bluuebunny/crossref_metadata_2025_split huggingface dataset:
Management of spinal trauma in pregnant patients: A systematic review of the literature
Authors: Rajkovic Christian , Kiss Adam , Lee Alyssa , Malhotra Aryan , Merckling Matthew , Jain Aarti , Subah Galadu , Zeller Sabrina , Zangbar Bardiya , Prabhakaran Kartik , Wainwright John , Kinon Merritt 
Published: August 2024

BACKGROUND
Despite the high incidence of spine trauma globally, traumatic spinal cord injury (tSCI) during pregnancy is considered a rare medical emergency. The literature on acute management of these patients is sparse compared with that of mothers with preexisting tSCI. This systematic review aims to evaluate management strategies for tSCI during pregnancy in improving neurologic, obstetric, and neonatal outcomes.

METHODS
A systematic review of PubMed/MEDLINE was performed without language restriction from inception until November 2, 2023 for patients who acquired tSCI during pregnancy. Excluded articles described postpartum trauma, trauma before pregnancy, or SCI of nontraumatic etiology such as neoplastic, vascular, hemorrhagic, or ischemic origin. Primary outcomes investigated were maternal American Spinal Injury Association (ASIA) grade, pregnancy termination, cesarean delivery, prematurity, and neonatal adverse events.

RESULTS
Data from 73 patients were extracted from 43 articles from 1955 to 2023. The mothers' median age was 24 years (interquartile range, 23–30 years), and the average gestational age at the time of injury was 21.1 ± 7.7 weeks. The thoracic spine was the most common segment affected (41.1%) and had the greatest proportion of complete tSCI (46.6%). Furthermore, ASIA score improvement was observed in 17 patients with 3 patients experiencing a 2-score improvement and 1 patient experiencing a 3-score improvement. Among these patients, 86% of ASIA B and 100% of ASIA C patients showed neurologic improvement, compared to only 17% of ASIA A patients. Surgically managed patients had a lower rate of neonatal adverse events than conservatively managed patients (11% vs. 34%).

CONCLUSION
Acute tSCI requires a coordinated effort between a multidisciplinary team with careful consideration. While maternal neurologic improvement was observed more often following a better ASIA grade on presentation, the presence of neonatal adverse events was less common in patients treated with surgery than in patients who were managed conservatively.

LEVEL OF EVIDENCE
Systematic review/Meta-analysis; Level IV.
Catastrophic Hunger in Gaza: Unprecedented Levels of Hunger Post-October 7th. A Real Population-Based Study from the Gaza Strip
Authors: Faris MoezAlIslam , Abutair Ayman S. , Elfarra Reham M. , Barqawi Nida. A. , Firwana Amal M. , Firwana Rawan M. , AbuHajjaj Madleen M. , Shamaly Shaimaa A. , AbuSamra Samar S. , Bashir Hanan S. , Abedalrahim Noor A. , Nofal Noor A. , Alshawaf Mhran K. , Al Shatali Rania M. , Ghaben Kafa I. , Alron Moayad I. , Alqeeq Sara S. , Al-Nabahin Aya O. , Badawi Reem A. 
Published: August 2024

AbstractBackgroundThe Gaza Strip, spanning approximately 365 square kilometers, has been a focal point of geopolitical tensions and humanitarian crises. The military escalation on October 7thexacerbated existing vulnerabilities, notably food security and hunger, with an estimated 85,750 deaths due to Israeli attacks, representing about 8% of the 2.34 million population. This research aims to inform policymakers and humanitarian organizations about strategies to mitigate hunger and improve food security in Gaza amidst this damaging war.MethodsA cross-sectional study was conducted from May to July 2024, assessing food insecurity and hunger among Palestinian households across the five governorates of Gaza. The study applied a quantitative research approach; the study involved 1209 households. The study utilized the Household Food Security Survey Module (HFSSM), Household Food Insecurity Access Scale (HFIAS), and Household Hunger Scale (HHS) to measure food insecurity and hunger. Self-reported anthropometric data were also collected. Data were analyzed using SPSS version 29, employing correlation tests, chi-square analysis, and logistic regression.ResultsOut of 1503 surveyed households, 1209 were included in the final analysis. The mean age of participants was 38 years, with 53.5% being female. Significant findings included high levels of food insecurity, with 100% of households experiencing some level of food insecurity according to HFSSM and 97.7% being severely food insecure per HFIAS. The results revealed a catastrophic, unprecedented, extremely high prevalence of hunger, reaching more than 95%. The HHS indicated that 88% of households experienced varying degrees of hunger. The war was associated with significant weight loss among individuals, with the average weight dropping from 74.6 kg before the war to 64.1 kg. Factors such as displacement, age, economic status, and educational level significantly impacted hunger severity.ConclusionThe study reveals a severe food insecurity and hunger crisis in the Gaza Strip, exacerbated by the ongoing damaging war by Israeli forces. The findings highlight the urgent need for coordinated efforts to address food security and support the resilience and recovery of affected communities. Policymakers and humanitarian organizations must develop targeted interventions to mitigate hunger and improve the living conditions in Gaza.
CO2protects cells from iron-Fenton oxidative DNA damage in E. coli and humans
Authors: Fleming Aaron M. , Dingman Justin C. , Burrows Cynthia J. 
Published: August 2024

