bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of an iPSC-based barrier model for blood-brain barrier investigations using the SBAD0201 stem cell line
Authors: Ozgür Burak , Puris Elena , Brachner Andreas , Appelt-Menzel Antje , Oerter Sabrina , Balzer Viktor , Holst Mikkel Roland , Christiansen Rasmus Folmann , Hyldig Kathrine , Buckley Stephen T. , Kristensen Mie , Auriola Seppo , Jensen Allan , Fricker Gert , Nielsen Morten Schallburg , Neuhaus Winfried , Brodin Birger
Published: December 2023

Background

Blood-brain barrier (BBB) models based on primary murine, bovine, and porcine brain capillary endothelial cell cultures have long been regarded as robust models with appropriate properties to examine the functional transport of small molecules. However, species differences sometimes complicate translating results from these models to human settings. During the last decade, brain capillary endothelial-like cells (BCECs) have been generated from stem cell sources to model the human BBB in vitro. The aim of the present study was to establish and characterize a human BBB model using human induced pluripotent stem cell (hiPSC)-derived BCECs from the hIPSC line SBAD0201.

Methods

The model was evaluated using transcriptomics, proteomics, immunocytochemistry, transendothelial electrical resistance (TEER) measurements, and, finally, transport assays to assess the functionality of selected transporters and receptor (GLUT-1, LAT-1, P-gp and LRP-1).

Results

The resulting BBB model displayed an average TEER of 5474 ± 167 Ω·cm2 and cell monolayer formation with claudin-5, ZO-1, and occludin expression in the tight junction zones. The cell monolayers expressed the typical BBB markers VE-cadherin, VWF, and PECAM-1. Transcriptomics and quantitative targeted absolute proteomics analyses revealed that solute carrier (SLC) transporters were found in high abundance, while the expression of efflux transporters was relatively low. Transport assays using GLUT-1, LAT-1, and LRP-1 substrates and inhibitors confirmed the functional activities of these transporters and receptors in the model. A transport assay suggested that P-gp was not functionally expressed in the model, albeit antibody staining revealed that P-gp was localized at the luminal membrane.

Conclusions

In conclusion, the novel SBAD0201-derived BBB model formed tight monolayers and was proven useful for studies investigating GLUT-1, LAT-1, and LRP-1 mediated transport across the BBB. However, the model did not express functional P-gp and thus is not suitable for the performance of drug efflux P-gp reletated studies.
Growing-season carbon budget of alpine meadow ecosystem in the Qinghai Lake Basin: a continued carbon sink through this century according to the Biome-BGC model
Authors: Zhang Meng-ya , Ma Yu-jun , Chen Peng , Shi Fang-zhong , Wei Jun-qi
Published: December 2023

Background

The alpine meadow is one of the most important ecosystems in the Qinghai-Tibet Plateau (QTP), and critically sensitive to climate change and human activities. Thus, it is crucial to precisely reveal the current state and predict future trends in the carbon budget of the alpine meadow ecosystem. The objective of this study was to explore the applicability of the Biome-BGC model (BBGC) in the Qinghai Lake Basin (QLB), identify the key parameters affecting the variation of net ecosystem exchange (NEE), and further predict the future trends in carbon budget in the QLB.

Results

The alpine meadow mainly acted as carbon sink during the growing season. For the eco-physiological factors, the YEL (Yearday to end litterfall), YSNG (Yearday to start new growth), CLEC (Canopy light extinction coefficient), FRC:LC (New fine root C: new leaf C), SLA (Canopy average specific leaf area), C:Nleaf(C:N of leaves), and FLNR (Fraction of leaf N in Rubisco) were confirmed to be the top seven parameters affecting carbon budget of the alpine meadow. For the meteorological factors, the sensitivity of NEE to precipitation was greater than that to vapor pressure deficit (VPD), and it was greater to radiation than to air temperature. Moreover, the combined effect of two different meteorological factors on NEE was higher than the individual effect of each one. In the future, warming and wetting would enhance the carbon sink capacity of the alpine meadow during the growing season, but extreme warming (over 3.84 ℃) would reduce NEE (about 2.9%) in the SSP5-8.5 scenario.

Conclusion

Overall, the alpine meadow ecosystem in the QLB generally performs as a carbon sink at present and in the future. It is of great significance for the achievement of the goal of carbon neutrality and the management of alpine ecosystems.
First report of kdr mutations in the voltage-gated sodium channel gene in the arbovirus vector, Aedes aegypti, from Nouakchott, Mauritania
Authors: Ould Lemrabott Mohamed Aly , Briolant Sébastien , Gomez Nicolas , Basco Leonardo , Ould Mohamed Salem Boukhary Ali
Published: December 2023

Background

Since 2014, dengue epidemics have occurred almost annually in Nouakchott, the capital city of Mauritania, coinciding with the recent establishment of Aedes aegypti, the primary vector of dengue, in the city. Anopheles arabiensis, the primary vector of malaria, is also abundant not only in Nouakchott but also in most areas of the country. Resistance to insecticides has been studied in An. arabiensis but not in Ae. aegypti in Mauritania. The objective of the present study was to establish the baseline data on the frequencies of knockdown resistance (kdr) mutations in the voltage-gated sodium channel (vgsc) gene in Ae. aegypti collected in Nouakchott to improve vector control.

