bluuebunny/crossref_metadata_2025 huggingface dataset:
Discordant renal progression of Fabry disease in male monozygotic twins: a case report
Authors: Lee Do-Yun , Jeong Jun-Yeong , Lee Seung-Eun , Lee Jae-Hun , Moon Ju-Young , Jung Su Woong , Lee Sang-Ho , Kim Yang Gyun
Published: June 2023

Background: Fabry disease (FD) is a rare X-linked lysosomal storage disease caused by mutations in the GLA gene that encodes α-galactosidase A (α-GAL). Clinical phenotypes tend to vary in monozygotic female twins because mutations are located on the X-chromosome, whereas similar phenotypes are found in male monozygotic twins. Here we report the case of male monozygotic twins with FD presenting with distinguishable renal phenotypes.

Case: A 49-year-old male patient who visited the hospital with proteinuria 14 years prior was readmitted for the same issue. His monozygotic twin brother had started hemodialysis 6 months prior due to renal failure of unknown origin. The patient’s renal function was within the normal range, while his spot urine protein-to-creatinine ratio was 557 mg/g. Echocardiography revealed left ventricular hypertrophy (LVH). The findings of a renal biopsy were consistent with FD. Genetic testing identified a c.656T>C mutation in the GLA gene, and α-GAL activity was significantly decreased. Genetic screening of his family clarified that his mother, older sister, twin brother, and his daughter had the same genetic mutations. The patient received enzyme replacement therapy 34 times. Subsequently, migalastat was initiated that continues today. Renal function and proteinuria remain stable, and the LVH has mildly improved.

Conclusion: This is the first case of male monozygotic twins expressing different progressions of FD. Our findings demonstrate the possibility that environmental or epigenetic factors may critically influence genotype–phenotype discordance.
Merosin-deficient congenital muscular dystrophy type 1a: detection of LAMA2 variants in Vietnamese patients
Authors: Tran Van Khanh , Nguyen Ngoc-Lan , Tran Lan Ngoc Thi , Le Phuong Thi , Tran Anh Hai , Pham Tuan L. A. , Lien Nguyen Thi Kim , Xuan Nguyen Thi , Thanh Le Tat , Ta Thanh Van , Tran Thinh Huy , Nguyen Huy-Hoang
Published: June 2023

Background: Merosin-deficient congenital muscular dystrophy type 1A (MDC1A), also known as laminin-α2 chain-deficient congenital muscular dystrophy (LAMA2-MD), is an autosomal recessive disease caused by biallelic variants in the LAMA2 gene. In MDC1A, laminin- α2 chain expression is absent or significantly reduced, leading to some early-onset clinical symptoms including severe hypotonia, muscle weakness, skeletal deformity, non-ambulation, and respiratory insufficiency.

Methods: Six patients from five unrelated Vietnamese families presenting with congenital muscular dystrophy were investigated. Targeted sequencing was performed in the five probands. Sanger sequencing was carried out in their families. Multiplex ligation-dependent probe amplification was performed in one family to examine an exon deletion.

Results: Seven variants of the LAMA2 (NM_000426) gene were identified and classified as pathogenic/likely pathogenic variants using American College of Medical Genetics and Genomics criteria. Two of these variants were not reported in the literature, including c.7156-5_7157delinsT and c.8974_8975insTGAT. Sanger sequencing indicated their parents as carriers. The mothers of family 4 and family 5 were pregnant and a prenatal testing was performed. The results showed that the fetus of the family 4 only carries c.4717 + 5G>A in the heterozygous form, while the fetus of the family 5 carries compound heterozygous variants, including a deletion of exon 3 and c.4644C>A.

Conclusion: Our findings not only identified the underlying genetic etiology for the patients, but also provided genetic counseling for the parents whenever they have an offspring.
Identification of immunity-related lncRNAs and construction of a ceRNA network of potential prognostic biomarkers in acute myeloid leukemia
Authors: Xue Jia , Chen Haoran , Lu Jinqi , Zhang Haojun , Geng Jie , He Peifeng , Lu Xuechun
Published: June 2023

Objective: Using bioinformatics analyses, this study aimed to identify lncRNAs related to the immune status of acute myeloid leukemia (AML) patients and ascertain the potential impact in immunity-related competing endogenous RNA (ceRNA) networks on AML prognosis.

