bluuebunny/crossref_metadata_2025 huggingface dataset:
The Gibraltar slab dynamics and its influence on past and present-day Alboran domain deformation: Insights from thermo-mechanical numerical modelling
Authors: Gea Pedro J. , Negredo Ana M. , Mancilla Flor de Lis
Published: February 2023

The origin and tectonic evolution of the Gibraltar Arc system is the result of a complex geodynamic evolution involving the convergence of the Eurasian and African plates and the dynamic impact of the Gibraltar slab. Although geologic and geophysical data collected in the last few years have increased our knowledge of the Gibraltar Arc region, it is still unclear which are the mechanical links between the Gibraltar slab and the past deformation of the overriding Alboran lithosphere, as well as to which degree this subduction system is presently active. In this study, we use 2D numerical modelling to investigate the impact of the Gibraltar slab dynamics on the deformation of the overriding Alboran lithosphere. Our model simulates a WE generic vertical section at an approximate latitude of 36°N and considers an initial setup at about Burdigalian times (∼20 Ma), when the subduction front position is relatively well constrained by recent tectonic reconstructions. Our modelling shows a switch in the overriding plate (OP) stress state from extensional stresses during the slab rollback to compressional stresses near the trench when the rollback velocity decreases, caused by the change in slab-induced mantle flow. We also find that much of the crustal and lithospheric deformation occur during fast slab rollback and OP extension in the first 10 Myr of evolution, while after that only moderate deformation associated with subduction is predicted. Finally, we find that despite the subduction rollback ceases, the ongoing motion of the deeper portion of the slab induces a mantle flow that causes some amount of west-directed basal drag of the Alboran lithosphere. This basal drag generates interplate compresional stresses compatible with the distribution of intermediate-depth earthquakes in western Alboran.
Thyroid hormone action controls multiple components of cell junctions at the ventricular zone in the newborn rat brain
Authors: O’Shaughnessy Katherine L. , McMichael Benjamin D. , Sasser Aubrey L. , Bell Kiersten S. , Riutta Cal , Ford Jermaine L. , Stoker Tammy E. , Grindstaff Rachel D. , Pandiri Arun R. , Gilbert Mary E.
Published: February 2023

Thyroid hormone (TH) action controls brain development in a spatiotemporal manner. Previously, we demonstrated that perinatal hypothyroidism led to formation of a periventricular heterotopia in developing rats. This heterotopia occurs in the posterior telencephalon, and its formation was preceded by loss of radial glia cell polarity. As radial glia mediate cell migration and originate in a progenitor cell niche called the ventricular zone (VZ), we hypothesized that TH action may control cell signaling in this region. Here we addressed this hypothesis by employing laser capture microdissection and RNA-Seq to evaluate the VZ during a known period of TH sensitivity. Pregnant rats were exposed to a low dose of propylthiouracil (PTU, 0.0003%) through the drinking water during pregnancy and lactation. Dam and pup THs were quantified postnatally and RNA-Seq of the VZ performed in neonates. The PTU exposure resulted in a modest increase in maternal thyroid stimulating hormone and reduced thyroxine (T4). Exposed neonates exhibited hypothyroidism and T4 and triiodothyronine (T3) were also reduced in the telencephalon. RNA-Seq identified 358 differentially expressed genes in microdissected VZ cells of hypothyroid neonates as compared to controls (q-values ≤0.05). Pathway analyses showed processes like maintenance of the extracellular matrix and cytoskeleton, cell adhesion, and cell migration were significantly affected by hypothyroidism. Immunofluorescence also demonstrated that collagen IV, F-actin, radial glia, and adhesion proteins were reduced in the VZ. Immunohistochemistry of integrin αvβ3 and isoforms of both thyroid receptors (TRα/TRβ) showed highly overlapping expression patterns, including enrichment in the VZ. Taken together, our results show that TH action targets multiple components of cell junctions in the VZ, and this may be mediated by both genomic and nongenomic mechanisms. Surprisingly, this work also suggests that the blood-brain and blood-cerebrospinal fluid barriers may also be affected in hypothyroid newborns.
AIP gene germline variants in adult Polish patients with apparently sporadic pituitary macroadenomas
Authors: Trofimiuk-Müldner Małgorzata , Domagała Bartosz , Sokołowski Grzegorz , Skalniak Anna , Hubalewska-Dydejczyk Alicja
Published: February 2023

Introduction

Up to 5% of all pituitary tumors are hereditary e.g. due to MEN1 or aryl hydrocarbon receptor-interacting protein (AIP) genes mutations.

Objectives

The study was aimed at the assessment of the frequency and characteristics of AIP-mutation related tumors in patients with apparently sporadic pituitary macroadenomas in the Polish population.

Materials and methods

The study included 131 patients (57 males, 74 females; median age 42 years) diagnosed with pituitary macroadenomas, and with a negative family history of familial isolated pituitary adenoma (FIPA) or multiple endocrine neoplasia type 1 (MEN1) syndromes. Sanger sequencing was used for the assessment of AIP gene variants. The study was approved by the Ethics Board of JUMC.

