bluuebunny/crossref_metadata_2025 huggingface dataset:
Revealing Elysium Planitia's Young Geologic History: Constraints on Lava Emplacement, Areas, and Volumes
Authors: Voigt J. R. C. , Hamilton C. W. , Steinbrügge G. , Christoffersen M. S. , Nerozzi S. , Kerber L. , Holt J. W. , Carter L. M.
Published: December 2023

Elysium Planitia includes several outflow channels that were likely carved by aqueous erosion and subsequently infilled by younger lava flows, making Elysium Planitia the youngest volcanic terrain on Mars. Studying this region is critical for constraining the recent hydrological and thermal evolution of the planet. Here, we investigate the lava flow areas, thicknesses, and volumes in Elysium Planitia using Context (CTX) camera images in combination with SHAllow RADar (SHARAD) sounder data. Compiling 1,777 reflectors over an area of 9,126,790 km2 allows us to reconstruct the subsurface landscape evolution over time. Our findings show that Elysium Planitia is composed of material from about 40 episodes of effusive volcanic activity. We report volumes for individual eruptions of 4,000 ± 1,600 km3 infilling Athabasca Valles, 12,200 ± 2,500 km3 in Marte Vallis, and 16,000 ± 4,000 km3 in Rahway Valles for the major flow units and volumes as small as 100 ± 50 km3 in Cerberus Plains. The surface morphologies and inferred dielectric properties of lobe interfaces suggests that the regions consists of basaltic lava. The region also experienced multiple aqueous flooding events. Although, we found evidence of past lava–water interactions, present‐day ground‐ice (if present) is likely limited to local patches. Further, the pre‐eruption landscape reveals that the aqueously carved Marte Vallis is more areal extensive, but shallower than previously suggested, with a likely paleo‐flow direction from northwest to southeast. The channel is most likely sourced from a segment in the northwestern portion of Cerberus Fossae, and is now buried by multiple Late Amazonian lavas with the same lava flow direction.
One Health assessment of persistent organic chemicals and PFAS for consumption of restored anadromous fish
Authors: Melnyk Lisa Jo , Lazorchak James M. , Kusnierz Daniel H. , Perlman Gary D. , Lin John , Venkatapathy Raghuraman , Sundaravadivelu Devi , Thorn Jonathan , Durant James , Pugh Katherine , Stover Michael A.
Published: December 2023

Background

Restoration efforts have led to the return of anadromous fish, potential source of food for the Penobscot Indian Nation, to the previously dammed Penobscot River, Maine.

Objective

U.S. Environmental Protection Agency (EPA), Penobscot Indian Nation’s Department of Natural Resources (PINDNR), and Agency for Toxic Substances and Disease Registry (ATSDR), measured contaminants in six species of anadromous fish. Fish tissue concentrations were then used, along with exposure parameters, to evaluate potential human and aquatic-dependent wildlife risk.

Methods

PINDNR collected, filleted, froze, and shipped fish for analysis of polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), dioxins/furans, and per- and polyfluoroalkyl substances (PFAS). Contaminant levels were compared to reference doses (where possible) and wildlife values (WVs).

Results

Chemical concentrations ranged from 6.37 nanogram per gram (ng/g) wet weight (ww) in American Shad roe to 100 ng/g ww in Striped Bass for total PCBs; 0.851 ng/g ww in American Shad roe to 5.92 ng/g ww in large Rainbow Smelt for total PBDEs; and 0.037 ng/g ww in American Shad roe to 0.221 ng/g ww in Striped Bass for total dioxin/furans. PFAS concentrations ranged between 0.38 ng/g ww of PFBA in Alewife to 7.86 ng/g ww of PFUnA in Sea Lamprey. Dioxin/furans and PFOS levels indicated that there are potential human health risks. The WV for mink for total PCBs (72 ng/g) was exceeded in Striped Bass and the WV for Kestrel for PBDEs (8.7 ng/g) was exceeded in large Rainbow Smelt. Mammalian wildlife consuming Blueback Herring, Striped Bass, and Sea Lamprey may be at risk based on PFOS WVs from Canada.

Impact

Anadromous fish returning to the Penobscot River potentially could represent the restoration of a major component of tribal traditional diet. However, information about contaminant levels in these fish is needed to guide the tribe about consumption safety. Analysis of select species of fish and risk calculations demonstrated the need for a protective approach to consumption for both humans and wildlife. This project demonstrates that wildlife can also be impacted by contamination of fish and their risks can be as great or greater than those of humans. A One Health approach addresses this discrepancy and will lead to a healthier ecosystem.
Curation of causal interactions mediated by genes associated with autism accelerates the understanding of gene-phenotype relationships underlying neurodevelopmental disorders
Authors: Iannuccelli Marta , Vitriolo Alessandro , Licata Luana , Lo Surdo Prisca , Contino Silvia , Cheroni Cristina , Capocefalo Daniele , Castagnoli Luisa , Testa Giuseppe , Cesareni Gianni , Perfetto Livia
Published: December 2023

