bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hypoxic conditions affect transcriptome of endometrial stromal cells in endometriosis and promote TGFBI axis
Authors: Sarsenova Meruert , Boggavarapu Nageswara Rao , Kask Keiu , Modhukur Vijayachitra , Samuel Külli , Karro Helle , Gemzell-Danielsson Kristina , Lalitkumar Parameswaran Grace Luther , Salumets Andres , Peters Maire , Lavogina Darja 
Published: December 2024

BackgroundEndometriosis is characterized by the ectopic growth of endometrial-like cells, causing chronic pelvic pain, adhesions and impaired fertility in women of reproductive age. Usually, these lesions grow in the peritoneal cavity in a hypoxic environment. Hypoxia is known to affect gene expression and protein kinase (PK) activity. We aimed to explore the changes in the transcriptome and PK activity characteristic of eutopic and ectopic endometrium in endometriosis under hypoxia.MethodsEutopic (EuESCs) and ectopic (EcESCs) endometrial stromal cells were exposed to hypoxia (1% O2) or normoxia (20% O2) for 48 hours. We assessed PK activity and examined transcriptome using mRNA-seq in cells cultured under hypoxic or normoxic conditions. Enzyme-linked immunosorbent assay, quantitative reverse transcription-PCR and immunohistochemistry were performed for the downstream analysis of Transforming Growth Factor Beta Induced (TGFBI) expression.ResultsThe kinase assay revealed a minor decrease in cAMP-dependent PK (PKAc) and Akt activity and a trend towards an increase in Rho-dependent PK (ROCK) activity in response to exposure to hypoxic conditions in EcESCs. A wider examination of the hypoxia-mediated changes in transcriptomes of cultured cells revealed that the genes related to aerobic glycolysis and cellular metabolism were upregulated in EuESCs exposed to hypoxia. In contrast, EcESCs had a single differentially expressed gene (TGFBI) upregulated under hypoxic conditions. This gene was also found to be overexpressed in EuESCs exposed to hypoxia vs normoxia, and in EcESCs vs EuESCs in normoxia. The level of secreted TGFBI in the spent culture media was accordingly high in the EcESC cultures and in the EuESC culture exposed to hypoxia. In the eutopic endometrial tissue biopsies, TGFBI mRNA and protein expression depended on the menstrual cycle phase, with higher levels observed in the proliferative phase. TGFBI staining showed the protein localized to the stroma and around the blood vessels. In the secretory phase, TGFBI protein expression was stronger in ectopic endometrium compared to paired eutopic endometrium.ConclusionsWithin this study, we showed hypoxia-mediated transcriptome changes characteristic of EuESCs and EcESCs and identified TGFBI as a potential therapeutic target for endometriosis due to its role in fibrosis and angiogenesis.
Towards a more secure reconstruction-based anomaly detection model for power transformer differential protection
Authors: Jahromi Martiya Zare , Khalaf Mohsen , Kassouf Marthe , Kundur Deepa 
Published: December 2024

IntroductionCyberattacks against Power Transformer Differential Protection (PTDP) have the potential to cause significant disruption and widespread blackouts in power infrastructure. Recent literature has demonstrated how reconstruction-based anomaly detection models can play a critical role in enhancing the security of PTDP against such attacks. However, these models themselves are vulnerable to cyber threats. Adversarial sample generation is an example of a threat against reconstruction-based anomaly detection models.MethodsTo address this threat, we propose an approach for adversarial training of such models appropriate for PTDPs. We then review and compare the effect of adversarial training on the performance of four different model architectures. To demonstrate the efficacy of our proposed approach for improved security and performance in PTDP scenarios, the IEEE PSRC D6 benchmark test system is tested in an OPAL-RT environment.ResultsSimulation results show the effectiveness of the proposed method for improved detection of cyberattacks.
Leaf-level physiological strategies related to productivity and plasticity of Populus in the Southeastern United States
Authors: Renninger Heidi J. , Pitts Justin J. , Wang Jiaxin 
Published: December 2024