Results

AIP variants were identified in five of the 131 included subjects (3.8%): one diagnosed with Cushing’s disease, two with acromegaly, and two with non-secreting adenomas. Patients harboring hereditary AIP gene alterations did not differ from the rest of the study group in median age at diagnosis (41.0 vs. 42.5 years, P=0.8), median largest tumor diameter (25 vs. 24 mm, P=0.6), gender distribution (60.0% vs. 56.3% females, P=0.8), secreting tumor frequency (60.0% vs. 67.5%, P=0.7), or acromegaly diagnosis frequency (40.0% vs.37.3%, P=0.9).

Conclusions

In our series of apparently sporadic pituitary macroadenomas, AIP gene variant carriers did not differ substantially from patients with negative genetic testing. A risk factor-centred approach to AIP genetic screening may result in missing germline variants. Considering the clinical impact of such genetic variants and their relatively low penetrance, it is, however, doubtful if general genetic screening benefits the whole cohort of pituitary macroadenoma patients and their families.
Zinc restores functionality in porcine prepubertal Sertoli cells exposed to subtoxic cadmium concentration via regulating the Nrf2 signaling pathway
Authors: Mancuso Francesca , Arato Iva , Bellucci Catia , Lilli Cinzia , Eugeni Elena , Aglietti Maria Chiara , Stabile Anna Maria , Pistilli Alessandra , Brancorsini Stefano , Gaggia Francesco , Calvitti Mario , Baroni Tiziano , Luca Giovanni
Published: February 2023

Introduction

Among substances released into the environment by anthropogenic activities, the heavy metal cadmium (Cd) is known to induce severe testicular injury causing male subfertility/infertility. Zinc (Zn) is another heavy metal that, unlike Cd, is physiologically present in the testis, being essential for spermatogenesis. We aimed to examine the possibility that 50 µM ZnCl2 could counteract the toxic effects induced by Cd in an in vitro model of porcine prepubertal Sertoli cells (SCs) exposed to both subtoxic (5 μM) and toxic (10 μM) concentrations of CdCl2 for 48 h.

Materials and Methods

Apoptosis, cell cycle, and cell functionality were assessed. The gene expression of Nrf2 and its downstream antioxidant enzymes, ERK1/2, and AKT kinase signaling pathways were evaluated.

Materials and Results

We found that Zn, in co-treatment with subtoxic and toxic Cd concentration, increased the number of metabolically active SCs compared to Cd exposure alone but restored SC functionality only in co-treatment with subtoxic Cd concentration with respect to subtoxic Cd alone. Exposure of Cd disrupted cell cycle in SCs, and Zn co-treatment was not able to counteract this effect. Cd alone induced SC death through apoptosis and necrosis in a dose-dependent manner, and co-treatment with Zn increased the pro-apoptotic effect of Cd. Subtoxic and toxic Cd exposures activated the Nrf2 signaling pathway by increasing gene expression of Nrf2 and its downstream genes (SOD, HO-1, and GSHPx). Zn co-treatment with subtoxic Cd attenuated upregulation on the Nrf2 system, while with toxic Cd, the effect was more erratic. Studying ERK1/2 and AKT pathways as a target, we found that the phosphorylation ratio of p-ERK1/2 and p-AKT was upregulated by both subtoxic and toxic Cd exposure alone and in co-treatment with Zn.

Discussion

Our results suggest that Zn could counteract Cd effects by increasing the number of metabolically active SCs, fully or partially restoring their functionality by modulating Nrf2, ERK1/2, and AKT pathways. Our SC model could be useful to study the effects of early Cd exposure on immature testis, evaluating the possible protective effects of Zn.
A comprehensive review on EV power converter topologies charger types infrastructure and communication techniques
Authors: Vishnuram Pradeep , R Narayanamoorthi , P Suresh , K Vijayakumar , Bajaj Mohit , Khurshaid Tahir , Nauman Ali , Kamel Salah
Published: February 2023

The energy transition is a crucial effort from many sectors and levels to create a more integrated, carbon-neutral society. More than 20% of all greenhouse gas emissions are attributed to the transportation sector, predominantly concentrated in metropolitan areas. As a result, various technological hurdles are encountered and overcome. It facilitates the adoption of electric vehicles (EVs) run on renewable energy, making them a practical option in the fight against climate change and the completion of the energy revolution. Recent developments suggest that EVs will replace internal combustion engine (ICE) during the next few months. The EV either gets all of its power from batteries and ultra capacitors or some of it from both. In a plug-in electric vehicle, the battery or ultra-capacitor is charged by an AC supply connected to a grid line. In a hybrid electric vehicle, the ICE charges the battery or ultra-capacitor. Regenerative braking is another way to charge the battery from the traction motor. In a plug-in electric vehicle, the energy from of the battery or ultra-capacitor is put back into the AC grid line. Electronic converters are essential to converting power from the grid line to the traction motor and back again. This paper examines the current state of the electric vehicle market throughout the world and its potential future developments. Power electronics converters (PEC) and energy storage devices significantly impact electric vehicles’ efficiency. Furthermore, general opinions about EVs are soon in this sector, as well as research topics that are still open to industry and University researchers.
Transient stability enhancement using optimized PI tuning of static synchronous series compensator in wind power conversion system
Authors: Ramalingegowda Chethan Hiremarali , Rudramoorthy Mageshvaran
Published: February 2023

