bluuebunny/crossref_metadata_2025 huggingface dataset:
Inflammatory bowel disease has a negative causal effect on chronic obstructive pulmonary disease: A two-sample bidirectional mendelian randomization study
Authors: Tian Li , Yang Xiaobin , Zheng Yansen , Peng Chaosheng
Published: March 2023

Background
Inflammatory bowel disease (IBD) and its main subtypes, including Crohn's disease (CD) and ulcerative colitis (UC), have been suggested to be linked with chronic obstructive pulmonary disease (COPD) progression, but the potential bidirectional causal association between them remains unclear.
Methods
We drew on summary statistics from the large-scale genome-wide association studies and adopted the inverse variance weighting (IVW)method as the main mendelian randomization analysis method to estimate the causal effect.
Results
There was no evidence support that COPD was associated with increased risk of IBD and two main subtypes (UC and CD) (IBD: odds ratio (OR) [95% confidence interval (CI)] = 0.99[0.90–1.09], P = 8.63×10− 1; UC: OR [95% CI] = 0.96[0.86–1.07], P = 4.70×10− 1; CD: OR [95% CI] = 1.10[0.89–1.35], P = 3.81×10− 1;). The IVW method provided evidence for a negative causal effect of IBD and two main subtypes (UC and CD) on COPD (IBD: OR [95% CI] = 0.93[0.89–0.97], P = 4.86×10− 4; UC: OR [95% CI] = 0.94[0.90–0.98], P = 6.57×10− 3; CD: OR [95% CI] = 0.96[0.94–0.99], P = 4.92×10− 3). The results of the sensitivity analyses were robust and no evidence of heterogeneity and horizontal pleiotropy was observed.
Conclusions
The present study showed that COPD does not affect IBD, but IBD and its main subtypes (UC and CD) have a negative causal effect on COPD. And understanding the confounding factors that affect clinical research will help the clinical treatment and management of the two diseases.
Changes in Cerebral Connectivity and Brain Tissue Pulsations with the Antidepressant Response to an Equimolar Mixture of Oxygen and Nitrous Oxide: an MRI and Ultrasound study
Authors: Desmidt Thomas , Dujardin Paul-Armand , Andersson Frédéric , Brizard Bruno , Remeniéras Jean-Pierre , Gissot Valérie , Arlicot Nicolas , Barantin Laurent , Espitalier Fabien , Belzung Catherine , Tanti Arnaud , robert gabriel , Bulteau Samuel , Gallet Quentin , Kazour François , Cognet Sandrine , Camus Vincent , El-Hage Wissam , Poupin Pierre , Karim Helmet
Published: March 2023

Nitrous oxide (N2O) has recently emerged as a potential fast-acting antidepressant but the cerebral mechanisms involved in this effect remain speculative. We hypothesized that the antidepressant response to an Equimolar Mixture of Oxygen and Nitrous Oxide (EMONO) would be associated with changes in cerebral connectivity and brain tissue pulsations (BTP).
Thirty participants (20 depressed and 10 healthy controls - HC) were exposed to a one-hour single session of EMONO and followed for one week. Cerebral connectivity of the Anterior Cingulate Cortex (ACC, seed based resting state blood oxygen level dependent) and BTP (as assessed with ultrasound Tissue Pulsatility Imaging) were compared before and after exposure (as well as during exposure for BTP) among HC, non-responders and responders. Response was defined as a reduction of at least 50% in the MADRS score one week after exposure.
Nine (45%) depressed participants were considered responders and eleven (55%) non-responders. In responders, we observed a significant reduction in the connectivity of the subgenual ACC with the precuneus. Connectivity of the supracallosal ACC with the mid-cingulate also significantly decreased after exposure in HC and in non-responders. BTP significantly increased in the 3 groups between baseline and gas exposure, but the increase in BTP within the first ten minutes was only significant in responders.
We found that a single session of EMONO can rapidly modify the functional connectivity in the ACC, especially in the subgenual region, which appears to contribute to the antidepressant response. In addition, larger increases in BTP, associated with a significant rise in cerebral blood flow, appear to promote the antidepressant response, possibly by facilitating optimal drug delivery to the brain. Our study identified potential cerebral mechanisms related to the antidepressant response of N2O, as well as potential markers for treatment response with this fast-acting antidepressant.
Metabolomic profiles in serum predict global functional neurological outcome at 3 and 12 months and death at 3 months following severe traumatic brain injury
Authors: Banoei Mohammad Mehdi , Lee Chel Hee , Hutchison James , Panenka William , Wellington Cheryl , Wishart David S , Winston Brent W.
Published: March 2023

