bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors related to renal deterioration in children and young adults with spina bifida: A longitudinal study using dimercaptosuccinic acid scans
Authors: Yamazaki Yuichiro , GOHBARA AYAKO , Eura Rumiko , Nishi Morihiro , Nishikawa Tomomi , Yamamoto Koji
Published: January 2023

Study Design: Retrospective, cohort study
Objectives: First, to investigate the prevalence of new DMSA abnormalities by age in patients with spina bifida, and second, to evaluate the age differences in risk factors for new DMSA abnormalities.
Setting: Children’s hospital in Yokohama, Japan
Methods: All patients with spina bifida requiring clean intermittent catheterization who visited from 2009 to 2021 were enrolled. Inclusion criteria consisted of having at least two DMSA scans performed at age ≤12 years and ≥13 years. Patients with no sequential data from video urodynamic studies were excluded. Risk factors for new DMSA abnormalities were evaluated in two different growth stages (age ≤12 years, age ≥13 years).
Results Fifty-seven patients with a median follow-up of 18 years were included. At the end of the study, 22 patients (39%) had DMSA abnormalities. The number of patients having new DMSA abnormalities in childhood (age ≤12 years) and in young adulthood (age ≥13 years) was 10 (18%) and 12 (21%), respectively. After the LASSO logistic analysis, three variables (maximum detrusor pressure, vesicoureteral reflux, and bladder trabeculation) were identified as factors related to new DMSA abnormalities in children. On the other hand, vesicoureteral reflux was the only related factor in young adults.
Conclusions: In children with spina bifida, there was no age tendency in the development of new DMSA abnormalities. Vesicoureteral reflux was related to new DMSA abnormalities in both childhood and young adulthood. However, video urodynamics parameters were related to new DMSA abnormalities only in childhood.
Residual-based a posteriori error analysis of an ultra-weak discontinuous Galerkin method for nonlinear second-order initial-value problems
Authors: Baccouch Mahboub
Published: January 2023

Note: Please see pdf for full abstract with equations.
In this paper, we propose and analyze implicit residual-based a posteriori error estimates for the ultra-weak discontinuous Galerkin (UWDG) method for nonlinear second-order initial-value problems for ordinary differential equations of the form u′′ = ƒ(x, u). We prove that the UWDG error on each element can be split into two parts. The significant part is proportional to the (p + 1)-degree polynomial (1 − ξ)2P2,0p−1(ξ), ξ ∈ [−1, 1], where P2,0p−1(ξ) is the (p − 1)-degree Jacobi polynomial, when piecewise polynomials of degree at most p ≥ 2 are used. The second part of the error converges with order p + 2 in the L2-norm. These results allow us to construct a posteriori UWDG error estimates. The proposed residual-based a posteriori error estimators of this paper are reliable, efficient, and are obtained by solving a local problem with no side conditions on each element. Furthermore, we prove that, for smooth solutions, these a posteriori error estimates converge to the exact errors in the L2-norm under mesh refinement. The order of convergence is proved to be p + 2. Finally, we prove that the global effectivity index converges to unity at O(h) rate. Several numerical experiments are provided to validate the theoretical results.
AMS subject classifications (2020)}: 65L05, 65L20, 65L50, 65L60, 65L70.
Ambulance referral of more than 2 hours could result in a higher prevalence of medical- devices-related pressure injuries (MDRPIs) with different characteristics compared to the inpatient setting: A descriptive observational study
Authors: luo zhenyu , Liu Sihui , Yang Linhe , Zhong Shuyan , Bai Lihua
Published: January 2023

Background
Medical device-related pressure injuries(MDRPI) are prevalent and attracting more attention. During ambulance transfer, the shear force caused by braking and acceleration; extensive medical equipment crowed in a narrow space add external risk factors for MDRPIs. However, there is insufficient research on the relationship between MDRPIs and ambulance transfers. This study aims to clarify the prevalence and characteristics of MDRPI during ambulance transfer.
Method
A descriptive observational study was conducted with convenience sampling. Before starting the study, six PI specialist nurses certified by the Chinese Nursing Association trained emergency department nurses for three MDRPI and Braden Scale sessions, one hour for each session. Data and images of PIs and MDRPIs are uploaded via the OA system by emergency department nurses and reviewed by these six specialist nurses. The information collection begins on 1 July 2022 and ends on 1 August 2022. Demographic and clinical characteristics and a list of medical devices were collected by emergency nurses using a screening form developed by researchers.
Results
One hundred one referrals were eventually included. The mean age of participants was (58.3±11.69) years, predominantly male (67.32%, n=68), with a mean BMI of 22.48±2.2. The mean referral time among participants was 2.26 ± 0.26 hours, the mean BRADEN score was 15.32 ± 2.06, 53.46% (n=54) of participants were conscious, 73.26% (n=74) were in the supine position, 23.76% (n=24) were in the semi-recumbent position, and only 3 (2.9%) were in the lateral position. Eight participants presented with MDRPIs, and all MDRPIs are stage 1. Patients with spinal injuries are most prone to MDRPIs (n=6). The jaw is the area most prone to MDRPIs, caused by the cervical collar (40%, n=4), followed by the heel (30%, n=3) and nose bridge (20%, n=2) caused by the respiratory devices and spinal board.
Conclusion
During long ambulance referrals, the prevalence of MDRPIs is higher than in some inpatient settings. The characteristics and related high-risk devices are also different. The prevention of MDRPIs during ambulance referrals deserves more research.
Correlation between prognostic indicator FGFR1 and immune infiltrates in non‑small cell lung cancer
Authors: Wang Xianhui , Li Xihua , Liu Dandan , Tang Zhiping
Published: January 2023