Methods

Resting Ae. aegypti mosquitoes were collected in 2017 and 2018 in Teyarett and Dar Naim districts in Nouakchott using a battery-powered aspirator. Polymerase chain reaction (PCR) and DNA sequencing were performed to detect the presence of five kdr mutations known to be associated with pyrethroid resistance: L982W, S989P, I1011M/G, V1016G/I, and F1534C.

Results

A total of 100 female Ae. aegypti mosquitoes were identified among collected resting culicid fauna, of which 60% (60/100) were unfed, 12% (12/100) freshly blood-fed, and 28% (28/100) gravid. Among the mutations investigated in this study, 989P, 1016G, and 1534C were found to be widespread, with the frequencies of 0.43, 0.44, and 0.55, respectively. Mutations were not found in codons 982 and 1011. No other mutations were detected within the fragments analyzed in this study. Genotype distribution did not deviate from Hardy–Weinberg equilibrium. The most frequent co-occurring point mutation patterns among Ae. aegypti mosquitoes were the heterozygous individuals 989SP/1016VG/1534FC detected in 45.1% of mosquitoes. In addition, homozygous mutant 1534CC co-occurred simultaneously with homozygous wild type 989SS and 1016VV in 30.5% of mosquito specimens. Inversely, homozygous wild-type 1534FF co-occurred simultaneously with homozygous mutant 989PP and 1016GG in 19.5% of the mosquitoes.

Conclusions

To our knowledge, this is the first study reporting the presence of three point mutations in the vgsc gene of Ae. aegypti in Mauritania. The findings of the present study are alarming because they predict a high level of resistance to pyrethroid insecticides which are commonly used in vector control in the country. Therefore, further studies are urgently needed, in particular phenotypic characterization of insecticide resistance using the standardized test.

Graphical Abstract
Differential expression of the inflammatory ciita gene may be accompanied by altered bone properties in intact sex steroid-deficient female rats
Authors: Jensen Vivi FH , Swanberg Maria , Herlin Maria , McGuigan Fiona E , Jørgensen Niklas R , Akesson Kristina E
Published: December 2023

Objective

The class II transactivator (CIITA), encoded by the CIITA gene, controls expression of immune response regulators, which affect bone homeostasis. Previously, we investigated a functional CIITA polymorphism in elderly women. Women carrying the allele associated with lower CIITA levels displayed higher bone mineral density (BMD), but also higher bone loss. The present exploratory study in a rat model sought to investigate effects of differential expression of Ciita on bone structural integrity and strength. Two strains DA (normal-to-high expression) and DA.VRA4 (lower expression) underwent ovariectomy (OVX) or sham-surgery at ~ 14-weeks of age (DA OVX n = 8, sham n = 4; DA.VRA4 OVX n = 10, sham n = 2). After 16-weeks, femoral BMD and bone mineral content (BMC) were measured and morphometry and biomechanical testing performed.

Results

In DA.VRA4 rats, BMD/BMC, cross-sectional area and biomechanical properties were lower. Ciita expression was accompanied by OVX-induced changes to cross-sectional area and femoral shaft strength; DA rats had lower maximum load-to-fracture. Thus, while lower Ciita expression associated with lower bone mass, OVX induced changes to structural and mechanical bone properties were less pronounced.

Conclusion

The data tentatively suggests association between Ciita expression and structural and mechanical bone properties, and a possible role in bone changes resulting from estrogen deficiency.
Impact of an online training tool on individual and organizational resilience and mindfulness among radiological personnel in Norway
Authors: Gransjøen Ann Mari
Published: December 2023

Background

Heavy workloads and increasing demands for productivity have contributed to rising rates of stress and burnout among radiological staff. Different forms of mindfulness and resilience-training might assist with stress management and protect these employees against burnout.

Aim

The objective of this study is to evaluate the impact of an online training tool on individual and organizational resilience, mindfulness and quality of care.

Methods

An online questionnaire was used, consisting of the Connor-Davidson Resilience Scale, the Mindful Attention Awareness Scale, the Benchmark Resilience Tool, and questions pertaining to quality, safety, and burnout (baseline = 68 participants between July 2022 - October 2022, follow-up = 13 participants between November 2022 - February 2023). Descriptive statistics and a paired-sampled t-test were used for statistical analysis.

Results and conclusions

Few participants reported completing any of the exercises. The baseline group had significantly higher mean resilience (p = 0.018) and mindfulness scores (p = < 0.001), mean decrease in scores was 7.46 for resilience and 1.7 for mindfulness. In conclusion, both individual and organizational resilience are perceived as low among radiological personnel in Norway. However, it does not seem to affect quality and safety.
Mesenchymal stem cell-based therapy for autoimmune-related fibrotic skin diseases—systemic sclerosis and sclerodermatous graft-versus-host disease
Authors: Yang Han , Cheong Sousan , He Yunfan , Lu Feng
Published: December 2023

Background

Systemic sclerosis (SSc) and sclerodermatous graft-versus-host disease (Scl-GVHD)—characterized by similar developmental fibrosis, vascular abnormalities, and innate and adaptive immune response, resulting in severe skin fibrosis at the late stage—are chronic autoimmune diseases of connective tissue. The significant immune system dysfunction, distinguishing autoimmune-related fibrosis from mere skin fibrosis, should be a particular focus of treating autoimmune-related fibrosis. Recent research shows that innovative mesenchymal stem cell (MSC)-based therapy, with the capacities of immune regulation, inflammation suppression, oxidation inhibition, and fibrosis restraint, shows great promise in overcoming the disease.