Power systems are expanding comprehensively with the increase in load demand from both residential and industrial usage. Renewable energy is penetrating the power system to satisfy the power needs of the load demand. With its potential to generate power and compensate for a large portion of the load demand, wind generators make a major renewable power contribution. Power oscillations inherent in wind generator integration with the grid are a power quality issue to be addressed. Oscillation damping using flexible AC transmission system (FACTS) devices is a relevant solution for the power quality issue. There are multiple reasons for power oscillation. Mainly, power systems encounter fault conditions. The faults can be cleared, and the power system tries to retain stability. Sometimes, the system fails due to a longer settling time. A series-connected FACTS device utilized as a series compensator is referred to as a static synchronous series compensator (SSSC). Controlling the flow of electricity over a transmission line using this method is incredibly efficient. The capacity to switch between a capacitive and an inductive reactance characteristic is necessary. The SSSC regulates the flow of power in transmission lines to which it is linked by adjusting both the magnitude of the injected voltage and the phase angle of the injected voltage in series with the transmission line. This allows the SSSC to manage the power flow in the transmission lines. It does it by inserting a voltage that can be controlled into a transmission line in series with the fundamental frequency. This paper develops the optimally tuned SSSC in the wind-integrated grid system to dampen the oscillation. Teacher–learner-based optimization (TLBO) and gray wolf optimization (GWO) algorithms are used to tune the PI controller to improve the damping response. The obtained results show that the damping performance of the proposed controller is better than that of the other traditional controllers.
Managing an invasive tree in coastal dunes: The importance of follow-up treatments to improve the recovery of protected habitats
Authors: Duarte Liliana Neto , Marchante Elizabete , Marchante Hélia
Published: February 2023

Conservation of biodiversity in protected areas is often threatened by invasive alien plants (IAPs), and its successful management requires proper planning, resources, and monitoring to adjust future interventions. Although follow-up controls and evaluation of different management actions through monitoring programs are crucial in an adaptive management strategy, they are often neglected.Acacia longifoliais one of the most widespread IAPs in the Portuguese coastal areas, causing several negative impacts. This study reports the results of different control methods ofA. longifoliain two forest plantations over coastal dunes in two protected sites in Portugal, under different management regimes and for over 4 years. The best results were achieved after hand pulling, but due to its high cost, this method is not suitable for large areas. Mechanical cuts, which include the use of brush hogs, brush cutters, and chainsaws, resulted in variable levels of resprouting ofA. longifoliastumps. Follow-up treatments, whether mechanical and/or chemical, reduced the number ofA. longifoliaresprouts and kept its cover below 20% and height below 50 cm. Furthermore, controlling with brush cutters/hogs reduced the seed bank ofA. longifoliaby 74% while that with a disc harrow allowed an even greater reduction (91%). In areas where no follow-up treatments were carried out,A. longifoliastarted producing flowers two and a half years after the initial treatment, restarting the cycle of seed production. Nevertheless, a biological control agent that reducesA. longifoliaseed production (Trichilogaster acaciaelongifoliae) establishment was confirmed in the controlled areas, suggesting that new seed production by these plants will be soon controlled. Although species characteristic of the protected habitats are currently poorly represented, it is expected that they begin to emerge with the reduction ofA. longifolia. Our results stress the importance of persistence of follow-up treatments if higher success in IAPs control is to be achieved, not only because of the resprouting ability of many species (despite this not being very common inA. longifolia) but also because invasive plants can produce extensive persistent seed banks. The role of the management regime on the level of success in controlling IAPs will be discussed.
Retrieve of total suspended matter in typical lakes in China based on broad bandwidth satellite data: Random forest model with Forel-Ule Index
Authors: Zhai Mingjian , Zhou Xiang , Tao Zui , Lv Tingting , Zhang Hongming , Li Ruoxi , Huang Yuxuan
Published: February 2023

Total Suspended Matter is the core parameter of water color remote sensing and the important indicator for water quality evaluation of lakes. Rapid and high-precision monitoring of TSM is an important guarantee for water quality remote-sensing applications. China has launched many broad-bandwidth remote sensing satellites, all of which have similar bandwidth. The coordinated observation of multiple satellites can effectively meet the large-scale and high-frequency dynamic monitoring requirements of TSM concentration in lakes. This study proposed a machine-learning model to retrieve the TSM concentration from broad bandwidth satellites. The reliability and accuracy of various retrieve models (i.e., linear regression model, support vector regression model, random forest model, and back propagation neural networks model) were evaluated through the in-situ datasets of TSM concentration in lakes. The RF model was selected as the retrieved model of TSM concentration using broad bandwidth satellites. The results showed that 1) Compared with four machine learning models, the RF model can provide better performance (R2=0.88, Mean Absolute Percentage Error (MAPE) = 22.5%). Similarly, compared with the documented six TSM retrieve model, the RF retrieve model also has substantial advantages. 2) the Forel-Ule Index (FUI) can effectively enhance the precision and accuracy of the TSM retrieve model. 3) The RF model has good generalization ability and accuracy in the validation datasets (Lake Chagan: MAPE = 3.7%, Lake Changdang: MAPE = 4.3%). 4) The RF model was applied to the broad bandwidth satellites retrieve of TSM concentrations in Lake Bosten, Lake Chagan, and Lake Changdang, and the MAPEs were 5.3%, 8.1%, and 12.1%, respectively. This study showed that the RF model could effectively improve the retrieve performance and generalization ability of the broad bandwidth satellite’s TSM concentration, which meets the accuracy requirements of high-frequency dynamic monitoring of TSM concentration.
LPIH2V: LncRNA-protein interactions prediction using HIN2Vec based on heterogeneous networks model
Authors: Wei Meng-Meng , Yu Chang-Qing , Li Li-Ping , You Zhu-Hong , Ren Zhong-Hao , Guan Yong-Jian , Wang Xin-Fei , Li Yue-Chao
Published: February 2023