Background
Fibroblast growth factor receptor 1(FGFR1) plays a indispensable role in the tumorigenesis and therapy. However, the relationship of FGFR1 in the prognosis and immune infiltration remains to be elucidated.
Methods
FGFR1 expression was analyzed in different databases, respectively. Clinicopathological parameters and survival datas were analyzed by Kaplan-Meier plotter. The correlations between FGFR1 and immune infiltrates were conducted by Tumor Immune Estimation Resource (TIMER). Genetic alterations of FGFR1 and DNA methylation were assessed by cBioPortal and MethSuev. FGFR1 co-expressed and functional networks were analyzed by LinkedOmics in nonsmall cell lung cancer (NSCLC).
Results
FGFR1 expression was significantly lower in NSCLC than normal tissues, and high FGFR1 significantly correlated with favorable overall survival (OS) in lung squamous cell carcinomas (LUSC). FGFR1 can predict tumor prognosis independently of other factors in OS by Cox analyses. Moreover, FGFR1 expression was significantly correlated with the infiltrating multiple tumor immune cell markers both in NSCLC. Additonaly, the gene alteration and prognostic value of the DNA methylation patterns of FGFR1 in NSCLC were carried out. Furthermore, a functional network analysis confirmed the function of FGFR1 in regulating tumorigenesis and vasculogenesis.
Conclusions
FGFR1 may be used as a biomarker for prognosis and evaluating immune infiltration in NSCLC.
Interrelation between the lipid accumulation product index and diabetic kidney disease in patients with type 2 diabetes mellitus
Authors: Tang Min , Yao Shuangshuang , Zhen Qin , Wei Xiaohui , Cao Han , Tan Yitong , Liu Fang , Wang Yufan , Peng Yongde , Fan Nengguang
Published: January 2023

Aims: The purpose of this study was to determine the relation between the lipid accumulation product index (LAPI) and diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus (T2DM).
Methods: Herein, 931 patients were enrolled and their data were collected. Then the interrelation between LAPI and DKD was assessed using multivariate logistic regression analyses (LRAs) and by a restricted cubic spline (RCS). Receiver operating characteristic (ROC) curves were plotted to compare the performance of discrepant indicators of abdominal obesity (AO) in predicting DKD.
Results: After adjusting for several confounders, the odds ratio for DKD was increased evidently in the third LAPI tertile compared with that in the first LAPI tertile. In addition, the RCS revealed a positive interrelationbetween LAPI and DKD. As illustrated by ROC curves, LAPI showed better performance in predicting DKD than the other indicators.
Conclusions: LAPI is positively linked with DKD, so LAPI may be a suitable indicator for clinically screening patients at risk of DKD.
Effects of carrimycin on biomarkers of inflammation and immune function in tumor patients with sepsis: a multicenter double-blind randomized controlled trial
Authors: Nan Chuanchuan , Zhang Xiaowu , Huang Wei , Zhu Biao , Zhao Jianghong , Lu Song , Xian Lewu , Liu Kaizhong , Ma Gang , Yang Wei , Huang Mingguang , Zhou Dongmin , Zhang Ming , Duan Yan , Wu Guixin , Jiang Zhengying , Zhang Li , He Xinrong , Chen Yuhong , Xing Xuezhong , Wang Changsong , Wang Donghao , Yu Kaijiang
Published: January 2023

Background

With progress in tumor treatments, patient survival has been significantly extended; nevertheless, tumors and tumor treatments increase the risk of sepsis. Carrimycin may act as an immune-regulating treatment for tumor-related sepsis. We aimed to evaluate whether carrimycin regulates inflammation and immune function in tumor patients with sepsis.

Methods

We conducted a multicenter, randomized, placebo-controlled, double-blind clinical trial involving tumor patients with sepsis. The participant inclusion criteria were as follows: 1. age ≥ 18 and ≤ 75 years old; 2. condition consistent with sepsis 3.0 diagnostic criteria; 3. SOFA score of 2–13; and 4. patients with malignant tumors. Enrolled patients were assigned to either carrimycin treatment (400 mg/day) or placebo treatment (400 mg/day) orally once a day for 7 days. The primary outcome was immune-related indicators.

Results

A total of 120 patients were randomized, of whom 47 were assigned to receive carrimycin and 52 placebo. In immune and inflammation indicators, the HLA-DR and CD8 + T-cell levels showed promising trends, although there was no significant difference between the carrimycin and placebo groups (P > 0.05). In the CD4 < 38.25 subgroup, the HLA-DR level of the carrimycin group was significantly better than that of the placebo group at 1 day after administration (P = 0.023). In the CD8 < 25.195 subgroup, the degree of decrease in IL-8 in the carrimycin group was significantly higher than that in the placebo group at 1 (P = 0.027) and 3 (P = 0.034) days after administration. The CD8 + T-cell subset level of the carrimycin group was significantly better than that of the placebo group at 3 (P = 0.027) and 5 (P = 0.035) days after administration. The levels of SOFA, APACHE II, PCT and CRP were significantly reduced by carrimycin intervention. No serious adverse events were recorded.