Background
Prognostication is very important to clinicians and families during the early management of severe traumatic brain injury (sTBI), however, there are no gold standard biomarkers to determine prognosis in sTBI. As has been demonstrated in several diseases, early measurement of serum metabolomic profiles can be used as sensitive and specific biomarkers to predict outcome.
Methods
We prospectively enrolled adults with sTBI (Glasgow coma scale, GCS ≤ 8) in a multicenter Canadian TBI (CanTBI) study. Serum samples were drawn on the 1st and 4th day following injury for metabolomic profiling. The Glasgow outcome scale extended (GOSE) was collected at 3- and 12-months post-injury. Targeted direct infusion liquid chromatography tandem mass spectrometry (DI/LC-MS/MS) and untargeted proton nuclear magnetic resonance spectroscopy (1H-NMR) were used to profile serum metabolites. Multivariate analysis was used to determine the association between serum metabolomics and GOSE, dichotomized into favorable (GOSE 5–8) and unfavorable (GOSE 1–4), outcomes.
Results
Serum metabolic profiles on days 1 and 4 post-injury were highly predictive (Q2 > 0.4–0.5) and highly accurate (AUC > 0.99) to predict GOSE outcome at 3- and 12-months post-injury and mortality at 3 months. The metabolic profiles on day 4 were more predictive (Q2 > 0.55) than those measured on day 1 post-injury. Unfavorable outcomes were associated with considerable metabolite changes from day 1 to day 4 compared to favorable outcomes. Increased lysophosphatidylcholines, acylcarnitines, energy-related metabolites (glucose, lactate), aromatic amino acids and glutamate were associated with poor outcome and mortality.
Discussion
Metabolomic profiles were strongly associated with prognosis of GOSE outcome at 3 and 12 months and mortality following sTBI in adults. The current findings strongly support the use of serum metabolomics, which are shown to be better than clinical data, in determining prognosis in adults with sTBI in the early days post-injury. Our findings, however, require validation in a larger cohort of adults with sTBI before using in clinical practice.
Size-dependent active site and its catalytic mechanism for CO2 hydrogenation reactivity and selectivity over Re/TiO2
Authors: Yang Bin , Wang Yifu , Gao Biao , Zhang lingxia , Guo Limin
Published: March 2023

The relationship of structure sensitive between metal size and CO2 hydrogenation performance are still unclear. Herein, using a unique set of well-defined TiO2-support rhenium (Re) catalysts and systematical characterizations, we clearly demonstrate the size-dependent active site and reaction mechanism is closely related to size effect. A wave-like size dependent activity of CO2 conversion is also identified. In the size range from single atom to 1.0 nm, reverse water gas shift (RWGS) reaction controls CO2 hydrogenation and its turn over frequency decrease with the size increasing. Whereas, over 1.0 nm cluster, CO2 methanation is the main reaction and exhibits a volcano-like size dependent performance. Mechanistic studies reveal the perimeter sites in single atom catalysts dictate RWGS reaction via formate pathways. In contrast, the active site in Re cluster is edge site, where CO2 reduce to CO via redox pathway and subsequently hydrogenate to methane over edge site. This discovery may deepen the mechanistic understanding of structure sensitive.
PPARα and PPARγ are expressed in midbrain dopamine neurons and modulate dopamine- and cannabinoid-mediated behavior in mice
Authors: Xi Zheng-Xiong , Hempel Briana , Crissman Madeline , Pari Sruti , Klein Benjamin , Bi Guo-Hua , Alton Hannah
Published: March 2023

Peroxisome proliferator-activated receptors (PPARs) are a family of nuclear receptors that regulate gene expression. Δ9-tetrahydrocannabinol (Δ9-THC) is a PPARg agonist and some endocannabinoids are natural activators of PPARa and PPARg. Therefore, both the receptors are putative cannabinoid receptors. However, little is known regarding their cellular distributions in the brain and functional roles in cannabinoid action. Here we first used RNAscope in situ hybridization and immunohistochemistry assays to examine the cellular distributions of PPARα and PPARγ expression in the mouse brain. We found that PPARα and PPARγ are highly expressed in ~70% midbrain dopamine (DA) neurons and in ~50% GABAergic and ~50% glutamatergic neurons in the amygdala. However, no PPARα/γ signal was detected in GABAergic neurons in the nucleus accumbens. We then used a series of behavioral assays to determine the functional roles of PPARα/γ in the CNS effects of Δ9-THC. We found that optogenetic stimulation of midbrain DA neurons was rewarding as assessed by optical intracranial self-stimulation (oICSS) in DAT-cre mice. Δ9-THC and a PPARγ (but not PPARα) agonist dose-dependently inhibited oICSS, suggesting that dopaminergic PPARγ modulates DA-dependent behavior. Surprisingly, pretreatment with PPARα or PPARγ antagonists dose-dependently attenuated the Δ9-THC-induced reduction in oICSS and anxiogenic effects. In addition, a PPARγ agonist increased, while PPARa or PPARγ antagonists decreased open-field locomotion. Pretreatment with PPARa or PPARγ antagonists potentiated Δ9-THC-induced hypoactivity and catalepsy but failed to alter Δ9-THC-induced analgesia, hypothermia and immobility. These findings provide the first anatomical and functional evidence supporting an important role of PPARa/g in DA-dependent behavior and cannabinoid action.
Neurokinin-1 receptor antagonist aprepitant regulates autophagy and apoptosis through ROS/JNK pathway in intrahepatic cholangiocarcinoma
Authors: Yang Yang , Cao Xueyan , Wang Yuting , Wu Xinyu , Zhou Ping , Miao Lin , Deng Xueting
Published: March 2023

