bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neuroinflammation-on-a-chip for multiple sclerosis research: a narrative review
Authors: Berjaoui Christin , Kachouh Charbel , Joumaa Safaa , Hussein Ghayyad Mohammad , Abate Bekele Bisrat , Ajirenike Rita , Al Maaz Zeina , Awde Sara , Wojtara Magda , Nazir Abubakar , Uwishema Olivier 
Published: May 2024

Introduction:
Multiple sclerosis (MS) is a chronic inflammatory condition that impacts the central nervous system. It is distinguished by processes like demyelination, gliosis, neuro-axonal harm, and inflammation. The prevailing theory suggests that MS originates from an immune response directed against the body’s own antigens within the central nervous system.

Aim:
The main aim of this research paper “Neuroinflammation-on-a-Chip” for studying multiple sclerosis is to enhance our comprehension of MS development, demonstrate the application of cutting-edge technology, and potentially provide valuable insights for therapeutic approaches.

Methods:
The available literature for this Narrative Review was searched on various bibliographic databases, PubMed, NCBI, and many other medical references using an individually verified, prespecified approach. Studies regarding the significance of MS and its neuroinflammatory pathogenesis in addition to the development and optimization of neuroinflammatory-on-a-chip and the advancement in innovations in this field have been reviewed in this research for a better understanding of “Neuroinflammation-on-a-chip for multiple sclerosis”. The level of evidence of the included studies was considered as per the Centre for Evidence-Based Medicine recommendations.

Results:
Several studies have indicated that the brain-chip model closely mimics cortical brain tissue compared to commonly used conventional cell culture methods like the Transwell culture system. Additionally, these studies have clearly demonstrated that further research using brain chips has the potential to enhance our understanding of the molecular mechanisms and roles of blood-brain barrier (BBB) transporters in both normal and disease conditions.

Conclusion:
Understanding neuroinflammation processes remains essential to establish new MS treatments approaches. The utilization of brain chips promises to advance our understanding of the molecular processes involving BBB transporters, both in normal and diseased states. Further research needs to be addressed in order to enhance the performance and understanding of neuroinflammation on a chip, hence aiming to provide more effective treatments for all CNS diseases.
Prevalence of sleep disorders in patients with advanced cancer: a cross-sectional study
Authors: Gyawali Siddinath , Tiwari Sagar , Sah Guru Sharan , Panthi Bishal , Upreti Apil , Pokhrel Biraj , Gyawali Bindu , Khanal Pratima , Shrestha Rakshya , Paudel Bishal 
Published: May 2024

Background:
Patients with advanced cancer are more susceptible to develop sleep disorders like insomnia, restlessness, hypersomnolence, and sleep apnea due to a series of stressful events and side effects of chemotherapeutic agents. Poor sleep quality is associated with bad cancer outcomes and substandard quality of life. The authors assessed the prevalence of sleep disorders among advanced cancer patients in a tertiary center in Nepal.

Methods:
Patients with stage three and four solid malignancies were enrolled from February 2023 to July 2023 to assess their sleep status. The data were collected using the Pittsburgh Sleep Quality Index (PSQI) questionnaire, analyzed using the Statistical Package for the Social Sciences (SPSS) version 27, and subgroup exploration was done to assess the relationship of poor sleep quality with gender, marital status, malignancy type, and treatment received. An ethical clearance was obtained from the Institutional Review Committee (IRC).

Results:
The authors evaluated data from 357 patients in the study. Of them, 58.3% were female and 41.7% were male. The mean age of the patients was 51.1 years. Among total cancer patients, 56% had significant sleep disorders. A significant association was observed between the quality of sleep and gender, type of malignancy, and treatment methods (p value <0.05). A majority of the patients demonstrated increased sleep latency, struggling to fall asleep swiftly.