LncRNA-protein interaction plays an important role in the development and treatment of many human diseases. As the experimental approaches to determine lncRNA–protein interactions are expensive and time-consuming, considering that there are few calculation methods, therefore, it is urgent to develop efficient and accurate methods to predict lncRNA-protein interactions. In this work, a model for heterogeneous network embedding based on meta-path, namely LPIH2V, is proposed. The heterogeneous network is composed of lncRNA similarity networks, protein similarity networks, and known lncRNA-protein interaction networks. The behavioral features are extracted in a heterogeneous network using the HIN2Vec method of network embedding. The results showed that LPIH2V obtains an AUC of 0.97 and ACC of 0.95 in the 5-fold cross-validation test. The model successfully showed superiority and good generalization ability. Compared to other models, LPIH2V not only extracts attribute characteristics by similarity, but also acquires behavior properties by meta-path wandering in heterogeneous networks. LPIH2V would be beneficial in forecasting interactions between lncRNA and protein.
Partial SAA patients benefit from delayed response of IST
Authors: Wang Ting , Wang Chaomeng , Liu Chunyan , Shao Zonghong , Fu Rong
Published: February 2023

Introduction

Severe aplastic anemia(SAA)is a severe disease characterized by immune-mediated bone marrow failure and pancytopenia. Immunosuppressive therapy (ATG plus CsA, IST) is the standard treatment for patients who are not suitable for allogeneic hematopoietic stem cell transplantation (allo-HSCT). Some patients have a delayed response after 6 months of ATG, and unnecessary to be given secondary ATG or allo-HSCT. We attempted to distinguish patients who may get potential delayed response from those who were really not responsive to IST.

Methods

We collected data from 45 SAA patients who were assessed no-response to IST at 6 months after rATG and failed to receive secondary ATG or allo-HSCT.

Results

CsA plus eltrombopag (EPAG) group has an extra 75% response rate while CsA maintenance group has an extra 44% response rate at 12 months. ATG was applied within 30 days after diagnosis, ATG dosage was suffificient (ATG/lymphocyte ≥2), and absolute reticulocyte count (ARC) was ≥30×109 /L at 6 months, indicated patients could get delayed response and benefifit from CsA maintenance. Addition of EPAG could give an even better response. Otherwise, secondary ATG or allo-HSCT treatment were recommended to be given immediately.

Clinical Trial Registration

https://www.chictr.org.cn/searchproj.aspx, identifier ChiCTR2300067615.
Specific in situ immuno-imaging of pulmonary-resident memory lymphocytes in human lungs
Authors: Humphries Duncan C. , O’Connor Richard A. , Stewart Hazel L. , Quinn Tom M. , Gaughan Erin E. , Mills Beth , Williams Gareth O.S. , Stone James M. , Finlayson Keith , Chabaud-Riou Martine , Boudet Florence , Dhaliwal Kevin , Pavot Vincent
Published: February 2023

Introduction

Pulmonary-resident memory T cells (TRM) and B cells (BRM) orchestrate protective immunity to reinfection with respiratory pathogens. Developing methods for the in situ detection of these populations would benefit both research and clinical settings.

Methods

To address this need, we developed a novel in situ immunolabelling approach combined with clinic-ready fibre-based optical endomicroscopy (OEM) to detect canonical markers of lymphocyte tissue residency in situ in human lungs undergoing ex vivo lung ventilation (EVLV).

Results

Initially, cells from human lung digests (confirmed to contain TRM/BRM populations using flow cytometry) were stained with CD69 and CD103/CD20 fluorescent antibodies and imaged in vitro using KronoScan, demonstrating it’s ability to detect antibody labelled cells. We next instilled these pre-labelled cells into human lungs undergoing EVLV and confirmed they could still be visualised using both fluorescence intensity and lifetime imaging against background lung architecture. Finally, we instilled fluorescent CD69 and CD103/CD20 antibodies directly into the lung and were able to detect TRM/BRM following in situ labelling within seconds of direct intra-alveolar delivery of microdoses of fluorescently labelled antibodies.

Discussion

In situ, no wash, immunolabelling with intra-alveolar OEM imaging is a novel methodology with the potential to expand the experimental utility of EVLV and pre-clinical models.
Suppression of MR1 by human cytomegalovirus inhibits MAIT cell activation
Authors: Ashley Caroline L. , McSharry Brian P. , McWilliam Hamish E. G. , Stanton Richard J. , Fielding Ceri A. , Mathias Rommel A. , Fairlie David P. , McCluskey James , Villadangos Jose A. , Rossjohn Jamie , Abendroth Allison , Slobedman Barry
Published: February 2023

Introduction

The antigen presentation molecule MHC class I related protein-1 (MR1) is best characterized by its ability to present bacterially derived metabolites of vitamin B2 biosynthesis to mucosal-associated invariant T-cells (MAIT cells).