Methods: AML-related RNA-seq FPKM data, AML-related miRNA expression microarray data, and gene sets associated with immunity-related pathways were, respectively, obtained from the TCGA, GEO, and ImmReg databases. An immunity-related ceRNA network was then constructed according to the predicted interactions between AML-related mRNAs, lncRNAs, and miRNAs. After performing LASSO and multivariate Cox regression analyses, lncRNAs in the ceRNA network were used to establish an AML prognostic model. According to mutual regulatory relationships and consistent trends of expression among candidate ceRNAs, two ceRNA subnetworks related to the AML prognostic model were determined. Finally, the correlation between the expression levels of mRNAs, lncRNAs, and miRNAs in each ceRNA subnetwork and immune cell infiltration (assessed by combining the ESTIMATE and CIBERSORT methods and ssGSEA) was analyzed.

Results: A total of 424 immunity-related differentially expressed (IR-DE) mRNAs (IR-DEmRNAs), 191 IR-DElncRNAs, and 69 IR-DEmiRNAs were obtained, and a ceRNA network of 20 IR-DElncRNAs, 6 IR-DEmRNAs, and 3 IR-DEmiRNAs was established. Univariate Cox regression analysis was conducted on 20 IR-DElncRNAs, and 7 of these were identified to be significantly correlated with the overall survival (OS) time in AML patients. Then, two IR-DElncRNAs (MEG3 and HCP5) were screened as independent OS-related factors by LASSO and multivariable Cox regression analyses, and a prognostic model was constructed to evaluate the survival risk in AML patients. Survival analyses indicated that the OS of patients was often poor in the high-risk group. Additionally, from this model, two ceRNA regulatory pathways, namely, MEG3/miR-125a-5p/SEMA4C and HCP5/miR-125b-5p/IL6R, which were potentially involved in the immune regulation of AML prognosis were identified.

Conclusion: lncRNAs HCP5 and MEG3 may act as key ceRNAs in the pathogenesis in AML by regulating immune cell representation as part of the regulatory lncRNA-miRNA-mRNA axes. The candidate mRNAs, lncRNAs, and miRNAs included in the ceRNA network identified here may serve as useful prognostic biomarkers and immunotherapeutic targets for AML.
Auto-scaling edge cloud for network slicing
Authors: Mazied EmadElDin A. , Nikolopoulos Dimitrios S. , Hanafy Yasser , Midkiff Scott F.
Published: June 2023

This paper presents a study on resource control for autoscaling virtual radio access networks (RAN slices) in next-generation wireless networks. The dynamic instantiation and termination of on-demand RAN slices require efficient autoscaling of computational resources at the edge. Autoscaling involves vertical scaling (VS) and horizontal scaling (HS) to adapt resource allocation based on demand variations. However, the strict processing time requirements for RAN slices pose challenges when instantiating new containers. To address this issue, we propose removing resource limits from slice configuration and leveraging the decision-making capabilities of a centralized slicing controller. We introduce a resource control agent (RC) that determines resource limits as the number of computing resources packed into containers, aiming to minimize deployment costs while maintaining processing time below a threshold. The RAN slicing workload is modeled using the Low-Density Parity Check (LDPC) decoding algorithm, known for its stochastic demands. We formulate the problem as a variant of the stochastic bin packing problem (SBPP) to satisfy the random variations in radio workload. By employing chance-constrained programming, we approach the SBPP resource control (S-RC) problem. Our numerical evaluation demonstrates that S-RC maintains the processing time requirement with a higher probability compared to configuring RAN slices with predefined limits, although it introduces a 45% overall average cost overhead.
Ferroptosis-related gene HIC1 in the prediction of the prognosis and immunotherapeutic efficacy with immunological activity
Authors: Wu Yanlin , Lin Zhengjun , Tang Xianzhe , Tong Zhongyi , Ji Yuqiao , Xu Yingting , Zhou Ziting , Yang Jing , Li Zhihong , Liu Tang
Published: June 2023

Background

Hypermethylated in Cancer 1 (HIC1) was originally confirmed as a tumor suppressor and has been found to be hypermethylated in human cancers. Although growing evidence has supported the critical roles of HIC1 in cancer initiation and development, its roles in tumor immune microenvironment and immunotherapy are still unclear, and no comprehensive pan-cancer analysis of HIC1 has been conducted.

Methods

HIC1 expression in pan-cancer, and differential HIC1 expression between tumor and normal samples were investigated. Immunohistochemistry (IHC) was employed to validate HIC1 expression in different cancers by our clinical cohorts, including lung cancer, sarcoma (SARC), breast cancer, and kidney renal clear cell carcinoma (KIRC). The prognostic value of HIC1 was illustrated by Kaplan-Meier curves and univariate Cox analysis, followed by the genetic alteration analysis of HIC1 in pan-cancer. Gene Set Enrichment Analysis (GSEA) was conducted to illustrate the signaling pathways and biological functions of HIC1. The correlations between HIC1 and tumor mutation burden (TMB), microsatellite instability (MSI), and the immunotherapy efficacy of PD-1/PD-L1 inhibitors were analyzed by Spearman correlation analysis. Drug sensitivity analysis of HIC1 was performed by extracting data from the CellMiner™ database.