Autism spectrum disorder (ASD) comprises a large group of neurodevelopmental conditions featuring, over a wide range of severity and combinations, a core set of manifestations (restricted sociality, stereotyped behavior and language impairment) alongside various comorbidities. Common and rare variants in several hundreds of genes and regulatory regions have been implicated in the molecular pathogenesis of ASD along a range of causation evidence strength. Despite significant progress in elucidating the impact of few paradigmatic individual loci, such sheer complexity in the genetic architecture underlying ASD as a whole has hampered the identification of convergent actionable hubs hypothesized to relay between the vastness of risk alleles and the core phenotypes. In turn this has limited the development of strategies that can revert or ameliorate this condition, calling for a systems-level approach to probe the cross-talk of cooperating genes in terms of causal interaction networks in order to make convergences experimentally tractable and reveal their clinical actionability. As a first step in this direction, we have captured from the scientific literature information on the causal links between the genes whose variants have been associated with ASD and the whole human proteome. This information has been annotated in a computer readable format in the SIGNOR database and is made freely available in the resource website. To link this information to cell functions and phenotypes, we have developed graph algorithms that estimate the functional distance of any protein in the SIGNOR causal interactome to phenotypes and pathways. The main novelty of our approach resides in the possibility to explore the mechanistic links connecting the suggested gene-phenotype relations.
Intranasal oxytocin in a genetic animal model of autism
Authors: Szabó Jakub , Mlynár Matúš , Feješ Andrej , Renczés Emese , Borbélyová Veronika , Ostatníková Daniela , Celec Peter
Published: December 2023

Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders mainly characterized by deficient sociability and repetitive behaviors. Effective treatment for the core symptoms of ASD is still lacking. Behavioral interventions show limited effectiveness, while pharmacotherapy focuses on the amelioration of secondary symptomatology. Oxytocin (OXT) is a neuropeptide known for its prosocial impact, making it a candidate drug for ASD treatment. Its alleviating effect has been and still is widely researched, but outcomes reported by clinical studies are ambiguous. We examined the effect of daily intranasal OXT (0.8 IU/kg) administration for 4 weeks on the ASD-like phenotype in Shank3−/− adult mice. Animals treated with OXT spent twice as much time interacting with the social partner as early as after 2 weeks of treatment. Furthermore, OXT-treated mice exhibited reduced explorative behavior by 50%, after 4 weeks of treatment, and a 30% reduction in repetitive behavior, 4 weeks after treatment termination. One-fold higher sociability and 30% reduced exploration due to OXT lasted up to 4 weeks following the treatment termination. However, social disinterest was elevated by roughly 10% as well, indicating a form of social ambivalence. Obtained results support the therapeutic potential of intranasally administered OXT in alleviating social shortfalls in a genetic model of ASD. Subsequent research is necessary to elucidate the benefits and risks of the long-term OXT administration, as well as its applicability in other ASD models and the potential treatment effect on social communication, which was not measured in the present study.
Cerebral organoids with chromosome 21 trisomy secrete Alzheimer’s disease-related soluble aggregates detectable by single-molecule-fluorescence and super-resolution microscopy
Authors: Fertan Emre , Böken Dorothea , Murray Aoife , Danial John S. H. , Lam Jeff Y. L. , Wu Yunzhao , Goh Pollyanna A. , Alić Ivan , Cheetham Matthew R. , Lobanova Evgeniia , Zhang Yu P. , Nižetić Dean , Klenerman David
Published: December 2023

Understanding the role of small, soluble aggregates of beta-amyloid (Aβ) and tau in Alzheimer’s disease (AD) is of great importance for the rational design of preventative therapies. Here we report a set of methods for the detection, quantification, and characterisation of soluble aggregates in conditioned media of cerebral organoids derived from human iPSCs with trisomy 21, thus containing an extra copy of the amyloid precursor protein (APP) gene. We detected soluble beta-amyloid (Aβ) and tau aggregates secreted by cerebral organoids from both control and the isogenic trisomy 21 (T21) genotype. We developed a novel method to normalise measurements to the number of live neurons within organoid-conditioned media based on glucose consumption. Thus normalised, T21 organoids produced 2.5-fold more Aβ aggregates with a higher proportion of larger (300–2000 nm2) and more fibrillary-shaped aggregates than controls, along with 1.3-fold more soluble phosphorylated tau (pTau) aggregates, increased inflammasome ASC-specks, and a higher level of oxidative stress inducing thioredoxin-interacting protein (TXNIP). Importantly, all this was detectable prior to the appearance of histological amyloid plaques or intraneuronal tau-pathology in organoid slices, demonstrating the feasibility to model the initial pathogenic mechanisms for AD in-vitro using cells from live genetically pre-disposed donors before the onset of clinical disease. Then, using different iPSC clones generated from the same donor at different times in two independent experiments, we tested the reproducibility of findings in organoids. While there were differences in rates of disease progression between the experiments, the disease mechanisms were conserved. Overall, our results show that it is possible to non-invasively follow the development of pathology in organoid models of AD over time, by monitoring changes in the aggregates and proteins in the conditioned media, and open possibilities to study the time-course of the key pathogenic processes taking place.
Aberrant epithelial cell interaction promotes esophageal squamous-cell carcinoma development and progression
Authors: Chen Liping , Zhu Shihao , Liu Tianyuan , Zhao Xuan , Xiang Tao , Hu Xiao , Wu Chen , Lin Dongxin
Published: December 2023

