bluuebunny/crossref_metadata_2025 huggingface dataset:
Methyl 3,4-dihydroxybenzoate alleviates oxidative damage in granulosa cells by activating Nrf2 antioxidant pathway
Authors: Li Shishi , Fan Yuhang , Shu Chongyi , Zhou Yier , Shu Jing
Published: April 2024

Oxidative damage induced granulosa cells (GCs) apoptosis was considered as a significant cause of compromised follicle quality, antioxidants therapy has emerged as a potential method for improving endometriosis pregnancy outcomes. Here, we found that GCs from endometriosis patients show increased oxidative stress level. Methyl 3,4-dihydroxybenzoate (MDHB), a small molecule compound that is extracted from natural plants, reversed tert-butyl hydroperoxide (TBHP) induced GCs oxidative damage. Therefore, the aim of this study was to assess the protective effect of MDHB for GCs and its potential mechanisms. TUNEL staining and immunoblotting of cleaved caspase-3/7/9 showed MDHB attenuated TBHP induced GCs apoptosis. Mechanistically, MDHB treatment decreased cellular and mitochondria ROS production, improved the mitochondrial function by rescuing the mitochondrial membrane potential (MMP) and ATP production. Meanwhile, MDHB protein upregulated the expression of vital antioxidant transcriptional factor Nrf2 and antioxidant enzymes SOD1, NQO1 and GCLC to inhibited oxidative stress state, further beneficial to oocytes and embryos quality. Therefore, MDHB may represent a potential drug candidate in protecting granulosa cells in endometriosis, which can improve pregnancy outcomes for endometriosis-associated infertility.
Quantitative analysis of apparent diffusion coefficients to predict neurological prognosis in cardiac arrest survivors: an observational derivation and internal–external validation study
Authors: Yoon Jung A , Kang Changshin , Park Jung Soo , You Yeonho , Min Jin Hong , In Yong Nam , Jeong Wonjoon , Ahn Hong Jun , Jeong Hye Seon , Kim Yong Hwan , Lee Byung Kook , Kim Dongha
Published: April 2024

Background

This study aimed to validate apparent diffusion coefficient (ADC) values and thresholds to predict poor neurological outcomes in out-of-hospital cardiac arrest (OHCA) survivors by quantitatively analysing the ADC values via brain magnetic resonance imaging (MRI).

Methods

This observational study used prospectively collected data from two tertiary academic hospitals. The derivation cohort comprised 70% of the patients randomly selected from one hospital, whereas the internal validation cohort comprised the remaining 30%. The external validation cohort used the data from another hospital, and the MRI data were restricted to scans conducted at 3 T within 72–96 h after an OHCA experience. We analysed the percentage of brain volume below a specific ADC value at 50-step intervals ranging from 200 to 1200 × 10–6 mm2/s, identifying thresholds that differentiate between good and poor outcomes. Poor neurological outcomes were defined as cerebral performance categories 3–5, 6 months after experiencing an OHCA.

Results

A total of 448 brain MRI scans were evaluated, including a derivation cohort (n = 224) and internal/external validation cohorts (n = 96/128, respectively). The proportion of brain volume with ADC values below 450, 500, 550, 600, and 650 × 10–6 mm2/s demonstrated good to excellent performance in predicting poor neurological outcomes in the derivation group (area under the curve [AUC] 0.89–0.91), and there were no statistically significant differences in performances among the derivation, internal validation, and external validation groups (all P > 0.5). Among these, the proportion of brain volume with an ADC below 600 × 10–6 mm2/s predicted a poor outcome with a 0% false-positive rate (FPR) and 76% (95% confidence interval [CI] 68–83) sensitivity at a threshold of > 13.2% in the derivation cohort. In both the internal and external validation cohorts, when using the same threshold, a specificity of 100% corresponded to sensitivities of 71% (95% CI 58–81) and 78% (95% CI 66–87), respectively.

Conclusions

In this validation study, by consistently restricting the MRI types and timing during quantitative analysis of ADC values in brain MRI, we observed high reproducibility and sensitivity at a 0% FPR. Prospective multicentre studies are necessary to validate these findings.
siRNA treatment targeting integrin α11 overexpressed via EZH2-driven axis inhibits drug-resistant breast cancer progression
Authors: Chaudhary Prakash , Yadav Kiran , Lee Ho Jin , Kang Keon Wook , Mo Jongseo , Kim Jung-Ae
Published: April 2024

Background

Breast cancer, the most prevalent cancer in women worldwide, faces treatment challenges due to drug resistance, posing a serious threat to patient survival. The present study aimed to identify the key molecules that drive drug resistance and aggressiveness in breast cancer cells and validate them as therapeutic targets.

Methods

Transcriptome microarray and analysis using PANTHER pathway and StemChecker were performed to identify the most significantly expressed genes in tamoxifen-resistant and adriamycin-resistant MCF-7 breast cancer cells. Clinical relevance of the key genes was determined using Kaplan-Meier survival analyses on The Cancer Genome Atlas dataset of breast cancer patients. Gene overexpression/knockdown, spheroid formation, flow cytometric analysis, chromatin immunoprecipitation, immunocytochemistry, wound healing/transwell migration assays, and cancer stem cell transcription factor activation profiling array were used to elucidate the regulatory mechanism of integrin α11 expression. Tumour-bearing xenograft models were used to demonstrate integrin α11 is a potential therapeutic target.