Results

HIC1 expression was abnormally expressed in most cancers, and remarkable associations between HIC1 expression and prognostic outcomes of patients in pan-cancer were detected. HIC1 was significantly correlated with T cells, macrophages, and mast cell infiltration in different cancers. Moreover, GSEA revealed that HIC1 was significantly involved in immune-related biological functions and signaling pathways. There was a close relationship of HIC1 with TMB and MSI in different cancers. Furthermore, the most exciting finding was that HIC1 expression was significantly correlated with the response to PD-1/PD-L1 inhibitors in cancer treatment. We also found that HIC1 was significantly correlated with the sensitivity of several anti-cancer drugs, such as axitinib, batracylin, and nelarabine. Finally, our clinical cohorts further validated the expression pattern of HIC1 in cancers.

Conclusions

Our investigation provided an integrative understanding of the clinicopathological significance and functional roles of HIC1 in pan-cancer. Our findings suggested that HIC1 can function as a potential biomarker for predicting the prognosis, immunotherapy efficacy, and drug sensitivity with immunological activity in cancers.
Cancer/testis antigens: promising immunotherapy targets for digestive tract cancers
Authors: Ai Huihan , Yang Hang , Li Liang , Ma Jie , Liu Kangdong , Li Zhi
Published: June 2023

Digestive tract cancers, including esophageal, gastric, and colorectal cancers, are the major cause of death among cancer patients worldwide due to the heterogeneity of cancer cells, which limits the effectiveness of traditional treatment methods. Immunotherapy represents a promising treatment strategy for improving the prognosis of patients with digestive tract cancers. However, the clinical application of this approach is limited by the absence of optimal targets. Cancer/testis antigens are characterized by low or absent expression in normal tissues, but high expression in tumor tissues, making them an attractive target for antitumor immunotherapy. Recent preclinical trials have shown promising results for cancer/testis antigen-targeted immunotherapy in digestive cancer. However, practical problems and difficulties in clinical application remain. This review presents a comprehensive analysis of cancer/testis antigens in digestive tract cancers, covering their expression, function, and potential as an immunotherapy target. Additionally, the current state of cancer/testis antigens in digestive tract cancer immunotherapy is discussed, and we predict that these antigens hold great promise as an avenue for breakthroughs in the treatment of digestive tract cancers.
Alveolar macrophages in pulmonary alveolar proteinosis: origin, function, and therapeutic strategies
Authors: Huang Xinmei , Cao Mengshu , Xiao Yonglong
Published: June 2023

Pulmonary alveolar proteinosis (PAP) is a rare pulmonary disorder that is characterized by the abnormal accumulation of surfactant within the alveoli. Alveolar macrophages (AMs) have been identified as playing a pivotal role in the pathogenesis of PAP. In most of PAP cases, the disease is triggered by impaired cholesterol clearance in AMs that depend on granulocyte-macrophage colony-stimulating factor (GM-CSF), resulting in defective alveolar surfactant clearance and disruption of pulmonary homeostasis. Currently, novel pathogenesis-based therapies are being developed that target the GM-CSF signaling, cholesterol homeostasis, and immune modulation of AMs. In this review, we summarize the origin and functional role of AMs in PAP, as well as the latest therapeutic strategies aimed at addressing this disease. Our goal is to provide new perspectives and insights into the pathogenesis of PAP, and thereby identify promising new treatments for this disease.
Strategies to reinvigorate exhausted CD8+ T cells in tumor microenvironment
Authors: Guan Qianting , Han Meiwen , Guo Qinghao , Yan Fangfei , Wang Ming , Ning Qin , Xi Dong
Published: June 2023