Conclusions

In tumor patients with sepsis, especially those with immunocompromised function, carrimycin regulates the immune status by increasing the HLA-DR level and plays an anti-infective role to improve the severity of the disease but does not affect 28-day all-cause mortality.
The trial was registered in the Chinese Clinical Trial Registry (http://www.chictr.org.cn) with the number ChiCTR2000032339 on April 26, 2020.
Therapeutic effect of Ginsenoside Rb1 against stress urinary Incontinence induced by Mechanical trauma in Rats
Authors: Chen Shaohui , Zhang Sanyuan , Li Hongmei , Wei Bingyan
Published: January 2023

The authors have requested that this preprint be removed from Research Square.
LINC01134 promotes the progression of colorectal cancer through enhancing SLC1A5 mRNA stability
Authors: Li Yao , Jinxiu Wu , Nailing Wang
Published: January 2023

Colorectal cancer (CRC) is one of the most common malignant tumors with a poor prognosis. Long noncoding RNAs (lncRNAs) were reported to play a vital role in regulating the progression of cancers and had been become the focus of intense research in cancer biology. Meanwhile, LINC01134 functions as an oncogene in many cancers, but the possible roles and mechanisms in the occurrence and development of CRC are still unclear. This study aimed to explore the biological mechanism of LINC01134 in the progression of CRC. First, we found LINC01134 was highly expressed in CRC tissues and associated with worse clinical stages and poor prognosis, which was in line with that in CRC cell lines. Functional experiments indicated that silencing of LINC01134 attenuated CRC cells proliferation and induced the apoptosis both in vitro and in vivo. Mechanistically, weighted gene co-expression analysis identified that LINC01134 was positively related to SLC1A5, which was also upregulated and associated with poor prognosis in CRC. Going further, RNA–RNA interaction in vitro analysis and analysis of mRNA stability indicated that LINC01134 could directly bind to SLC1A5 mRNA and enhance SLC1A5 mRNA stability. Notably, silencing of SLC1A5 could partly reverse the promotion effect of LINC01134 overexpression on proliferation and the inhibitory effect on cells apoptosis in CRC cells. Our findings showed that LINC01134 acted as an oncogene in CRC via directly binding to SLC1A5 mRNA and enhancing SLC1A5 mRNA stability, which suggested that LINC01134 might act as a promising therapeutic target for CRC.
Power for clinical and statistical significance
Authors: Bishara Samuel
Published: January 2023

This paper explores the implication of utilising statistical power for superiority, rather than equivalence, in clinical trials, with a specific illustration for unpaired continuous parametric variables using a simple adjustment to the power calculation which has been previously described. The advantages of such an approach, is that it separates the notion of the likely difference between two groups (the effect size) and the minimum clinically significant difference, without which logically inconsistent positions might be held. In the post hoc scenario this approach can shed further light on the value of undertaking further studies, which is not apparent form the standard power calculation which purely reflects the obtained p-value. The trend for increased trial size and the mirror approach of non-inferiority studies, that is sometimes adopted, implies a trend for overall reduction in the clinical effectives of newer studies, which could be countered by powering for superiority.
Pollution characteristics and Groundwater ion source analysis of the last 20 years in a semi-arid region of northwest China
Authors: Liu Yang , Li Fengjie , Ayyamperumal Ramamoorthy , Wang Wengfang
Published: January 2023

Groundwater hydrochemistry analysis can be used to assess the general quality of groundwater as well as how groundwater has changed over time and how anthropogenic activities have affected it. In this study, total dissolved solids (TDS), pH and 10 ions (Na+, K+, Mg2+, Ca2+, Cl-, SO42-, NO3-, CO32-, HCO3- and F-) were measured at 34 sites in the main urban area of Lanzhou, a major city in northwest China, by means of boreholes in 2002 and 2022 respectively. The evolution of groundwater chemistry in the region over a twenty-year period due to mineral weathering and dissolution, ion exchange, and urban activity was explained using a geochemical model, chlor-alkalinity index, and correlations between Cl- and NO3- in the urban area. In addition, statistical methods were used to analyze groundwater ion sources and compare the ion source characteristics over a twenty-year period to reveal the extent to which urbanization and industrialization have influenced groundwater. The results show that overall groundwater quality in the area has improved over the last two decades, with little change in groundwater chemistry type. Furthermore, the chemical ions in groundwater were influenced less by industrialization and more by urban anthropogenic activities, which include not only urban wastewater discharge but also the rapid reduction of groundwater levels due to extensive urban construction activities. It is recommended that groundwater quality be further improved through enhanced municipal management measures, which should focus on the threat posed by groundwater precipitation in addition to considering the control of sewage discharge.
Second order universal filter using voltage follower topology
Authors: Almutairi Fatima , Almutairi Reem
Published: January 2023

In this paper, a voltage mode multi input single output second order universal filter based on the voltage follower concept is proposed. The MISO filter offers low-pass, band-pass, high-pass, all-pass and band-stop filters which is digital selecting by the input. The filter design consists of positive feedback and feed forwards path to implement a universal filter. The positive feedback is used to increase the quality factor of the filter. The feed forwards path is necessary to create zeros for the band-stop and high-pass filter. The proposed filter has many advantages such as an electronically tunable filter response, low power consumption and area. The performance of the proposed design has been tested using CMOS 130nm process technology.
Gastrointestinal helminths of two Storm Petrel species, Oceanites oceanicus and Fregetta tropica, from Antarctica
Authors: Fusaro Bruno , Lorenti Eliana , Panisse Guillermo , Fornillo Valentina , Fuentes Lautaro , Libertelli Marcela , Ansaldo Martin , Diaz Julia I.
Published: January 2023