Epithelial-mesenchymal transition (EMT) and proliferation play important roles in epithelial cancer formation and progression, but what molecules and how they trigger EMT is largely unknown. Here we performed spatial transcriptomic and functional analyses on samples of multistage esophageal squamous-cell carcinoma (ESCC) from mice and humans to decipher these critical issues. By investigating spatiotemporal gene expression patterns and cell–cell interactions, we demonstrated that the aberrant epithelial cell interaction via EFNB1-EPHB4 triggers EMT and cell cycle mediated by downstream SRC/ERK/AKT signaling. The aberrant epithelial cell interaction occurs within the basal layer at early precancerous lesions, which expands to the whole epithelial layer and strengthens along the cancer development and progression. Functional analysis revealed that the aberrant EFNB1-EPHB4 interaction is caused by overexpressed ΔNP63 due to TP53 mutation, the culprit in human ESCC tumorigenesis. Our results shed new light on the role of TP53-TP63/ΔNP63-EFNB1-EPHB4 axis in EMT and cell proliferation in epithelial cancer formation.
Eculizumab treatment in paediatric patients diagnosed with aHUS after haematopoietic stem cell transplantation: a HSCT-TMA case series from Japanese aHUS post-marketing surveillance
Authors: Ito Shuichi , Saito Atsuro , Sakurai Ayako , Watanabe Kenichiro , Karakawa Shuhei , Miyamura Takako , Yokosuka Tomoko , Ueki Hideaki , Goto Hiroaki , Yagasaki Hiroshi , Kinoshita Mariko , Ozeki Michio , Yokoyama Norifumi , Teranishi Hirofumi
Published: December 2023

Haematopoietic stem-cell transplantation (HSCT)-associated thrombotic microangiopathy (HSCT-TMA) is a serious complication with high mortality. Accumulating evidence suggests that complement dysregulation is potentially involved in the development of HSCT-TMA. We retrospectively analysed the clinical characteristics and outcomes of thirteen paediatric patients who were diagnosed with atypical haemolytic uremic syndrome and treated with eculizumab to manage HSCT-TMA during post-marketing surveillance in Japan. The median time from HSCT to TMA was 31 days (Interquartile range, IQR;21–58) and the median doses of eculizumab was three (IQR;2–5). Seven patients (54%) were alive at the last follow-up while six died due to complications related to HSCT. Six of seven survivors initiated eculizumab after insufficient response to plasma therapy. Following eculizumab treatment, median platelet counts and LDH levels in all survivors significantly improved and renal function improved in 4/7 patients. All survivors possessed potential risk factors of complement overactivation. During the follow-up period after eculizumab discontinuation (median;111.5 days, IQR;95–555), no TMA recurrence was observed. In this analysis, eculizumab showed benefit in over half of this paediatric patient population. Ongoing clinical studies are expected to optimize the treatment regimen of terminal complement pathway inhibitor, and it may become a therapeutic option for paediatric HSCT-TMA in the future.
Pharmacological inhibition of MALT1 (mucosa-associated lymphoid tissue lymphoma translocation protein 1) induces ferroptosis in vascular smooth muscle cells
Authors: Yan Binjie , Belke Darrell , Gui Yu , Chen Yong-Xiang , Jiang Zhi-Sheng , Zheng Xi-Long
Published: December 2023

MALT1 (mucosa-associated lymphoid tissue lymphoma translocation protein 1) is a human paracaspase protein with proteolytic activity via its caspase-like domain. The pharmacological inhibition of MALT1 by MI-2, a specific chemical inhibitor, diminishes the response of endothelial cells to inflammatory stimuli. However, it is largely unknown how MALT1 regulates the functions of vascular smooth muscle cells (SMCs). This study aims to investigate the impact of MALT1 inhibition by MI-2 on the functions of vascular SMCs, both in vitro and in vivo. MI-2 treatment led to concentration- and time-dependent cell death of cultured aortic SMCs, which was rescued by the iron chelator deferoxamine (DFO) or ferrostatin-1 (Fer-1), a specific inhibitor of ferroptosis, but not by inhibitors of apoptosis (Z-VAD-fmk), pyroptosis (Z-YVAD-fmk), or necrosis (Necrostatin-1, Nec-1). MI-2 treatment downregulated the expression of glutathione peroxidase 4 (GPX4) and ferritin heavy polypeptide 1 (FTH1), which was prevented by pre-treatment with DFO or Fer-1. MI-2 treatment also activated autophagy, which was inhibited by Atg7 deficiency or bafilomycin A1 preventing MI-2-induced ferroptosis. MI-2 treatment reduced the cleavage of cylindromatosis (CYLD), a specific substrate of MALT1. Notably, MI-2 treatment led to a rapid loss of contractility in mouse aortas, which was prevented by co-incubation with Fer-1. Moreover, local application of MI-2 significantly reduced carotid neointima lesions and atherosclerosis in C57BL/6J mice and apolipoprotein-E knockout (ApoE−/−) mice, respectively, which were both ameliorated by co-treatment with Fer-1. In conclusion, the present study demonstrated that MALT1 inhibition induces ferroptosis of vascular SMCs, likely contributing to its amelioration of proliferative vascular diseases.
Genetic basis of osteogenesis imperfecta from a single tertiary centre in South Africa
Authors: Coetzer Kimberly Christine , Zöllner Ekkehard , Moosa Shahida
Published: December 2023