CD8+ T cell exhaustion is a stable dysfunctional state driven by chronic antigen stimulation in the tumor microenvironment (TME). Differentiation of exhausted CD8+ T cells (CD8+ TEXs) is accompanied by extensive transcriptional, epigenetic and metabolic reprogramming. CD8+ TEXs are mainly characterized by impaired proliferative and cytotoxic capacity as well as the increased expression of multiple co-inhibitory receptors. Preclinical tumor studies and clinical cohorts have demonstrated that T cell exhaustion is firmly associated with poor clinical outcomes in a variety of cancers. More importantly, CD8+ TEXs are regarded as the main responder to immune checkpoint blockade (ICB). However, to date, a large number of cancer patients have failed to achieve durable responses after ICB. Therefore, improving CD8+ TEXs may be a breakthrough point to reverse the current dilemma of cancer immunotherapy and eliminate cancers. Strategies to reinvigorate CD8+ TEXs in TME mainly include ICB, transcription factor-based therapy, epigenetic therapy, metabolism-based therapy and cytokine therapy, which target on different aspects of exhaustion progression. Each of them has its advantages and application scope. In this review, we mainly focus on the major advances of current strategies to reinvigorate CD8+ TEXs in TME. We summarize their efficacy and mechanisms, identify the promising monotherapy and combined therapy and propose suggestions to enhance the treatment efficacy to significantly boost anti-tumor immunity and achieve better clinical outcomes.
Comparison of C-reactive protein with distinct hyperinflammatory biomarkers in association with COVID-19 severity, mortality and SARS-CoV-2 variants
Authors: Paranga Tudorita Gabriela , Pavel-Tanasa Mariana , Constantinescu Daniela , Plesca Claudia Elena , Petrovici Cristina , Miftode Ionela-Larisa , Moscalu Mihaela , Cianga Petru , Miftode Egidia Gabriela
Published: June 2023

C-reactive protein (CRP) has been one of the most investigated inflammatory-biomarkers during the ongoing COVID-19 pandemics caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The severe outcome among patients with SARS-CoV-2 infection is closely related to the cytokine storm and the hyperinflammation responsible for the acute respiratory distress syndrome and multiple organ failure. It still remains a challenge to determine which of the hyperinflammatory biomarkers and cytokines are the best predictors for disease severity and mortality in COVID-19 patients. Therefore, we evaluated and compared the outcome prediction efficiencies between CRP, the recently reported inflammatory modulators (suPAR, sTREM-1, HGF), and the classical biomarkers (MCP-1, IL-1β, IL-6, NLR, PLR, ESR, ferritin, fibrinogen, and LDH) in patients confirmed with SARS-CoV-2 infection at hospital admission. Notably, patients with severe disease had higher serum levels of CRP, suPAR, sTREM-1, HGF and classical biomarkers compared to the mild and moderate cases. Our data also identified CRP, among all investigated analytes, to best discriminate between severe and non-severe forms of disease, while LDH, sTREM-1 and HGF proved to be excellent mortality predictors in COVID-19 patients. Importantly, suPAR emerged as a key molecule in characterizing the Delta variant infections.
Energy allocation trade-offs as a function of age in fungiid corals
Authors: Grinblat Mila , Eyal-Shaham Lee , Eyal Gal , Ben-Zvi Or , Harii Saki , Morita Masaya , Sakai Kazuhiko , Hirose Mamiko , Miller David J. , Loya Yossi
Published: June 2023

To compete effectively, living organisms must adjust the allocation of available energy resources for growth, survival, maintenance, and reproduction throughout their life histories. Energy demands and allocations change throughout the life history of an organism, and understanding their energy allocation strategies requires determination of the relative age of individuals. As most scleractinian corals are colonial, the relationship between age and mass/size is complicated by colony fragmentation, partial mortality, and asexual reproduction. To overcome these limitations, solitary mushroom corals, Herpolitha limax from Okinawa, Japan and Fungia fungites from Okinawa and the Great Barrier Reef (GBR), Australia, were used to investigate how energy allocation between these fundamental processes varies as a function of age. Measurements of the relative growth, biochemical profiles, fecundity of individuals of different sizes, and the settlement success of their progeny have revealed physiological trade-offs between growth and reproduction, with increasing body mass ultimately leading to senescence. The importance of energy allocation for reproduction led us to examine the reproductive strategies and sex allocation in the two studied species. In the present study, the smallest individuals of both species studied were found to invest most of their energy in relative growth, showing higher lipid and carbohydrate content than the later stages. In medium-sized corals, this pattern was overturned in favour of reproduction, manifesting in terms of both the highest fecundity and settlement success of the resulting brooded larvae. Finally, a phase of apparent senescence was observed in the largest individuals, characterized by a decrease in most of the parameters measured. In addition, complex reproductive plasticity has been revealed in F. fungites in the GBR, with individual females releasing eggs, embryos, planulae, or a combination of these. These data provide the most direct estimates currently available for physiological, age-related trade-offs during the life history of a coral. The unusual reproductive characteristics of the GBR F. fungites indicate previously unknown layers of complexity in the reproductive biology of corals and have implications for their adaptive potential across a wide geographical scale.
Tools for faculty assessment of interdisciplinary competencies of healthcare students: an integrative review
Authors: Brownie Sharon , Blanchard Denise , Amankwaa Isaac , Broman Patrick , Haggie Marrin , Logan Carlee , Pearce Amy , Sampath Kesava , Yan Ann-Rong , Andersen Patrea
Published: June 2023