Results

Integrin α11 was consistently upregulated in drug-resistant breast cancer cells, and its silencing inhibited cancer stem cells (CSCs) and epithelial-mesenchymal transition (EMT) while restoring sensitivity to anticancer drugs. HIF1α, GLI-1, and EZH2 contributed the most to the regulation of integrin α11 and EZH2 expression, with EZH2 being more necessary for EZH2 autoinduction than HIF1α and GLI-1. Additionally, unlike HIF1α or EZH2, GLI-1 was the sole transcription factor activated by integrin-linked focal adhesion kinase, indicating GLI-1 as a key driver of the EZH2-integrin α11 axis operating for cancer stem cell survival and EMT. Kaplan-Meier survival analysis using The Cancer Genome Atlas (TCGA) dataset also revealed both EZH2 and integrin α11 could be strong prognostic factors of relapse-free and overall survival in breast cancer patients. However, the superior efficacy of integrin α11 siRNA therapy over EZH2 siRNA treatment was demonstrated by enhanced inhibition of tumour growth and prolonged survival in murine models bearing tumours.

Conclusion

Our findings elucidate that integrin α11 is upregulated by EZH2, forming a positive feedback circuit involving FAK-GLI-1 and contributing to drug resistance, cancer stem cell survival and EMT. Taken together, the results suggest integrin α11 as a promising prognostic marker and a powerful therapeutic target for drug-resistant breast cancer.
Identifying latent genetic interactions in genome-wide association studies using multiple traits
Authors: Bass Andrew J. , Bian Shijia , Wingo Aliza P. , Wingo Thomas S. , Cutler David J. , Epstein Michael P.
Published: April 2024

The "missing" heritability of complex traits may be partly explained by genetic variants interacting with other genes or environments that are difficult to specify, observe, and detect. We propose a new kernel-based method called Latent Interaction Testing (LIT) to screen for genetic interactions that leverages pleiotropy from multiple related traits without requiring the interacting variable to be specified or observed. Using simulated data, we demonstrate that LIT increases power to detect latent genetic interactions compared to univariate methods. We then apply LIT to obesity-related traits in the UK Biobank and detect variants with interactive effects near known obesity-related genes (URL:https://CRAN.R-project.org/package=lit).
DNA methylation of imprint control regions associated with Alzheimer’s disease in non-Hispanic Blacks and non-Hispanic Whites
Authors: Cevik Sebnem E. , Skaar David A. , Jima Dereje D. , Liu Andy J. , Østbye Truls , Whitson Heather E. , Jirtle Randy L. , Hoyo Cathrine , Planchart Antonio
Published: April 2024

Alzheimer’s disease (AD) prevalence is twice as high in non-Hispanic Blacks (NHBs) as in non-Hispanic Whites (NHWs). The objective of this study was to determine whether aberrant methylation at imprint control regions (ICRs) is associated with AD. Differentially methylated regions (DMRs) were bioinformatically identified from whole-genome bisulfite sequenced DNA derived from brain tissue of 9 AD (5 NHBs and 4 NHWs) and 8 controls (4 NHBs and 4 NHWs). We identified DMRs located within 120 regions defined as candidate ICRs in the human imprintome (https://genome.ucsc.edu/s/imprintome/hg38.AD.Brain_track). Eighty-one ICRs were differentially methylated in NHB-AD, and 27 ICRs were differentially methylated in NHW-AD, with two regions common to both populations that are proximal to the inflammasome gene, NLRP1, and a known imprinted gene, MEST/MESTIT1. These findings indicate that early developmental alterations in DNA methylation of regions regulating genomic imprinting may contribute to AD risk and that this epigenetic risk differs between NHBs and NHWs.
Postoperative delayed massive bleeding in gastric cancer: a case report
Authors: Lu Zhongting , Qin Chenhui , Zhang Mingxuan , Li Tao
Published: April 2024

Background

Postoperative delayed bleeding of gastric cancer is a complication of radical gastrectomy with low incidence rate and high mortality.

Case presentation

This case report presents the case of a 63-year-old female patient of Mongolian ethnicity who was diagnosed with gastric malignancy during a routine medical examination and underwent Billroth's I gastric resection in our department. However, on the 24th day after the surgery, she was readmitted due to sudden onset of hematemesis. Gastroscopy, abdominal CT, and digital subtraction angiography revealed postoperative anastomotic fistula, rupture of the duodenal artery, and bleeding from the abdominal aorta. The patient underwent three surgical interventions and two arterial embolizations. The patient’s condition stabilized, and she was discharged successfully.

Conclusion

Currently, there are no specific guidelines for the diagnosis and treatment of pseudoaneurysms in the abdominal cavity resulting from gastric cancer surgery. Early digital subtraction angiography examination should be performed to assist in formulating treatment plans. Early diagnosis and treatment contribute to an improved overall success rate of rescue interventions.
Synergistic effect of human uterine cervical mesenchymal stem cell secretome and paclitaxel on triple negative breast cancer
Authors: Eiro Noemi , Fraile Maria , Escudero-Cernuda Sara , Sendon-Lago Juan , Gonzalez Luis O. , Fernandez-Sánchez Maria Luisa , Vizoso Francisco J.
Published: April 2024

Background

Triple-negative breast cancer (TNBC) is the most lethal subtype of breast cancer and, despite its adverse effects, chemotherapy is the standard systemic treatment option for TNBC. Since, it is of utmost importance to consider the combination of different agents to achieve greater efficacy and curability potential, MSC secretome is a possible innovative alternative.