IntroductionPopulus and its hybrids are attractive bioenergy crops and the southeastern United States has broad ability to supply bioenergy markets with woody biomass. Breeding and hybridization have led to superior eastern cottonwood (Populus deltoides W. Bartram ex Marshall) and hybrid poplars adapted to a wide variety of site types not suited for agricultural production. In order to maximize productivity and minimize inputs, genotypes need to efficiently use available site resources and tolerate environmental stresses. In addition, we need to determine plasticity of traits and their coordination across sites to select traits that will broadly characterize genotypes. Therefore, our study objectives were to determine (1) which leaf traits were correlated with growth, (2) if traits and genotypes exhibited significant plasticity across sites, and (3) how traits were coordinated within and across sites and Populus taxa.MethodsWe measured trees at two sites in northeastern Mississippi, United States: one upland and one alluvial terrace site. Genotypes included eastern cottonwoods as well as F1 crosses of eastern cottonwood and P. maximowiczii (Henry), P. nigra (L.) and P. trichocarpa (Torr. &amp; Gray).ResultsWe found that sites differed in which leaf traits were correlated with productivity; with water use efficiency specifically being positively correlated with growth at an alluvial terrace site, but negatively correlated with growth at an upland site. Tree height growth, leaf isotope composition (δ13C and δ15N), as well as leaf mass per area (LMA) exhibited the least plasticity across sites, while physiological gas exchange parameters and leaf nitrogen concentration exhibited the highest plasticity. Broadly across taxa, leaf carbon isotope ratios were correlated with intrinsic water use efficiency, and stomatal conductance was positively correlated with photosynthetic nitrogen use efficiency across sites, while leaf nitrogen isotope ratios exhibited contrasting relationships with leaf nitrogen concentration.DiscussionOverall, these results allow us to refine selections of productive genotypes based on site conditions and site-specific relationships with physiological parameters to better match Populus taxa with sites and landowner objectives.
Clinical and immunological features in patients with neuroimmune complications of COVID-19 during Omicron wave in China: a case series
Authors: Gong Siyin , Deng Bo , Yu Hai , Zhang Xiang , Yang Wenbo , Chen Xiangjun 
Published: December 2024

PurposeThis study aimed to present clinical and immunological features in patients with neuroimmune complications of COVID-19 during Omicron wave in China.MethodsPatients with neuroimmune complications associated with COVID-19 were retrospectively analyzed in Huashan Hospital from December 2022 to April 2023, during the widespread prevalence of Omicron variants in China. Demographic information, symptoms, electrophysiological findings, cerebrospinal fluid(CSF) test results and immunological markers, Magnetic Resonance Imaging(MRI) characteristics, treatment strategies and outcomes of these patients were reviewed and analyzed.ResultsA total of 53 cases of neuroimmune complications were included, with 7 cases of non-immune complications taken as controls. Neuroimmune complications comprised: 7 cases of Guillain-Barre syndrome/chronic inflammatory demyelinating polyneuropathy, 11 cases of spinal meningitis/myelitis, 2 cases of neuromyelitis optica spectrum disorder, 2 cases of myelin oligodendrocyte glycoprotein antibody-associated disease, 1 case of acute disseminated encephalomyelitis, 10 cases of autoimmune encephalitis, 17 cases of other encephalopathy/encephalitis and 3 cases of cerebellitis. SARS-CoV-2 was only detected in the CSF sample of one neuroimmune complications patient. CSF-restricted oligoclonal bands were detected in 11.1% (5/45) of neuroimmune patients, but absent in non-immune cases (0.0%, 0/5). Autoantibody testing identified specific antibodies in 26.5%(13/49) of neuroimmune cases and 0.0% (0/5) of non-immune cases. Glucocorticoids or intravenous immunoglobulins were administered as first-line treatments for all neuroimmune cases (100%, 53/53), whereas only 42.8% (3/7) of non-immune cases received these therapies. A baseline modified Rankin scale (mRS) score of 3 or above was present in the majority of both neuroimmune cases (96.2%, 51/53) and non-immune cases (71.4%, 5/7). At the end of a follow-up period, independent functional outcomes at day-90 with an mRS score below two were observed in a significant proportion of both neuroimmune cases (77.4%, 41/53) and non-immune case(71.4%, 5/7).ConclusionThe manifestations of neuroimmune complications of COVID-19 are diverse and can manifest with severe neurological deficits early in the course of the disease. The detection of immunological markers (such as autoantibody and oligoclonal bands) and immunotherapies can help to improve the prognosis of COVID-19 related neuroimmune complications.
ACE2 and TMPRSS2 genetic polymorphisms as potential predictors of COVID−19 severity and outcome in females
Authors: Matic Sanja , Milovanovic Dragan , Mijailovic Zeljko , Djurdjevic Predrag , Stefanovic Srdjan , Todorovic Danijela , Vitosevic Katarina , Canovic Vanja , Popovic Suzana , Dimitrijevic Nevena Milivojevic , Zivanovic Marko , Seklic Dragana , Aleksic Sanja , Djordjevic Nemanja , Vukic Milena , Vukovic Nenad , Filipovic Nenad , Baskic Dejan , Djordjevic Natasa 
Published: December 2024