Increasingly, interprofessional teamwork is required for the effective delivery of public health services in primary healthcare settings. Interprofessional competencies should therefore be incorporated within all health and social service education programs. Educational innovation in the development of student-led clinics (SLC) provides a unique opportunity to assess and develop such competencies. However, a suitable assessment tool is needed to appropriately assess student progression and the successful acquisition of competencies. This study adopts an integrative review methodology to locate and review existing tools utilized by teaching faculty in the assessment of interprofessional competencies in pre-licensure healthcare students. A limited number of suitable assessment tools have been reported in the literature, as highlighted by the small number of studies included. Findings identify use of existing scales such as the Interprofessional Socialization and Valuing Scale (ISVS) and the McMaster Ottawa Scale with Team Observed Structured Clinical Encounter (TOSCE) tools plus a range of other approaches, including qualitative interviews and escape rooms. Further research and consensus are needed for the development of teaching and assessment tools appropriate for healthcare students. This is particularly important in the context of interprofessional, community-partnered public health and primary healthcare SLC learning but will be of relevance to health students in a broad range of clinical learning contexts.
Umbilical artery thrombosis and maternal positive autoimmune antibodies: two case reports and a literature review
Authors: Li Xin , Chen Wei , Liu Tianjiao , Cai Jian , Wei Sumei , Du Yuhua , Liu Chunyan , Gong Zhaolin , Cheng Linbo , Zhou Xiaoling , Xiong Min , Wang Tao , Li Yalan , Yang Xiao , Lai Fan
Published: June 2023

Background

Previous studies have shown that abnormal increases in autoimmune antibodies in pregnant women may increase the risk of maternal thrombosis. However, at our hospital, two pregnant women presented with umbilical artery thrombosis and positive maternal autoantibodies were detected in both, which led us to consider whether maternal autoantibodies also played a role in umbilical artery thrombosis.

Case presentation

Case 1: Fetal ultrasound of a 34-year-old pregnant woman at 30+4 weeks gestation showed two umbilical arteries, with an inner diameter of approximately 0.15 cm for the smaller was artery. However, only a single umbilical artery blood flow signal was detected. Due to fetal distress, which was noted on abnormal cardiotocography and Doppler ultrasound, an emergency cesarean section was performed at 31+1 weeks gestation. The Apgar score of the newborn was 3-8-8. Umbilical cord examination detected thrombosis in the two umbilical arteries. Moreover, blood test results during pregnancy showed nRNP/Sm antibody (+) and SS antibody (+++). Case 2: The first systematic ultrasound of a 33-year-old twin pregnancy at 24+3 weeks gestation was normal, but routine fetal ultrasound at 27+1 weeks gestation showed only one umbilical artery between fetus A and the placenta. Blood test results showed that the patient was anti-nRNP/Sm antibody (+) in the rheumatoid immune activity test at 27+3 weeks gestation. An emergency cesarean section was performed at 34+6 weeks gestation because of the single umbilical artery and abnormal maternal coagulation. Both umbilical cords of fetus A and B blood test results showed anti-nRNP/Sm antibody (++). The pathological examination of the umbilical cord and placenta showed the presence of old thrombosis in one of the umbilical arteries of fetus A.

Conclusions

Abnormal maternal autoantibodies may be a risk factor for umbilical artery thrombosis. For these pregnant women, conducting more detailed ultrasound monitoring might get early detection of UAT formation and avoid the occurrence of adverse pregnancy outcomes.
The relationship between the PICC tip position and weight gain, length growth of premature infants under ultrasonography: a correlation analysis study
Authors: Tao Xiaojun , Zhang Xianhong , Wang Jianhui , Chen Yanhan , Liu Xuexiu
Published: June 2023

Objective

This study aimed to analyze the correlation between PICC tip position and weight/length changes in preterm infants in different positions using ultrasonography.

Methods

The study is a prospective before and after self-control clinical trial. The study analyzed the distance between the PICC tip and the entrance of the heart under ultrasonography for premature infants who underwent PICC insertion. The infants were positioned and tracked weekly, and their weight and length were recorded. The Spearman rank correlation test was used to analyze the relationship between the displacement distance of the PICC tip under ultrasonography in different positions and weight/length changes.