Intrahepatic cholangiocarcinoma (iCCA) has a poor prognosis and limited treatment options. Aprepitant, a selective NK-1R antagonist, is capable of inhibiting the growth of various tumors in vitro and in vivo. To investigate the cytotoxic effects of aprepitant on the intrahepatic cholangiocarcinoma, we confirmed the expression of SP/NK-1R in clinical samples of iCCA by immunohistochemistry. MTT test showed that aprepitant could suppress cell viability of RBE and HCCC-9810. Meanwhile, aprepitant induced mitochondria-dependent apoptosis through ROS/JNK pathway in a dose-dependent manner. Additionally, anti-apoptotic drug z-VAD-fmk pretreatment could partly improve the decrease of cell viability induced by aprepitant, while ROS scavenger, NAC could cancel the cytotoxic effects of aprepitant in vitro. Therefore, these results indicated that autophagy is another downstream process of aprepitant-induced ROS accumulation. Changes in the expression of autophagy-related proteins and number of autophagosomes were detected by western blotting and electron microscopy, respectively. Furthermore, we observed the dynamic changes of autophagosome in RBE and HCCC-9810 treated with aprepitant by using mRFP-eGFP-LC3 adenovirus transfection. Moreover, aprepitant significantly inhibited the growth of iCCA xenografts. These findings reveal NK-1R as an potential therapeutic target against iCCA and highlight the anti-cancer ability of NK-1R antagonist aprepitant in iCCA.
Determination of the Lumbar Lordotic and Lumbosacral Angles in Normal Adults Ghanaian Population Using Radiologic Imaging Technique
Authors: Issahaku Shirazu , Sackey Eric , Tiburu Elvis. K. , Sackey Theophilus. A.
Published: March 2023

Changes in posture is among the risk factors of low back pain. The shape of the lumbar spine is influenced in a way by a strain on tendons and muscles because of abnormal posture. Little is known about what the nominal value of key radiologic angles for the Ghanaian populace is and accordingly, what comprises hypo-/hyper-lordosis. The Lumbar Lordotic Angle (LSA) and Lumbosacral Angle (LSA) are potential angles, for the examination of low back issues, in addition to treatment and diagnosis. The study was intended to measure LLA and LSA of this populace using the local data. A retrospective methodology was adopted to gather typical laterally prostrate lumbosacral radiographs of 140 subjects (15 years or more) in a recumbent position.
Results:
The normal LLA values varied between 20.90 to 68.00 with the mean (standard deviation) of 35.9 (9.82)° and there exist a significant difference with sex but insignificant variations among the age categories comparable to a number of the literature values. The normal LSA values varied between 15.00 and 51.00 with the mean (standard deviation) of 34.3 (7.45) ° and there was no significant variation with sex and among the age categories.
Conclusion:
Furthermore, it has been established that the measured values at which to consider hypolordosis (below LLA=17.9°; LSA=12.00), and hyper-lordosis (above LLA=72.0°; LSA=55.00) in the Ghana population. This study have also established that in all the various age groups between 15 and 80 years, there exist no significant difference in the mean LLA and LSA among the groups, and this affirms that the development of lumbar lordosis reaches a plateau when spine is fully developed. Furthermore, female LSA and LLA shows higher measured values compared to their male counterpart in the Ghanaian population which confirmed other study values in literature. Finally, a reference chart of LSA and LLA has also been developed for clinical application in Ghana.
Isolation may select for earlier and higher peak viral load but shorter duration in SARS-CoV-2 evolution
Authors: Sunagawa Junya , Kim Kwang Su , Park Hyeongki , Komorizono Ryo , Cho Sooyoun , Torres Lucia Ramirez , Woo Joohyeon , Jeong Yong Dam , Hart William , Thompson Robin , Aihara Kazuyuki , Iwami Shingo , Yamaguchi Ryo
Published: March 2023

During the COVID-19 pandemic, human behavior change as a result of nonpharmaceutical interventions such as isolation may have induced directional selection for viral evolution. By combining previously published empirical clinical data analysis and multi-level mathematical modeling, we found that the SARS-CoV-2 variants selected for as the virus evolved from the pre-Alpha to the Delta variant had earlier and higher infectious periods but a shorter duration of infection. Selection for increased transmissibility shapes the viral load dynamics, and the isolation measure is likely to be a driver of these evolutionary transitions. In addition, we showed that a decreased incubation period and an increased proportion of asymptomatic infection were also positively selected for as SARS-CoV-2 mutated to the extent that people did not isolate. We demonstrated that the Omicron variants evolved in these ways to adapt to human behavior. The quantitative information and predictions we present here can guide future responses in the potential arms race between pandemic interventions and viral evolution.
Regional homogeneity in patients with obsessive-compulsive disorder and depression: a resting state functional magnetic resonance imaging study
Authors: Yuan Xin , Zhu Yanyan , Xiao Li , Yuan Bin , Zou Jingzhi , Hu Zhizhong , Wu Yunhong , Li Pan , Hu Maorong , Zhou Fuqing
Published: March 2023

Objection: To explore the brain functional impairment in patients of obsessive-compulsive disorder (OCD) with and without depressive symptoms, and then analyze the correlation between the degree of impairment and the severity of symptoms.
Method: In this study, 14 patients with OCD who met the ICD-10 diagnostic criteria for "obsessive-compulsive disorder" were included; the OCD with depression (OCDd) group consisted of 15 patients; and 17 healthy controls (HC) matched for age and education were included. The Yale-Brown OCD Scale (Y-BOCS) and the 24-item Hamilton Assessment of Depression Scale (HAMD) were administered to the OCD group and the OCDd group. Resting-state functional brain magnetic resonance imaging was performed in three groups of participants.
Result: The OCDd group had lower scores on the HAMD, Y-BOCS, and obsessive-compulsive thinking subscales than the OCD group (P< 0.05). Scores on the OCDd subscale were negatively correlated with HAMD scores (R = -0.568, P = 0.027). The OCDd group had higher ReHo values in the lingual gyrus than the OCD group. The OCDd group had higher ReHo values in the lingual gyrus than the HC group, while the OCDd group had higher ReHo values than the HC group. These differences were statistically significant (P<0.05). After correction for multiple comparisons, there was no significant difference between the OCDd and HC groups (P>0.05). In the OCD group, the ReHo value of the tongue was negatively correlated with the Y-BOCs total score and the compulsive behavior subscale score (R = -0.609, -0.552, P = 0.016, 0.033).
Conclusion: Abnormal ReHo values in the lingual gyrus and right medial superior frontal gyrus were found in patients with OCD. No effect of OCD symptoms on the local coherence of brain function was observed, which may indicate that OCD symptoms are not responsible for the changes in local coherence of the brain, but are caused by depressive symptoms. In the OCD group, ReHo values of the lingual gyrus were negatively correlated with scores on the Y-BOCs total and obsessive-compulsive subscales, suggesting that abnormal local coherence of the lingual gyrus may be related to the severity of OCD.
The novel agrochemical fungicide ipflufenoquin drives cross-resistance to olorofim in the human pathogen Aspergillus fumigatus.
Authors: Rhijn Norman van , Storer Isabelle , Birch Mike , Oliver Jason , Bottery Michael , Bromley Michael
Published: March 2023