Methods

In the present study, we proposed to investigate the anti-tumor effect of the combination of a chemical agent (paclitaxel) with a complex biological product, secretome derived from human Uterine Cervical Stem cells (CM-hUCESC) in TNBC.

Results

The combination of paclitaxel and CM-hUCESC decreased cell proliferation and invasiveness of tumor cells and induced apoptosis in vitro (MDA-MB-231 and/or primary tumor cells). The anti-tumor effect was confirmed in a mouse tumor xenograft model showing that the combination of both products has a significant effect in reducing tumor growth. Also, pre-conditioning hUCESC with a sub-lethal dose of paclitaxel enhances the effect of its secretome and in combination with paclitaxel reduced significantly tumor growth and even allows to diminish the dose of paclitaxel in vivo. This effect is in part due to the action of extracellular vesicles (EVs) derived from CM-hUCESC and soluble factors, such as TIMP-1 and − 2.

Conclusions

In conclusion, our data demonstrate the synergistic effect of the combination of CM-hUCESC with paclitaxel on TNBC and opens an opportunity to reduce the dose of the chemotherapeutic agents, which may decrease chemotherapy-related toxicity.
Sex-dependent effects of chronic intermittent hypoxia: implication for obstructive sleep apnea
Authors: Mabry Steve , Bradshaw Jessica L. , Gardner Jennifer J. , Wilson E. Nicole , Cunningham Rebecca L.
Published: April 2024

Background

Obstructive sleep apnea (OSA) affects 10–26% of adults in the United States with known sex differences in prevalence and severity. OSA is characterized by elevated inflammation, oxidative stress (OS), and cognitive dysfunction. However, there is a paucity of data regarding the role of sex in the OSA phenotype. Prior findings suggest women exhibit different OSA phenotypes than men, which could result in under-reported OSA prevalence in women. To examine the relationship between OSA and sex, we used chronic intermittent hypoxia (CIH) to model OSA in rats. We hypothesized that CIH would produce sex-dependent phenotypes of inflammation, OS, and cognitive dysfunction, and these sex differences would be dependent on mitochondrial oxidative stress (mtOS).

Methods

Adult male and female Sprague Dawley rats were exposed to CIH or normoxia for 14 days to examine the impact of sex on CIH-associated circulating inflammation (IL-1β, IL-6, IL-10, TNF-α), circulating steroid hormones, circulating OS, and behavior (recollective and spatial memory; gross and fine motor function; anxiety-like behaviors; and compulsive behaviors). Rats were implanted with osmotic minipumps containing either a mitochondria-targeting antioxidant (MitoTEMPOL) or saline vehicle 1 week prior to CIH initiation to examine how inhibiting mtOS would affect the CIH phenotype.

Results

Sex-specific differences in CIH-induced inflammation, OS, motor function, and compulsive behavior were observed. In female rats, CIH increased inflammation (plasma IL-6 and IL-6/IL-10 ratio) and impaired fine motor function. Conversely, CIH elevated circulating OS and compulsivity in males. These sex-dependent effects of CIH were blocked by inhibiting mtOS. Interestingly, CIH impaired recollective memory in both sexes but these effects were not mediated by mtOS. No effects of CIH were observed on spatial memory, gross motor function, or anxiety-like behavior, regardless of sex.

Conclusions

Our results indicate that the impact of CIH is dependent on sex, such as an inflammatory response and OS response in females and males, respectively, that are mediated by mtOS. Interestingly, there was no effect of sex or mtOS in CIH-induced impairment of recollective memory. These results indicate that mtOS is involved in the sex differences observed in CIH, but a different mechanism underlies CIH-induced memory impairments.
Trust in public health policy in the time of the COVID-19 epidemic in Israel
Authors: Benbassat Jochanan
Published: April 2024

The government of Israel provides universal health care through four health care organizations (“sick funds”) that enjoy general public trust. In hindsight, the response of the government to the COVID-19 epidemic seems reasonable. In the first year of the epidemic, tests and vaccines were developed and other measures were taken, including social distancing, focusing on risk factors for infection and disease severity, and improving treatment. The COVID-19 mortality rate between January 2000 and June 2021 was around 750 per million inhabitants, well below the OECD average of 1300. Still, although the control measures were largely well received, the media and an ad hoc non-governmental Emergency Council for the coronavirus crisis in Israel criticized the government’s response to the epidemic thereby contributing to a decline in public trust in government policy. This commentary provides an overview of the importance of trust in medical institutions and the difficulties of evaluating healthcare decisions in an attempt to justify three conclusions. First, when physicians and self-appointed experts publicly disapprove of a government policy, they should consider the trade-off between improving care and undermining public trust. Second, when evaluating a medical decision, experts should not ask, “Would I have acted differently?” but rather, “Was the decision under review completely unreasonable?” Thirdly, criticism is certainly worth listening to. However, I believe that by calling for organized resistance against the government, the publicly announced establishment of the Emergency Council for the Corona crisis blatantly crossed the line between constructive criticism and destructive mistrust.
Gene-expression profiling of individuals resilient to Alzheimer's disease reveals higher expression of genes related to metallothionein and mitochondrial processes and no changes in the unfolded protein response
Authors: de Vries Luuk E. , Jongejan Aldo , Monteiro Fortes Jennifer , Balesar Rawien , Rozemuller Annemieke J. M. , Moerland Perry D. , Huitinga Inge , Swaab Dick F. , Verhaagen Joost
Published: April 2024