Conclusions:
More than half of the patients had poor sleep, which has an adverse impact on the prognosis of the disease and quality of life of cancer patients. Therefore, this aspect of cancer management requires special consideration for better quality of life and appropriate end-of-life care.
Incidental Apical Pleuroparenchymal Scarring on Computed Tomography
Authors: Toussie Danielle , Finkelstein Mark , Mendoza Dexter , Concepcion Jose , Stojanovska Jadranka , Azour Lea , Ko Jane P. , Moore William H. , Singh Ayushi , Sasson Arielle , Bhattacharji Priya , Eber Corey 
Published: May 2024

Purpose:
Apical pleuroparenchymal scarring (APPS) is commonly seen on chest computed tomography (CT), though the imaging and clinical features, to the best of our knowledge, have never been studied. The purpose was to understand APPS’s typical morphologic appearance and associated clinical features.

Patients and Methods:
A random generator selected 1000 adult patients from all 21516 chest CTs performed at urban outpatient centers from January 1, 2016 to December 31, 2016. Patients with obscuring apical diseases were excluded to eliminate confounding factors. After exclusions, 780 patients (median age: 64 y; interquartile range: 56 to 72 y; 55% males) were included for analysis. Two radiologists evaluated the lung apices of each CT for the extent of abnormality in the axial plane (mild: <5 mm, moderate: 5 to 10 mm, severe: >10 mm), craniocaudal plane (extension halfway to the aortic arch, more than halfway, vs below the arch), the predominant pattern (nodular vs reticular and symmetry), and progression. Cohen kappa coefficient was used to assess radiologists’ agreement in scoring. Ordinal logistic regression was used to determine associations of clinical and imaging variables with APPS.

Results:
APPS was present on 65% (507/780) of chest CTs (54% mild axial; 80% mild craniocaudal). The predominant pattern was nodular and symmetric. Greater age, female sex, lower body mass index, greater height, and white race were associated with more extensive APPS. APPS was not found to be associated with lung cancer in this cohort.

Conclusion:
Classifying APPS by the extent of disease in the axial or craniocaudal planes, in addition to the predominant pattern, enabled statistically significant associations to be determined, which may aid in understanding the pathophysiology of apical scarring and potential associated risks.
EDA2R-NIK signaling in cancer cachexia
Authors: Agca Samet , Kir Serkan 
Published: May 2024

Purpose of review
Cachexia is a debilitating condition causing weight loss and skeletal muscle wasting that negatively influences treatment and survival of cancer patients. The objective of this review is to describe recent discoveries on the role of a novel signaling pathway involving ectodysplasin A2 receptor (EDA2R) and nuclear factor κB (NFκB)-inducing kinase (NIK) in muscle atrophy.

Recent findings
Studies identified tumor-induced upregulation of EDA2R expression in muscle tissues in pre-clinical cachexia models and patients with various cancers. Activation of EDA2R by its ligand promoted atrophy in cultured myotubes and muscle tissue, which depended on NIK activity. The non-canonical NFκB pathway via NIK also stimulated muscle atrophy. Mice lacking EDA2R or NIK were protected from muscle loss due to tumors. Tumor-induced cytokine oncostatin M (OSM) upregulated EDA2R expression in muscles whereas OSM receptor-deficient mice were resistant to muscle wasting.

Summary
Recent discoveries revealed a mechanism involving EDA2R-NIK signaling and OSM that drives cancer-associated muscle loss, opening up new directions for designing anti-cachexia treatments. The therapeutic potential of targeting this mechanism to prevent muscle loss should be further investigated. Future research should also explore broader implications of the EDA2R-NIK pathway in other muscle wasting diseases and overall muscle health.
A functional approach to homeostatic regulation
Authors: Arias Clemente F. , Acosta Francisco J. , Bertocchini Federica , Fernández-Arias Cristina 
Published: May 2024