Widespread use of azole antifungals in agriculture has driven a pandemic of resistance in the pathogenic fungus Aspergillus fumigatus. A novel clinical antifungal, olorofim, promises to alleviate this problem but as it nears approval, a new agrochemical fungicide, ipflufenoquin with the same mechanism of action, has been approved by the US EPA. We show that exposure of A. fumigatus to ipflufenoquin can select for strains that are resistant to olorofim, potentially undermining decades of effort in clinical antifungal drug development.
Analysis of the three-dimensional contour of the human face and its relationship with age: a study in computed tomography
Authors: Tonelli Henrique , Freire Alexandre Rodrigues , de Paula Isabela Lesse , Prado Felippe Bevilacqua , Rossi Ana Cláudia
Published: March 2023

Objectives: The aim was to evaluate the three-dimensional contour of the face through the morphometric analysis of three facial angles in computed tomography scans of human skulls in different age categories.
Material and Methods: The sample consisted of 123 CT scans that were divided into three groups according to the age. The Mimics 18.0 software (Materialise, NV, Belgium) was used to perform the segmentation of the images of each CT scan. Using the 3D reconstructions of the CT scans, the angular measurements were obtained for the evaluation of the orbital, piriform and maxillary angles. A significance level of 5% was considered. Descriptive statistics were performed for each measurement in each age category and sex. Two-way ANOVA was performed, with multiple comparisons by Tukey's test.
Results: In females, there was a tendency for the piriform angle to increase from the young to the middle-aged group and decrease from the middle-aged to the elderly group.
Conclusions: Females are more prone to selective resorptions than males mainly in the middle third of the face.
Clinical relevance: There is a need to know how the face is remodeled in the process of aging and to understand this bony remodeling is important for application in facial analysis for execution of surgical and aesthetic procedures.
Trends and Risk Factors for Healthcare-Associated Vancomycin-Resistant Enterococci of Urinary Tract Infections in Taiwan
Authors: Hu Fu-Kang , Cheng Chih-Chien , Lin Fu-Huang , Hsu Sung-Teng , Yih Ng Daphne , Chang Feng-Yee , Chang Chi-Wen , Chien Wu-Chien , Fann Li-Yun , Chu Chi-Ming
Published: March 2023

Purpose: Vancomycin can be used to treat many bacterial infections, although the generation of vancomycin-resistant Enterococci (VRE) may cause adverse consequences. We analysed the trends and the risk factors for healthcare-associated urinary tract infections (UTIs) by VRE.
Methods: This retrospective study included patients who were hospitalized from 2009–2015 and had hospital-acquired enterococci infections who fulfilled the Centers for Disease Control and Ministry of Health and Welfare criteria, as determined by infection control professionals.
Results: The mean age of the 594 participants was 72.3 years. The proportion of men with enterococcal UTIs was 70%. The proportion of VRE infections among all enterococcal UTIs was lowest in 2009 (18.1%) and highest in 2015 (47.3%). An increasing trend in the proportion of patients with VRE UTIs was observed from 2009–2015. Length of hospitalization of more than 40 days, placement of double-lumen catheters, and placement of a nasogastric tube were associated with a higher risk of VRE in UTIs (odds ratio=1.93–2.72, all P <.05).
Conclusions: The use of unnecessary invasive catheters in patients with double-lumen catheters or nasogastric tubes should be reduced. Environmental disinfection and hand hygiene should be implemented.
A type C study of Braverman-Gaitsgory-Ginzburg's construction of sln representations
Authors: Dong Zhijie , ma haitao
Published: March 2023

In [FMX19], it is proved that the convolution algebra of top Borel-Moore homology on Steinberg variety of type B/C realizes U (slnθ) where slnθ is the fixed point subalgebra of involution on sln. So top Borel-Moore homology of the partial Springer’s fibers gives the representations of U (slnθ). In this paper, we study these representations using the Schur-Weyl duality and Springer theory.
The evolutionary fate of divergent genomes in hybrid zones between selfing and outcrossing species
Authors: Fyon Frédéric , Berbel-Filho Waldir
Published: March 2023