Some individuals show a discrepancy between cognition and the amount of neuropathological changes characteristic for Alzheimer’s disease (AD). This phenomenon has been referred to as ‘resilience’. The molecular and cellular underpinnings of resilience remain poorly understood. To obtain an unbiased understanding of the molecular changes underlying resilience, we investigated global changes in gene expression in the superior frontal gyrus of a cohort of cognitively and pathologically well-defined AD patients, resilient individuals and age-matched controls (n = 11–12 per group). 897 genes were significantly altered between AD and control, 1121 between resilient and control and 6 between resilient and AD. Gene set enrichment analysis (GSEA) revealed that the expression of metallothionein (MT) and of genes related to mitochondrial processes was higher in the resilient donors. Weighted gene co-expression network analysis (WGCNA) identified gene modules related to the unfolded protein response, mitochondrial processes and synaptic signaling to be differentially associated with resilience or dementia. As changes in MT, mitochondria, heat shock proteins and the unfolded protein response (UPR) were the most pronounced changes in the GSEA and/or WGCNA, immunohistochemistry was used to further validate these processes. MT was significantly increased in astrocytes in resilient individuals. A higher proportion of the mitochondrial gene MT-CO1 was detected outside the cell body versus inside the cell body in the resilient compared to the control group and there were higher levels of heat shock protein 70 (HSP70) and X-box-binding protein 1 spliced (XBP1s), two proteins related to heat shock proteins and the UPR, in the AD donors. Finally, we show evidence for putative sex-specific alterations in resilience, including gene expression differences related to autophagy in females compared to males. Taken together, these results show possible mechanisms involving MTs, mitochondrial processes and the UPR by which individuals might maintain cognition despite the presence of AD pathology.
Effect of spectacle lenses with aspherical lenslets on choroidal thickness in myopic children: a 3-year follow-up study
Authors: Huang Yingying , Li Xue , Zhuo Zuopao , Zhang Jiali , Que Tianxing , Yang Adeline , Drobe Björn , Chen Hao , Bao Jinhua
Published: April 2024

Background

To investigate the impact of wearing spectacle lenses with highly aspherical lenslets (HAL) for 3 years and the impact of switching from single-vision lenses (SVL) to HAL on choroidal thickness (ChT).

Methods

Fifty-one participants who had already worn HAL for 2 years continued wearing them for an additional year (HAL group). Further, 50 and 41 participants who had worn spectacle lenses with slightly aspherical lenslets (SAL) and SVL for 2 years, respectively, switched to wearing HAL for another year (SAL-HAL and SVL-HAL groups). Additionally, 48 new participants aged 10–15 years were enrolled to wear SVL at the third year (new-SVL group). ChT was measured every 6 months throughout the study.

Results

Significant differences were observed in the changes in ChT among the four groups at the third year (all P < 0.05 except for the outer nasal region: P = 0.09), with the new-SVL group showing larger reductions compared with the other three groups. However, none of the three HAL-wearing groups showed significant changes in ChT at the third year (all P > 0.05). When comparing the changes in ChT for 3 years among the HAL, SAL-HAL, and SVL-HAL groups, significant differences were found before switching to HAL, but these differences were abolished after all participants switched to HAL.

Conclusions

Compared to those in the SVL group, choroid thinning was significantly inhibited in all the HAL groups. Wearing HAL for 3 years no longer had a choroidal thickening effect but could still inhibit choroidal thinning compared to wearing SVL.

Trial registration

The study was registered at the Chinese Clinical Trial Registry (ChiCTR1800017683), http://www.chictr.org.cn/showproj.aspx?proj=29789.
Socioeconomic profile of families with spina bifida children in Turkey
Authors: Ay Larisa Andrada , Alataş Ibrahim , Özel Şeyhmus Kerem , Alizada Orkhan , Akkoyun Nesrin
Published: April 2024

Background

Spina bifida’s prevalence and incidence vary across geographical regions with sociodemographic characteristics and socioeconomic status of the populations having a significate influence over its epidemiology. This study aimed to outline the socioeconomic profile of families with spina bifida children, based on sociodemographic characteristics.

Methods

Between August and December 2022, 86 surveys completed by parents of children that underwent spina bifida repair in our institution were included in this analysis. The first part of the survey included questions based on sociodemographic characteristics. The second part of the survey was based on care provided by the families, regular follow-ups, participation in rehabilitation programs, and type of burdens perceived by the caregivers.

Results

A close look at the highest level of parent education showed that more than half of them were only middle school graduates. Occupational status in the perioconceptional period revealed that 77% of mothers were housewives/unemployed. 23% had a history of induced or spontaneous abortion. A high number of consanguine marriages were registered with 58% of the subjects being biologically related. 53% of the spina bifida children came from families with low household income. Only 15% of the spina bifida children had access to physiotherapy and 18% to rehabilitation programs.

Conclusions

Children with spinal dysraphism were more likely to come from families resulted from consanguineous marriages, with at least two children, low level of parent education and household income. Emotional and financial burden perceived by caregivers should be addressed in order to diminish the numerous challenges that this group of families encounter.
Autophagy-related genes in mesial temporal lobe epilepsy: an integrated bioinformatics analysis
Authors: Yang Man , Li Yinchao , Liu Xianyue , Zou Shangnan , Lei Lei , Zou Qihang , Zhang Yaqian , Fang Yubao , Chen Shuda , Zhou Liemin
Published: April 2024

Background

Autophagy plays essential roles in the development and pathogenesis of mesial temporal lobe epilepsy (mTLE). In this research, we aim to identify and validate the autophagy-related genes associated with mTLE through bioinformatics analysis and experimental validations.