Results

A total of 202 premature infants were included in the study, and 100% of them experienced changes in the PICC tip position. During the first week, 134 (66.33%) cases in a flexed position and 153 (75.74%) cases in a straight position showed displacement of the catheter toward the heart. The displacement distance of the tip during catheter retention was significantly correlated with weight change (rs = 0.681/0.661, P < 0.05) and length change (rs = 0.629/0.617, P < 0.05). In the third and fifth weeks, weight increased by 451 ± 178 and 750 (715–975) g, length increased by 1.50 (1.00–2.12) and 3.00 (2.00–3.70) cm, the catheter moved 1.27 ± 0.89 and 2.23 ± 0.95 cm, respectively, in a flexed position.

Conclusion

The PICC tip position in preterm infants is influenced by weight and length changes. It is crucial to use ultrasonography to track and locate the catheter within the first week of placement and to increase the frequency of catheter localization starting from the third and fifth weeks. The flexed position is recommended during catheter localization.
Soil nutrients, enzyme activities, and bacterial communities in varied plant communities in karst rocky desertification regions in Wushan County, Southwest China
Authors: Gao Lan , Wang Weihan , Liao Xingyu , Tan Xing , Yue Jiaxing , Zhang Wen , Wu Jiaojiao , Willison J. H. Martin , Tian Qiuling , Liu Yun
Published: June 2023

Vegetation restoration has become a common practice in karst rocky desertification (KRD) areas of southwestern China. The bacteria, which have made a connection between soil and plants, have been an important role in regulating the succession and restoration of karst vegetation. However, it is still unclear how soil bacterial communities and soil properties respond to natural vegetation restoration processes in karst areas. To address this gap, we investigated the soil nutrients, enzyme activity, and soil bacterial community among various plant communities, including farmland (FL), land with herbs only (SSI), herb-and-shrub land (SSII), woody thickets (SSIII), coniferous forest (SSIV), coniferous and broad-leaved mixed forest (SSV), and evergreen broad-leaved forest (SSVI). Our results found that SSII had the highest levels of soil organic matter, total nitrogen, available phosphorus, available nitrogen, sucrase, and β-glucosidase among all the plant communities. These results indicated that herb-and-shrub land have contributed to the rapid restoration of vegetation in KRD regions. FL exhibited the lowest levels of soil nutrients and enzyme activities, while showing the highest bacterial richness and diversity among all the plant communities. This suggested that appropriate human intervention can increase bacterial diversity and richness in the area. The predominant bacterial phylum also varied among the different plant communities, withActinobacteriabeing the most abundant in SSI, SSII, SSIII, and SSIV, whileProteobacteriawere the most abundant in SSV and SSVI. Furthermore, PCoA analysis demonstrated significant changes in the soil bacterial community structure, with SSI, SSII, SSIII, and SSIV had shared similar structures, while SSV and SSVI had comparable structures. As for soil characteristics, total phosphorus (TP) and total potassium (TK) were the primary factors affecting the soil bacterial community. SSV and SSVI had the most complex bacterial networks and were more stable than other groups. The generaKtedonobacter,norank_f_Anaerolineaceae, andVicinamibacterhad the highest betweenness centrality scores and were identified as keystone genera in the co-occurrence network in KRD areas. In summary, our results have demonstrated that herb-and-shrub can promote community succession and increase soil nutrient levels in KRD regions.
Response of the soil microbial community to petroleum hydrocarbon stress shows a threshold effect: research on aged realistic contaminated fields
Authors: Jia Wenjuan , Cheng Lirong , Tan Qiuyang , Liu Yueqiao , Dou Junfeng , Yang Kai , Yang Qing , Wang Senjie , Li Jing , Niu Geng , Zheng Lei , Ding Aizhong
Published: June 2023

Introduction

Microbes play key roles in maintaining soil ecological functions. Petroleum hydrocarbon contamination is expected to affect microbial ecological characteristics and the ecological services they provide. In this study, the multifunctionalities of contaminated and uncontaminated soils in an aged petroleum hydrocarbon-contaminated field and their correlation with soil microbial characteristics were analyzed to explore the effect of petroleum hydrocarbons on soil microbes.

Methods

Soil physicochemical parameters were determined to calculate soil multifunctionalities. In addition, 16S high-throughput sequencing technology and bioinformation analysis were used to explore microbial characteristics.

Results

The results indicated that high concentrations of petroleum hydrocarbons (565–3,613 mg•kg−1, high contamination) reduced soil multifunctionality, while low concentrations of petroleum hydrocarbons (13–408 mg•kg−1, light contamination) might increase soil multifunctionality. In addition, light petroleum hydrocarbon contamination increased the richness and evenness of microbial community (p < 0.01), enhanced the microbial interactions and widened the niche breadth of keystone genus, while high petroleum hydrocarbon contamination reduced the richness of the microbial community (p < 0.05), simplified the microbial co-occurrence network, and increased the niche overlap of keystone genus.