AbstractWhereas hydroxyl radical is commonly named as the Fenton product responsible for DNA and RNA damage in cells, here we demonstrate that the cellular reaction generates carbonate radical anion due to physiological levels of bicarbonate. Analysis of the metabolome, transcriptome and, in human cells, the nuclear genome shows a consistent buffering of H2O2-induced oxidative stress leading to one common pathway, namely guanine oxidation. Particularly revealing are nanopore-based studies of direct RNA sequencing of cytosolic and mitochondrial ribosomal RNA along with glycosylase-dependent qPCR studies of oxidative DNA damage in telomeres. The focusing of oxidative modification on one pathway is consistent with the highly evolved base excision repair suite of enzymes and their involvement in gene regulation in response to oxidative stress.
The amyloid oligomer modulator anle138b has disease modifying effects in a human IAPP transgenic mouse model of type 2 diabetes mellitus (hIAPP Ob/Ob mice)
Authors: Albariqi Mohammed M. H. , Baauw Sanne M.G. , Fens Sjors J.P.J. , Versteeg Sabine , Ryazanov Sergey , Leonov Andrei , Willemen Hanneke L.D.M. , Stathonikos Nikolas , Seychell Raina Marie , Saghir Adam El , Gerritsen Bram , Khemtemourian Lucie , Vassallo Neville , Giese Armin , Eijkelkamp Niels , Griesinger Christian , Höppener Jo W. M. 
Published: August 2024

SummaryCytotoxic aggregates of human islet amyloid polypeptide (hIAPP) contribute to type 2 diabetes mellitus (T2DM) pathogenesis by damaging pancreatic islet β cells and reducing insulin production. Anle138b is an amyloid oligomer modulator with disease modifying properties in mouse models of neurodegenerative diseases linked to protein aggregation and with favorable results in phase 1 clinical studies. We tested whether anle138b has disease modifying properties in a severe hIAPP transgenic mouse model of T2DM. Oral administration of anle138b in hIAPP Ob/Ob mice reduced hyperglycemia, decreased glycated hemoglobin levels, increased islet β-cell mass and improved islet function compared to non-treated mice. In contrast, anle138b administration did not affect these parameters in non-transgenic Ob/Ob mice, indicating that the anti-diabetic effects of anle138b are hIAPP-dependent.In vitro, anle138b inhibited hIAPP aggregation and toxic effects of hIAPP on mitochondria. These results indicate that anle138b is a promising drug candidate for treating and/or preventing T2DM -associated pathology.
Phase I/II Trial of Brogidirsen: Dual-Targeting Antisense Oligonucleotides for Exon 44 Skipping in Duchenne Muscular Dystrophy
Authors: Komaki Hirofumi , Takeshita Eri , Kunitake Katsuhiko , Ishizuka Takami , Shimizu-Motohashi Yuko , Ishiyama Akihiko , Sasaki Masayuki , Yonee Chihiro , Maruyama Shinsuke , Hida Eisuke , Aoki Yoshitsugu 
Published: August 2024