Methods

We obtained the dataset GSE143272 and high-throughput sequencing results of mTLE from public databases. Potential differentially expressed autophagy-related genes related to mTLE were identified using R software. Subsequently, genomes pathway enrichment analysis, protein-protein interactions (PPIs), and the gene ontology (GO) enrichment were performed for the selected autophagy-related genes. The mRNA expression profiles of hub genes were then used to establish a least absolute shrinkage and selection operator (LASSO) model. Finally, seven hub candidate autophagy-related genes were confirmed in hippocampus using the lithium-pilocarpine chronic epilepsy model.

Results

A total of 40 differential expression genes (DEGs) among the core autophagy-related genes were identified. The analysis results of PPI revealed that interactions among these DEGs. KEGG pathway and GO analysis of selected candidate autophagy-related genes indicated that those enriched terms mainly focused on macroautophagy, regulation of autophagy, cellular response to extracellular stimulus and mitochondrion disassembly. The results suggested that SQSTM1, VEGFA, BNIP and WIPI2 were consistent with the bioinformatics analysis. The expression levels of SQSTM1 and VEGFA in epilepsy model samples were significantly higher than those in normal control, while BNIP and WIPI2 expression levels were notably decreased. The final hub gene-based LASSO regression model accurately predicted the occurrence of epilepsy (AUC = 0.88).

Conclusions

Through bioinformatics analysis of public data, we identified 40 candidate autophagy-related genes associated with mTLE. SQSTM1, VEGFA, BNIP and WIPI2 may play significant roles in autophagy, influencing the onset and development of mTLE by regulating autophagy pathway. These findings deepen our understanding of mTLE, and may serve as sensitive and valuable indicators for the prognosis and diagnosis of this condition.
The gut-liver nexus: exploring gut microbiota dysbiosis in non-alcoholic fatty liver disease and its therapeutic implications
Authors: Swamikkannu Dinesh Mohan , Dasarapu Santhosha , Siva Rajendra Prasad Velivela , Nallam Javali , Pabba Satvika
Published: April 2024

Background

The human gut microbiota (GM) is a diverse ecosystem crucial for health, impacting physiological processes across the host's body. This review highlights the GM's involvement in Non-Alcoholic Fatty Liver Disease (NAFLD) and explores its diagnosis, treatment, and management.

Main Text

The GM influences gut functionality, digestion, immunity, and more. Short-chain fatty acids (SCFAs), produced by microbial fermentation, regulate metabolism, inflammation, and immune responses. Bile acids (BAs) modulate the microbiome and liver functions, affecting NAFLD progression. Dysbiosis and increased gut permeability contribute to NAFLD through bacterial components and metabolites reaching the liver, causing inflammation and oxidative stress. The microbiome's impact on immune cells further exacerbates liver damage. Symptoms of NAFLD can be subtle or absent, making diagnosis challenging. Imaging techniques assist in diagnosing and staging NAFLD, but liver biopsy remains vital for accurate assessment. Promising treatments include FXR agonists, GLP-1 agonists, and FGF19 and FGF21 mimetics, targeting various pathways associated with NAFLD pathogenesis. Fecal Microbiota Transplantation (FMT) emerges as a potential therapeutic avenue to restore gut microbiota diversity and alleviate NAFLD. Lifestyle interventions, such as dietary modifications, exercise, and probiotics, also play a pivotal role in managing NAFLD and restoring gut health.

Conclusion

Despite significant progress, the complex interplay between the gut microbiome, NAFLD, and potential treatments necessitates further research to unravel underlying mechanisms and develop effective therapeutic strategies.
Producing focused extreme ultraviolet vortex with Fermat-spiral photon sieves
Authors: Zhang Junyong , Cui Huaiyu , Liu Yuanyuan , Zhang Xiuping , Li You , Zhao Dongdi , Zhao Yongpeng , Zhan Qiwen
Published: April 2024

Extreme ultraviolet (EUV) light is difficult to focus due to strong absorption of most materials. Photon sieves (PS), rather than Fresnel zone plates (FZP), can focus EUV to smaller spot and suppress the higher orders of secondary maxima by several orders of magnitude. The number of pinholes used in PS is far more than that of transparent rings used in FZP, providing a great flexibility to manipulate structured focusing in EUV. In this work we investigate the Fermat-spiral PS to produce focused vortices with different topological charges. Experiment at the wavelength of 46.9 nm is carried out and multi-planar coherent diffractive imaging is used to retrieve the phase map of the focused EUV vortices. These results show the enormous potential of PS for manipulating EUV light. This study not only provides a compact, affordable substitute to focusing vortices where transmissive optics materials are unavailable, but also provides a route of converting various complex light manipulation ranging from visible light to EUV and soft x-ray.
Exploring the Concordance Between High-Risk Human Papillomavirus Infections in Cervical and Oral Sites Among Females: A Cross-Sectional Study in Punjab, Pakistan
Authors: Minhas Sadia , Kashif Muhammad , Idrees Muhammad , Ansari Farheen
Published: April 2024

PURPOSE

Human papillomavirus (HPV) is widely recognized as a key contributing factor in cervical and oropharyngeal cancers. However, there has been limited research on the prevalence of concurrent HPV infections in various anatomic regions. This study aimed to investigate the prevalence and specific types of high-risk HPV (HR-HPV) infections in the cervical and oral regions of females in Punjab, Pakistan.