ABSTRACTIn this work, we present a novel modeling framework for understanding the dynamics of homeostatic regulation. Inspired by engineering control theory, this framework incorporates unique features of biological systems. First, biological variables often play physiological roles, and taking this functional context into consideration is essential to fully understand the goals and constraints of homeostatic regulation. Second, biological signals are not abstract variables, but rather material molecules that may undergo complex turnover processes of synthesis and degradation. We suggest that the particular nature of biological signals may condition the type of information they can convey, and their potential role in shaping the dynamics and the ultimate purpose of homeostatic systems. We show that the dynamic interplay between regulated variables and control signals is a key determinant of biological homeostasis, challenging the necessity and the convenience of strictly extrapolating concepts from engineering control theory in modeling the dynamics of homeostatic systems. This work provides an alternative, unified framework for studying biological regulation and identifies general principles that transcend molecular details of particular homeostatic mechanisms. We show how this approach can be naturally applied to apparently different regulatory systems, contributing to a deeper understanding of homeostasis as a fundamental process in living systems.
Low-degree decompositions of flux vectors in faces of the flux cone
Authors: Wieder Frederik , Bockmayr Alexander 
Published: May 2024

AbstractDecomposing a flux vector into elementary flux modes (EFMs) is a well-known task in the constraint-based analysis of metabolic networks.Using geometric insights into the facial structure of the flux cone, we develop a new method for decomposition. To illustrate our approach, we consider a variety of genome-scale metabolic networks from the BiGG database. We decompose the optimal solutions to flux balance analysis problems into EFMs and compare different possible decompositions. Taking into account their degree allows understanding the interplay of the different EFMs that can participate in the decomposition of a given flux vector and highlights the particular importance of low-degree decompositions.The new method can be applied to genome-scale metabolic networks, where the whole set of EFMs is often too large to be computed in practice. The special properties of low-degree decompositions make them an interesting subject for future biological studies.
Granzyme K drives a newly-intentified pathway of complement activation
Authors: Donado Carlos A. , Jonsson A. Helena , Theisen Erin , Zhang Fan , Nathan Aparna , Rupani Karishma Vijay , Jones Dominique ,   Accelerating Medicines Partnership RA/SLE Network, Raychaudhuri Soumya , Dwyer Daniel F. , Brenner Michael B. 
Published: May 2024

AbstractGranzymes are a family of serine proteases mainly expressed by CD8+T cells, natural killer cells, and innate-like lymphocytes1,2. Although their major role is thought to be the induction of cell death in virally infected and tumor cells, accumulating evidence suggests some granzymes can regulate inflammation by acting on extracellular substrates2. Recently, we found that the majority of tissue CD8+T cells in rheumatoid arthritis (RA) synovium, inflammatory bowel disease and other inflamed organs express granzyme K (GZMK)3, a tryptase-like protease with poorly defined function. Here, we show that GZMK can activate the complement cascade by cleaving C2 and C4. The nascent C4b and C2a fragments form a C3 convertase that cleaves C3, allowing further assembly of a C5 convertase that cleaves C5. The resulting convertases trigger every major event in the complement cascade, generating the anaphylatoxins C3a and C5a, the opsonins C4b and C3b, and the membrane attack complex. In RA synovium, GZMK is enriched in areas with abundant complement activation, and fibroblasts are the major producers of complement C2, C3, and C4 that serve as targets for GZMK-mediated complement activation. Our findings describe a previously unidentified pathway of complement activation that is entirely driven by lymphocyte-derived GZMK and proceeds independently of the classical, lectin, or alternative pathways. Given the widespread abundance ofGZMK-expressing T cells in tissues in chronic inflammatory diseases and infection, GZMK-mediated complement activation is likely to be an important contributor to tissue inflammation in multiple disease contexts.
Sensitivity of estimates of the effectiveness of REDD+ projects to matching specifications and moving from pixels to polygons as the unit of analysis
Authors: Guizar-Coutiño Alejandro , Coomes David , Swinfield Tom , Jones Julia P G 
Published: May 2024