Main body

This review of recent studies aims to summarize the therapeutic effect and theoretical mechanisms of MSC-based therapy in treating autoimmune-related fibrotic skin diseases, SSc and Scl-GVHD, providing novel insights and references for further clinical applications. It is noteworthy that the efficacy of MSCs is not reliant on their migration into the skin. Working on the immune system, MSCs can inhibit the chemotaxis and infiltration of immune cells to the skin by down-regulating the expression of skin chemokines and chemokine receptors and reducing the inflammatory and pro-fibrotic mediators. ​Furthermore, to reduce levels of oxidative stress, MSCs may improve vascular abnormalities, and enhance the antioxidant defenses through inducible nitric oxide synthase, thioredoxin 1, as well as other mediators. The oxidative stress environment does not weaken MSCs and may even strengthen certain functions. Regarding fibrosis, MSCs primarily target the transforming growth factor-β signaling pathway to inhibit fibroblast activation. Here, miRNAs may play a critical role in ECM remodeling. Clinical studies have demonstrated the safety of these approaches, though outcomes have varied, possibly owing to the heterogeneity of MSCs, the disorders themselves, and other factors. Nevertheless, the research clearly reveals the immense potential of MSCs in treating autoimmune-related fibrotic skin diseases.

Conclusion

The application of MSCs presents a promising approach for treating autoimmune-related fibrotic skin diseases: SSc and Scl-GVHD. Therapies involving MSCs and MSC extracellular vesicles have been found to operate through three primary mechanisms: rebalancing the immune and inflammatory disorders, resisting oxidant stress, and inhibiting overactivated fibrosis (including fibroblast activation and ECM remodeling). However, the effectiveness of these interventions requires further validation through extensive clinical investigations, particularly randomized control trials and phase III/IV clinical trials. Additionally, the hypothetical mechanism underlying these therapies could be elucidated through further research.
The role of c-Jun for beating cardiomycyte formation in prepared embryonic body
Authors: Su Lide , Zhang Guofu , Jiang Lili , Chi Chao , Bai Bing , Kang Kai
Published: December 2023

Background

Morbidity and mortality associated with cardiovascular diseases, such as myocardial infarction, stem from the inability of terminally differentiated cardiomyocytes to regenerate, and thus repair the damaged myocardial tissue structure. The molecular biological mechanisms behind the lack of regenerative capacity for those cardiomyocytes remains to be fully elucidated. Recent studies have shown that c-Jun serves as a cell cycle regulator for somatic cell fates, playing a key role in multiple molecular pathways, including the inhibition of cellular reprogramming, promoting angiogenesis, and aggravation of cardiac hypertrophy, but its role in cardiac development is largely unknown. This study aims to delineate the role of c-Jun in promoting early-stage cardiac differentiation.

Methods

The c-Jun gene in mouse embryonic stem cells (mESCs) was knocked out with CRISPR-Cas9, and the hanging drop method used to prepare the resulting embryoid bodies. Cardiac differentiation was evaluated up to 9 days after c-Jun knockout (ko) via immunofluorescence, flow cytometric, and qPCR analyses.

Results

Compared to the wild-type control group, obvious beating was observed among the c-Jun-ko mESCs after 6 days, which was also associated with significant increases in myocardial marker expression. Additionally, markers associated with mesoderm and endoderm cell layer development, essential for further differentiation of ESCs into cardiomyocytes, were also up-regulated in the c-Jun-ko cell group.

Conclusions

Knocking out c-Jun directs ESCs toward a meso-endodermal cell lineage fate, in turn leading to generation of beating myocardial cells. Thus, c-Jun plays an important role in regulating early cardiac cell development.
On a logarithmic wave equation with nonlinear dynamical boundary conditions: local existence and blow-up
Authors: Irkıl Nazlı , Mahdi Khaled , Pişkin Erhan , Alnegga Mohammad , Boulaaras Salah
Published: December 2023

This paper deals with a hyperbolic-type equation with a logarithmic source term and dynamic boundary condition. Given convenient initial data, we obtained the local existence of a weak solution. Local existence results of solutions are obtained using the Faedo-Galerkin method and the Schauder fixed-point theorem. Additionally, under suitable assumptions on initial data, the lower bound time of the blow-up result is investigated.
Diagnostic value of a CT-based radiomics nomogram for discrimination of benign and early stage malignant ovarian tumors
Authors: Chen Jia , Yang Fei , Liu Chanzhen , Pan Xinwei , He Ziying , Fu Danhui , Jin Guanqiao , Su Danke
Published: December 2023

Background

This study aimed to identify the diagnostic value of models constructed using computed tomography-based radiomics features for discrimination of benign and early stage malignant ovarian tumors.

Methods

The imaging and clinicopathological data of 197 cases of benign and early stage malignant ovarian tumors (FIGO stage I/II), were retrospectively analyzed. The patients were randomly assigned into training data set and validation data set. Radiomics features were extracted from images of plain computed tomography scan and contrast-enhanced computed tomography scan, were then screened in the training data set, and a radiomics model was constructed. Multivariate logistic regression analysis was used to construct a radiomic nomogram, containing the traditional diagnostic model and the radiomics model. Moreover, the decision curve analysis was used to assess the clinical application value of the radiomics nomogram.