Hybridization is a natural process whereby two diverging evolutionary lineages reproduce and create offspring of mixed ancestry. Differences in mating systems (e.g., self-fertilization and outcrossing) are expected to affect the direction and extent of hybridization and introgression in hybrid zones. Among other factors, selfers and outcrossers are expected to differ in their mutation loads. This has been studied both theoretically and empirically; however, conflicting predictions have been made on the effects mutation loads of parental species with different mating systems can have on the genomic composition of hybrids. Here we develop a multi-locus, selective model to study the effects of selective interference and homozygosity on (i) the mutation load of selfers and outcrossers, and (ii) the long-term genetic composition of resulting hybrid populations. Notably, our results emphasize that in the long term, genes from the parental population with lesser mutation load will be over-represented in hybrid genomes, regardless of the hybrids own mating system. Under a large portion of the parameter space, we predict that selfers’ genomes are of higher quality and will prevail. However, this will ultimately depend on the intensity of genetic drift and selective interference in the system considered. Taken together, these results provide a “null” hypothesis for the genetic composition of hybrids in hybrid zones containing species with different mating systems.
Electronic communication between transition metal nanoparticle and single atom: Endohedral metallofullerenes single-atom catalysts for oxygen reduction reaction catalysis
Authors: Zhang Bo , Chen Xianjun
Published: March 2023

Civil-used proton exchange membrane fuel cell (PEMFC) may be the potential candidate for the construction of the global new energy system including the use of hydrogen energy. Nevertheless, the cathode oxygen reduction reaction (ORR) occurs sluggishly, reining the conversion efficiency of it, which hinders the further commercialization of PEMFC. Currently, the replacement of undesirable Pt catalysts by more stable and economical catalytic materials is the main topic in the field of ORR. Herein, ferromagnetic metal-based endohedral metallofullerenes (EMFs) electrocatalyst with single-atomic shell decoration (M4@MN4C60, M = Fe, Co, Ni) are theoretically constructed and evaluated by the density functional theory method. The encapsulation energy calculation reveals that the synthesis of all EMFs requires additional external energy supply, which can explain why few successfully experimental synesis of EMFs have been reported. Among all studied catalysts, the CoN4C60 stands out with the highest ORR performance comparable to Pt, and the Fe- and Ni- based EMFs shows considerable activity enhancement after the cluster encapsulation. The electronic structure calculation reveals that the encapsulated Fe4 cluster leads to an electron accumulation around the Fe atom in active center, thereby weakening the *OH binding and enhance the ORR performance.
Predictability of the Early Summer Surface Air Temperature over Western South Asia
Authors: Rashid Irfan Ur , Abid Muhammad Adnan , Osman Marisol , Kucharski Fred , Ashfaq Moetasim , Almazroui Mansour , Torres-Alavez José Abraham , Afzaal Muhammad
Published: March 2023

The Surface Air Temperature (SAT) variability over Western South Asia (WSA) is highest during the early summer (May-June) season, which leads to frequent seasonal heatwaves over the region. Therefore, it is important to understand the model’s ability in predicting the regional anomalous temperature conditions, which is the focus of this study using the European Centre for MediumRange Weather Forecast fifth generation (ECMWF-SEAS5) seasonal prediction system dataset for the period 1981-2022. The model skilfully predicts the El Niño-Southern Oscillation (ENSO) related interannual variability of the SAT over WSA compared to the reanalysis, mediated through the upper-level positive 200-hPa geopotential height anomalies, that lead to warm conditions over the regions during the negative ENSO phase. A negative ENSO-SAT relationship shows that warmer extreme temperature events are more frequent during La Niña, while the opposite may happen for El Niño years. The model shows a reasonable actual prediction skill of the SAT anomalies over the WSA region compared to the higher resolution observational and reanalysis datasets, while a low skill is noted for coarser resolutions, which shows that a choice of the observational dataset is important for the estimation of the model skill. Overall, the Potential Predictability of the SAT is comparable to its actual prediction skill over the WSA region. Moreover, the higher Potential Predictability of the SAT over WSA is noted during La Niña compared to El Niño, which is mainly contributed through the higher signal compared to the noise.
An optimization-based decision support tool for incremental train timetabling
Authors: Kloster Oddvar , Luteberget Bjørnar , Mannino Carlo , Sartor Giorgio
Published: March 2023

We consider the typical workflow of a route planner in the context of short-term train timetabling, that is the incremental process of adjustinga timetable for the next day or the next year. This process usually alternates between (1) making rough modifications to an existing timetable (e.g., shifting the departure of a train by half an hour) and then (2) making small adjustments to regain feasibility (e.g., reduce or increase thedwell time of some trains in some stations). The most time-consuming element of this process is related to the second step, that is to manually eliminate all conflicts that may arise after a timetable has been modified. In this work, we propose a mixed-integer programming model tailored to solve precisely this problem, that is to find a conflict-free timetable that is as close as possible to a given one. Previous related work mostly focused on creating complex models to produce “optimal” timetables from scratch, which ultimately resulted in little to no practical applications. By using a simpler model, and by trusting route planners in steering the process towards a timetable with the desired qualities, we can get closer to handle real life instances. The model has been integrated in a user interface that was tested and validated by Norwegian route planners to plan the yearly timetable of a busy railway line in Norway.
Resource use in the last year of life of prostate cancer patients - A register-based analysis
Authors: Banner Andreas , Wieser Sabine , Madersbacher Stephan
Published: March 2023