Osteogenesis imperfecta (OI) is a clinically heterogeneous disorder characterised by skeletal fragility and an increased fracture incidence. It occurs in approximately one in every 15–20,000 births and is known to vary considerably in its severity. This report aimed to use next-generation sequencing (NGS) technology to identify disease genes and causal variants in South African patients with clinical-radiological features of OI. A total of 50 affected individuals were recruited at Tygerberg Hospital’s Medical Genetics clinic. Patients were selected for a gene panel test (n = 39), a single variant test (n = 1) or exome sequencing (ES) (n = 12, 7 singletons, 1 affected duo, and 1 trio), depending on funding eligibility. An in-house genomic bioinformatics pipeline was developed for the ES samples using open-source software and tools. This study’s 100% diagnostic yield was largely attributable to an accurate clinical diagnosis. A causal variant in COL1A1 or COL1A2 was identified in 94% of this patient cohort, which is in line with previous studies. Interestingly, this study was the first to identify the common South African pathogenic FKBP10 variant in a patient of mixed ancestry, adding to what was previously known about this variant in our population. Additionally, a recurrent variant in COL1A2: c.1892G>T was discovered in 27 individuals (25 from three large unrelated families and two further individuals), facilitating the establishment of local testing for this variant in South African patients.
Immune-response 3′UTR alternative polyadenylation quantitative trait loci contribute to variation in human complex traits and diseases
Authors: Li Lei , Ma Xuelian , Cui Ya , Rotival Maxime , Chen Wenyan , Zou Xudong , Ding Ruofan , Qin Yangmei , Wang Qixuan , Quintana-Murci Lluis , Li Wei
Published: December 2023

Genome-wide association studies (GWASs) have identified thousands of non-coding variants that are associated with human complex traits and diseases. The analysis of such GWAS variants in different contexts and physiological states is essential for deciphering the regulatory mechanisms underlying human disease. Alternative polyadenylation (APA) is a key post-transcriptional modification for most human genes that substantially impacts upon cell behavior. Here, we mapped 9,493 3′-untranslated region APA quantitative trait loci in 18 human immune baseline cell types and 8 stimulation conditions (immune 3′aQTLs). Through the comparison between baseline and stimulation data, we observed the high responsiveness of 3′aQTLs to immune stimulation (response 3′aQTLs). Co-localization and mendelian randomization analyses of immune 3′aQTLs identified 678 genes where 3′aQTL are associated with variation in complex traits, 27.3% of which were derived from response 3′aQTLs. Overall, these analyses reveal the role of immune 3′aQTLs in the determination of complex traits, providing new insights into the regulatory mechanisms underlying disease etiologies.
Haplotype-resolved chromosomal-level genome assembly of Buzhaye (Microcos paniculata)
Authors: Liu Detuan , Tian Xiaoling , Shao Shicheng , Ma Yongpeng , Zhang Rengang
Published: December 2023

Microcos paniculata is a shrub used traditionally as folk medicine and to make herbal teas. Previous research into this species has mainly focused on its chemical composition and medicinal value. However, the lack of a reference genome limits the study of the molecular mechanisms of active compounds in this species. Here, we assembled a haplotype-resolved chromosome-level genome of M. paniculata based on PacBio HiFi and Hi-C data. The assembly contains two haploid genomes with sizes 399.43 Mb and 393.10 Mb, with contig N50 lengths of 43.44 Mb and 30.17 Mb, respectively. About 99.93% of the assembled sequences could be anchored to 18 pseudo-chromosomes. Additionally, a total of 482 Mb repeat sequences were identified, accounting for 60.76% of the genome. A total of 49,439 protein-coding genes were identified, of which 48,979 (99%) were functionally annotated. This haplotype-resolved chromosome-level assembly and annotation of M. paniculata will serve as a valuable resource for investigating the biosynthesis and genetic basis of active compounds in this species, as well as advancing evolutionary phylogenomic studies in Malvales.
Chromosome-level genome assembly of the Stoliczka’s Asian trident bat (Aselliscus stoliczkanus)
Authors: Lan Linjing , Zhang Xin , Yang Shanxiu , Li Lingjie , Mao Xiuguang
Published: December 2023

Stoliczka’s Asian trident bat (Aselliscus stoliczkanus) is a small-bodied species and very sensitive to climate change. Here, we presented a chromosome-level genome assembly of A. stoliczkanus by combining Illumina sequencing, Nanopore sequencing and high-throughput chromatin conformation capture (Hi-C) sequencing technology. The genome assembly was 2.18 Gb in size with 98.26% of the genome sequences anchored onto 14 autosomes and two sex chromosomes (X and Y). The quality of the genome assembly is very high with a contig and scaffold N50 of 72.98 and 162 Mb, respectively, Benchmarking Universal Single-Copy Orthologs (BUSCO) score of 96.6%, and the consensus quality value (QV) of 47.44. A total of 20,567 genes were predicted and 98.8% of these genes were functionally annotated. Syntenic blocks between A. stoliczkanus and Homo sapiens, together with previous comparative cytogenetic studies, provide valuable foundations for further comparative genomic and cytogenetic studies in mammals. The reference-quality genome of A. stoliczkanus contributes an important resource for conservative genomics and landscape genomics in predicting adaptation and vulnerability to climate change.
Variations of the trapezius branch of the accessory nerve: an anatomic study
Authors: Lin Matthew E. , Kim Celeste , Howard Adam , Kokot Niels
Published: December 2023