SummaryDuchenne muscular dystrophy (DMD) is a severe muscle disorder caused by mutations in the DMD gene, resulting in dystrophin loss. Exon-skipping using antisense oligonucleotides (ASO) is a promising approach that partially restores dystrophin by correcting the frameshift during pre-mRNA splicing. However, a weakness of the current approach is that it is mutation-specific and has poor efficacy. To address these, we aim to develop brogidirsen, a new dual-targeting ASO that targets two sequences in exon 44 of theDMDusing phosphorodiamidate morpholino oligomer. Here, we conducted an open-label, dose-escalation, Phase I/II trial to evaluate the safety, pharmacokinetics, and activity of brogidirsen, administered intravenously to six ambulant patients with DMD amenable to exon 44 skipping. The study consisted of a dose-escalation part to determine the optimal doses, followed by extended treatment with 40 mg/kg or 80 mg/kg weekly dose for 24 weeks. There were no serious adverse events related to brogidirsen. The results indicated a dose-dependent increase in dystrophin levels, reaching 10.27% and 15.79% of the normal level in the two cohorts. Motor functional tests suggested a trend toward maintaining or slightly improving motor function. There was a dose-dependent increase in Cmax and AUC0–t. High-throughput proteomic assays revealed that serum proteins such as PADI2, TTN, MYOM2, and MYLPF were observed to reduce, suggesting them as biomarkers for therapeutic effects. Notably, in vitro assays using urine-derived cells from patients with DMD support brogidirsen’s high efficacy in the first-in-human studies. These promising results warrant a subsequent multinational trial for DMD.
Crowder induced conformational fluctuations modulate the phase separation of yeast SUP35 NM domain
Authors: Roychowdhury Sumangal , Menon Sneha , Mandal Narattam , Mondal Jagannath , Chattopadhyay Krishnananda 
Published: August 2024

AbstractIntrinsically disordered proteins (IDPs) like Sup35NM can undergo liquid-liquid phase separation (LLPS) to form biomolecular condensates, a process influenced by their conformational flexibility and the crowded intracellular environment. This study investigates how molecular crowding, specifically the size and shape of crowders like Dextran and Ficoll, modulates the conformational states and phase separation behavior of Sup35NM. Using fluorescence correlation spectroscopy (FCS) and molecular dynamics simulations, we observed that Dextran, depending on its molecular weight, induces both compaction and expansion of Sup35NM, driving phase separation at certain thresholds. Notably, rod-like Dextran crowders promote phase separation, while spherical Ficoll does not, highlighting the impact of crowder geometry on IDP behavior. Computational modelling further revealed that the crowder shape influences Sup35NM’s conformational ensemble by modulating intra- and inter-domain interactions. These findings elucidate the role of crowding agents in IDP phase behavior, suggesting that cellular crowding may regulate IDP functionality through conformational control.
Temperature affects recombination rate plasticity and meiotic success between thermotolerant and cold tolerant yeast species
Authors: McNeill Jessica , Brandt Nathan , Schwarzkopf Enrique J. , Jimenez Mili , Smukowski Heil Caiti 
Published: August 2024

AbstractMeiosis is required for the formation of gametes in all sexually reproducing species and the process is well conserved across the tree of life. However, meiosis is sensitive to a variety of external factors, which can impact chromosome pairing, recombination, and fertility. For example, the optimal temperature for successful meiosis varies between species of plants and animals. This suggests that meiosis is temperature sensitive, and that natural selection may act on variation in meiotic success as organisms adapt to different environmental conditions. To understand how temperature alters the successful completion of meiosis, we utilized two species of the budding yeastSaccharomyceswith different temperature preferences: thermotolerantSaccharomyces cerevisiaeand cold tolerantSaccharomyces uvarum. We surveyed three metrics of meiosis: sporulation efficiency, spore viability, and recombination rate in multiple strains of each species. As per our predictions, the proportion of cells that complete meiosis and form spores is temperature sensitive, with thermotolerantS. cerevisiaehaving a higher temperature threshold for successful meiosis than cold tolerantS. uvarum. We confirmed previous observations thatS. cerevisiaerecombination rate varies between strains and across genomic regions, and add new results thatS. uvarumhas higher recombination rates thanS. cerevisiae. We find that temperature significantly influences recombination rate plasticity inS. cerevisiaeandS. uvarum, in agreement with studies in animals and plants. Overall, these results suggest that meiotic thermal sensitivity is associated with organismal thermal tolerance, and may even result in temporal reproductive isolation as populations diverge in thermal profiles.
Haematology dimension reduction, a large scale application to regular care haematology data
Authors: Joosse Huibert-Jan , Chumsaeng-Reijers Chontira , Huisman Albert , Hoefer Imo E , van Solinge Wouter W , Haitjema Saskia , van Es Bram 
Published: August 2024