METHODS

We conducted a cross-sectional study involving women seeking care for general gynecologic issues at the gynecologic Outpatient Department of Lady Wallington Hospital in Lahore. After interviews and clinical examinations, we collected whole-saliva samples and high vaginal swabs from each participant. HR-HPV detection and genotyping were performed using real-time polymerase chain reaction at both the anatomic sites.

RESULTS

In this study, 170 females, averaging 35.36 ± 8.305 years, participated. HR-HPV infection was more prevalent in the cervix (83/170 [48.8%]) than in the oral cavity (19/170 [11.2%]). Concordant HPV infections occurred in 10/170 participants (5.9%). HPV 16 was the most common genotype in cervical and oral locations, at rates of 21.8% and 5.3%, respectively, among concordant HR-HPV types. Socioeconomic status ( P = .013), age at first sexual intercourse ( P = .015), and history of oral sex ( P = .01) were significantly associated with concurrent HR-HPV infection in both regions.

CONCLUSION

This study suggests that HR-HPV cervical infections may increase the risk of oral transmission, especially during orogenital sexual practices. Thus, it is important to recognize that HPV infections may be linked in both areas. We emphasize the importance of comprehensive cervical and oral examinations and HPV vaccination in young women irrespective of their sexual practices.
Interplay of synchronization and cortical input in models of brain networks
Authors: Sawicki Jakub , Schöll Eckehard
Published: April 2024

It is well known that synchronization patterns and coherence have a major role in the functioning of brain networks, both in pathological and in healthy states. In particular, in the perception of sound, one can observe an increase in coherence between the global dynamics in the network and the auditory input. In this perspective article, we show that synchronization scenarios are determined by a fine interplay between network topology, the location of the input, and frequencies of these cortical input signals. To this end, we analyze the influence of an external stimulation in a network of FitzHugh-Nagumo oscillators with empirically measured structural connectivity, and discuss different areas of cortical stimulation, including the auditory cortex.
Tuning of magnetic bistability and domain wall dynamics in magnetic microwires
Authors: Zhukov Arcady , Corte-Leon Paula , Talaat Ahmed , Blanco Juan Maria , Gonzalez Alvaro , García-Gomez Alfonso , Zhukova Valentina
Published: April 2024

A unique combination of unusual magnetic properties, such as magnetic bistability associated with ultrafast domain wall propagation or ultrasoft magnetic properties, together with excellent mechanical and corrosion properties can be obtained in amorphous microwires. Such ferromagnetic microwires coated with insulating and flexible glass-coating with diameters ranging from 0.1 to 100

can be prepared using the Taylor-Ulitovsky method. Magnetic properties of glass-coated microwires are affected by chemical compositions of the metallic nucleus and can be substantially modified by post-processing. We provide an overview of the routes allowing tuning of hysteresis loops and domain wall dynamics in amorphous microwires and new experimental results on the dependence of hysteresis loops on external stimuli, such as applied stress and temperature.
A Body Shape Index as a Simple Anthropometric Marker of Abdominal Obesity and Risk of Cardiovascular Events
Authors: Kajikawa Masato , Maruhashi Tatsuya , Kishimoto Shinji , Yamaji Takayuki , Harada Takahiro , Saito Yusuke , Mizobuchi Aya , Tanigawa Shunsuke , Nakano Yukiko , Chayama Kazuaki , Goto Chikara , Yusoff Farina Mohamad , Nakashima Ayumu , Higashi Yukihito
Published: April 2024

Context

A Body Shape Index (ABSI) has been reported to have associations with cardiovascular risk factors. However, there is no information on the association between ABSI and incidence of cardiovascular events.

Methods

We investigated the associations between ABSI and first major cardiovascular events (death from cardiovascular disease, nonfatal acute coronary syndrome, and nonfatal stroke) in 1857 subjects from the database of Flow-Mediated Dilation Japan registry and from Hiroshima University Vascular Function registry.

Results

The areas under the curves of ABSI to predict the first major cardiovascular events were superior to BMI (men: P = .032, women: P = .015) and waist circumference in women (men: P = .078, women: P = .002). The subjects were divided into 2 groups based on the cutoff value of ABSI for predicting first major cardiovascular events: a low ABSI group (<0.0822 in men and <0.0814 in women) and a high ABSI group (≥0.0822 in men and ≥0.0814 in women). During a median follow-up period of 41.6 months, 56 subjects died (23 from cardiovascular causes), 16 had nonfatal acute coronary syndrome, and 14 had nonfatal stroke. The Kaplan-Meier curves for first major cardiovascular events were significantly different between the 2 groups (men, P < .001; women, P < .001). Multivariate analysis revealed that high ABSI remained an independent predictor of first major cardiovascular events (men: hazard ratio, 2.33; 95% CI, 1.07 to 5.06; P = .033; women: hazard ratio, 8.33; 95% CI, 1.06 to 65.49; P = .044).

Conclusion

High ABSI is independently associated with incidence of cardiovascular events. ABSI calculation should be performed for evaluation of risk of cardiovascular events.
Patient-Reported Outcomes in Autosomal Dominant Osteopetrosis: Findings From the Osteopetrosis Registry Study
Authors: Polgreen Lynda E , Villa-Lopez Eva , Chen Liz , Liu Ziyue , Katz Amy , Parks-Schenck Corinne , Hart Marian , Imel Erik A , Econs Michael J
Published: April 2024

Context

Autosomal dominant osteopetrosis (ADO) is a rare sclerotic bone disease characterized by impaired osteoclast activity, resulting in high bone mineral density and skeletal fragility. The full phenotype and disease burden on patients’ daily lives has not been systematically measured.