Results

Six textural features with the greatest diagnostic efficiency were finally screened. The value of the area under the receiver operating characteristic curve showed that the radiomics nomogram was superior to the traditional diagnostic model and the radiomics model (P < 0.05) in the training data set. In the validation data set, the radiomics nomogram was superior to the traditional diagnostic model (P < 0.05), but there was no statistically significant difference compared to the radiomics model (P > 0.05). The calibration curve and the Hosmer–Lemeshow test revealed that the three models all had a great degree of fit (All P > 0.05). The results of decision curve analysis indicated that utilization of the radiomics nomogram to distinguish benign and early stage malignant ovarian tumors had a greater clinical application value when the risk threshold was 0.4–1.0.

Conclusions

The computed tomography-based radiomics nomogram could be a non-invasive and reliable imaging method to discriminate benign and early stage malignant ovarian tumors.
Bilateral upper limb robot-assisted rehabilitation improves upper limb motor function in stroke patients: a study based on quantitative EEG
Authors: Tang Congzhi , Zhou Ting , Zhang Yun , Yuan Runping , Zhao Xianghu , Yin Ruian , Song Pengfei , Liu Bo , Song Ruyan , Chen Wenli , Wang Hongxing
Published: December 2023

Background

Upper limb dysfunction after stroke seriously affects quality of life. Bilateral training has proven helpful in recovery of upper limb motor function in these patients. However, studies evaluating the effectiveness of bilateral upper limb robot-assisted training on improving motor function and quality of life in stroke patients are lacking. Quantitative electroencephalography (EEG) is non-invasive, simple, and monitors cerebral cortical activity, which can be used to evaluate the effectiveness of interventions. In this study, EEG was used to evaluate the effect of end-drive bilateral upper extremity robot-assisted training on upper extremity functional recovery in stroke patients.

Methods

24 stroke patients with hemiplegia were randomly divided into a conventional training (CT, n = 12) group or a bilateral upper limb robot-assisted training (BRT, n = 12) group. All patients received 60 min of routine rehabilitation treatment including rolling, transferring, sitting, standing, walking, etc., per day, 6 days a week, for three consecutive weeks. The BRT group added 30 min of bilateral upper limb robot-assisted training per day, while the CT group added 30 min of upper limb training (routine occupational therapy) per day, 6 days a week, for 3  weeks. The primary outcome index to evaluate upper limb motor function was the Fugl-Meyer functional score upper limb component (FMA-UE), with the secondary outcome of activities of daily living (ADL), assessed by the modified Barthel index (MBI) score. Quantitative EEG was used to evaluate functional brain connectivity as well as alpha and beta power current source densities of the brain.

Results

Significant (p < 0.05) within-group differences were found in FMA-UE and MBI scores for both groups after treatment. A between-group comparison indicated the MBI score of the BRT group was significantly different from that of the CT group, whereas the FMA-UE score was not significantly different from that of the CT group after treatment. The differences of FMA-UE and MBI scores before and after treatment in the BRT group were significantly different as compared to the CT group. In addition, beta rhythm power spectrum energy was higher in the BRT group than in the CT group after treatment. Functional connectivity in the BRT group, under alpha and beta rhythms, was significantly increased in both the bilateral frontal and limbic lobes as compared to the CT group.

Conclusions

BRT outperformed CT in improving ADL in stroke patients within three months, and BRT facilitates the recovery of upper limb function by enhancing functional connectivity of the bilateral cerebral hemispheres.
Effects of fasting hyperglycemia in men on pregnancy outcomes of singleton pregnant women with cryo-thawed embryo transfer
Authors: Yang Li , Tian Xiangming , Li Huanhuan , Sun Junjian , Zhou Wenhui
Published: December 2023

Background

The relationship of metabolic issues to pregnancy outcomes during assisted reproductive technology (ART) is gaining much attention. Fasting Plasma Glucose (FPG) is one of the most common metabolic indicators. Abnormal FPG not only affects the quality of life of human body, but also has a bearing on reproductive health. However, most attentions are paid on women's physical health and reproductive assessment, the health status of the male partner on pregnancy outcomes during ART treatment is often neglected. This study investigated whether male fasting hyperglycemia (FH, FPG > 6.1 mmol/L) can affect live birth rates (LBR) in singleton intrauterine clinical pregnancy women with cryo-thawed embryo transfer (CET) cycles.

Material and methods

A retrospective cohort study (370 CET cycles with first singleton clinical intrauterine pregnancy and grouped by male FPG) was conducted to analyze the relationship between male FH and clinical pregnancy outcomes using binary logistic regression; the odds ratios (ORs) and 95% confidence intervals (CIs) were calculated as a measure of relevancy. Live birth rate was the main outcome measure.

Results

The live birth rate (LBR) was significantly lower [58.6% vs. 81.8%, P = 0.007, adjusted OR 0.635, 95% CI 0.456–0.884] and miscarriage rate (MR) was significantly higher [41.4% vs. 18.2%, P = 0.007, adjusted OR 1.575, 95% CI 1.131–2.195] in the FH group when compared with the Con group. There was no difference in healthy baby rate [88.2% vs. 89.6%, P = 0.058, adjusted OR 2.143, 95% CI 0.974–4.716] or abnormal birth weight rate (23.5% vs. 11.8%, P = 0.238, adjusted OR 2.859, 95% CI 0.777–10.460] between the FH and control group. No birth defects were observed in the present study.