IntroductionACE2 and TMPRSS2 represent the major gateways for SARS-CoV-2 cell entry. The presence of functional ACE2 and TMPRSS2 genetic polymorphisms that affect gene expression may affect the risk of severe form of COVID-19 and its fatal outcome.Material and patientsThis observational study enrolled 178 hospitalized patients diagnosed with SARS-CoV-2 infection at the University Clinical Centre of Kragujevac, Serbia. Demographic, clinical, and laboratory data were gathered at admission. Genotyping for single nucleotide polymorphisms of ACE2 (rs2106809 and rs2074192) and TMPRSS2 (rs2070788 and rs4818239) was performed using the Real-Time PCR method with TaqMan assays.ResultsControlling for other factors of influence, such as CCI, N/L ratio, LDH level, and pO2, we showed that females with TMPRSS2 rs2070788 A/A genotype were less likely to develop severe COVID-19 (odds ratio [OR] [95% confidence interval (95% CI)]: 0.030 [0.001; 0.862]). Additionally, the likelihood of dying of SARS-CoV-2 infection was lower in female carriers of at least one ACE2 rs2106809 C allele (OR [95% CI]: 0.004 [0.000; 0.981]).ConclusionOur findings indicate TMPRSS2 rs2070788 and ACE2 rs2106809 polymorphisms as independent predictors of severity and outcome of COVID-19 in females.
Metabolomics survey of uropathogenic bacteria in human urine
Authors: Chan Carly C. Y. , Groves Ryan A. , Rydzak Thomas , Lewis Ian A. 
Published: December 2024

IntroductionUrinary tract infections (UTIs) are one of the most prevalent infections in North America and are caused by a diverse range of bacterial species. Although uropathogenesis has been studied extensively in the context of macromolecular interactions, the degree to which metabolism may contribute to infection is unclear. Currently, most of what is known about the metabolic capacity of uropathogens has been derived from genomics, genetic knockout studies or transcriptomic analyses. However, there are currently very little empirical data on the metabolic activity of uropathogens when grown in urine.MethodsTo address this gap, we conducted a systematic survey of the metabolic activities of eight of the most common uropathogenic bacterial species that collectively represent 99% of uncomplicated UTIs.ResultsLiquid chromatography-mass spectrometry (LC–MS) analyses of human urine cultures revealed that uropathogens have four distinct metabolic clades. We generalized these clades as serine consumers (Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis), glutamine consumers (Pseudomonas aeruginosa), amino acid abstainers (Enterococcus faecalis and Streptococcus agalactiae), and amino acid minimalists (Staphylococcus aureus and Staphylococcus saprophyticus). These metabolic classifications can be further subdivided on a species-to-species level.DiscussionThis survey provides a framework to understanding the metabolic activity of the diverse range of uropathogens and how these species use divergent metabolic strategies to occupy the same niche.
Association of cardiovascular health with cognitive function and the mediating effect of depressive state
Authors: Hu Yiwei , Sun Xuelu , Guo Chen , Wu Ruiyun , Dou Jiahao , Song Shoufang , Guo Fanshun , Wei Jin 
Published: December 2024