Although modified radical neck dissections have increased in popularity to reduce morbidity secondary to intraoperative accessory nerve damage, inadvertent injury still often occurs. As this phenomenon is thought to be due to anatomic variation in the trapezius branch of the accessory nerve, it is imperative to better understand the nuances of these anatomic variations to better inform surgical decision-making. A total of 24 accessory nerves were dissected, exposed, and traced in 15 cadavers. Three aspects of the accessory nerve were identified and recorded: the course of the trapezius branch in relation to the sternocleidomastoid, the number of trapezius branches at muscle insertion, and the number of cervical rootlet contributions. Four different anatomic patterns for the trapezius branch were identified, with the most common being where the trapezius branch separates from the main accessory nerve just medial to the sternocleidomastoid and courses deep to the sternocleidomastoid (58.3%). Most (75%) trapezius branches entered the muscle as a single nerve, whereas some (21%) were inserted as two separate nerves. The number of cervical rootlet contributions for each trapezius branch varied from zero to three. Bilateral anatomic variations were also noted. Even when the accessory nerve and its branches are thought to be spared during neck dissection, patients may postoperatively present with different degrees of accessory nerve damage. There may be unrecognized anatomic pathways that the nerve takes that may confer a higher risk of unintentional damage, especially those that have greater exposure within the anterior triangle unprotected by the sternocleidomastoid.
Economic burden of multidrug-resistant tuberculosis on patients and households: a global systematic review and meta-analysis
Authors: Akalu Temesgen Yihunie , Clements Archie C. A. , Wolde Haileab Fekadu , Alene Kefyalew Addis
Published: December 2023

Multidrug-resistant tuberculosis (MDR-TB) is a major health threat worldwide, causing a significant economic burden to patients and their families. Due to the longer duration of treatment and expensive second-line medicine, the economic burden of MDR-TB is assumed to be higher than drug-susceptible TB. However, the costs associated with MDR-TB are yet to be comprehensively quantified. We conducted this systematic review and meta-analysis to determine the global burden of catastrophic costs associated with MDR-TB on patients and their households. We systematically searched five databases (CINHAL, MEDLINE, Embase, Scopus, and Web of Science) from inception to 2 September 2022 for studies reporting catastrophic costs on patients and affected families of MDR-TB. The primary outcome of our study was the proportion of patients and households with catastrophic costs. Costs were considered catastrophic when a patient spends 20% or more of their annual household income on their MDR-TB diagnosis and care. The pooled proportion of catastrophic cost was determined using a random-effects meta-analysis. Publication bias was assessed using visualization of the funnel plots and the Egger regression test. Heterogeneity was assessed using I2, and sub-group analysis was conducted using study covariates as stratification variables. Finally, we used the Preferred Reporting Items for Reporting Systematic Review and Meta-Analysis-20 (PRISMA-20). The research protocol was registered in PROSPERO (CRD42021250909). Our search identified 6635 studies, of which 11 were included after the screening. MDR-TB patients incurred total costs ranging from $USD 650 to $USD 8266 during treatment. The mean direct cost and indirect cost incurred by MDR-TB patients were $USD 1936.25 (SD ± $USD 1897.03) and $USD 1200.35 (SD ± $USD 489.76), respectively. The overall burden of catastrophic cost among MDR-TB patients and households was 81.58% (95% Confidence Interval (CI) 74.13–89.04%). The catastrophic costs incurred by MDR-TB patients were significantly higher than previously reported for DS-TB patients. MDR-TB patients incurred more expenditure for direct costs than indirect costs. Social protection and financial support for patients and affected families are needed to mitigate the catastrophic economic consequences of MDR-TB.
OPEFB pretreatment using the low-cost N,N,N-dimethylbutylammonium hydrogen sulfate ionic liquid under varying conditions
Authors: Shikh Zahari S. M. Shahrul Nizan , Liu Yichen , Yao Putian , Ideris Mahfuzah Samirah , Azman Hazeeq Hazwan , Hallett Jason P.
Published: December 2023

This study investigates the effects of temperature and period on the pretreatment of OPEFB using the low-cost N,N,N-dimethylbutylammonium hydrogen sulfate ionic liquid ([DMBA][HSO4] IL) with 20 wt% of water. The results demonstrate that higher pretreatment temperatures (120, 150, and 170 °C) and longer periods (0.5, 1, and 2 h) enhanced lignin recovery, resulting in increased purity of the recovered pulp and subsequently enhanced glucose released during enzymatic hydrolysis. However, at 170 °C, prolonging the period led to cellulose degradation and the formation of pseudo-lignin deposited on the pulps, resulting in a decreasing-trend in glucose released. Finally, the analysis of extracted lignin reveals that increasing pretreatment severity intensified lignin depolymerisation and condensation, leading to a decrease in number average molecular weight (Mn), weight average molecular weight (Mw) and polydispersity index (Đ) values.
Mathematical models of apparent viscosity as a function of water–cement/binder ratio and superplasticizer in cement pastes
Authors: Yuan Yong , Wang Xiaoyun , Chen Xi , Xiao Peng , Koenders Eduardus , Dai Ying
Published: December 2023

The water–cement/binder ratio and the admixture of water-reducing agents strongly affect the rheological properties of cement pastes. This study develops mathematical models to predict the apparent viscosity of cement pastes with varying water-cement/binder ratios and polycarboxylate-based superplasticizer content by introducing the power law shear stress-shear strain relation of non-Newtonian fluids into the Navier–Stokes motion equations. The developed models are compared with the results of rheological experiments and verified for their accuracy in simulating the apparent viscosity of cement pastes. These models provide insight into the rheological behaviour of cement pastes and could have practical applications in the construction industry.
Changes in plasma endocan level are related to circulatory but not respiratory failure in critically ill patients with COVID-19
Authors: Lipińska-Gediga Małgorzata , Lemańska-Perek Anna , Gozdzik Waldemar , Adamik Barbara
Published: December 2023