AbstractBackgroundThe routine diagnostic process increasingly entails the processing of high-volume and high-dimensional data. This processing may provide scaling issues that limit the implementation of these types of data into research as well as integrated diagnostics in routine care. Here, we investigate whether we can use existing dimension reduction techniques to provide visualisations and analyses for a complete bloodcount (CBC) while maintaining representativeness of the original data. We considered over 3 million CBC measurements encompassing over 70 parameters of cell frequency, size and complexity from the UMC Utrecht UPOD database. We evaluated PCA as an example of a linear dimension reduction techniques and UMAP, TriMap and PaCMAP as non-linear dimension reduction techniques. We assessed their technical performance using quality metrics for dimension reduction as well as biological representation by evaluating preservation of diurnal, age and sex patterns, cluster preservation and the identification of leukemia patients.ResultsWe found that PCA performs systematically better than the UMAP, TriMap and PaCMAP in representing the underlying data. Biological relevance was retained for periodicity in the data. However, we also observed a decrease in predictive performance of the reduced data for both age and sex, as well as an overestimation of clusters within the reduced data. Finally, we were able to identify the diverging patterns for leukemia patients after use of dimensionality reduction methods.ConclusionsWe conclude that for hematology data, the use of unsupervised dimension reduction techniques should be limited to data visualization applications, as implementing them in diagnostic pipelines may lead to decreased quality of integrated diagnostics in routine care.
Wild corvids learn social tolerance to exploit new information
Authors: Arbon Josh J , Truskanov Noa , Stott Emily , McIvor Guillam E , Thornton Alex 
Published: August 2024

AbstractSocial tolerance is crucial in facilitating the evolution of cooperation, social cognition and culture, but it is unknown whether animals can optimise their social tolerance through learning. We presented wild jackdaws (Corvus monedula) with a novel social information problem using automated feeders: to access food, adults had to inhibit their tendency to displace juveniles and instead show tolerance by occupying an adjacent perch. Adults learned to tolerate juveniles, generalising across juveniles as a cohort, demonstrating learning of a new information-use strategy.
Transcriptomic dynamics of petal development in the one-day flower species, Japanese morning glory (Ipomoea nil)
Authors: Nakagawa Soya , Hoshino Atsushi , Ito Kazuyo , Nishide Hiroyo , Shiratake Katsuhiro , Nagano Atsushi J. , Sakakibara Yasubumi 
Published: August 2024

SUMMARYVarious aspects of Japanese morning glory(Ipomoea nil) petals, such as color, pattern, shape, flower opening time, and senescence, have been extensively studied. To facilitate such studies, transcriptome data were collected from flower petals at 3-h intervals over 3.5 days; the data was collected from 72 h before and 12 h after flower opening, accounting for 29 timepoints. Data analysis revealed substantial transcriptomic changes before and after flower opening. The expression patterns of cell division marker genes indicated that cell division practically stops at approximately 48 h before flower opening. Furthermore, the increased expression of genes encoding transporters for sugars, amino acids, nucleic acids, and autophagy-related genes was observed after flower opening, indicating the translocation of nutrients from senescing petal cells to other developing tissues. Correlations were found between the temporal expression patterns of the three transcriptional regulators and expression patterns of different sets of structural genes within the anthocyanin biosynthesis pathway, indicating differential reliance on each regulator for the activation of specific structural genes. Furthermore, clock genes were identified. Three copies of the clock geneELF3did not exhibit circadian rhythms, potentially allowingI. nilto adapt to high-latitude regions. The temporal transcriptome data and interactive database (https://ipomoeanil.nibb.ac.jp/fpkm/) offer valuable insights into gene expression dynamics, periodicity, and correlations and provide a crucial resource for further research onI. niland other plant species.
Transglutaminase 2 function in glioblastoma tumor efferocytosis
Authors: Lui Margarita , Sevinc Filiz , Elgafarawi Mara , Munoz David G. , Keillor Jeffrey W , Sinclair John , Catana Dragosh , Woulfe John , Lorimer Ian AJ 
Published: August 2024