AbstractThere is a substantial interest in the potential of carbon credits generated by Reducing Emissions from tropical Deforestation and Degradation (REDD+) and traded on the voluntary carbon market for generating the finance needed to slow forest loss. However, such credits have become marred in controversy. Recent global-scale analysis using a range of methods for estimating the counterfactual rate of deforestationex postsuggest that many REDD+ projects have overestimated their effectiveness at reducing deforestation and consequently issued more credits than can be justified. All such methods include potentially arbitrary choices which can affect the estimate of the treatment effect. In addition, using pixels as the sampling unit, as some of the studies do, can introduce biases. One study which has been widely cited in the debate (Guizar-Coutiño et al. 2022) estimated avoided deforestation using statistical matching of pixels and a single set of matching options. We estimate avoided deforestation from the same set of projects using 7-hectare plots rather than pixels to sample deforestation and explore the sensitivity of the results to matching choices (exploring 120 matched sets in total). We filtered the results on three criteria: 1) post-matching covariate balance, 2) proportion of REDD+ samples that were successfully matched, and 3) similarity of trends in deforestation rates prior to REDD+ implementation (parallel trends). While one of the 44 REDD+ projects failed these quality control process, we estimate treatment effects for the remaining 43 projects. There was a substantial correlation between our new estimates and those published in Guizar-Coutiño et al. 2022 (0.72 measured in annual percent change, and 0.9 measured in total area change) and our headline estimate of 0.22% per yr (95% CI: 0.13 to 0.34) is essentially unchanged. At a time when confidence in the voluntary carbon markets is low, we hope these results provide reassurance that ex-post counterfactual estimates of avoided deforestation are consistent, helping accelerate their widespread adoption and rebuild trust in nature-based climate solutions.
Optimal Protein Allocation Controls the Inhibition of GltA and AcnB inNeisseria gonorrhoeae
Authors: Shahreen Nabia , Chowdhury Niaz Bahar , Saha Rajib 
Published: May 2024

AbstractNeisseria gonorrhea(Ngo) is a major concern for global public health due to its severe implications for reproductive health. Understanding its metabolic phenotype is crucial for comprehending its pathogenicity. Despite Ngo’s ability to encode TCA cycle proteins, GltA and AcnB, their activities are notably restricted. To investigate this phenomenon, we used the iNgo_557 metabolic model and incorporated a constraint on total cellular protein content. Our results indicate that low cellular protein content severely limits GltA and AcnB activity, leading to a shift towards acetate overflow for ATP production, which is more efficient in terms of protein usage. Surprisingly, increasing cellular protein content alleviates this restriction on GltA and AcnB and delays the onset of acetate overflow, highlighting protein allocation as a critical determinant in understanding Ngo’s metabolic phenotype. These findings underscore the significance of Ngo’s metabolic adaptation in light of optimal protein allocation, providing a blueprint to understand Ngo’s metabolic landscape.
Effects of vertical sleeve gastrectomy prior to pregnancy on bone mass, microarchitecture and material properties in the female rat
Authors: Couchot Malory , Schmitt Françoise , Mermet Morgane , Fassot Céline , Mabilleau Guillaume 
Published: May 2024

ABSTRACTObesity is a major public health issue worldwide. Despite various approaches to weight loss, the most effective technique for reducing obesity, as well as diabetes and associated diseases, is bariatric surgery. Increasingly, young women without children are undergoing bariatric surgery, vertical sleeve gastrectomy (VSG) being the most common procedure nowadays. However, despite several reports suggesting bone loss after VSG, little is known about the potential additive effects of gestation and lactation after VSG to bone health. This study investigated the combined effects of pre-gestational VSG and subsequent gestation/lactation on bone metabolism in a rat model fed a high fat high sugar (HFHS) diet, with a focus on bone biomechanics, mass, microarchitecture and material properties. Furthermore, bone mass and remodelling was followed longitudinally by microCT prior to surgery, 4 weeks post-surgery, after weaning and at sacrifice. Significant alterations in bone mass and microarchitecture, characterized by changes in trabecular thickness and number, as well as changes in bone formation and resorption were influenced by both surgery and reproductive demands. Mechanical testing at sacrifice demonstrated compromised long bone fragility, in rat with HFHS regardless of the surgical procedure (Sham or VSG). Furthermore, analysis of bone material properties highlighted potential disruptions in the pattern of bone mineralization in sham and VSG animals fed a HFHS diet. These findings underscore the complex interplay between pre-gestational VSG and subsequent gestation/lactation in modulating bone metabolism. Understanding these combined effects is essential for optimizing surgical strategies and developing targeted interventions to mitigate potential bone-related complications associated with VSG in reproductive-aged individuals.
Individual variation in breeding phenology and postnatal development in northern bats (Eptesicus nilssonii)
Authors: Fjelldal Mari Aas , van der Kooij Jeroen 
Published: May 2024