Objective

We developed an online registry to ascertain population-based data on the spectrum and rate of progression of disease and to identify relevant patient-centered outcomes that could be used to measure treatment effects and guide the design of future clinical trials.

Methods

Cross-sectional data from participants with osteopetrosis were collected using an online REDCap-based database. Thirty-four participants with a confirmed diagnosis of ADO, aged 4-84 years were included. Participants aged 18 years and older completed the PROMIS 57, participants aged 8-17 years completed the PROMIS Pediatric 49, and parents of participants aged <18 years completed the PROMIS Parent Proxy 49.

Results

Based on the PROMIS 57, relative to the general population, adults with ADO reported low physical function and low ability to participate in social roles and activities, and high levels of anxiety, fatigue, sleep problems, and pain interference. Daily pain medications were reported by 24% of the adult population. In contrast, neither pediatric participants nor their parent proxy reported a negative impact on health-related quality of life.

Conclusion

Data from this registry demonstrate the broad spectrum of ADO disease severity and high impact on health-related quality of life in adults with ADO.
Prepubertal Children With Obesity Have High Free IGF-1 Levels and Accelerated Growth Despite Reduced Pappalysin Levels
Authors: Martín-Rivada Álvaro , Martos-Moreno Gabriel Á , Guerra-Cantera Santiago , Campillo-Calatayud Ana , Oxvig Claus , Frystyk Jan , Chowen Julie A , Barrios Vicente , Argente Jesús
Published: April 2024

Background

Prepubertal children with obesity frequently have enhanced growth, accelerated skeletal maturation, and changes in the growth hormone–insulin-like growth factor (GH–IGF) axis. However, the involvement of pappalysins (PAPP-A, PAPP-A2) and stanniocalcins (STC1, STC2) as regulators of IGF bioavailability has not been studied in obesity.

Objective

We aimed to determine the effects of childhood obesity and weight reduction on serum levels of PAPP-A, PAPP-A2, STC1, and STC2 and their relationship with IGF bioavailability, growth, and other components of the GH–IGF system.

Methods

Prepubertal children with severe obesity (150, 50% males/females, age: 7.72 ± 2.05 years, BMI z-score: 4.95 ± 1.70, height z-score: 1.28 ± 1.04) were studied at diagnosis and after a minimum of 0.5 BMI z-score reduction. Two hundred and six healthy age- and sex-matched children were used as controls.

Results

Children with obesity had decreased serum concentrations of PAPP-A, PAPP-A2 and STC2, but increased total and free IGF-I, intact IGFBP-3, acid-labile subunit (ALS), IGF-II, and insulin levels, with no difference in the free IGF-I/total IGF-I ratio. Neither the standardized body mass index (BMI) nor height correlated with any biochemical parameter analyzed. A decrease in IGF-II, insulin, and ALS with an increase in IGFBP-2 and -5, STC2, and PAPP-A were observed after weight loss.

Conclusion

Increased circulating total and free IGF-I, insulin, and IGF-II may all contribute to the increased rate of prepubertal growth and bone maturation observed in children with obesity, with STC2 possibly being involved.
BMP4 in Human Endometrial Stromal Cells Can Affect Decidualization by Regulating FOXO1 Expression
Authors: Huang Yanjie , Dai Fangfang , Chen Liping , Li Zhidian , Liu Hua , Cheng Yanxiang
Published: April 2024

Context

Recurrent spontaneous abortion (RSA) is defined as the loss of 2 or more consecutive intrauterine pregnancies with the same sexual partner in the first trimester. Despite its significance, the etiology and underlying mechanisms of RSA remain elusive. Defective decidualization is proposed as one of the potential causes of RSA, with abnormal decidualization leading to disturbances in trophoblast invasion function.

Objective

To assess the role of bone morphogenetic protein 4 (BMP4) in decidualization and RSA.

Methods

Decidual samples were collected from both RSA patients and healthy controls to assess BMP4 expression. In vitro cell experiments utilized the hESC cell line to investigate the impact of BMP4 on decidualization and associated aging, as well as its role in the maternal-fetal interface communication. Subsequently, a spontaneous abortion mouse model was established to evaluate embryo resorption rates and BMP4 expression levels.

Results

Our study identified a significant downregulation of BMP4 expression in the decidua of RSA patients compared to the normal control group. In vitro, BMP4 knockdown resulted in inadequate decidualization and inhibited associated aging processes. Mechanistically, BMP4 was implicated in the regulation of FOXO1 expression, thereby influencing decidualization and aging. Furthermore, loss of BMP4 hindered trophoblast migration and invasion via FOXO1 modulation. Additionally, BMP4 downregulation was observed in RSA mice.