Conclusion

Male FH is an independent risk factor for lower LBR and higher MR in singleton intrauterine pregnancy women with CET cycles.
Identification of risk factors for disseminated cryptococcosis in non-hiv patients: a retrospective analysis
Authors: Zhang Fan , Zhou Yiqing , Tang Xiaoqi , Li Minghui
Published: December 2023

Objective

This study aimed to investigate the potential risk factors associated with disseminated cryptococcosis in HIV-negative individuals.

Methods

A total of 106 HIV-negative patients with cryptococcal disease were enrolled. The observation group consisted of patients with disseminated cryptococcosis (DC), whereas the control groups included patients with pulmonary cryptococcosis (PC) and cryptococcal meningitis (CM). Univariate and multivariate logistic regression algorithms were used to explore the significant clinical and laboratory characteristics that affect the progression of cryptococcal infections. Finally, receiver operating characteristics (ROC) curves are applied to assess the diagnostic value of identified risk factors.LE: Kindly check the edit made in the title.I agree

Results

Of the 106 patients, 57 were diagnosed with pulmonary cryptococcosis, 22 with cryptococcal meningitis, and 27 with disseminated cryptococcosis. The logistic regression equation included five variables: diabetes, decompensated liver cirrhosis, long-term use of immunosuppressive agents, decreased serum albumin level, and elevated plasma cytokine IL-10 level. The ROC curves showed that albumin (AUC > 0.7), IL-10 (AUC > 0.7) and decompensated liver cirrhosis (AUC > 0.6) have relatively high diagnostic capacity in predicting the progression of Cryptococcus.

Conclusion

This study identified elevated IL-10 levels as an independent risk factor for developing disseminated cryptococcosis in the control groups. Furthermore, decompensated liver cirrhosis and decreased serum albumin independently affected the progression of cryptococcosis in the CM and PC groups, respectively.
SPP1 is associated with adverse prognosis and predicts immunotherapy efficacy in penile cancer
Authors: Zou Yuantao , Tan Xingliang , Yuan Gangjun , Tang Yi , Wang Yanjun , Yang Cong , Luo Sihao , Wu Zhiming , Yao Kai
Published: December 2023

Background

The effect of SPP1 in squamous cell carcinoma of the penis (PSCC) remained unknown. We attempted to clarify the function of the SPP1 gene in PSCC.

Method

Eight paired penile cancer specimens (including penile cancer tissue, paracancerous tissue, and positive lymph node tissue) subjected to whole transcriptome sequencing were analysed to identify differentially expressed genes. We used immunohistochemistry to detect the expression of SPP1 protein and immune cell related proteins in penile cancer tissue. Then, we performed weighted gene coexpression network analysis (WGCNA) to identify the genes related to SPP1 in penile cancer tissue and positive lymph node tissue. Based on the GSE57955 dataset, the CIBERSORT and ssGSEA algorithms were carried out to investigate the immune environment of PSCC. GSVA analysis was conducted to identify the signaling pathways related to SPP1 subgroups. Enzyme-linked immunosorbent assay (ELISA) method was adopted to detect SPP1 level in the serum of 60 patients with penile cancer.

Results

Differential analysis indicated that SPP1 was the most differentially upregulated gene in both penile cancer tissues and positive lymph node tissues. Survival analysis suggested that the prognosis of the low-SPP1 group was significantly poorer than that of the high-SPP1 group. Subsequently, immune-related bioinformatics showed that SPP1 was significantly associated with B cells, CD8 + T cells, CD4 + T cells, macrophages, helper T cells, neutrophils and dendritic cells. The immunohistochemical results showed that the high-SPP1 group was characterized by relatively high expression of CD16 and relatively low expression of CD4. GSVA analysis indicated that high-SPP1 group was significantly associated with immune-related pathways such as PD-L1 expression and the PD-1 checkpoint pathway in cancer and the TNF signaling pathway. ELISA demonstrated that the serum level of SPP1 in patients with positive lymph node metastasis of penile cancer was significantly higher than that in patients with negative lymph node metastasis of penile cancer.

Conclusion

Our study shows that the SPP1 gene might be an effective biomarker for predicting the prognosis and the efficacy of immunotherapy in PSCC patients.
Pre-migratory flights in migrant songbirds: the ecological and evolutionary importance of understudied exploratory movements
Authors: Züst Zephyr , Mukhin Andrey , Taylor Philip D. , Schmaljohann Heiko
Published: December 2023

Across the animal kingdom, from honeybees to cranes to beavers, exploratory movements to exploit resources, scout prospective territories, or otherwise gain valuable experiences and information that promote fitness have been documented. For example, exploratory movements to investigate potential dispersal targets have been observed in roe deer, Northern cardinals, and tigers alike. However, despite how widespread these movements are, a cohesive definition of exploratory movements has been lacking. We first provide a clear definition of exploratory movements, and use one particular group—migratory songbirds—to catalogue exploratory movements across the annual cycle. The exceptional mobility of migratory songbirds results in exploratory movements not only at a local scale, but also on a regional scale, both in and out of the breeding season. We review the extent to which these movements are made within this group, paying particular attention to how such movements confer fitness benefits, as by securing high-quality territories, prospecting for extra-pair paternity, or even exploiting ephemeral resources. We then zoom in one step further to a particular exploratory movement that has been, to date, almost completely overlooked within this group: that of pre-migratory flights. These flights, which occur during the transitional period between the stationary breeding period and the onset of migration, occur at night and may not be made by all individuals in a population—reasons why these flights have been heretofore critically understudied. We provide the first definition for this behaviour, summarise the current knowledge of this cryptic movement, and hypothesise what evolutionary/ecological advantages conducting it may confer to the individuals that undertake it. As these flights provide experience to the individuals that undertake them, we expect that birds that make pre-migratory flights are better equipped to survive migration (direct fitness benefits) and, due to orientation/navigation abilities, may also reach preferred territories on breeding and wintering grounds faster (indirect fitness benefits). We hope to encourage ecologists to consider such hidden movements in their research concepts and to enhance the framework of movement ecology by this behaviour due to its presumed high biological importance to the annual cycle of birds.
Spatio-temporal dynamics of microglia phenotype in human and murine cSVD: impact of acute and chronic hypertensive states
Authors: Morton Lorena , Arndt Philipp , Garza Alejandra P. , Henneicke Solveig , Mattern Hendrik , Gonzalez Marilyn , Dityatev Alexander , Yilmazer-Hanke Deniz , Schreiber Stefanie , Dunay Ildiko R.
Published: December 2023