Although knowledge about parasitic diseases in Antarctic birds is scarce, an increasing number of studies are currently being carried out in this area. The importance of the host-parasite relationship in Antarctic seabirds is key to understanding trophic ecology and epidemiology of infection diseases, especially in those birds with extensive migratory routes that can act as reservoirs and distributors of diseases. This study aims to provide information on helminths of two Storm Petrel species, the Wilson’s storm-petrel Oceanites oceanicus and the Black-bellied storm-petrel Fregetta tropica. Twenty individuals were analysed: 18 O. oceanicus (8 adults, 10 chicks) and 2 F. tropica (adults); 89% of the O. oceanicus were parasitized with the nematode Stegophorus macronectes, whereas 100% of F. tropica was parasitized by at least one of three parasite species identified: S. macronectes, Seuratiasp., and Tetrabothrius sp. The low richness of parasites observed is associated with a stenophagic diet. However, a clear difference is observed between both species related to a higher fish ingestion by F. tropica, unlike O. oceanicus with a higher ingestion of krill.
Glucocorticoid nanoformulations relieve chronic pelvic pain syndrome and may alleviate depression in mice
Authors: Yang Yang , Hu Ruimin , Zheng Jun , Wang Qianmei , Xu Senlin , Zhou Zhansong , Zhang Dinglin , Shen Wenhao
Published: January 2023

Background
Chronic pelvic pain syndrome (CPPS) is a typical symptom of chronic prostatitis (CP) in males that may cause abnormal urination, sexual dysfunction, or depression and significantly affect the quality of life of the patient. Currently, there is no effective treatment for CPPS due to its recurrence and intractability. For synergistic CPPS therapy, we developed pH/reactive oxygen species (ROS) dual-responsive dexamethasone (Dex) nanoformulations using a ROS-responsive moiety and phytochemical modified α-cyclodextrin (α-CD) as the carrier.
Results
Dex release from the nanoformulations can be controlled in acidic and/or ROS-rich microenvironments. The fabricated Dex nanoformulations can also be efficiently internalized by lipopolysaccharide (LPS)-stimulated macrophages, prostatic epithelial cells, and stromal cells. Moreover, the levels of proinflammatory factors (e.g., TNF-α, IL-1β, and IL-17A) in these cells were significantly decreased by Dex nanoformulations treatment through the release of Dex, phytochemical and elimination of ROS. In vivo experiments demonstrated notable accumulation of the Dex nanoformulations in prostate tissue to alleviate the symptoms of CPPS through the downregulation of proinflammatory factors. Interestingly, depression in mice may be relieved due to alleviation of their pelvic pain.
Conclusion
We fabricated Dex nanoformulations for the effective management of CPPS and alleviation of depression in mice.
The Relationship Between Alpha Power and Heart Rate Variability Commonly Seen in Various Mental States
Authors: Kawashima Tomoya , Shiratori Honoka , Amano Kaoru
Published: January 2023

Although researchers have widely explored the relationship between EEG and heart rate variability (HRV), the results are not always consistent mainly due to the variety of tasks. In particular, several factors, such as mental fatigue and sleepiness, can affect the alpha power, which makes it difficult to obtain a direct relationship between alpha and heart rate activities. This study investigates the brain–heart interplay that is consistently observed in various mental states: listening to music and resting. To eliminate the indirect effects of mental states on alpha power, subjective fatigue and sleepiness in the resting condition and their emotional valence and arousal in the music condition were measured. A partial correlation analysis in the music condition, which excluded the indirect effects of emotional valence and arousal level, showed a positive correlation between the power of the occipital alpha2 component (10-12 Hz) and nHF, a measure of parasympathetic activity. In a similar vein, a partial correlation analysis in the resting condition, excluding subjective fatigue and sleepiness effects, showed a positive correlation between the occipital alpha2 component and nHF. These results indicate a brain–heart interplay that is frequently observed in various subjective states and that still exists after eliminating the effects of other variables.
Framework for the Full N-Body Problem in SE(3) and its Reduction to the Circular Restricted Full Three-Body Problem
Authors: Nazari Morad , Canales David , McCann Brennan , Butcher Eric , Howell Kathleen
Published: January 2023

A novel, compact formalism of rigid body motion dynamics is presented in a general reference frame based on the geometric mechanics framework. This formalism, proposed on the special Euclidean space (SE(3)) of the Lie group, naturally accounts for the orbit/attitude coupling due to the gravitational moments and forces. It is demonstrated that the structure of the rigid body dynamics equations is preserved in different coordinate frames. Then, using the expression of gravitational potential, this global framework is applied to the circular restricted full three-body problem (CRF3BP) of a near-rectilinear halo orbit (NRHO) similar to that of Gateway, where the equations are uniquely provided in the body frame of the spacecraft and the barycentric rotating frame. For the sake of propagation and consistency with the classical circular restricted three-body problem (CR3BP), the equations of the CRF3BP are also presented in a non-dimensional form. Trajectories computed with different inertia tensors are compared with those obtained using the traditional equations of motion of a point-mass spacecraft subject to the gravitational fields of two larger primaries. The comparison between CRF3BP and CR3BP suggests: (a) the need for computation of customized families of halo orbits considering inertia properties of each spacecraft; and (b) the use of attitude-only control for station-keeping in future NRHO missions to reduce station-keeping costs which would otherwise be relatively large if the point-mass approximation were used.
Plugged-in Electric Vehicle-Assisted Demand Response Strategy for Residential Energy Management
Authors: Alfaverh Khaldoon , Alfaverh Fayiz , Szamel Laszlo
Published: January 2023