AbstractBats inhabiting northern latitudes are faced with short reproductive seasons during which they must produce and rear pups before fattening up in time to survive the winter hibernation. Therefore, the timing of parturition has considerable impacts on future fitness prospects for mother and pup; however, little is known about individual variation in breeding phenology and its consequences for postnatal development within bat populations. Here, we studied the phenology of breeding inEptesicus nilssoniiacross seven years using data collected by day-to-day monitoring of a breeding colony in Norway (60.1°N) for which the identity and age of each mother (N = 8) and pup (N = 28) were known. By applying mixed-effect models, we found that arrival at the colony was largely dependent on late spring temperatures for all females, but that there were strong and consistent individual differences in arrival time across years. Females generally arrived ∼31.6 days (± 0.8 SE) before giving birth but could delay the timing of parturition by leaving the colony during early gestation if faced with poor weather conditions. However, females arriving late expressed shorter gestations, and pups born later in the season were born smaller but had higher growth rates during the most rapid growth period (<10 days old). The within-individual effects suggest that the higher growth rates could be due to mothers compensating for late parturition rather than by improved food availability. Date of parturition did not influence adult body size in pups. Pups became volant at the earliest only 13.1 days after birth (mean: 15.3 ± 1.6 SD) and approached adult flight patterns during their first flight week. Our unique results suggest thatE. nilssoniiis highly adapted to a short breeding season and is able to buffer unfavourable weather conditions to avoid slowing pup development, although the mechanistic drivers remain unknown.
Functions of the AP2/ERF family transcription factor AIL7 in immunity against soilborne clubroot pathogen in Arabidopsis
Authors: Jayawardhane Kethmi Nirmani , Somarathna Tharangani , Manoli Victor P. , Hwang Sheau-Fang , Strelkov Stephen E. , Singer Stacy D. , Chen Guanqun 
Published: May 2024

AbstractSoilborne pathogens can be highly devastating, and clubroot, caused byPlasmodiophora brassicae, is particularly destructive to cruciferous plants. Although many AP2/ERF family transcription factors (TFs) have crucial physiological functions, very little is known regarding their functions in the context of soilborne diseases. Here we investigated the roles of AINTEGUMENTA-LIKE 7 (AIL7), an AIL sub-family TF in the AP2/ERF family, in plant immunity against clubroot. Unexpectedly, bothAIL7overexpression and mutant Arabidopsis lines exhibited increased tolerance toP. brassicae. Subsequent analysis revealed significant transcriptional alterations in genes linked to pathogen response, along with notable differences in genes associated with salicylic acid (SA) and jasmonic acid (JA) defense pathways, compared to wild-type plants. Interestingly, there was a tendency for up-regulation of SA- and JA-related genes inAIL7overexpression and mutant lines in the absence, rather than presence, ofP. brassicae. Subsequent phytohormone analyses confirmed these results. Taken together, AIL7 has an important role in maintaining constitutive systemic acquired resistance, involving phytohormone mediated defense, and this, rather than an accumulation of SA followingP. brassicaechallenge, primes the plants for improved clubroot resistance, which would shed light on exploring the functions of other AP2/ERF family TFs in plant immunity against soilborne pathogens.