Vascular risk factors such as chronic hypertension are well-established major modifiable factors for the development of cerebral small vessel disease (cSVD). In the present study, our focus was the investigation of cSVD-related phenotypic changes in microglia in human disease and in the spontaneously hypertensive stroke-prone rat (SHRSP) model of cSVD. Our examination of cortical microglia in human post-mortem cSVD cortical tissue revealed distinct morphological microglial features specific to cSVD. We identified enlarged somata, an increase in the territory occupied by thickened microglial processes, and an expansion in the number of vascular-associated microglia. In parallel, we characterized microglia in a rodent model of hypertensive cSVD along different durations of arterial hypertension, i.e., early chronic and late chronic hypertension. Microglial somata were already enlarged in early hypertension. In contrast, at late-stage chronic hypertension, they further exhibited elongated branches, thickened processes, and a reduced ramification index, mirroring the findings in human cSVD. An unbiased multidimensional flow cytometric analysis revealed phenotypic heterogeneity among microglia cells within the hippocampus and cortex. At early-stage hypertension, hippocampal microglia exhibited upregulated CD11b/c, P2Y12R, CD200R, and CD86 surface expression. Detailed analysis of cell subpopulations revealed a unique microglial subset expressing CD11b/c, CD163, and CD86 exclusively in early hypertension. Notably, even at early-stage hypertension, microglia displayed a higher association with cerebral blood vessels. We identified several profound clusters of microglia expressing distinct marker profiles at late chronic hypertensive states. In summary, our findings demonstrate a higher vulnerability of the hippocampus, stage-specific microglial signatures based on morphological features, and cell surface protein expression in response to chronic arterial hypertension. These results indicate the diversity within microglia sub-populations and implicate the subtle involvement of microglia in cSVD pathogenesis.
Association between APOE-ε4 allele and cognitive function is mediated by Alzheimer’s disease pathology: a population-based autopsy study in an admixed sample
Authors: Paradela Regina Silva , Justo Alberto Fernando Oliveira , Paes Vítor Ribeiro , Leite Renata E. P. , Pasqualucci Carlos A. , Grinberg Lea T. , Naslavsky Michel Satya , Zatz Mayana , Nitrini Ricardo , Jacob-Filho Wilson , Suemoto Claudia Kimie
Published: December 2023

Background

Apolipoprotein E ε4 allele (APOE-ε4) is the main genetic risk factor for late-onset Alzheimer’s disease (AD) and may impact cognitive function also via other neuropathological lesions. However, there is limited evidence available from diverse populations, as APOE associations with dementia seem to differ by race. Therefore, we aimed to evaluate the pathways linking APOE-ε4 to cognitive abilities through AD and non-AD neuropathology in an autopsy study with an admixed sample.

Methods

Neuropathological lesions were evaluated following international criteria using immunohistochemistry. Participants were classified into APOE-ε4 carriers (at least one ε4 allele) and non-carriers. Cognitive abilities were evaluated by the Clinical Dementia Rating Scale sum of boxes. Mediation analyses were conducted to assess the indirect association of APOE-ε4 with cognition through AD-pathology, lacunar infarcts, hyaline arteriosclerosis, cerebral amyloid angiopathy (CAA), Lewy body disease (LBD), and TAR DNA-binding protein 43 (TDP-43).

Results

We included 648 participants (mean age 75 ± 12 years old, mean education 4.4 ± 3.7 years, 52% women, 69% White, and 28% APOE-ε4 carriers). The association between APOE-ε4 and cognitive abilities was mediated by neurofibrillary tangles (β = 0.88, 95% CI = 0.45; 1.38, p < 0.001) and neuritic plaques (β = 1.36, 95% CI = 0.86; 1.96, p < 0.001). Lacunar infarcts, hyaline arteriosclerosis, CAA, LBD, and TDP-43 were not mediators in the pathway from APOE-ε4 to cognition.