Demand response (DR) management systems are a potentially growing market due to their ability to maximize energy savings by allowing customers to manage their energy consumption at times of peak demand in response to financial incentives from the electricity supplier. Successful execution of a demand response program requires an effective management system where the home energy management system (HEMS) is a promising solution nowadays. HEMS is developed to manage energy use in households and to conduct the management of energy supply, either from the grid or the alternative energy sources like solar or wind power plants. With the increase of vehicle electrification, in order to achieve a more reliable and efficient smart grid (SG), cooperation between electric vehicles (EVs) and residential systems is required. This cooperation could involve not only vehicle to grid (V2G) operation but a vehicle to home (V2H) too. V2H operation is used to transfer the power and relevant data between EVs and residential systems. This paper provides an efficient HEMS enhanced by smart scheduling and an optimally designed charging and discharging strategy for plugged-in electric vehicles (PEVs). The proposed design uses a fuzzy logic controller (FLC) for smart scheduling and to take the charging (from the grid)/discharging (supply the household appliances) decision without compromising the driving needs. Simulations are presented to demonstrate how the proposed strategies can help to reduce electricity costs by 19.28% and 14.27% with 30% and 80% state of charge (SOC) of the PEV respectively compared to the case where G2V operation only used along with the photovoltaic (PV) production, improve energy utilization by smoothing the energy consumption profile and satisfy the user’s needs by ensuring enough EV battery SOC for each planned trip.
Adaptive Estimation of Measurement Error in Chemiresistive Sensors and Its Correlation with Sensitivity
Authors: Sharma Alfa , Sharma Akash , Yadav Subhash Chand , Acharya Achyuta Nanda , Shirage Parasharam M.
Published: January 2023

We study the correspondence between sensitivity and adsorption/desorption induced hysteresis in ZnSnO3 resistive sensors. The ZnSnO3 humidity sensor made at 100°C present lower degree of error (1.21±0.12 %RH) associated with sensitivity of 0.11±0.01 kΩ(%RH)-1 whereas the 500°C annealed analogous showed an increased degree of measurement error value (1.48±0.23% RH) along with sensitivity of 0.14±0.02 kΩ(%RH)-1 within the humidity range of 8-97% RH. A proportionate increase in sensitivity and measurement error is evident with increase in annealing temperature. The principal component analysis (PCA) shows the migration of measurement errors from high to low RH level subject to annealing of sensing material. The trade-off relation between sensitivity and measurement error is observed for sensors with enactment of annealing emphasizes the prominence of revising the adsorption/desorption hysteresis as an crucial feature in development of metal oxide based chemiresistive sensors.
Prospective of early warning mapping in Flash flood mitigation and future planning in Marsa Alam, Egypt
Authors: Naggar Hadeel El
Published: January 2023

Most of the Arab region is at risk of natural disasters with significant economic, social, and environmental impacts. In Egypt, floods are a real threat to biological life and assets. Significant efforts must be made to overcome damages caused by floods, either on the country level or the regional one. This study will overview one of Egypt's tourist areas, Marsa Allam. It is considered an economic asset and tourism destination; therefore, it should be protected from flood risk. The study will demonstrate a flood mitigation, preparedness, and early warning project in Marsa Allam will be presented as one of the most critical stages to protect this area from the coming flood disasters.
Treatment and Outcome of Patients with Graves' Disease and Metastatic Differentiated Thyroid Cancer
Authors: Besic Nikola , Vidergar-Kralj Barbara
Published: January 2023

Background
There are only limited data in the literature about treatment of patients who have Graves' disease (GD) and metastatic thyroid cancer. The aim of our study was to report on our experience about the treatment and outcome of patients with Graves' disease and metastatic thyroid cancer in our country.
Methods
Altogether, 28 patients (eight males, 20 females; 49–85 years of age; median 74 years) were treated because of differentiated thyroid cancer and distant metastasis at the time of diagnosis during a 10-year period (from 2010 to 2019) in the Republic of Slovenia. The subject of our retrospective study were four patients (three men, one female; 64–76 years of age, median 73 years) who had Graves' disease and metastatic thyroid cancer. Papillary carcinoma, Hürthle cell carcinoma, follicular and poorly differentiated thyroid carcinoma were diagnosed in 13, six, five and four patients, respectively. Graves’ disease was present in two patients with Hürthle cell carcinoma, one with papillary and one with poorly differentiated thyroid carcinoma.
Results
The mean age of patients without GD and with GD was 74 years and 71 years, respectively (p = 0.36). There was a trend for male predominance in patients with GD (p = 0.06). There was no statistical difference in size of primary tumors (p = 0.36), pT stage (p = 0.52) or pN stage (p = 1.00) between the group of patients without GD and with GD. Patients received multimodal treatment (total thyroidectomy N = 18, neck dissection N = 4, preoperative chemotherapy N = 3, ablation of thyroid remnant with radioiodine N = 18, therapy with radioiodine N = 18, external beam radiotherapy of the neck region N = 7 patients, external beam radiotherapy of other localisations N = 6, targeted therapy N = 10). Three patients (1/3 with GD) received only palliative treatment. The median length of follow-up was 3.33 years (range 0.04–7.83) and 5-year disease-specific survival was 51%. One of four patients with GD and 14 of 24 patients without GD died of thyroid cancer. There was no statistical difference in disease-specific survival between patients group of without GD and with GD (p = 0.59).
Conclusion
In our country, 14% of patients with metastatic differentiated thyroid carcinoma at the time of diagnosis had Graves’ disease. There was no difference in the treatment, outcome or survival of patients with GD in comparison to those without GD.
Orientability through the algebraic multiplicity
Authors: Lopez-Gomez Julian , Sampedro Juan Carlos
Published: January 2023

