACKGROUND:
Autosomal recessive renal tubular dysgenesis is a rare, usually fatal inherited disorder of the renin-angiotensis system (RAS). Herein, we report an adolescent individual experiencing an unknown chronic kidney disease and aim to provide novel insights into disease mechanisms.

METHODS:
Exome sequencing for a gene panel associated with renal disease was performed. The RAS was assessed by comprehensive biochemical analysis in blood. Renin expression was determined in primary tubular cells by quantitative polymerase chain reaction and in situ hybridization on kidney biopsy samples. Allele frequencies of heterozygous and biallelic deleterious variants were determined by analysis of the Genomics England 100,000 Genomes Project.

RESULTS:

The patient was delivered prematurely after oligohydramnios was detected during pregnancy. Postnatally, he recovered from third-degree acute kidney injury but developed chronic kidney disease stage G3b over time. Exome sequencing revealed a previously reported pathogenic homozygous missense variant, p.(Arg375Gln), in the
AGT
(angiotensinogen) gene. Blood AGT concentrations were low, but plasma renin concentration and gene expression in kidney biopsy, vascular, and tubular cells revealed strong upregulation of renin. Angiotensin II and aldosterone in blood were not abnormally elevated.

CONCLUSIONS:

Renal tubular dysgenesis may present as chronic kidney disease with a variable phenotype, necessitating broad genetic analysis for diagnosis. Functional analysis of the RAS in a patient with
AGT
mutation revealed novel insights regarding compensatory upregulation of renin in vascular and tubular cells of the kidney and in plasma in response to depletion of AGT substrate as a source of Ang II (similarly observed with hepatic
AGT
silencing for the treatment of hypertension).
Feature attention graph neural network for estimating brain age and identifying important neural connections in mouse models of genetic risk for Alzheimer’s disease
Authors: Moon Hae Sol , Mahzarnia Ali , Stout Jacques , Anderson Robert J. , Han Zay Yar , Tremblay Jessica T. , Badea Cristian T. , Badea Alexandra 
Published: July 2024

Abstract
Alzheimer’s disease (AD), a widely studied neurodegenerative disorder, poses significant research challenges due to its high prevalence and complex etiology. Age, a critical risk factor for AD, is typically assessed by comparing physiological and estimated brain ages. This study utilizes mouse models expressing human alleles of APOE and human nitric oxide synthase 2 (hNOS2), replicating genetic risks for AD alongside a human-like immune response. We developed a multivariate model that incorporates brain structural connectomes, APOE genotypes, demographic traits (age and sex), environmental factors such as diet, and behavioral data to estimate brain age. Our methodology employs a Feature Attention Graph Neural Network (FAGNN) to integrate these diverse datasets. Behavioral data are processed using a 2D convolutional neural network (CNN), demographic traits via a 1D CNN, and brain connectomes through a graph neural network equipped with a quadrant attention module that accentuates critical neural connections. The FAGNN model demonstrated a mean absolute error in age prediction of 31.85 days and a root mean squared error of 41.84 days, significantly outperforming simpler models. Our analysis further focused on the brain age delta, which assesses accelerated or delayed aging by comparing brain age, predicted by FAGNN, to the chronological age. A high-fat diet and the presence of the human NOS2 gene were identified as significant accelerators of brain aging in the old age group. Key neural connections identified by FAGNN, such as those between the cingulum, corpus callosum, striatum, hippocampus, thalamus, hypothalamus, cerebellum, and piriform cortex, were found to be significant in the aging process. Validation using diffusion MRI-based metrics, including fractional anisotropy and return-to-origin probability measures across these connections, revealed significant age-related differences. These findings suggest that white matter degradation in the connections highlighted by FAGNN plays a key role in aging. Our findings suggest that the complex interplay of APOE genotype with sex, immunity, and environmental factors modulates brain aging and enhance our understanding of AD risk in mouse models of aging.
Transferability and Explainability of Deep Learning Emulators for Regional Climate Model Projections: Perspectives for Future Applications
Authors: Baño-Medina Jorge , Iturbide Maialen , Fernández Jesús , Gutiérrez José Manuel 
Published: July 2024