Conclusion

The association between APOE-ε4 and cognitive abilities was partially mediated by AD-pathology. On the other hand, cerebrovascular lesions and other neurodegenerative diseases did not mediate the association between APOE-ε4 and cognition.
miRNA-211 maintains metabolic homeostasis in medulloblastoma through its target gene long-chain acyl-CoA synthetase 4
Authors: Yuan Menglang , Mahmud Iqbal , Katsushima Keisuke , Joshi Kandarp , Saulnier Olivier , Pokhrel Rudramani , Lee Bongyong , Liyanage Wathsala , Kunhiraman Haritha , Stapleton Stacie , Gonzalez-Gomez Ignacio , Kannan Rangaramanujam M. , Eisemann Tanja , Kolanthai Elayaraja , Seal Sudipta , Garrett Timothy J. , Abbasi Saed , Bockley Kimberly , Hanes Justin , Chapagain Prem , Jallo George , Wechsler-Reya Robert J. , Taylor Michael D. , Eberhart Charles G. , Ray Animesh , Perera Ranjan J.
Published: December 2023

The prognosis of childhood medulloblastoma (MB) is often poor, and it usually requires aggressive therapy that adversely affects quality of life. microRNA-211 (miR-211) was previously identified as an important regulator of cells that descend from neural cells. Since medulloblastomas primarily affect cells with similar ontogeny, we investigated the role and mechanism of miR-211 in MB. Here we showed that miR-211 expression was highly downregulated in cell lines, PDXs, and clinical samples of different MB subgroups (SHH, Group 3, and Group 4) compared to normal cerebellum. miR-211 gene was ectopically expressed in transgenic cells from MB subgroups, and they were subjected to molecular and phenotypic investigations. Monoclonal cells stably expressing miR-211 were injected into the mouse cerebellum. miR-211 forced expression acts as a tumor suppressor in MB both in vitro and in vivo, attenuating growth, promoting apoptosis, and inhibiting invasion. In support of emerging regulatory roles of metabolism in various forms of cancer, we identified the acyl-CoA synthetase long-chain family member (ACSL4) as a direct miR-211 target. Furthermore, lipid nanoparticle-coated, dendrimer-coated, and cerium oxide-coated miR-211 nanoparticles were applied to deliver synthetic miR-211 into MB cell lines and cellular responses were assayed. Synthesizing nanoparticle-miR-211 conjugates can suppress MB cell viability and invasion in vitro. Our findings reveal miR-211 as a tumor suppressor and a potential therapeutic agent in MB. This proof-of-concept paves the way for further pre-clinical and clinical development.

Graphical Abstract
Profiles of pregnant women encountering motor vehicle crashes in Taiwan, 2008–2017
Authors: Chang Ya-Hui , Chien Yu-Wen , Chang Chiung-Hsin , Chen Ping-Ling , Lu Tsung-Hsueh , Chiu Chang-Ta , Li Chung-Yi
Published: December 2023

Background

Understanding demographic profiles is essential to the assessment of health burden imposed by motor vehicle crashes (MVCs) on pregnant women. However, Asian studies that have examined it are lacking. The study aimed to describe the demographic characteristics and prevalence of MVCs involving pregnant women in Taiwan.

Methods

A cross-sectional study conducted by the Taiwan Birth Notification dataset from 2008 to 2017 was linked with the police-reported traffic collision registry to identify pregnant women involved in MVCs. The pregnant women were categorized according to their gestational age, age at delivery, the role of road user (driver, passenger, or pedestrian), and vehicle types (car, two-wheeled motor vehicle, or others). A chi-square test was performed for the significance test.

Results

A total of 22,134 (1.13%) pregnant women were involved in MVCs in the study period. Two-wheeled motor vehicle (47.9%) and driver (81.4%) were the mainly reported vehicle type and road user at the crash scenes, respectively. The majority of MVCs occurred in pregnant women aged 28–34 years. The number of MVCs rapidly declined after 37 weeks of gestation, especially two-wheeled motor vehicle or car crashes. However, the number of pedestrian victims climbed up during the third trimester.

Conclusion

Pregnant women are susceptible to MVCs regardless of their gestational age, role of a road user, or type of vehicle. The findings of this study emphasize the need for increased awareness of traffic collision prevention among pregnant women aged 28–34. In addition, improving pedestrian safety is essential for the reduction of pregnant victims.
The clinical, radiological, and surgical characteristics of anterior perforated substance glioma: a retrospective study
Authors: Wang Zhiliang , Li Lianwang , Wang Zheng , Chen Xuzhu , Zhang Zhong
Published: December 2023

Background

To explore the clinical, radiological, and surgical characteristics of anterior perforated substance (APS) gliomas.

Methods

Twenty patients with APS glioma who were treated with surgery between March 2019 and January 2022 from Tiantan hospital were retrospectively reviewed. The clinical, histological and radiological data were collected.

Results

Twenty patients, including 7 males (55%) and 13 females (45%), with a mean age at diagnosis of 37.9 years (range, 28–53 years) underwent operative intervention for APS. Headaches and dizziness were the most common preoperative symptoms in the majority patients (14, 70%). Based on radiological features of MRI, the APS was classified into two subtypes, type A and type B. Seven patients (40%) in type A indicated a clear tumor margin, while 13 patients (60%) in type B showed an ill-defined margin. The surgical approach including frontal, temporal, and coronal frontal incisions for type A and type B tumors, respectively. Three patients in type A received total resection, while one patient in type B were total resected. Pathologically, 12 cases (60%, 12/20) were diagnosed as astrocytoma and 8 cases (20%, 8/20) were oligodendroglioma. Meanwhile, 17 cases (85%, 17/20) had MGMT promotor methylation.