Methods

Through in vitro human cytomegalovirus (HCMV) infection in the presence of MR1 ligand we investigate the modulation of MR1 expression. Using coimmunoprecipitation, mass spectrometry, expression by recombinant adenovirus and HCMV deletion mutants we investigate HCMV gpUS9 and its family members as potential regulators of MR1 expression. The functional consequences of MR1 modulation by HCMV infection are explored in coculture activation assays with either Jurkat cells engineered to express the MAIT cell TCR or primary MAIT cells. MR1 dependence in these activation assays is established by addition of MR1 neutralizing antibody and CRISPR/Cas-9 mediated MR1 knockout.

Results

Here we demonstrate that HCMV infection efficiently suppresses MR1 surface expression and reduces total MR1 protein levels. Expression of the viral glycoprotein gpUS9 in isolation could reduce both cell surface and total MR1 levels, with analysis of a specific US9 HCMV deletion mutant suggesting that the virus can target MR1 using multiple mechanisms. Functional assays with primary MAIT cells demonstrated the ability of HCMV infection to inhibit bacterially driven, MR1-dependent activation using both neutralizing antibodies and engineered MR1 knockout cells.

Discussion

This study identifies a strategy encoded by HCMV to disrupt the MR1:MAIT cell axis. This immune axis is less well characterized in the context of viral infection. HCMV encodes hundreds of proteins, some of which regulate the expression of antigen presentation molecules. However the ability of this virus to regulate the MR1:MAIT TCR axis has not been studied in detail.
Endoglin in head and neck neoplasms
Authors: Litwiniuk-Kosmala Małgorzata , Makuszewska Maria , Czesak Małgorzata
Published: February 2023

Tumors of the head and neck region form a heterogeneous group of pathologies, including various benign lesions and malignant neoplasms. Endoglin, also known as CD105, is an accessory receptor for transforming growth factor beta (TGF-β), that regulates angiogenesis, both under physiological and pathological conditions. It is highly expressed in proliferating endothelial cells. Therefore, it is considered as a marker of tumor-related angiogenesis. In this review we discuss the role of endoglin as a possible marker of carcinogenesis, as well as a potential target for antibody-based therapies in the neoplasms of the head and neck region.
Structure and function of African swine fever virus proteins: Current understanding
Authors: Yang Sicheng , Miao Chun , Liu Wei , Zhang Guanglei , Shao Junjun , Chang Huiyun
Published: February 2023

African swine fever virus (ASFV) is a highly infectious and lethal double-stranded DNA virus that is responsible for African swine fever (ASF). ASFV was first reported in Kenya in 1921. Subsequently, ASFV has spread to countries in Western Europe, Latin America, and Eastern Europe, as well as to China in 2018. ASFV epidemics have caused serious pig industry losses around the world. Since the 1960s, much effort has been devoted to the development of an effective ASF vaccine, including the production of inactivated vaccines, attenuated live vaccines, and subunit vaccines. Progress has been made, but unfortunately, no ASF vaccine has prevented epidemic spread of the virus in pig farms. The complex ASFV structure, comprising a variety of structural and non-structural proteins, has made the development of ASF vaccines difficult. Therefore, it is necessary to fully explore the structure and function of ASFV proteins in order to develop an effective ASF vaccine. In this review, we summarize what is known about the structure and function of ASFV proteins, including the most recently published findings.
Genotype heterogeneity of high-risk human papillomavirus infection in Ethiopia
Authors: Seyoum Ayichew , Seyoum Berhanu , Gure Tadesse , Alemu Addisu , Belachew Anteneh , Abeje Dessalegn , Aseffa Abraham , Howe Rawleigh , Mulu Andargachew , Mihret Adane
Published: February 2023

Cervical cancer is a vaccine-preventable sexually transmitted disease. In the year 2020, there were an estimated 604,000 new cases and 342,000 deaths worldwide. Although its incidence is global, it is much higher in sub-Saharan African countries. In Ethiopia, there is a scarcity of data about the prevalence of high-risk HPV infection and its association with cytological profiles. Therefore, this study was conducted to fill this information gap. A hospital-based cross-sectional study was conducted from April 26 to August 28, 2021, and enrolled 901 sexually active women. Socio-demographic and other relevant bio-behavioral and clinical data were collected using a standardized questionnaire. Visual inspection with acetic acid [VIA] was done as an initial screening method for cervical cancer. The cervical swab was then collected using L-Shaped FLOQSwabs in eNAT nucleic acid preservation and transportation medium. A Pap test was done to determine the cytological profile. Nucleic acid was extracted using STARMag 96 ProPrep Kit on SEEPREP32. A Real-time multiplex assay was performed to amplify and detect the HPV L1 gene used for genotyping. The data were entered into Epi data version 3.1 software and exported to STATA version 14 for analysis. A total of 901 (age range from 30 to 60 years, mean age = 34.8 years, and SD± 5.8) women were screened for cervical cancer using VIA and 832 women had a valid co-testing (Pap test and HPV DNA testing) results for further process. The overall prevalence of hr HPV infection was 13.1%. Out of 832 women, 88% of them had normal and 12% had abnormal Pap test results. The proportion of high risk HPV was significantly higher among women with abnormal cytology (X2 = 688.446, p < 0.001) and younger age (X2 = 15.3408, p = 0.018). Among 110 women with hr HPV, 14 genotypes (HPV-16, -18, -31, -33, -35, -39, -45, -51, -52, -56, -58, -59, -66, and -68) were identified while HPV-16, -31, -52, -58, and -35 genotypes were highly prevalent. The high risk HPV infection continues to be a significant public health problem among women 30–35 years old. The presence of high-risk HPV irrespective of genotypes is highly correlated with cervical cell abnormalities. Genotype heterogeneity is observed suggesting the importance of periodic geospatial genotyping surveillance for vaccine effectiveness.
Probing microdomain Ca2+ activity and synaptic transmission with a node-based tripartite synapse model
Authors: Liu Langzhou , Gao Huayi , Li Jinyu , Chen Shangbin
Published: February 2023