BACKGROUND: Given the paucity of literature on the end of life (EOL) of prostate-cancer (PC) patients, we investigated medication prescription pattern and hospitalization during their final year of life.
METHODS: The data base of the Österreichische Gesundheitskasse Vienna (ÖGK-W) was used to identify all men who died with the diagnosis PCa between 1.1.2015 and 31.12.2021 and who were under androgen deprivation therapy and/or new hormonal therapy. Patient age, prescription patterns and hospitalizations during the last year of life were recorded, odds ratios for age groups were analyzed.
RESULTS: A total of 1 109 patients were included. ADT was given in 86.7% (n=962) and NHT in 62.8% (n=696). Overall, prescription of analgesics increased from 41% (n=455) during the first to 65.1% (n=722) in the last quarter of the final year of life. Prescription of NSAIDs was almost consistent (18-20%) whereas the number of patients receiving other non-opioids (paracetamol, metamizole) more than doubled (18% to 39%). Older men had lower prescription rates for NSAID (OR: 0.47, 95% CI: 0.35-0.64), non-opioids (OR: 0.43, 95% CI: 0.32-0.57), opioids (OR: 0.45, 95% CI: 0.34-0.6) and adjuvant analgesics (OR: 0.42, 95% CI: 0.28-0.65). Approximately 2/3 of patients (n=733) died in the hospital with a median of four hospitalizations. The length of admission was less than 50d in 61.9%, 51-100d in 30.6% and >100d in 7.6%. Younger patients (<70yrs) were more likely to die in the hospital (OR: 1.66, 95% CI: 1.15-2.39), had a higher median rate of hospitalizations (n=6) and longer duration of admissions.
CONCLUSIONS: Resource use increases during the last year life of PCa patients with highest rates in younger men. Hospitalization rates were high and 2/3 died in the hospital, both showing clear age dependency with higher rates, duration and death in the hospital for younger men.
MFMDet: Multi-scale Face Mask Detection using Improved Cascade rcnn
Authors: Cao Ruyi , Mo Wanghao , Zhang Wendong
Published: March 2023

COVID-19 is spreading globally, posing a great risk and challenging to the world. And wearing a mask can reduce the spread of the virus and the speed of virus transmission, which is an effective mean to combat the spread of coronavirus. To limit the spread of the virus, the requirement to wear a mask is now becoming more common in public places around the world. Nowadays mask wearing detection has become an important task for computer vision to help the global community. The mask detection task involves complex and diverse scenarios with problems of missed and false detection caused by face features being obscured, varying target scales, poor detection of small targets, and small differences in features between correctly and incorrectly worn masks. For this reason, we propose a new mask detection model, MFMDet, which uses Recursive Feature Pyramid to process the multi-scale features extracted by the backbone network, increasing the global features and the perceptual field, and enhancing the detector's ability to adjust to different scales. To ensure the accurate extraction of valid information, we introduce modulated deformable RoIpooling into the detection head to make the network better adapt to the deformation of the target and enhance the spatial and task awareness of the detection head. In addition, we use Joint Image Hybrid Augmentation to increase the number of training samples and diversity to enhance the model generalization ability. Experimental results show that our method improved by 2.5 AP over the baseline, comparing to the baseline on the PWMFD dataset and outperforms other existing target detection algorithms. We also conducted experiments on the WMD dataset to further validate the generalization ability and effectiveness of the proposed method.
An Intelligent diagnosis method for rolling bearings based on Ghost module and adaptive weighting module
Authors: Qiang Ruiru , Zhao Xiaoqiang
Published: March 2023

The vibration signals of rolling bearings are inevitably influenced by noise as well as by working conditions. The use of one-dimensional original signals converted into images for rolling bearing fault diagnosis has achieved good results, but ignores the large size of the model and the speed of diagnosis, so it is not suitable for practical fault diagnosis. To address this problem, we propose a neural network based on Ghost modules and dynamic attention mechanisms. The method uses the Ghost module and coordinate attention to compress model size and reduce computational effort while improving the network's perception of the input signals. In addition, to enable efficient use of similar feature maps generated by convolution, an adaptive weighting module is proposed to further simplify the learning process and reduce network training time. The validity of the proposed method was verified on a dataset provided by Case Western Reserve University and the Mechanical Failure Prevention Technology Society. The results show that the proposed method not only has good noise immunity in noisy environments, but also has good diagnostic performance and good generalization performance under different loads. Under the same experimental conditions, the method proposed in this paper is compared with some methods and the results show the superiority of the proposed method in the diagnosis of rolling bearing faults.
Tamoxifen resistance induction results in mitoxantrone resistance in MCF-7 breast cancer cells via upregulation of ABCG2 expression
Authors: Ghalehno Asefeh Dahmardeh , Abdi Hakime , Boustan Arad , Jamialahmadi Khadijeh , Mosaffa Fatemeh
Published: March 2023

One of the important barriers in the treatment of breast cancer is the development of tamoxifen resistance. Different mechanisms underlying tamoxifen resistance were identified. In this thesis, we aimed to assess the effect of tamoxifen resistance induction on ABCG2 gene/protein expression level and function in the parent MCF-7 breast cancer cell line and its tamoxifen-resistant (MCF-7/TAMR) cell line.
The ABCG2 mRNA and protein expression were compared in MCF-7 and its tamoxifen-resistant derivative MCF-7/TAMR cells using Real-time PCR and western blot methods, respectively. For investigating the effect of tamoxifen-induced resistance on cross-resistance to other chemotherapy drugs such as mitoxantrone (as a well-known ABCG2 substrate), an MTT assay was used. Flow cytometry was applied to compare ABCG2 pump function between two cell lines using mitoxantrone accumulation assay. ABCG2 mRNA expression was also analyzed in tamoxifen-sensitive (TAM-S) (N=9) and tamoxifen-resistant (TAM-R) (N=9) breast tumor tissues.
Our results indicated that the levels of ABCG2 mRNA, protein, and activity were significantly higher in MCF-7/TAMR cells compared to tamoxifen sensitive cell line and mitoxantrone was less toxic in the resistant cell line. Data further discovered that tamoxifen-resistant cells with high ABCG2 activation had a poor response when given rescue mitoxantrone chemotherapy. ABCG2 was also upregulated in tissue samples obtained from tamoxifen-resistant ER+ breast cancer patients compared to tamoxifen-sensitive patients. Increased expression of the ABCG2 mRNA and protein is a phenomenon that occurs after the emergence of resistance to tamoxifen and can cause cross-resistance to mitoxantrone in MCF-7 breast cancer cells.
Steroidogenic activity of methylated resveratrol analogue 3,4,5,4′-tetramethoxystilbene (DMU-212) in human luteinized granulosa cells in a primary three-dimensional in vitro model
Authors: Józkowiak Małgorzata , Kobylarek Dominik , Bryja Artur , Gogola-Mruk Justyna , Czajkowski Mikołaj , Skupin-Mrugalska Paulina , Kempisty Bartosz , Spaczyński Robert Z. , Piotrowska-Kempisty Hanna
Published: March 2023