Conclusion

In this study, we performed the first systematic research of patients with APS glioma. Most of patients with APS presented headaches and dizziness symptoms. The APS glioma was further divided into two major radiological subtypes with relevant different surgical approaches. The APS glioma in type A were more likely to receive total resection.
Utility of the low physical activity questionnaire for hemodialysis patients with frailty: a cross-sectional study
Authors: Yamabe Sachi , Yamamoto Shohei , Harada Manae , Suzuki Yuta , Imamura Keigo , Yoshikoshi Shun , Osada Shiwori , Matsunaga Atsuhiko
Published: December 2023

Background

The low physical activity questionnaire (LoPAQ), which has been developed to assess the low levels of physical activity in patients on dialysis, is so far available only in English. Moreover, no study has examined whether the LoPAQ can be used to screen for frailty in patients on hemodialysis. The purpose of this study was to translate the original LoPAQ into Japanese and evaluate its utility in screening for frailty among patients on hemodialysis.

Methods

For this cross-sectional study, we enrolled patients from two hemodialysis facilities in Japan between April 2018 and June 2019. We used the LoPAQ to calculate physical activity for one week, with pedometer steps (steps/week) as the standard reference. We used Spearman’s rank test and two multiple linear regression models to assess the relationship between the Japanese LoPAQ results and pedometer step counts. Finally, we examined whether the LoPAQ had the ability to screen for frailty (Fried scale ≥ 3) using area under the curves.

Results

In total, 220 patients on hemodialysis completed the LoPAQ and wore a pedometer for one week. Their mean age was 67.8 ± 11.6 years, and 59.1% were men. The LoPAQ showed a total physical activity of 825.0 kilocalories/week and walking activity of 315.0 kilocalories/week. The LoPAQ total physical activity and walking activity were significantly correlated with pedometer step counts (r = 0.37–0.53, P < 0.01). Furthermore, LoPAQ total physical activity and walking activity were associated with pedometer step counts despite adjusting for covariates (β: 3.33–5.45, P < 0.001, β: 8.63–16.80, P < 0.001, respectively). In addition, the LoPAQ total physical activity and walking activity showed good values in the area under the curves to identify frailty (0.72 and 0.73, respectively).

Conclusions

Physical activity assessed using the LoPAQ significantly correlated with pedometer step counts in Japanese patients on hemodialysis. Furthermore, the LoPAQ total physical activity and walking activity had a moderate screening ability for frailty. The results indicate that the LoPAQ questionnaire is useful as a physical activity assessment tool and as a screening tool for frailty in patients on hemodialysis.
A case of progressive multifocal leukoencephalopathy in a post-kidney transplant patient with improvement after discontinuation of immunosuppressive drugs and combination therapy with mefloquine and mirtazapine
Authors: Sone Neri , Nishiwaki Hiroki , Shimokawa Mayu , Kawanishi Keishu , Oshiro Tsuyoshi , Takami Reiji , Taira Natsuki , Amagasa Masahito , Omiya Shinya , Maezumi Tadahide , Nabeshima Yoko , Nakamichi Kazuo , Miura Yoshiharu , Koiwa Fumihiko
Published: December 2023

Background

Progressive multifocal leukoencephalopathy is a rare disease, but the prognosis is very poor, especially in the immunosuppressed state with a non-HIV background, and there is no established treatment.

Case presentations

A 49-year-old patient who had undergone a renal transplant and was receiving prednisolone and mycophenolate mofetil treatment was admitted for peritoneal dialysis initiation. While hospitalized, he experienced aphasia and other percutaneous symptoms. Magnetic resonance imaging of the brain revealed a subcortical demyelinating lesion. JC virus DNA was identified in cerebrospinal fluid, and he was diagnosed with progressive multifocal leukoencephalopathy. Immunosuppressant was ceased, and he was treated with mefloquine and mirtazapine. The patient subsequently underwent a head MRI scan, confirming lesion reduction, improved activities of daily life, and survival.

Conclusions

Progressive multifocal leukoencephalopathy is commonly observed in patients with compromised immune systems, which was the case for this patient due to long-standing immunosuppressive medication usage and end-stage renal failure necessitating dialysis.
Vaccine inequity: a threat to Africa’s recovery from COVID-19
Authors: Wei Calvin R. , Kamande Samuel , Lang’at Godwin C.
Published: December 2023

Background

Vaccine inequity is a reality facing the Sub-Saharan Africa region as vaccine nationalism from high-income countries (HICs) leads to limited access to the lifesaving vaccines needed to end the pandemic. In Africa, a significant portion of the population has yet to be vaccinated against Covid-19; however, the barriers to accessing such vaccines, including capacity challenges, still persist despite the implementation of the COVAX facility meant to support the lower- and middle-income countries (LMICs) to boost vaccination.

Methods

This study involved a systemic narrative review where literature search was conducted using the NCBI’s PMC and BMC databases based on defined keywords. Three authors were involved in the literature search and consensus was applied to settle disagreements and validate the findings.

Results

In this systematic narrative review, we report that vaccine nationalism remains a challenge for LMICs as HICs still hoard vaccines and even bypass COVAX to procure doses directly from the manufacturers. Factors that promote vaccine hesitancy in Africa include misinformation regarding the Covid-19 vaccine, a lack of trust in politicians and the pharmaceutical industry, and concerns about vaccine safety and efficacy. The policies implemented to enhance vaccine coverage in Africa, such as mandates, community engagement, and partnerships, all seek to promote equity of vaccination and ending Covid-19.

Conclusion

Covid-19 vaccine inequity persists and contributes to prolonged pandemic in LMICs. In response, African governments have taken certain measures to enhance vaccine uptake but more needs to be done to address resistance to vaccines.