BackgroundAlthough previous research has substantiated lifestyle and cardiovascular-related measures have some impact on cognitive function, studies focusing on the correlation between Life’s Essential 8 (LE8), an indicator for quantifying cardiovascular health (CVH), and cognitive function are limited. Consequently, this study sought to explore the potential link between CVH and cognitive function as well as to determine if depressive states mediated the relationship.MethodsA total of 2,263 individuals were selected from the 2011–2014 National Health and Nutrition Examination Survey (NHANES). Post-averaged LE8 scores was classified as low CVH (0–49), moderate CVH (50–79), and high CVH (80–100) according to the American Heart Association (AHA). Cognitive function was evaluated using the Animal Fluency Test (AFT), the Digit Symbol Substitution Test (DSST), the instant recall test (IRT), and the delayed recall test (DRT). The Z-score is figured by subtracting the average of the scores of four test sections and dividing by the standard deviation. Models of multi-variable linear regression were employed to appraise the relationships between CVH and the Z-score for cognitive function. Depression was assessed through the utilization of the Patient Health Questionnaire (PHQ-9). Points of 10 or above indicated a positive diagnosis. Weighted linear regression and restricted cubic spline (RCS) were employed to evaluate the correlation between CVH and cognitive function. Pearson’s test was utilized to explore the interrelation among primary variables and mediated effects analyses of depressive states.ResultsA significant positive linear relationship was observed between LE8 score and cognitive function Z-score. In all models, there was a positive correlation between higher Z-score for cognitive function and every ten points added to the LE8 score, which evaluates CVH. The findings of the mediating effect study indicated that the effects of cardiovascular health on cognitive function were partially mediated by depression.ConclusionResults showed a meaningful positive linear correlation between the level of CVH and cognitive function, with a mediating role for depression. These results accentuate the significance of sustaining high CVH and avoiding depression to improve cognitive functioning.
Modifying reaction time tasks parameters in the automated IntelliCage identifies heightened impulsivity and impaired attention in the 3xTg-AD model of Alzheimer’s disease
Authors: Judd Jessica M. , Winslow Wendy , McDonough Ian , Mistry Faizan , Velazquez Ramon 
Published: December 2024

BackgroundThe 3xTg-AD transgenic mouse model of Alzheimer’s disease (AD) is an important tool to investigate the relationship between development of pathological amyloid-β (Aβ) and tau, neuroinflammation, and cognitive impairments. Traditional behavioral tasks assessing aspects of learning and memory, such as mazes requiring spatial navigation, unfortunately suffer from several shortcomings, including the stress of human handling and not probing species-typical behavior. The automated IntelliCage system was developed to circumvent such issues by testing mice in a social environment while measuring multiple aspects of cognition. Water consumption can serve as a primary motivator for task engagement. Once animals adapt to the cage and can access water, mice can be subjected to operant tasks. Each of the four corners of a cage contains doors to manipulate access to water, visual LED cues, and a valve allowing administration of an air puff. Previously, we detected significant impairments in 3xTg-AD mice in the IntelliCage, however a high failure rate and genotypical differences in water motivation were observed.MethodsHere, we implemented an IntelliCage paradigm where mice underwent progressively more difficult reaction time tasks to assess attention and impulsivity, behaviors mediated by the prefrontal cortex. Mice were placed in the IntelliCage at 11.5 months of age, which corresponds with the presence of widespread pathology.ResultsAs the difficulty of the reaction time tasks increased, 3xTg-AD mice exhibited lower percent Correct Responses than NonTg. When implementing varying pre-cue durations, where animals are required to wait between the initiation of the trial and the LED turning on (which then requires a nose-poke to access water), 3xTg-AD mice prematurely nose-poked on trials requiring a longer delay before a second nose poke would allow water access, demonstrating heightened impulsivity. The presence of soluble and insoluble fractions of cortical Aβ40 and 42, and phosphorylated tau epitopes threonine 181 and serine 396 confirmed the presence of neuropathological hallmarks in 3xTg-AD mice.ConclusionTogether, this study describes a novel protocol that overcomes motivational differences and detects attention and impulsivity deficits in 3xTg-AD mice utilizing the IntelliCage.
Day 3 neutrophil-to-lymphocyte ratio and its derived indices predict 90-day poor outcomes following mechanical thrombectomy in acute ischemic stroke patients
Authors: Gao Weiwei , Annadurdyyev Arslan , Yu Lingfeng , Huang Rong , Liu Bin , Lin Yixiong , Li Huaiyi , Zhu Renjing 
Published: December 2024