The aim of this prospective, observational study was to assess whether changes in the level of endocan, a marker of endothelial damage, may be an indicator of clinical deterioration and mortality in critically ill COVID-19 patients. Endocan and clinical parameters were evaluated in 40 patients with acute respiratory failure on days 1–5 after admission to the intensive care unit. Endocan levels were not related to the degree of respiratory failure, but to the presence of cardiovascular failure. In patients with cardiovascular failure, the level of endocan increased over the first 5 days (1.63, 2.50, 2.68, 2.77, 3.31 ng/mL, p = 0.016), while in patients without failure it decreased (1.51, 1.50, 1.56, 1.42, 1.13 ng/mL, p = 0.046). In addition, mortality was more than twice as high in patients with acute cardiovascular failure compared to those without failure (68% vs. 32%, p = 0.035). Baseline endocan levels were lower in viral than in bacterial infections (1.57 ng/mL vs. 5.25 ng/mL, p < 0.001), with a good discrimination between infections of different etiologies (AUC of 0.914, p < 0.001). In conclusion, endocan levels are associated with the occurrence of cardiovascular failure in COVID-19 and depend on the etiology of the infection, with higher values for bacterial than for viral sepsis.
Face coverings increase apparent honesty and cooperativeness
Authors: Lobmaier Janek S. , Knoch Daria
Published: December 2023

People readily make inferences about trait-like characteristics of another person’s face. Since the recent global COVID-19 pandemic, the widespread use of hygienic face masks has led to large proportions of the face being covered. We investigated the effect of face masks on the inference of prosocially relevant characteristics, namely cooperativeness and honesty. Portraits of participants of previous studies from which we knew their “true” prosocial tendencies served as stimuli. These facial stimuli were presented once with and once without a hygienic face mask to 60 naïve participants who rated the faces for cooperativeness and honesty. Results revealed that wearing face masks made people generally appear more cooperative and more honest than without a mask, but that these ratings were unrelated to the true prosocial tendencies of these people. Together, these findings have important implications for social interactions, particularly in contexts where nonverbal communication is essential, such as in healthcare settings, job interviews, and social gatherings.
Genetic and potential antigenic evolution of influenza A(H1N1)pdm09 viruses circulating in Kenya during 2009–2018 influenza seasons
Authors: Owuor D. Collins , de Laurent Zaydah R. , Nyawanda Bryan O. , Emukule Gideon O. , Kondor Rebecca , Barnes John R. , Nokes D. James , Agoti Charles N. , Chaves Sandra S.
Published: December 2023

Influenza viruses undergo rapid evolutionary changes, which requires continuous surveillance to monitor for genetic and potential antigenic changes in circulating viruses that can guide control and prevention decision making. We sequenced and phylogenetically analyzed A(H1N1)pdm09 virus genome sequences obtained from specimens collected from hospitalized patients of all ages with or without pneumonia between 2009 and 2018 from seven sentinel surveillance sites across Kenya. We compared these sequences with recommended vaccine strains during the study period to infer genetic and potential antigenic changes in circulating viruses and associations of clinical outcome. We generated and analyzed a total of 383 A(H1N1)pdm09 virus genome sequences. Phylogenetic analyses of HA protein revealed that multiple genetic groups (clades, subclades, and subgroups) of A(H1N1)pdm09 virus circulated in Kenya over the study period; these evolved away from their vaccine strain, forming clades 7 and 6, subclades 6C, 6B, and 6B.1, and subgroups 6B.1A and 6B.1A1 through acquisition of additional substitutions. Several amino acid substitutions among circulating viruses were associated with continued evolution of the viruses, especially in antigenic epitopes and receptor binding sites (RBS) of circulating viruses. Disease severity declined with an increase in age among children aged < 5 years. Our study highlights the necessity of timely genomic surveillance to monitor the evolutionary changes of influenza viruses. Routine influenza surveillance with broad geographic representation and whole genome sequencing capacity to inform on prioritization of antigenic analysis and the severity of circulating strains are critical to improved selection of influenza strains for inclusion in vaccines.
The effect of donor against recipient one-way HLA mismatch on liver transplantation outcomes from a multicenter registry analysis
Authors: Park Sunghae , Choi Young Rok , Joo Dong Jin , You Young Kyoung , Kim Bong-Wan , Nah Yang Won , Cho Jai Young , Kim Tae-Seok , Hong Geun , Ju Man Ki , Suh Suk-Won , Yang Jae Do , Park Pyoung Jae , Jeong Jaehong , Moon Ju Ik , Kim Dong-Sik , Rhu Jinsoo ,   The Korean Organ Transplantation Registry Study Group
Published: December 2023

Donor against recipient one-way Human leukocyte antigen (HLA) mismatch (D → R one-way HLA MM) seemed strongly associated with graft-versus-host disease (GVHD). The aim of this study is to investigate the relevance of D → R one-way HLA MM in outcome of liver transplantation (LT). We retrospectively analyzed 2670 patients in Korean Organ Transplantation Registry database between April 2014 and December 2020. The patients were categorized into two groups whether D → R one-way HLA MM or not and evaluated the outcomes of LT between the two groups. 18 patients were found to be D → R one-way HLA MM. The incidence of GVHD (0.3% vs. 22.2%, p < 0.001) and mortality rate (11.6% vs. 38.9%, p = 0.003) was much higher in D → R one-way HLA MM group. D → R one-way HLA MM at 3 loci was seemed to be strongly associated with the incidence of GVHD (OR 163.3, p < 0.001), and found to be the strongest risk factor for patient death (HR 12.75, p < 0.001). Patients with D → R one-way HLA MM at 3 loci showed significantly lower overall survival (p < 0.001) but there were no significant differences in rejection-free survival and death-censored graft survival. D → R one-way HLA MM at 3 loci not only affects the overall survival of LT patients but also the incidence of GVHD.
Comparative analysis of neutrophil-to-lymphocyte ratio and remnant cholesterol in predicting cardiovascular events and mortality in general adult population
Authors: Wang Qian-Chen , Wang Zhen-Yu
Published: December 2023