Astrocytic fine processes are the most minor structures of astrocytes but host much of the Ca2+ activity. These localized Ca2+ signals spatially restricted to microdomains are crucial for information processing and synaptic transmission. However, the mechanistic link between astrocytic nanoscale processes and microdomain Ca2+ activity remains hazily understood because of the technical difficulties in accessing this structurally unresolved region. In this study, we used computational models to disentangle the intricate relations of morphology and local Ca2+ dynamics involved in astrocytic fine processes. We aimed to answer: 1) how nano-morphology affects local Ca2+ activity and synaptic transmission, 2) and how fine processes affect Ca2+ activity of large process they connect. To address these issues, we undertook the following two computational modeling: 1) we integrated the in vivo astrocyte morphological data from a recent study performed with super-resolution microscopy that discriminates sub-compartments of various shapes, referred to as nodes and shafts to a classic IP3R-mediated Ca2+ signaling framework describing the intracellular Ca2+ dynamics, 2) we proposed a node-based tripartite synapse model linking with astrocytic morphology to predict the effect of structural deficits of astrocytes on synaptic transmission. Extensive simulations provided us with several biological insights: 1) the width of nodes and shafts could strongly influence the spatiotemporal variability of Ca2+ signals properties but what indeed determined the Ca2+ activity was the width ratio between nodes and shafts, 2) the connectivity of nodes to larger processes markedly shaped the Ca2+ signal of the parent process rather than nodes morphology itself, 3) the morphological changes of astrocytic part might potentially induce the abnormality of synaptic transmission by affecting the level of glutamate at tripartite synapses. Taken together, this comprehensive model which integrated theoretical computation and in vivo morphological data highlights the role of the nanomorphology of astrocytes in signal transmission and its possible mechanisms related to pathological conditions.
A case report of neuronal intranuclear inclusion disease with paroxysmal peripheral neuropathy-like onset lacking typical signs on diffusion-weighted imaging
Authors: Fu Jiayu , Zhao Chen , Hou Guanghao , Liu Xiaoxuan , Zheng Mei , Zhang Yingshuang , Zhang Shuo , Zheng Danfeng , Zhang Yixuan , Huang Xiao , Ye Shan , Fan Dongsheng
Published: February 2023

Background

Neuronal intranuclear inclusion disease (NIID) is a slowly progressive neurodegenerative disease characterized by eosinophilic hyaline intranuclear inclusions and the GGC repeats in the 5'-untranslated region of NOTCH2NLC. The prevalent presence of high-intensity signal along the corticomedullary junction on diffusion-weighted imaging (DWI) helps to recognize this heterogeneous disease despite of highly variable clinical manifestations. However, patients without the typical sign on DWI are often misdiagnosed. Besides, there are no reports of NIID patients presenting with paroxysmal peripheral neuropathy-like onset to date.

Case presentation

We present a patient with NIID who suffered recurrent transient numbness in arms for 17 months. Magnetic resonance imaging (MRI) showed diffuse, bilateral white matter lesions without typical subcortical DWI signals. Electrophysiological studies revealed mixed demyelinating and axonal sensorimotor polyneuropathies involving four extremities. After excluding differential diagnosis of peripheral neuropathy through body fluid tests and a sural nerve biopsy, NIID was confirmed by a skin biopsy and the genetic analysis of NOTCH2NLC.

Conclusion

This case innovatively demonstrates that NIID could manifest as paroxysmal peripheral neuropathy-like onset, and addresses the electrophysiological characteristics of NIID in depth. We broaden the clinical spectrum of NIID and provide new insights into its differential diagnosis from the perspective of peripheral neuropathy.
Risk of cervical pre-cancer and cancer in women with multiple sclerosis exposed to high efficacy disease modifying therapies
Authors: Bridge Francesca , Brotherton Julia M. L. , Foong Yi , Butzkueven Helmut , Jokubaitis Vilija G. , Van der Walt Anneke
Published: February 2023

There is a growing need to better understand the risk of malignancy in the multiple sclerosis (MS) population, particularly given the relatively recent and widespread introduction of immunomodulating disease modifying therapies (DMTs). Multiple sclerosis disproportionately affects women, and the risk of gynecological malignancies, specifically cervical pre-cancer and cancer, are of particular concern. The causal relationship between persistent human papillomavirus (HPV) infection and cervical cancer has been definitively established. To date, there is limited data on the effect of MS DMTs on the risk of persistent HPV infection and subsequent progression to cervical pre-cancer and cancer. This review evaluates the risk of cervical pre-cancer and cancer in women with MS, including the risk conferred by DMTs. We examine additional factors, specific to the MS population, that alter the risk of developing cervical cancer including participation in HPV vaccination and cervical screening programs.
People solve rebuses unwittingly—Both forward and backward: Empirical evidence for the mental effectiveness of the signifier
Authors: Olyff Giulia , Bazan Ariane
Published: February 2023

Introduction

Freud proposed that names of clinically salient objects or situations, such as for example a beetle (Käfer) in Mr. E’s panic attack, refer through their phonological word form, and not through their meaning, to etiologically important events—here, “Que faire?” which summarizes the indecisiveness of Mr. E’s mother concerning her marriage with Mr. E’s father. Lacan formalized these ideas, attributing full-fledged mental effectiveness to the signifier, and summarized this as “the unconscious structured as a language”. We tested one aspect of this theory, namely that there is an influence of the ambiguous phonological translation of the world upon our mental processing without us being aware of this influence.