This paper establishes some hidden connections between the theory of generalized algebraic multiplicities, $\chi$, and the notion of orientability of vector bundles. The novel approach adopted in it facilitates the definition of several invariants closely related to the first Stiefel--Whitney characteristic class through some path integration techniques.
Pressure-flow characteristics of a microchannel combining super- hydrophobicity and wall compliance
Authors: Amit Kumar , Assam Ashwani , Raj Abhishek
Published: January 2023

This paper reports a computational and theoretical investigation of pressure-flow characteristics of a microchannel having a superhydrophobic bottom wall with embedded air-cavities and, thin deformable membrane as the top wall. Two-way fluid-structure interaction (FSI) and unsteady volume of fluid (VOF) methods are employed for fluid-solid boundary and liquid-air interface at ridge-cavity, respectively. A novel theoretical model has been developed for the pressure-flow characteristics of microchannel with deformable top and superhydrophobic bottom wall. The theoretical and numerical results for pressure drop across the microchannel have shown a good agreement with a maximum deviation of 6.69%. Four distinct types of microchannels viz, smooth (S) (rigid non-textured), smooth with deformable top (SDT), smooth with superhydrophobic bottom (SSB) and, smooth with superhydrophobic bottom and deformable top wall (SSBT) have been investigated for the comparison of their pressure-flow characteristics. The Poiseuille Numbers (fRe) for SSBDT microchannel is found to be lowest with an average of 18.7% and maximum of 23.5% lower than S microchannel at 𝑅𝑒 = 60. Up to 48.59% of reduction in pressure drop was observed for the SSBDT microchannel as compared to smooth (S) microchannel of same dimensions. Further, critical Reynolds Number (Recritical) (at which the air-water interface breaks and super-hydrophobicity vanishes) was found to be ∼ 20% higher for SSBDT microchannel compared to SSB microchannel. Thus, the wall compliance in SSBDT microchannel is found to increase the capability to sustain the super-hydrophobicity at higher Re numbers.
Dose-dependent efficacy of bevacizumab in recurrent glioblastoma
Authors: Melhem Jawad M. , Tahir Ali , Calabrese Eirena , Granovskaya Inga , Atenafu Eshetu G. , Sahgal Arjun , Lim-Fat Mary Jane , Perry James R.
Published: January 2023

Background
Bevacizumab (BEV), at a standard dose of 10 mg/kg every 2 weeks is associated with prolonged progression-free survival (PFS) but no improvement in overall survival (OS) in recurrent glioblastoma (rGBM). Few studies have examined the potential dose-dependent efficacy of BEV. In Ontario, reimbursement for the costs of BEV varies, and as a result, our practice began to routinely use lower dose regimens. The main aim of this study was to ensure that there was no harm to patients who received the low dose protocol.
Methods
A single-center retrospective study of patients given BEV for rGBM between 2015–2020 was performed. Clinical and treatment data including BEV dose regimen (SD [10 mg/kg every 2 weeks] vs LD [5 mg/kg every 2–3 weeks or 10 mg/kg every 3 weeks]) received at the time of rGBM diagnosis were captured. Overall survival (OS) and progression-free survival (PFS) on BEV were compared using the Kaplan-Meier product-limit method. Log-rank test was used to compare potential predictive factors. Cox regression model was performed for multivariable analysis of OS and PFS.
Results
A total of 96 patients were included with a median follow-up duration of 6.84 months (range 1.12–50.63 months) from the date of the first infusion. The LD group consisted of 55 of the 96 patients. By virtue of funding mechanisms for BEV, the median age in the LD group was significantly higher (62 vs 54 years p = 0.009). There was no difference in MGMT status between the 2 groups (p = 0.60). Eight patients received lomustine with BEV (3 from the SD and 5 from the LD. The LD group had prolonged median PFS (5.89 months versus 3.22 months; p = 0.0112) and OS (10.23 months versus 6.28 months; p = 0.0010). Multivariable analysis including the dose of BEV, the extent of resection, gender, and age revealed that standard dose of BEV, subtotal resection, and female sex were associated with worse overall survival. Nine patients in the SD group vs 18 patients in the LD group reported an adverse event related to BEV.
Conclusions
For patients with recurrent GBM, we found that a low dose regimen of BEV was associated with prolonged OS and PFS compared to the standard dose regimen. Lower dose schedules may be a better and more cost-effective option for patients with rGBM. Lower costs might provide more equitable access to this very important palliative drug.
Has Invasive Amur Honeysuckle (Lonicera maackii (Rupr.) Maxim) Met its Match? Interspecies Comparisons of Photosynthesis and Shoot Allocation in Heavy Shade
Authors: Schulz Kurt E.
Published: January 2023