ObjectiveTo investigate the dynamic changes in neutrophil–to–lymphocyte ratio (NLR) and its derived indices following mechanical thrombectomy (MT) in patients with acute ischemic stroke (AIS) and evaluate their predictive value for prognosis.MethodsThis single-center retrospective cohort study included AIS patients who underwent MT at Zhongshan Hospital of Xiamen University from January 2018 to February 2024. Peripheral blood samples were collected on admission, day 1, and day 3 after MT to determine the NLR, derived NLR (dNLR), and neutrophil–monocyte–to–lymphocyte ratio (NMLR). The primary endpoint was poor functional outcome at 90 days (modified Rankin scale score 3–6). The secondary endpoints included post-operative hemorrhagic transformation, malignant cerebral edema, in-hospital mortality, and 90-day all-cause mortality. Receiver operating characteristic (ROC) curve analysis was used to evaluate predictive performance, and multivariate logistic regression models were employed to explore the independent associations between inflammatory markers and prognosis.ResultsA total of 423 eligible patients were included. Both groups showed similar dynamic trends in inflammatory markers, peaking on day 1 post-MT and subsequently declining. However, the poor outcome group (n = 255, 60.28%) maintained higher levels on day 3, whereas the good outcome group showed a significant decreasing trend. ROC curve analysis revealed that the NLR (AUC = 0.85, 95% CI: 0.81–0.89), dNLR (AUC = 0.86, 95% CI: 0.82–0.89), and NMLR (AUC = 0.85, 95% CI: 0.81–0.89) on day 3 post-MT had the strongest predictive power for 90-day poor outcomes. After comprehensive adjustment for confounders, these inflammatory markers were independently associated with 90-day poor outcomes: for each unit increase in the NLR, the risk of poor outcome increased by 38% (OR = 1.38, 95% CI: 1.28–1.49, p &lt; 0.001); for dNLR, it increased by 104% (OR = 2.04, 95% CI: 1.73–2.40, p &lt; 0.001); and for NMLR, it increased by 35% (OR = 1.35, 95% CI: 1.26–1.45, p &lt; 0.001).ConclusionInflammatory markers (NLR, dNLR, and NMLR) on day 3 post-MT can serve as independent predictors of prognosis in AIS patients treated with MT. Dynamic monitoring of inflammatory markers may facilitate early risk stratification and guide individualized treatment strategies.
Neuromonitoring modalities predicting neurological impairment in pediatric congenital heart disease: a systematic review
Authors: Van Loo Liselotte , Cools Bjorn , Dereymaeker Anneleen , Jansen Katrien 
Published: December 2024

The increased risk of neurodevelopmental impairment in children with congenital heart disease (CHD) has been established, but the search for targeted neurological predictors of adverse outcome is ongoing. This systematic review reports on the utility of three functional neuromonitoring modalities, Near-infrared Spectroscopy (NIRS), electroencephalography (EEG) and biochemical biomarkers, in predicting either clinical neurodevelopmental outcome or structural brain abnormalities after pediatric CHD surgery. Medline, Embase, CENTRAL, Web of Science, clinicaltrials.gov and ICTRP were systematically searched for eligible articles. Original research articles, written in English, published before November 2023 and reporting on perioperative NIRS, EEG or biomarkers and their association with clinical neurodevelopmental outcome or neuroimaging in children &lt;17 years undergoing surgery for CHD were included. The search yielded 11,367 citations, of which 40 papers were included in the final review: sixteen articles (n = 908 cases) reported on NIRS, twelve (n = 1,163) on EEG and fifteen (n = 903) on biochemical biomarkers. Three papers reported on a combination of modalities. Median age at time of surgery was 9 (IQR 7–57) days. Postoperative MRI was performed before discharge at varying timepoints. Median age at clinical outcome assessment was 15 (IQR 12–24) months. Limited evidence supports an association of cerebral oxygen extraction, cerebral desaturation and cerebral autoregulation with outcome, but there was significant heterogeneity in results. Perioperative electroencephalographic ictal discharges and abnormal background were associated with impaired neurological outcome and abnormal neuroimaging. Numerous biochemical biomarkers have been reported but showed no consistent relationship with outcome, except for lactate, which could serve as a predictor of poor outcome. There is a need for larger homogeneous cohorts of children with CHD to determine which perioperative modalities might serve as predictors of neurodevelopmental outcome or neuroimaging abnormalities.Systematic review registrationhttp://www.crd.york.ac.uk/PROSPERO, CRD42023479344