Methods

For this, we used a rebus priming paradigm, including 14 French rebuses, composed of two images depicting common objects, such as paon /pã/ “peacock” and terre /tεr/ “earth,” together forming the rebus panthère /pãtεr/ “panther.” These images were followed by a target word semantically related to the rebus resolution, e.g., félin “feline,” upon which the participants, unaware of the rebus principle, produced 6 written associations. A total of 1,458 participants were randomly assigned either to Experiment 1 in which they were shown the rebus images in either forward or in reverse order or to Experiment 2, in which they were shown only one of both rebus images, either the first or the last.

Results and discussion

The results show that the images induced inadvertent rebus priming in naïve participants. In other words, our results show that people solve rebuses unwittingly independent of stimulus order, thereby constituting empirical evidence for the mental effectiveness of the signifier.
A clinical prediction model for lung metastasis risk in osteosarcoma: A multicenter retrospective study
Authors: Zheng Shengping , Chen Longhao , Wang Jiaming , Wang Haosheng , Hu Zhaohui , Li Wanying , Xu Chan , Ma Minmin , Wang Bing , Huang Yangjun , Liu Qiang , Tang Zhi-Ri , Liu Guanyu , Wang Tingting , Li Wenle , Yin Chengliang
Published: February 2023

Background

Lung metastases (LM) have a poor prognosis of osteosarcoma. This study aimed to predict the risk of LM using the nomogram in patients with osteosarcoma.

Methods

A total of 1100 patients who were diagnosed as osteosarcoma between 2010 and 2019 in the Surveillance, Epidemiology and End Results (SEER) database were selected as the training cohort. Univariate and multivariate logistic regression analyses were used to identify independent prognostic factors of osteosarcoma lung metastases. 108 osteosarcoma patients from a multicentre dataset was as valiation data. The predictive power of the nomogram model was assessed by receiver operating characteristic curves (ROC) and calibration plots, and decision curve analysis (DCA) was utilized to interpret the accurate validity in clinical practice.

Results

A total of 1208 patients with osteosarcoma from both the SEER database(n=1100) and the multicentre database (n=108) were analyzed. Univariate and multivariate logistic regression analyses showed that Survival time, Sex, T-stage, N-stage, Surgery, Radiation, and Bone metastases were independent risk factors for lung metastasis. We combined these factors to construct a nomogram for estimating the risk of lung metastasis. Internal and external validation showed significant predictive differences (AUC 0.779, 0.792 respectively). Calibration plots showed good performance of the nomogram model.

Conclusions

In this study, a nomogram model for predicting the risk of lung metastases in osteosarcoma patients was constructed and turned out to be accurate and reliable through internal and external validation. Moreover we built a webpage calculator (https://drliwenle.shinyapps.io/OSLM/) taken into account nomogram model to help clinicians make more accurate and personalized predictions.
99mTc-rituximab tracer injection for guiding internal mammary sentinel lymph nodes biopsy in primary breast cancer: A prospective observational study
Authors: Chen Wenxin , Su Yaodong , Zhang Hui , Zhang Yu , Zhu Lin , Lin Mengbo , Lin Zhiyi , Yu Mingdian , Yang Shengping , Zhang Yanmin
Published: February 2023

Objective

To explore the use of 99mTc-rituximab tracer injection for internal mammary sentinel lymph node (IM-SLN) detection in patients with primary breast cancer.

Methods

This prospective observational study enrolled female patients with primary breast cancer between September 2017 and June 2022 at Fujian Provincial Hospital. The participants were divided into the peritumoral group (two subcutaneous injection points on the surface of the tumor), two-site group (injections into the glands at 6 and 12 o’clock around the areola area), and four-site group (injections into the gland at 3, 6, 9, and 12 o’clock around the areola area). The outcomes were the detection rates of the IM-SLNs and axillary sentinel lymph nodes (A-SLNs).

Results

Finally, 133 patients were enrolled, including 53 in the peritumoral group, 60 in the two-site group, and 20 in the four-site group. The detection rate of the IM-SLNs in the peritumoral group (9.4% [5/53]) was significantly lower than in the two-site (61.7% [37/60], P<0.001) and four-site (50.0% [10/20], P<0.001) groups. The detection rates of A-SLNs among the three groups were comparable (P=0.436).