Abstract
Regional climate models (RCMs) are essential tools for simulating and studying regional climate variability and change. However, their high computational cost limits the production of comprehensive ensembles of regional climate projections covering multiple scenarios and driving Global climate models (GCMs) across regions. RCM emulators based on deep learning models have recently been introduced as a cost-effective and promising alternative that requires only short RCM simulations to train the models. Therefore, evaluating their transferability to different periods, scenarios, and GCMs becomes a pivotal and complex task in which the inherent biases of both GCMs and RCMs play a significant role. Here, we focus on this problem by considering the two different emulation approaches introduced in the literature as perfect and imperfect, that we here refer to as perfect prognosis (PP) and model output statistics (MOS), respectively, following the well-established downscaling terminology. In addition to standard evaluation techniques, we expand the analysis with methods from the field of explainable artificial intelligence (XAI), to assess the physical consistency of the empirical links learnt by the models. We find that both approaches are able to emulate certain climatological properties of RCMs for different periods and scenarios (soft transferability), but the consistency of the emulation functions differs between approaches. Whereas PP learns robust and physically meaningful patterns, MOS results are GCM dependent and lack physical consistency in some cases. Both approaches face problems when transferring the emulation function to other GCMs (hard transferability), due to the existence of GCM-dependent biases. This limits their applicability to build RCM ensembles. We conclude by giving prospects for future applications.

Significance Statement
Regional climate model (RCM) emulators are a cost-effective emerging approach for generating comprehensive ensembles of regional climate projections. Promising results have been recently obtained using deep learning models. However, their potential to capture the regional climate dynamics and to emulate other periods, emission scenarios, or driving global climate models (GCMs) remains an open issue that affects their practical use. This study explores the potential of current emulation approaches incorporating new explainable artificial intelligence (XAI) evaluation techniques to assess the reliability and transferability of the emulators. Our findings show that the different global and regional model biases involved in the different approaches play a key role in transferability. Based on the results obtained, we provide some prospects for potential applications of these models in challenging problems.
Vertical Velocity Dynamics in the North Atlantic and Implications for AMOC
Authors: Fraser Neil J. , Fox Alan D. , Cunningham Stuart A. , Rath Willi , Schwarzkopf Franziska U. , Biastoch Arne 
Published: July 2024

Abstract
The Atlantic meridional overturning circulation (MOC) is traditionally monitored in terms of zonally integrated transport either in depth space or in density space. While this view has the advantage of simplicity, it obscures the rich and complex three-dimensional structure, so that the exact physics of the downwelling and upwelling branch remains poorly understood. The near-equivalence of the depth- and density-space MOC in the subtropics suggests that vertical and diapycnal volumes transports are intimately coupled, whereas the divergence of these two metrics at higher latitudes indicates that any such coupling is neither instantaneous nor local. Previous work has characterized the surface buoyancy forcing and mixing processes which drive diapycnal volume transport. Here, we develop a new analytical decomposition of vertical volume transport based on the vorticity budget. We show that most terms can be estimated from observations and provide additional insights from a high-resolution numerical simulation of the North Atlantic. Our analysis highlights the roles of 1) relative vorticity advection for the sinking of overflow water at the northern subpolar North Atlantic boundaries and 2) the geostrophic β effect for the sinking of dense waters in the intergyre region. These results provide insights into the coupling between density- and depth-space overturning circulations.

Significance Statement
The purpose of this study is to better understand where and why dense water sinks in the North Atlantic. This is important because dense water sinking in the North Atlantic is a crucial component of the global thermohaline circulation. Our results reveal the primary controls on dense water sinking at a regional level and highlight the importance of mesoscale processes at high latitudes in shaping the circulation and heat distribution throughout the Atlantic Ocean.
Improving energy consumption for dynamic intake and exhaust FAÇADES: A new setup design: Part B
Authors: Hosseinalipour S.M. , Al-Taee Ammar A. Hussain , Asiaei Sasan 
Published: July 2024