Purpose
One of the main functions of granulosa cells (GCs) is the secretion of steroid hormones. Resveratrol is a natural polyphenol, known for its beneficial health effects, such as improving reproductive health. However, its application is limited due to poor bioavailability. Methoxy derivative of resveratrol (DMU-212) was shown to be more lipophilic, and consequently more bioavailable. However, since the addition of methoxy groups to the stilbene scaffold was found to make the molecule insoluble in water, DMU-212 was loaded into liposomes. This study aimed to evaluate how the liposomal formulation of DMU-212 (lipDMU-212) alters estradiol and progesterone secretion of human ovarian GCs in a primary three-dimensional cell culture model.
Methods
DMU-212-loaded liposomes were prepared by thin film hydration followed by extrusion. Cell viability was measured after exposure of GCs spheroids to liposomal formulation of DMU-212 using CellTiter-Glo® 3D Cell Viability Assay. The secretion of estradiol and progesterone was determined using commercial ELISA kits. RT-qPCR was conducted to analyze expression of steroidogenesis-related genes.
Results
lipDMU-212 was found to significantly increase estradiol and progesterone secretion in a dose-dependent manner by enhancing expression of CYP11A1, HSD3B1, CYP17A1, CYP19A1, and HSD17B1 genes. Furthermore, our study suggests that lipDMU-212 increases the FSH activity.
Conclusions
This is the first study to describe the steroidogenic activity of liposomal formulation of DMU-212, possibly through increasing the StAR and CYP19A1 expression. These findings suggest that lipDMU-212 might have a beneficial effect in the treatment of disorders related to estrogen deficiency and hyperandrogenism, such as PCOS.
Antimicrobial mouthwashes as a preventive measure against Covid-19 - a comparative analysis of their effects on human chondrocytes and cartilage
Authors: Cai Xiaoyu , Venkatesan Jagadeesh K , Schmitt Gertrud , Reda Bashar , Cucchiarini Magali , Hannig Matthias , Madry Henning
Published: March 2023

Objectives
Antimicrobial mouthwashes are recommended as a preventive measure against SARS-Cov-2. This study compared the cytotoxicity of octenidine dihydrochloride and chlorhexidine gluconate at different concentrations on human chondrocytes and cartilage.
Materials and methods
Primary cultures of normal adult human articular chondrocytes were exposed to octenidine dihydrochloride (0.001562%, 0.003125%, 0.00625%, 0.0125%, 0.025%, 0.05%, and 0.1%), chlorhexidine gluconate (0.003125%, 0.00625%, 0.0125%, 0.025%, 0.05%, 0.1%, and 0.2%), and control (Dulbecco's modified Eagle medium or phosphate buffered saline) for 30 seconds. Normal human articular cartilage explants were exposed to octenidine dihydrochloride (0.1% versus control) and chlorhexidine gluconate (0.1% versus control) for 30 seconds. The viability of human articular chondrocytes was measured by Trypan blue staining, Cell Proliferation Reagent WST-1, and Live/Dead staining. The proliferation of human articular chondrocytes was measured using the Cell Proliferation Reagent WST-1. The viability of human articular cartilage explants was measured by using Live/Dead staining.
Results
Octenidine dihydrochloride and chlorhexidine gluconate exposure decreased cell viability and proliferation in a dose-dependent manner in primary adult human normal articular chondrocytes. Octenidine dihydrochloride and chlorhexidine gluconate exposure decreased cell viability in human articular cartilage explant cultures.
Conclusion
The degree of toxicity varied between octenidine dihydrochloride and chlorhexidine gluconate, with chlorhexidine gluconate being less toxic than octenidine dihydrochloride at the same concentration. Additionally, both octenidine dihydrochloride and chlorhexidine gluconate evaluation had cytotoxic effects on human articular cartilage. Therefore, dosing for the antimicrobial mouthwash ingredients administration would ideally be determined to remain below IC50.
Clinical relevance
Our study supports the in vitro safety of antimicrobial mouthwashes on articular chondrocytes. The data do not suggest to advise such antimicrobial mouthwashes as a general Covid prophylaxis.
Physical and drug release characteristics of nanoliposomes modified poly(vinyl alcohol) (PVA)/poly(ethylene glycol) (PEG) hydrogels
Authors: Jezeh Atefe Jafari , Entezam Mehdi , Haghiralsadat Bibi Fatemeh , Nikukar Habib , Khonakdar Hossein Ali
Published: March 2023