This study aimed to investigate the predictive value of neutrophil-to-lymphocyte ratio (NLR) and Remnant Cholesterol (Remnant-C) in relation to cardiovascular events and all-cause mortality in the general population. A population-based study. We conducted a retrospective cohort study analyzing data from the National Health and Nutrition Examination Survey (NHANES) spanning the years of 2011–2018, with follow-up for mortality status until December 31, 2019. Kaplan‒Meier and Cox proportional hazards regression analyses were used to evaluate the associations between NLR, Remnant-C, and cardiovascular events as well as all-cause mortality. Overall, 9409 individuals with both complete blood count and blood lipids were included in the analysis. Baseline NLR and Remnant-C were calculated. During the follow-up (median, 59.3 months), 177 cardiovascular events and 561 all-cause mortality occurred. In fully adjusted model, people with NLR > 2.26 were significantly associated with higher risk of cardiovascular events (HR 2.14, 95% CI 1.30–3.52, P < 0.001) and all-cause mortality (HR 1.66, 95% CI 1.30–2.12, P < 0.001). NLR exhibited a positive correlation with Remnant-C (r = 0.04, P < 0.001). Elevated NLR levels shown stronger association with cardiovascular events (HR 1.21, 95% CI 1.14–2.28, P < 0.001) compared with Remnant-C (HR 1.02, 95% CI 1.00–1.04, P = 0.020). Our findings suggest that NLR and Remnant-C are potential predictive markers for cardiovascular events in the general population. We observed a correlation between NLR and Remnant-C, and high NLR levels demonstrate a stronger association with the prediction of cardiovascular events and all-cause mortality compared with Remnant-C.
Comparing storm resolving models and climates via unsupervised machine learning
Authors: Mooers Griffin , Pritchard Mike , Beucler Tom , Srivastava Prakhar , Mangipudi Harshini , Peng Liran , Gentine Pierre , Mandt Stephan
Published: December 2023

Global storm-resolving models (GSRMs) have gained widespread interest because of the unprecedented detail with which they resolve the global climate. However, it remains difficult to quantify objective differences in how GSRMs resolve complex atmospheric formations. This lack of comprehensive tools for comparing model similarities is a problem in many disparate fields that involve simulation tools for complex data. To address this challenge we develop methods to estimate distributional distances based on both nonlinear dimensionality reduction and vector quantization. Our approach automatically learns physically meaningful notions of similarity from low-dimensional latent data representations that the different models produce. This enables an intercomparison of nine GSRMs based on their high-dimensional simulation data (2D vertical velocity snapshots) and reveals that only six are similar in their representation of atmospheric dynamics. Furthermore, we uncover signatures of the convective response to global warming in a fully unsupervised way. Our study provides a path toward evaluating future high-resolution simulation data more objectively.
Usefulness of thalamic beta activity for closed-loop therapy in essential tremor
Authors: Guehl Dominique , Guillaud Etienne , Langbour Nicolas , Doat Emilie , Auzou Nicolas , Courtin Edouard , Branchard Olivier , Engelhardt Julien , Benazzouz Abdelhamid , Eusebio Alexandre , Cuny Emmanuel , Burbaud Pierre
Published: December 2023

A partial loss of effectiveness of deep brain stimulation of the ventral intermediate nucleus of the thalamus (VIM) has been reported in some patients with essential tremor (ET), possibly due to habituation to permanent stimulation. This study focused on the evolution of VIM local-field potentials (LFPs) data over time to assess the long-term feasibility of closed-loop therapy based on thalamic activity. We performed recordings of thalamic LFPs in 10 patients with severe ET using the ACTIVA™ PC + S (Medtronic plc.) allowing both recordings and stimulation in the same region. Particular attention was paid to describing the evolution of LFPs over time from 3 to 24 months after surgery when the stimulation was Off. We demonstrated a significant decrease in high-beta LFPs amplitude during movements inducing tremor in comparison to the rest condition 3 months after surgery (1.91 ± 0.89 at rest vs. 1.27 ± 1.37 µV2/Hz during posture/action for N = 8/10 patients; p = 0.010), 12 months after surgery (2.92 ± 1.75 at rest vs. 2.12 ± 1.78 µV2/Hz during posture/action for N = 7/10 patients; p = 0.014) and 24 months after surgery (2.32 ± 0.35 at rest vs 0.75 ± 0.78 µV2/Hz during posture/action for 4/6 patients; p = 0.017). Among the patients who exhibited a significant decrease of high-beta LFP amplitude when stimulation was Off, this phenomenon was observed at least twice during the follow-up. Although the extent of this decrease in high-beta LFPs amplitude during movements inducing tremor may vary over time, this thalamic biomarker of movement could potentially be usable for closed-loop therapy in the long term.
Heat-vision based drone surveillance augmented by deep learning for critical industrial monitoring
Authors: Lim Do Yeong , Jin Ik Jae , Bang In Cheol
Published: December 2023