Dynamic insulation technology adjusts thermal resistance to reduce building energy consumption in response to climate changes. Sustainable building practices prioritize optimizing the building envelope to enhance energy efficiency and regulate the interaction between indoor and outdoor environments. The previous part of this study (Part A) provided an overview of dynamic insulation technology and its potential effectiveness in Iraqi structures with intermittent heating and cooling. The successful implementation of dynamic thermal insulation necessitates careful planning and design solutions that balance performance and efficiency. This paper (Part B) three wall models (static, dynamic, modified dynamic) to evaluate their thermal performance during the heating season. The results demonstrate that the intake facade achieves a preheating efficiency of 77% for the dynamic wall and 81.8% for the modified dynamic wall at the maximum permissible fresh air limit. This improvement in efficiency enhances the quality and conditions of fresh air intake. Additionally, the modified dynamic wall exhibits a notable 50% reduction in pressure loss compared to the dynamic wall, resulting in lower intake or exhaust fan power and thus energy consumption. The results of this paper will guide the presentation of cooling season results and the experimental aspect of future work, offering valuable insights for further exploration. Practical applications This study aims to enhance the efficiency of dynamic facades by investigating the physical phenomena within wall layers. The paper delves into the determination of optimal airflow patterns within facades, the assessment of airflow path modifications, and the evaluation of energy efficiency achieved by implementing dynamic insulation at the intake and exhaust facades during the heating season. The findings contribute to streamlining design complexities and expanding design options for specific climates, thereby ensuring the pragmatic implementation of this technology.
Infectious keratitis in pediatric population aged less than two years: a tertiary eye institute experience
Authors: Soleimani Mohammad , Baharnoori Seyed Mahbod , Ghafarian Sadegh , Atighehchian Mehrnaz , Cheraqpour Kasra , Tabatabaei Seyed Ali , Ghanbari Hamidreza , Soleimanzadeh Mahdi , Bijani Faezeh Moghimpour , Almasi Solmaz , Zeidabadinejad Haniyeh , Davarpanah Ali , Sajedi Marzieh , Sefidan Bahram Bohrani , Habeel Samer , Masoumi Ahmad , Zamani Mohammad Hossein , Djalilian Ali R. 
Published: July 2024

Abstract
Background
Infectious keratitis is a serious ocular condition, which can lead to corneal scarring, vision loss, and even blindness. Pediatric infectious keratitis accounts for about 13% of all cases, although there is a lack of comprehensive data regarding keratitis in less than two years of age population group. This study was aimed to determine predisposing factors, clinical characteristics, microbial profile, and management of infectious keratitis in a population of children aged less than two years.

Materials and methods
A retrospective study was carried out in a tertiary eye institute over a period of 18 years from July 2005 to December 2022. Collected data was analyzed for demographics, predisposing factors, clinical features, and treatment methods.

Results
Fifty-seven cases of keratitis were identified. Age of the patients ranged from 1 to 24 months (Median: 6, interquartile range: 2–10). Thirty cases were male (52.6%). Predisposing factors were identified in 39 cases (68.4%): consisting of prior ocular trauma (n = 15), previous intraocular surgery (n = 11), ocular surface disease (n = 10), nasolacrimal duct obstruction (n = 4), prematurity (n = 3), developmental delay (n = 2), TORCH infection (n = 1), and contact lens (n = 1). Corneal thinning was observed in 29 eyes (50.9%), which progressed to perforation in 13 eyes (22.8%). Three patients developed endophthalmitis (95% CI, 1.5–13.4%). Most eyes had negative smear (60.4%) and culture (59.6%) results. Pseudomonas aeruginosa was the most common microorganism (11 of 21). Candida albicans was isolated in one case. In vitro susceptibility results showed good coverage of the combined ceftazidime and vancomycin regimen (100%). Surgical procedures were carried out in 35 eyes (61.4%) and 15 eyes required tectonic procedures (26.3%).