Conclusion

Our study demonstrates that light petroleum hydrocarbon contamination has a certain improvement effect on soil multifunctionalities and microbial characteristics. While high contamination shows an inhibitory effect on soil multifunctionalities and microbial characteristics, which has significance for the protection and management of petroleum hydrocarbon-contaminated soil.
Development of a targeted amplicon sequencing method for genotyping Cyclospora cayetanensis from fresh produce and clinical samples with enhanced genomic resolution and sensitivity
Authors: Leonard Susan R. , Mammel Mark K. , Gharizadeh Baback , Almeria Sonia , Ma Zhihai , Lipman David J. , Torrence Mary E. , Wang Chunlin , Musser Steven M.
Published: June 2023

Outbreaks of cyclosporiasis, an enteric illness caused by the parasiteCyclospora cayetanensis, have been associated with consumption of various types of fresh produce. Although a method is in use for genotypingC. cayetanensisfrom clinical specimens, the very low abundance ofC. cayetanensisin food and environmental samples presents a greater challenge. To complement epidemiological investigations, a molecular surveillance tool is needed for use in genetic linkage of food vehicles to cyclosporiasis illnesses, estimation of the scope of outbreaks or clusters of illness, and determination of geographical areas involved. We developed a targeted amplicon sequencing (TAS) assay that incorporates a further enrichment step to gain the requisite sensitivity for genotypingC. cayetanensiscontaminating fresh produce samples. The TAS assay targets 52 loci, 49 of which are located in the nuclear genome, and encompasses 396 currently known SNP sites. The performance of the TAS assay was evaluated using lettuce, basil, cilantro, salad mix, and blackberries inoculated withC. cayetanensisoocysts. A minimum of 24 markers were haplotyped even at low contamination levels of 10 oocysts in 25 g leafy greens. The artificially contaminated fresh produce samples were included in a genetic distance analysis based on haplotype presence/absence with publicly availableC. cayetanensiswhole genome sequence assemblies. Oocysts from two different sources were used for inoculation, and samples receiving the same oocyst preparation clustered together, but separately from the other group, demonstrating the utility of the assay for genetically linking samples. Clinical fecal samples with low parasite loads were also successfully genotyped. This work represents a significant advance in the ability to genotypeC. cayetanensiscontaminating fresh produce along with greatly expanding the genomic diversity included for genetic clustering of clinical specimens.
Engraving of stainless-steel wires to improve optical quality of closed-loop wire-guided flow jet systems for optical and X-ray spectroscopy
Authors: Picchiotti Alessandra , Precek Martin , Zymaková Anna , Erichlandwehr Tim , Liu Yingliang , Wiste Tuomas , Kahan Petr , Fernandez-Cuesta Irene , Andreasson Jakob
Published: June 2023

This paper describes performance enhancement developments to a closed-loop pump-driven wire-guided flow jet (WGJ) for ultrafast X-ray spectroscopy of liquid samples. Achievements include dramatically improved sample surface quality and reduced equipment footprint from 7 × 20 cm2 to 6 × 6 cm2, cost, and manufacturing time. Qualitative and quantitative measurements show that micro-scale wire surface modification yields significant improvements to the topography of the sample liquid surface. By manipulating their wettability, it is possible to better control the liquid sheet thickness and to obtain a smooth liquid sample surface, as demonstrated in this work.
The Oncolytic herpes simplex virus type-1 (HSV-1) vaccine strain VC2 causes intratumor infiltration of functionally active T cells and inhibition of tumor metastasis and pro-tumor genes VEGF and PDL1 expression in the 4T1/Balb/c mouse model of stage four breast cancer
Authors: Nabi Rafiq , Musarrat Farhana , Menk P. Lima Jose Cesar , Langohr Ingeborg M. , Chouljenko Vladimir N. , Kousoulas Konstantin G.
Published: June 2023

Introduction: Oncolytic viruses (OVs) provide new modalities for cancer therapy either alone or in combination with synergistic immunotherapies and/or chemotherapeutics. Engineered Herpes Simplex Virus Type-1 (HSV-1) has shown strong promise for the treatment of various cancers in experimental animal models as well as in human patients, with some virus strains licensed to treat human melanoma and gliomas. In the present study we evaluated the efficacy of mutant HSV-1 (VC2) in a late stage, highly metastatic 4T1 murine syngeneic.