Amur honeysuckle (Lonicera maackii (Rupr.) Maxim) is a notorious invader of forests and forest edges throughout eastern North America. The species is difficult to exterminate and reestablishes readily. A perpetual presence of Amur honeysuckle in most forests is largely a forgone conclusion. Forests throughout the eastern U.S. are changing due to canopy closure after historical disturbance and long-term fire prevention. Fire intolerant species, especially sugar maple (Acer saccharum Marshall.), are coming to dominate forest canopies, creating shady understories and forest dynamics that pivot on shade tolerance. Two shade tolerant understory shrubs, pawpaw (Asimina triloba Adans.) and spicebush (Lindera benzoin Thunb.) compete with honeysuckle in maple understories. Based on field observations we hypothesized that these native species were more shade tolerant than invasive honeysuckle. We examined shade tolerance in honeysuckle, pawpaw, and spice bush by comparing photosynthetic light responses, leaf characteristics, and allocation to leaf area versus stem mass (leaf area ratio, LAR) in annual shoots. Honeysuckle had comparable light responses measured on a leaf area basis, but mass-based measurements show it is less efficient paying back carbon invested in leaf tissue. This arises because honeysuckle is unable to reduce specific leaf mass to the level of pawpaw and spicebush. LAR is distinctly higher in pawpaw and spicebush, suggesting an advantage in heavy shade. Since the great majority of photosynthesis in these species occurs under a closed canopy, we suggest honeysuckle will diminish in maple-dominated stands. Informal observations of greater height growth in pawpaw and spicebush in the field support this.
Deep learning synthesis of cone-beam computed tomography from zero echo time magnetic resonance imaging
Authors: Choi Hyeyeon , Yun Jong Pil , Lee Ari , Han Sang-Sun , Kim Sang Woo , Lee Chena
Published: January 2023

Cone-beam computed tomography (CBCT) produces high resolution of hard tissue even in small voxel size, but the process is associated with radiation exposure and poor soft tissue imaging. Thus, we synthesized a CBCT image from the magnetic resonance imaging (MRI), using deep learning and to assess its clinical accuracy. We collected patients who underwent both CBCT and MRI simultaneously in our institution. MRI data were registered with CBCT data, and both data were prepared into 512 slices of axial, sagittal, and coronal sections. A deep learning-based synthesis model was trained and the output data were evaluated by comparing the original and synthetic CBCT (syCBCT). According to expert evaluation, syCBCT images showed better performance in terms of artifacts and noise criteria but had poor resolution compared to the original CBCT images. In syCBCT, hard tissue showed better clarity with significantly different MAE and SSIM. This study result would be a basis for replacing CBCT with non-radiation imaging that would be helpful for patients planning to undergo both MRI and CBCT.
Deciphering the Sex Bias in Housekeeping Gene Expression in Adipose Tissue: a Comprehensive Meta-analysis of Transcriptomic Studies
Authors: Guaita-Cespedes Maria , Grillo-Risco Rubén , Hidalgo Marta R. , Fernández-Veledo Sonia , Burks Deborah Jane , Iglesia-Vayá María de la , Galán Amparo , Garcia Francisco Garcia
Published: January 2023

Background: As the housekeeping genes (HKG) generally involved in maintaining essential cell functions are typically assumed to exhibit constant expression levels across cell types, they are commonly employed as internal controls in gene expression studies. Nevertheless, HKG may vary gene expression profile according to different variables introducing systematic errors into experimental results. Sex bias can indeed affect expression display, however, up to date, sex has not been typically considered as a biological variable.
Methods: In this study, we evaluate the expression profiles of six classical housekeeping genes (four metabolic: GAPDH, HPRT, PPIA, and UBC, and two ribosomal: 18S and RPL19) to determine expression stability in adipose tissues (AT) of Homo sapiens and Mus musculus and check sex bias and their overall suitability as internal controls. We also assess the expression stability of all genes included in distinct whole-transcriptome microarrays available from the Gene Expression Omnibus database to identify sex-unbiased housekeeping genes (suHKG) suitable for use as internal controls. We perform a novel computational strategy based on meta-analysis techniques to identify any sexual dimorphisms in mRNA expression stability in AT and to properly validate potential candidates.
Results: Just above half of the considered studies informed properly about the sex of the human samples, however, not enough female mouse samples were found to be included in this analysis. We found differences in the HKG expression stability in humans between female and male samples, with females presenting greater instability. We propose a suHKG signature including experimentally validated classical HKG like PPIA and RPL19 and novel potential markers for human AT and discarding others like the extensively used 18S gene due to a sex-based variability display in adipose tissue. Orthologs have also been assayed and proposed for mouse WAT suHKG signature. All results generated during this study are readily available by accessingan open web resource (https://bioinfo.cipf.es/metafun-HKG) for consultation and reuse in further studies.
Conclusions: This sex-based research proves that certain classical housekeeping genes fail to function adequately as controls when analyzing human adipose tissue considering sex as a variable. We confirm RPL19 and PPIA suitability as sex-unbiased human and mouse housekeeping genes derived from sex-specific expression profiles, and propose new ones such as RPS8 and UBB.
Biliatresone and Biliary atresia – Disease modelling in C57BL/6J neonates
Authors: Schmidt Hans Christian , Hagens Johanna , Schuppert Pauline , Appl Birgit , Raluy Laia Pagerols , Trochimiuk Magdalena , Philippi Clara , Li Zhongwen , Reinshagen Konrad , Tomuschat Christian
Published: January 2023