ABSTRACTGlioblastoma is an aggressive and incurable type of brain cancer. Regions of tissue necrosis are a distinctive pathological feature of this cancer. These arise through thrombosis of tumor vasculature, driven by tumor-derived pro-coagulation factors. In studies of transglutaminase 2 (TGM2), we observed that TGM2 mRNA expression in glioblastoma was primarily in a subset of tumor-infiltrating myeloid cells with hypoxia gene expression signatures. Analysis of xenograft and human glioblastoma samples by immunohistochemistry showed that macrophages in the vicinity of necrotic regions expressed very high levels of TGM2. These macrophages were engaged in the phagocytosis of apoptotic cells, a process known as efferocytosis. In cell culture, incubation of macrophages with apoptotic cells induced TGM2 expression in macrophages, and TGM2 inhibitors blocked efferocytosis. In patient-derived glioblastoma organoids cultured in 5% O2, a basal level of apoptosis was observed, and endogenous macrophages were observed in the process of clearing apoptotic cells. Clearance of apoptotic cells was reduced in organoids treated with a TGM2 inhibitor. Apoptotic cells and efferocytosis were both markedly lower in organoids grown in 20% O2. These data, together with previous work, define a model in which necrotic regions in glioblastoma induce hypoxia-driven apoptosis, which in turn promotes efferocytosis by macrophages. TGM2 is both a marker of efferocytosis and a target for efferocytosis inhibition in this process. Efferocytosis is a potent immunosuppressive mechanism, so this process provides an additional mechanism by which large glioblastoma tumors can evade immune responses.
The receptor-like kinase ALE2 promotes giant cell formation in the sepal epidermis
Authors: Clark Frances K. , McGory Jessica , Russell Nicholas J. , Formosa-Jordan Pau , Roeder Adrienne H. K. 
Published: August 2024

AbstractDuring sepal development inArabidopsis thaliana, epidermal pavement cells differentiate into small cells and large, highly endoreduplicated giant cells. While the placement of giant cells differs between sepals, the number of giant cells is fairly consistent. The HD-ZIP class IV transcription factor ATML1 has been found to promote giant cell formation. ATML1 protein fluctuates within epidermal nuclei of developing sepals and high ATML1 concentrations reached in the G2 phase of the cell cycle strongly correlates with giant cell fate specification. A genetic screen for reduced giant cell number identified the receptor-like kinase ABNORMAL LEAF SHAPE2 (ALE2) as being important for giant cell formation. We find that ALE2 functions genetically upstream of ATML1 in promoting the formation of giant cells. We observe that nuclear-localized mCitrine-ATML1 fluctuates inale2mutants much as it does in wild type and, importantly, nuclear mCitrine-ATML1 reaches similarly high peak concentrations inale2-1mutants as in wild type. This indicates that ALE2 functions upstream of ATML1 by affecting protein activity rather than gene expression or protein degradation. One function of ATML1 is to promote transcription of the CDK inhibitor LGO. We find that LGO transcription is delayed and decreased inale2-1mutants as compared to wild-type plants, consistent with ATML1 having impaired protein function inale2mutants. Overall, we find that the receptor-like kinase ALE2 is necessary to sensitize cells of the developing sepal epidermis to fluctuations of the transcription factor ATML1.
Optimizing Plant Biofactories: Enhancing Recombinant Protein Production inNicotiana benthamianathrough Phytoplasma Effectors
Authors: Rahman Md Saifur , Goulet Marie-Claire , Michaud Dominique 
Published: August 2024

AbstractMolecular farming, which utilizes plants as biofactories for recombinant protein production, offers an innovative and cost-effective alternative to traditional expression systems. Despite its advantages, plant-based production faces challenges such as low transgene expression and protein instability. Recent studies have highlighted the potential ofNicotiana benthamianaaxillary stem leaves to enhance protein yield. This study explored the development ofN. benthamianalines expressing TENGU without signal peptide (T-SP), a phytoplasma effector known to induce plant dwarfism and increase shoot growth. TENGU and other effectors, such as SAP05 and SAP11, were introduced to create phenotypic variations that favor recombinant protein production. This study aimed to optimize these transgenic lines for increased biomass and protein yields by leveraging vertical farming conditions for scalable production. The results demonstrated significant improvements in leaf number, biomass, and five times more soluble protein content in T-SP lines compared to control lines, suggesting a promising approach for efficient molecular farming.