Conclusion

The two-site or four-site intra-gland injection of 99mTc-rituximab tracer might achieve a higher detection rate of IM-SLNs and a comparable detection rate of A-SLNs compared with the peritumoral method. The location of the primary focus has no impact on the detection rate of the IM-SLNs.
Inhibitor of apoptosis proteins as therapeutic targets in bladder cancer
Authors: Wolf Philipp
Published: February 2023

Evasion from apoptosis is a hallmark of cancer. Inhibitor of apoptosis proteins (IAPs) contribute to this hallmark by suppressing the induction of cell death. IAPs were found to be overexpressed in cancerous tissues and to contribute to therapeutic resistance. The present review focuses on the IAP members cIAP1, cIAP2, XIAP, Survivin and Livin and their importance as potential therapeutic targets in bladder cancer.
The safety and efficacy of remimazolam tosylate for induction and maintenance of general anesthesia in pediatric patients undergoing elective surgery: Study protocol for a multicenter, randomized, single-blind, positive-controlled clinical trial
Authors: Fang Yu-Bo , Wang Cheng-Yu , Gao Yu-Qing , Cai Yu-Hang , Chen Jia , Zhang Xu-Lin , Dong Le-Qi , Shang-Guan Wang-Ning , Liu Hua-Cheng
Published: February 2023

Introduction: Remimazolam is an ultra-short-acting benzodiazepine sedative agent commonly used in general anesthesia, procedural sedation, and intensive care unit (ICU) sedation. This study aimed to explore the efficacy and safety of remimazolam versus propofol for the induction and maintenance of general anesthesia in preschool-age children undergoing elective surgery.

Methods and analysis: In this multicenter, randomized, single-blind, positive-controlled non-inferior clinical trial, one hundred ninety-two children aged 3–6 years will be randomly allocated as a 3:1 ratio into two groups: Group R with an intravenous dose of remimazolam 0.3 mg/kg for the induction of anesthesia followed by a constant infusion rate of remimazolam 1–3 mg/kg/h to maintain anesthesia, and Group P with an intravenous dose of propofol 2.5 mg/kg for the induction of anesthesia followed by a constant infusion rate of propofol 4–12 mg/kg/h to maintain anesthesia. The primary outcome will be the rate of the successful induction and maintenance of anesthesia. The secondary outcomes will include the time to LoC, the Bispectral Index (BIS) value, awakening time, extubation time, post-anesthesia care unit (PACU) discharge time, usage of additional sedative drugs during the induction period, usage of remedial drugs in PACU, emergence delirium, pain in PACU, behavior scores at day 3 after surgery, parental and anesthesiologists’ satisfaction, and adverse events.

Ethics and dissemination: This study has been approved by the ethics review boards at all participating hospitals. The Ethics Committee of the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University (Reference No. LCKY 2020-380, November 13, 2020) is the central ethics committee.
The challenges of open data for future epidemic preparedness: The experience of the 2022 Ebolavirus outbreak in Uganda
Authors: Branda Francesco , Mahal Ahmed , Maruotti Antonello , Pierini Massimo , Mazzoli Sandra
Published: February 2023

On 20 September 2022, the Ministry of Health in Uganda, together with the World Health Organization—Regional Office for Africa (WHO AFRO) confirmed an outbreak of EVD due to Sudan ebolavirus in Mubende District, after one fatal case was confirmed. Real-time information are needed to provide crucial information to understand transmissibility, risk of geographical spread, routes of transmission, risk factors of infection, and provide the basis for epidemiological modelling that can inform response and containment planning to reduce the burden of disease. We made an effort to build a centralized repository of the Ebola virus cases from verified sources, providing information on dates of symptom onset, locations (aggregated to the district level), and when available, the gender and status of hospitals, reporting bed capacity and isolation unit occupancy rate according to the severity status of the patient. The proposed data repository provides researchers and policymakers timely, complete, and easy-accessible data to monitor the most recent trends of the Ebola outbreak in Ugandan districts with informative graphical outputs. This favors a rapid global response to the disease, enabling governments to prioritize and adjust their decisions quickly and effectively in response to the rapidly evolving emergency, with a solid data basis.
Prevalence and global trends of polypharmacy in patients with chronic kidney disease: A systematic review and meta-analysis
Authors: Naseralallah Lina , Khatib Malkan , Al-Khulaifi Azhar , Danjuma Mohammed
Published: February 2023

Background and objectives: Polypharmacy and chronic kidney disease (CKD) are becoming increasingly common due to an ageing population and the rise of multimorbidity. In line with the therapeutic guidelines, managing CKD and its complications necessitates prescribing multiple medications, which predisposes patients to polypharmacy. The aim of this systematic review and meta-analysis is to describe the prevalence of polypharmacy in patients with CKD and to explore the global trends of factors driving any apparent variability in prevalence estimates.

Methods: PubMed, Scopus, the Cochrane Database of Systematic Reviews (CDSR), and Google Scholar were searched from 1999 to November 2021. Study selection, data extraction, and critical appraisal were conducted by two independent reviewers. The pooled prevalence of polypharmacy was estimated utilizing the random effects model using the default double arcsine transformation.

Results: This review involved 14 studies comprising of 17 201 participants, a significant proportion of which were males (56.12%). The mean age of the review population was 61.96 (SD ± 11.51) years. The overall pooled prevalence of polypharmacy amongst patients with CKD was 69% (95% CI: 49%–86%) (I2 = 100%, p < 0.0001), with a proportionately higher prevalence in North America and Europe as compared to Asia.

Conclusion: The results from this meta-analysis showed a high pooled prevalence estimates of polypharmacy amongst patient cohorts with CKD. The exact interventions that are likely to significantly mitigate its effect remain uncertain and will need exploration by future prospective and systematic studies.

Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/], identifier [CRD42022306572].