The main objective of this research is to investigate how curcumin liposomal nanocarriers influence the drug release behaviour of PVA/PEG hydrogels in relation to physico-mechanical properties. For this purpose, optimal nanoliposomes from drug loading and release viewpoints, prepared by the thin-film hydration method, were incorporated into the hydrogel composition. Hydrogel samples were physically crosslinked using the freeze-thaw procedure. According to the atomic force microscopy and field-emission scanning electron microscopy observations, nanoliposomes showed a spherical morphology with an average particle size of 100 nm and narrow size distribution. The X-ray diffraction results revealed that adding nanoliposomes to the hydrogel increases the degree of PVA chains crystallinity, enhances tensile modulus and tensile strength of the hydrogel, while decreasing swelling and dehydration rates. SEM micrographs observation displayed that the porosity in the hydrogel structure in the presence of nanoliposomes increases. Nevertheless, in agreement with physical properties, drug release from nanoliposome-in-hydrogel is slower and more controlled as compared to that from free curcumin hydrogel, especially in the early stages. The MTT assay results indicated that although all hydrogel samples are non-toxic, human foreskin fibroblast cell proliferation on hydrogel in the presence of curcumin-loaded nanoliposomes has improved somewhat.
Development and Effectiveness Evaluation of a Propolis Hydroalcoholic Solution With Glycine in Reducing Microorganisms and Removing Helminth Eggs in Leafy Greens
Authors: Silveira Juliana , Alfredo Natália Almeida Corrêa , Beux Marcia Regina , Leal Diego Averaldo Guiguet , Ferreira Sila Mary Rodrigues
Published: March 2023

The main goal of this study was to evaluate the effectiveness of a propolis hydroalcoholic solution with glycine on the reduction of microorganisms and removal of helminth eggs in lettuce leaves. Three experimental groups were evaluated in triplicate or replicates: microbiological (ME), parasitological (PE), and microbiological and parasitological (MPE). Prior to the experiments, the initial concentration of native microbiota was assessed by counting mesophilic aerobes, molds and yeasts, using conventional microbiological techniques. Lettuce leaves were washed in tap water and subjected to different immersion treatments: in propolis hydroalcoholic solution (PHS), in propolis hydroalcoholic solution at pH 5.5 (PHS2), and in propolis hydroalcoholic solution with glycine (PHS-glycine). In ME, the propolis hydroalcoholic solution combined or not with glycine, was evaluated on the reduction of native microbiota. Residual microbiological contamination was assessed. In the PE, the effect of PHS2 and PHS-glycine was evaluated on the removal of a known number of Ascaris suum eggs on leaves artificially contaminated. In MPE, PHS-glycine was evaluated on the reduction of native microbiota and removal of eggs. A reduction of more than 2 log CFU/g were observed in ME. In PE, PHS-glycine removed 37.22% of eggs. In MPE, the PHS-glycine reduced 3.3 CFU/g mesophilic aerobes, 5.0 log CFU/g fungi, and 35.53% of eggs from vegetable. The results highlight the efficiency of the solution on reducing or eliminating different contaminants in vegetables and reinforce the need for the development of hygiene methods that do not harm human health and are reproducible at household level.
Evaluation of RC Elements Under High-Temperature Conditions with different Locations: Analytical Investigation
Authors: Parthasarathi N. , Satyanarayanan K. S. , Prakash M. , Vishal M.
Published: March 2023

Developments in the field of construction has taken an encompassing transformation in the design of structures. Concrete technology has also seen several advancements with the inclusion of reinforcement materials like steel and iron in them which are called as the (RC) Reinforced Concrete. Amidst several developments in the technology of the structural design for a quality construction, RC structural element failure under higher temperature with load remains as one of the most critical mechanisms to be addressed with the recent advancements. There are several methods and studies that try to rule out such failure mechanism with certain improvised methodologies in the fire resistivity behavior of concrete structures. Nevertheless, only a few studies have concentrated on the interaction between the structural and functional elements in the emergence of fire. Considering this, the present work concentrates on the behavior of RC infilled frames with elements like beam, column and beam column joints under higher temperatures and load for which the ABAQUS finite element software is used. The model is simulated with a transient state analysis and characteristics like deflection, stiffness, principal stress are studied for the RC beam, column and beam column joints with varied temperature and load. The outcome of the simulation shows the effect of load and temperature on RC elements and the respective performance graphs are plotted.
Results of Ultrasonography, Uroflowmetry, Voiding Diary Evaluation in Children With Monosymptomatic Primary Enuresis Nocturna
Authors: Yener Sevim , İlçe Zekeriya
Published: March 2023

Objective
To assess examine the results of urinary system ultrasonography, uroflowmetry and voiding diary for children patients presenting with primary monosymptomatic enuresis nocturna.
Patients and methods
Patients aged 5-17 years with enuresis nocturna were retrospectively analyzed. Urinary system ultrasonography (USG), uroflowmetry (UFM), complete urinalysis and two-day voiding diary were recorded for all patients. Comorbid diseases and surgeries were determined with a detailed history.
Results
A total of 842 patients were identified. History of previous surgery was present in 113 (13.4%) patients. Abnormal USG findings were detected in 117 (13.9%) patients.Urinary system USG findings of 17 patients with urinary tract infection were abnormal. In the two-day voiding diary, the bladder volume was found to be equivalent to the expected bladder volume in 54.2% of the patients, while the bladder volume detected in the first uroflowmetry was low in 65% of the patients.
Conclusion
Although the patients do not have urinary system symptoms other than night urinary incontinence at the time of admission, there may be accompanying pathologies. In addition, we think that a voiding diary measurement that has been properly explained and described to the family may be more reliable in cases where UFM cannot be repeated.