This study examines the application of drone-assisted infrared (IR) imaging with vision grayscale imaging and deep learning for enhanced abnormal detection in nuclear power plants. A scaled model, replicating the modern pressurized water reactor, facilitated the data collection for normal and abnormal conditions. A drone, equipped with dual vision and IR cameras, captured detailed operational imagery, crucial for detecting subtle anomalies within the plant's primary systems. Deep learning algorithms were deployed to interpret these images, aiming to identify component abnormals not easily discernible by traditional monitoring. The object detection model was trained to classify normal and abnormal component states within the facility, marked by color-coded bounding boxes for clarity. Models like YOLO and Mask R-CNN were evaluated for their precision in anomaly detection. Results indicated that the YOLO v8m model was particularly effective, showcasing high accuracy in both detecting and adapting to system anomalies, as validated by high mAP scores. The integration of drone technology with IR imaging and deep learning illustrates a significant stride toward automating abnormal detection in complex industrial environments, enhancing operational safety and efficiency. This approach has the potential to revolutionize real-time monitoring in safety–critical settings by providing a comprehensive, automated solution to abnormal detection.
A genome-wide association, polygenic risk score and sex study on opioid use disorder treatment outcomes
Authors: McEvoy Alannah , Chawar Caroul , Lamri Amel , Hudson Jacqueline , Minuzzi Luciano , Marsh David C. , Thabane Lehana , Paterson Andrew D. , Samaan Zainab
Published: December 2023

Opioid use disorder continues to be a health concern with a high rate of opioid related deaths occurring worldwide. Medication Assisted Treatments (MAT) have been shown to reduce opioid withdrawal, cravings and opioid use, however variability exists in individual’s treatment outcomes. Sex-specific differences have been reported in opioid use patterns, polysubstance use and health and social functioning. Candidate gene studies investigating methadone dose as an outcome have identified several candidate genes and only five genome-wide associations studies have been conducted for MAT outcomes. This study aimed to identify genetic variants associated with MAT outcomes through genome-wide association study (GWAS) and test the association between genetic variants previously associated with methadone dose through a polygenic risk score (PRS). Study outcomes include: continued opioid use, relapse, methadone dose and opioid overdose. No genome-wide significance SNPs or sex-specific results were identified. The PRS identified statistically significant results (p < 0.05) for the outcome of methadone dose (R2 = 3.45 × 10–3). No other PRS was statistically significant. This study provides evidence for association between a PRS and methadone dose. More research on the PRS to increase the variance explained is needed before it can be used as a tool to help identify a suitable methadone dose within this population.
Consolidation of LVFRT capabilities of microgrids using energy storage devices
Authors: Moheb Aya M. , El-Hay Enas A. , El-Fergany Attia A.
Published: December 2023

The performance and dependability of distribution networks may be enhanced by the incorporation of microgrids (MGs). However, it is necessary to enhance low voltage fault-ride-through (LVFRT), which has the capacity to prevent abrupt grid disconnections during LV occurrences under problematic circumstances. In this study, a control strategy for energy storage elements (ESDs) which includes batteries and supercapacitors is proposed to enhance LVFRT under balanced and unbalanced faults. The MG comprises wind farms and/or photovoltaic arrays. Based on the dynamic simulations using MATLAB/SIMULINK, the ESDs can enhance LVFRT capability. A comparison of the conventional crowbar scheme and ESDs is realized, and the latter has a better performance than the former in retaining the DC-link voltage within satisfactory bounds. For the purpose of maintaining the DC-link voltage at a reference level, the battery stores extra power in the DC-bus of three systems. LVFRT is improved by the crowbar circuit, however the resistance consumes the extra power. Super capacitors (SCs) prevent DC voltage fluctuations, reduce active power oscillations, and hasten system stabilization when present. At an advanced stage of this effort, the coot bird optimizer (CBO) is applied to generate the best gains of bi-directional converter PI-controller and the ESDs ratings to have minimum ripples in the DC-bus voltage and to boost the LVFRT capability of the MGs. The viability of the proposed method based on the CBO’s results is indicated with further validations under different operating scenarios.
In vitro production of naked mole-rats’ blastocysts from non-breeding females using in vitro maturation and intracytoplasmic sperm injection
Authors: Simone Raffaella , Čižmár Daniel , Holtze Susanne , Michel Geert , Sporbert Anje , Okolo Charlotte , Hildebrandt Thomas B.
Published: December 2023

The African naked mole-rat (Heterocephalus glaber) is an attractive model for cancer and aging research due to its peculiar biological traits, such as unusual long life span and resistance to cancer. The establishment of induced pluripotent stem cells (iPSCs) would be a useful tool for in vitro studies but, in this species, the reprogramming of somatic cells is problematic because of their stable epigenome. Therefore, an alternative approach is the derivation of embryonic stem cells from in vitro-produced embryos. In this study, immature oocytes, opportunistically retrieved from sexually inactive females, underwent first in vitro maturation (IVM) and then in vitro fertilization via piezo-intracytoplasmic sperm injection (ICSI). Injected oocytes were then cultivated with two different approaches: (i) in an in vitro culture and (ii) in an isolated mouse oviduct organ culture system. The second approach led to the development of blastocysts, which were fixed and stained for further analysis.