Conclusion

Our findings highlighted the downregulation of BMP4 in both RSA patients and mice. BMP4 in human endometrial stromal cells was shown to modulate decidualization by regulating FOXO1 expression. Loss of BMP4 may contribute to the pathogenesis of RSA, suggesting potential avenues for abortion prevention strategies.
MCT4 and CD147 colocalize with MMP14 in invadopodia and support matrix degradation and invasion by breast cancer cells
Authors: Meng Signe , Sørensen Ester E. , Ponniah Muthulakshmi , Thorlacius-Ussing Jeppe , Crouigneau Roxane , Larsen Tanja , Borre Magnus T. , Willumsen Nicholas , Flinck Mette , Pedersen Stine F.
Published: April 2024

Expression levels of the lactate–H+ cotransporter MCT4 (also known as SLC16A3) and its chaperone CD147 (also known as basigin) are upregulated in breast cancers, correlating with decreased patient survival. Here, we test the hypothesis that MCT4 and CD147 favor breast cancer invasion through interdependent effects on extracellular matrix (ECM) degradation. MCT4 and CD147 expression and membrane localization were found to be strongly reciprocally interdependent in MDA-MB-231 breast cancer cells. Overexpression of MCT4 and/or CD147 increased, and their knockdown decreased, migration, invasion and the degradation of fluorescently labeled gelatin. Overexpression of both proteins led to increases in gelatin degradation and appearance of the matrix metalloproteinase (MMP)-generated collagen-I cleavage product reC1M, and these increases were greater than those observed upon overexpression of each protein alone, suggesting a concerted role in ECM degradation. MCT4 and CD147 colocalized with invadopodia markers at the plasma membrane. They also colocalized with MMP14 and the lysosomal marker LAMP1, as well as partially with the autophagosome marker LC3, in F-actin-decorated intracellular vesicles. We conclude that MCT4 and CD147 reciprocally regulate each other and interdependently support migration and invasiveness of MDA-MB-231 breast cancer cells. Mechanistically, this involves MCT4–CD147-dependent stimulation of ECM degradation and specifically of MMP-mediated collagen-I degradation. We suggest that the MCT4–CD147 complex is co-delivered to invadopodia with MMP14.
Host caveolin-1 facilitates Zika virus infection by promoting viral RNA replication
Authors: Zhang Qian , Zhang Yue , Jiu Yaming
Published: April 2024

Zika virus (ZIKV) has gained notoriety in recent years because there are no targeted therapies or vaccines available so far. Caveolin-1 (Cav-1) in host cells plays crucial functions in the invasion of many viruses. However, its specific involvement in ZIKV infection has remained unclear. Here, we reveal that depleting Cav-1 leads to a substantial reduction in ZIKV RNA levels, protein expression and viral particle production, indicating that ZIKV exploits Cav-1 for its infection. By dissecting each stage of the viral life cycle, we unveil that, unlike its invasion role in many other viruses, Cav-1 depletion selectively impairs ZIKV replication, resulting in altered replication dynamics and reduced strand-specific RNA levels, but does not affect viral entry, maturation and release. These results reveal an unforeseen function of Cav-1 in facilitating ZIKV replication, which provides new insights into the intricate interaction between Cav-1 and ZIKV and underscores Cav-1 as a potential candidate for anti-ZIKV approaches.
Case Report: Tongue deviation due to supranuclear injury with a rare semiological feature
Authors: Santander Maury Mayra Alejandra , Muñoz Rodriguez Sergio Andres , Camargo Camargo Loida
Published: April 2024

Abstract* Hypoglossal nerve injuries are classified according to their anatomical localization in: Infranuclear, nuclear, and supranuclear. Supranuclear injuries can occur in cerebral cortex, corticobulbar tracts, internal capsule, cerebral peduncles, or in the pons, and most often caused by a stroke. These lesions usually do not generate a significant alteration of tongue motility due to the bilateral innervation of both nuclei from the cortex. We present a case of a 43-year-old male with dysarthria, left central facial paralysis, and an important tongue palsy and deviation to the same side. Brain CT revealed a right frontotemporal stroke with little hemorrhagic transformation, and an EKG that showed auricular fibrillation. He received treatment with amiodarone and rivaroxaban was initiated when a second brain CT scan showed no evidence of hemorrhage. This case is remarkable due the unusual presentation in a supranuclear lesion of the hypoglossal nerve. It is important to enrich the semiology and consider the possibility of cortical cerebrovascular events in patients with acute deviation of the tongue, even in the absence of involvement of other cranial nerves; or marked ipsilateral motor implication.
Determinant factors of gross domestic product (GDP) in Association of Southeast Asian Nations (ASEAN) member countries
Authors: Shafrullah Faris , Indrawati Leni , Ismail Solahuddin , Ihsan Faris , Pratiwi Putri Ayu , Karno Karno
Published: April 2024

Background The gross domestic product (GDP) of Association of Southeast Asian Nations (ASEAN) member states can be used to determine their overall economic growth. In order to increase GDP, all emerging nations in Southeast Asia are stating to depend on foreign direct investment (FDI), the tourism industry, international visitors visiting ASEAN member nations banking credit, and low inflation rates. High inflation is a problem that developed and developing countries will definitely face. One of the problems faced by ASEAN member countries is that most of the member countries are in the developing country category. For ASEAN member countries, high inflation levels will encourage economic instability. GDP is less than optimal because of these classic problems in developing countries so that economic growth is not as planned. The ASEAN Economic Community (AEC), which ASEAN established, is seen as a way to reduce unemployment, alleviate poverty by boosting the travel and tourism industry and increasing investment, as well as to offer or distribute credit to businesses at low interest rates in order to boost GDP. The purpose of this study is to investigate and analyze how the GDP of ASEAN member nations is affected by FDI, foreign visitors, bank credit, and inflation. s: We analyzed panel data for seven ASEAN members from 2002 to 2020. FDI, foreign tourists, banking credit, and inflation are the research factors examined as independent variables that have an impact on GDP, the dependent variable. Results The study’s findings indicate that while inflation has a large negative impact on GDP, FDI, foreign tourism, and bank credit have a considerable positive impact on GDP. Conclusions FDI, foreign tourists, bank credit, and inflation have a significant influence on GDP in ASEAN member countries.