Conclusion
Despite good coverage of medical treatment over cultured isolates, surgical tectonic intervention was required in nearly a quarter of cases to resolve the corneal infection. This finding indicates the necessity of prompt patient referring, corneal sampling and initiation of the treatment.
Comparative genomic analysis of nickel homeostasis in cable bacteria
Authors: Hiralal Anwar , Geelhoed Jeanine S. , Neukirchen Sinje , Meysman Filip J. R. 
Published: July 2024

Abstract
Background
Cable bacteria are filamentous members of the Desulfobulbaceae family that are capable of performing centimetre‑scale electron transport in marine and freshwater sediments. This long‑distance electron transport is mediated by a network of parallel conductive fibres embedded in the cell envelope. This fibre network efficiently transports electrical currents along the entire length of the centimetre‑long filament. Recent analyses show that these fibres consist of metalloproteins that harbour a novel nickel‑containing cofactor, which indicates that cable bacteria have evolved a unique form of biological electron transport. This nickel‑dependent conduction mechanism suggests that cable bacteria are strongly dependent on nickel as a biosynthetic resource. Here, we performed a comprehensive comparative genomic analysis of the genes linked to nickel homeostasis. We compared the genome‑encoded adaptation to nickel of cable bacteria to related members of the Desulfobulbaceae family and other members of the Desulfobulbales order.

Results
Presently, four closed genomes are available for the monophyletic cable bacteria clade that consists of the genera Candidatus Electrothrix and Candidatus Electronema. To increase the phylogenomic coverage, we additionally generated two closed genomes of cable bacteria: Candidatus Electrothrix gigas strain HY10‑6 and Candidatus Electrothrix antwerpensis strain GW3‑4, which are the first closed genomes of their respective species. Nickel homeostasis genes were identified in a database of 38 cable bacteria genomes (including 6 closed genomes). Gene prevalence was compared to 19 genomes of related strains, residing within the Desulfobulbales order but outside of the cable bacteria clade, revealing several genome‑encoded adaptations to nickel homeostasis in cable bacteria. Phylogenetic analysis indicates that nickel importers, nickel‑binding enzymes and nickel chaperones of cable bacteria are affiliated to organisms outside the Desulfobulbaceae family, with several proteins showing affiliation to organisms outside of the Desulfobacterota phylum. Conspicuously, cable bacteria encode a unique periplasmic nickel export protein RcnA, which possesses a putative cytoplasmic histidine‑rich loop that has been largely expanded compared to RcnA homologs in other organisms.

Conclusion
Cable bacteria genomes show a clear genetic adaptation for nickel utilization when compared to closely related genera. This fully aligns with the nickel‑dependent conduction mechanism that is uniquely found in cable bacteria.
Evaluation of the effect of trendelenburg position duration on intracranial pressure in laparoscopic hysterectomies using ultrasonographic optic nerve sheath diameter measurements
Authors: Guloglu Hulya , Cetinkaya Dilek , Oge Tufan , Bilir Ayten 
Published: July 2024

Abstract
Background
During laparoscopic surgery, pneumoperitoneum and Trendelenburg positioning applied to provide better surgical vision can cause many physiological changes as well as an increase in intracranial pressure. However, it has been reported that cerebral autoregulation prevents cerebral edema by regulating this pressure increase. This study aimed to investigate whether the duration of the Trendelenburg position had an effect on the increase in intracranial pressure using ultrasonographic optic nerve sheath diameter (ONSD) measurements.

Methods
The near infrared spectrometry monitoring of patients undergoing laparoscopic hysterectomy was performed while awake (T0); at the fifth minute after intubation (T1); at the 30th minute (T2), 60th minute (T3), 75th minute (T4), and 90th minute (T5) after placement in the Trendelenburg position; and at the fifth minute after placement in the neutral position (T6). Results: The study included 25 patients. The measured ONSD values were as follows: T0 right/left, 4.18±0.32/4.18±0.33; T1, 4.75±0.26/4.75±0.25; T2, 5.08±0.19/5.08±0.19; T3, 5.26±0.15/5.26±0.15; T4, 5.36±0.11/5.37±0.12; T5, 5.45±0.09/5.48±0.11; and T6, 4.9±0.24/4.89±0.22 ( p < 0.05 compared with T0). ). No statistical difference was detected in all measurements in terms of MAP, HR and ETCO2 values compared to the T0 value (p > 0.05).

Conclusions
It was determined that as the Trendelenburg position duration increased, the ONSD values ​​increased. This suggests that as the duration of Trendelenburg positioning and pneumoperitoneum increases, the sustainability of the mechanisms that balance the increase in intracranial pressure becomes insufficient.

Trial registration
This study was registered at Clinical Trials.gov on 21/09/2023 (registration number NCT06048900).