Exposure to plant toxins or microbiota that are able to digest common food ingredients to toxic structures might be responsible for biliary atresia (BA). An isoflavonoid, biliatresone is known to effectively alter the extrahepatic bile duct (EHBD) development in BALB/c mice. Biliatresone causes a reduction of Glutathione (GSH) levels, SOX17 downregulation and is effectively countered with N-Acetyl-L-cysteine (NAC) treatment in vitro. Therefore, reversing GSH-loss appears to be a promising treatment target for a translational approach. Since BALB/c mice have been described as sensitive in various models, we evaluated the toxic effect of biliatresone in robust C57BL/6J mice and confirmed its toxicity. Comparison between BALB/c and C57BL/6J mice revealed similarity in the toxic model, indicating that the onset of BA induced by biliatresone is independent of the strain specific different immune systems. Affected neonates exhibited clinical symptoms of BA, such as jaundice, ascites, clay-colored stools, yellow urine and impaired weight gain. The gallbladders of jaundiced neonates were hydropic and EHBD were twisted and enlarged. Serum and histological analysis proved cholestasis. No anomalies were seen in the liver and EHBD of control animals. With our study we join a chain of evidence confirming the BA-inducing effect of biliatresone.
Correlation of plasma procalcitonin and C-reactive protein levels with disease severity in critically ill patients with mixed-pathogen bloodstream infections of both Enterococcus spp. and Candida spp.
Authors: Li Yan
Published: January 2023

Background:Antibiotic overuse and increase of rates of invasive treatments, the incidence of bloodstream infections (BSIs) caused by mixed-pathogens (fungi and bacteria) has been on the rise. This retrospective observational study investigated the clinical significance of inflammatory biomarkers in predicting prognosis of critically ill patients with mixed-BSIs due toEnterococcusspp. andCandidaspp.Methods:Patients who were admitted to intensive care unit (ICU) from January 2018 to December 2020 were included. Of the total 66 enrolled patients, 35 and 31 patients were assigned to mixed- (fungi and bacteria) and single- (bacteria only) pathogen BSI groups, respectively. On the one hand, we compared the diffferences in plasma procalcitonin (PCT) and C-reactive protein (CRP) levels and disease severity (including Acute Physiology and Chronic Health Evaluation [APACHE] II scores, ICU stay duration, and 30-day mortality) between these two groups. On the other hand, their correlations with disease severity were also analysed.Results:The plasma CRP levels in the mixed-pathogen BSI group was higher than that in the single-pathogen BSI group; the same trend was observed for the disease severity. In the Spearman’s rank correlation analysis, plasma CRP levels were positively correlated with disease severity in the mixed-pathogen BSI group. Further, plasma PCT levels were also positively correlated with APACHE II scores and ICU stay duration. In contrast, in the single-pathogen BSI group, plasma PCT levels were positively correlated with APACHE II scores only, whereas plasma CRP levels did not correlate positively with 30-day mortality.Conclusions:In summary, mixed-pathogen BSIs caused byEnterococcusspp. andCandidaspp. lead to higher plasma PCT and CRP levels in comparison to BSI caused byEnterococcusspp. only, thereby resulting in a higher disease severity in critically ill ICU admitted patients.
Compounds of natural origin as anti-protease in SARS-CoV-2 using combinatory In silico approaches
Authors: Dwivedi Manish , Vidya Sree , Yadav Shalini , Dubey Kshatresh Dutta
Published: January 2023

SARS-CoV-2 is one of the deadly outbreaks in the present era and still showing its presence around the globe. Researchers have demonstrated various vaccines till now which may provide only protection but the cure is not possible after infection and we are seeking for efficient therapeutic leads to cure this infectious disease. In the current work, we investigated the main protease (Mpro) protein in SARS-CoV-2 which is crucial during viral particle formation and further, proposed five compounds of plant origin with the therapeutic potential. The 1000 compounds were screened from various plant-based resources and further physiochemical characterization and assessment of drug likeliness of phytocompounds were performed using SwissADME. Eventually, we screened 95 compounds out of 1000 molecules based on docking analysis using AutoDock Vina. Five compounds were selected having the highest affinity for Mpro, followed by the analysis of interaction using molecular dynamic (MD) simulation. Docking and MD simulation studies elucidated the promising stable interaction of selected 5 ligands with Mpro. During MD simulation of 100ns, Abacopterin F showed the lowest binding energy (-37.13 kCal/mol) with the highest affinity towards Mpro and this compound may be proposed as lead molecule for further investigation which interact and modulate the activity of the Mpro required for viral particle formation. However, in-vitro and in-vivo experimental validation would be needed to process the selected phytomolecules as a therapeutic lead against SARS-CoV-2.
THE ASSEMBLAGE OF INTERRELIGIOUS DIALOGUE AND TOURISM
Authors: Taufiqurrohim Taufiqurrohim
Published: January 2023

The touristic place provides discourses that are worth examining as to which how the management of the site, its internal contestation and development, as well as experiences of its visitors. Examining a heritage of the ancient Majapahit kingdom in Java, this article discusses the assemblage of tourism and religious sites and the extent the site serves as a reservoir for interreligious dialog in contemporary Indonesia. It tries to point out how interreligious dialogue is at work in this site and how surrounding communities participate and respond to the perseverance of the site. Finally, accentuating Swidler’s theory of dialogues, this paper looks at the practice of interreligious dialogue at a touristic site and how religious harmony is negotiated by Buddhist and Muslim through the site and the construction of “the other” by both religious communities.