Method: VC2 was constructed VC2 using double red recombination technology. For in-vivo efficacy we utilized a late stage 4T1 syngeneic and immunocompetent BALB/cJ mouse model breast cancer model which exhibits efficient metastasis to the lung and other organs.

Results: VC2 replicated efficiently in 4T1 cells and in cell culture, achieving titers similar to those in African monkey kidney (Vero) cells. Intra-tumor treatment with VC2 did not appreciably reduce average primary tumor sizes but a significant reduction of lung metastasis was noted in mice treated intratumorally with VC2, but not with ultraviolet-inactivated VC2. This reduction of metastasis was associated with increased T cell infiltration comprised of CD4+ and CD4+CD8+ double-positive T cells. Characterization of purified tumor infiltrating T cells revealed a significant improvement in their proliferation ability compared to controls. In addition, significant T cell infiltration was observed in the metastatic nodules associated with reduction of pro-tumor PD-L1 and VEGF gene transcription.

Conclusion: These results show that VC2 therapy can improve anti-tumor response associated with a better control of tumor metastasis. improve T cell responses and reduce pro-tumor biomarker gene transcription. VC2 holds promise for further development as an oncolytic and immunotherapeutic approach to treat breast and other cancers.
White matter changes in fetal brains with ventriculomegaly
Authors: Horgos Bianca , Mecea Miruna , Boer Armand , Buruiana Andrei , Ciortea Razvan , Mihu Carmen-Mihaela , Florian Ioan Stefan , Florian Alexandru Ioan , Stamatian Florin , Szabo Bianca , Albu Camelia , Susman Sergiu , Pascalau Raluca
Published: June 2023

Introduction

Ventriculomegaly (VM) is a fetal brain malformation which may present independently (isolated form) or in association with different cerebral malformations, genetic syndromes or other pathologies (non-isolated form).

Methods

This paper aims to study the effect of ventriculomegaly on the internal tridimensional architecture of fetal brains by way of Klingler's dissection. Ventriculomegaly was diagnosed using fetal ultrasonography during pregnancy and subsequently confirmed by necropsy. Taking into consideration the diameter of the lateral ventricle (measured at the level of the atrium), the brains were divided into two groups: moderate ventriculomegaly (with atrial diameter between 13 and 15 mm) and severe ventriculomegaly (with atrial diameter above 15 mm).

Results and discussion

The results of each dissection were described and illustrated, then compared with age-matched reference brains. In the pathological brains, fascicles in direct contact with the enlarged ventricles were found to be thinner and displaced inferiorly, the opening of the uncinate fasciculus was wider, the fornix was no longer in contact with the corpus callosum and the convexity of the corpus callosum was inverted. We have studied the prevalence of neurodevelopmental delay in children born with ventriculomegaly in the literature and discovered that a normal developmental outcome was found in over 90% of the mild VM cases, approximately 75% of the moderate and 60% in severe VM, with the correlated neurological impairments ranging from attention deficits to psychiatric disorders.
In search of a composite biomarker for chronic pain by way of EEG and machine learning: where do we currently stand?
Authors: Rockholt Mika M. , Kenefati George , Doan Lisa V. , Chen Zhe Sage , Wang Jing
Published: June 2023

Machine learning is becoming an increasingly common component of routine data analyses in clinical research. The past decade in pain research has witnessed great advances in human neuroimaging and machine learning. With each finding, the pain research community takes one step closer to uncovering fundamental mechanisms underlying chronic pain and at the same time proposing neurophysiological biomarkers. However, it remains challenging to fully understand chronic pain due to its multidimensional representations within the brain. By utilizing cost-effective and non-invasive imaging techniques such as electroencephalography (EEG) and analyzing the resulting data with advanced analytic methods, we have the opportunity to better understand and identify specific neural mechanisms associated with the processing and perception of chronic pain. This narrative literature review summarizes studies from the last decade describing the utility of EEG as a potential biomarker for chronic pain by synergizing clinical and computational perspectives.
An integrated full-head OPM-MEG system based on 128 zero-field sensors
Authors: Alem Orang , Hughes K. Jeramy , Buard Isabelle , Cheung Teresa P. , Maydew Tyler , Griesshammer Andreas , Holloway Kendall , Park Aaron , Lechuga Vanessa , Coolidge Collin , Gerginov Marja , Quigg Erik , Seames Alexander , Kronberg Eugene , Teale Peter , Knappe Svenja
Published: June 2023

Compact optically-pumped magnetometers (OPMs) are now commercially available with noise floors reaching 10 fT/Hz1/2. However, to be used effectively for magnetoencephalography (MEG), dense arrays of these sensors are required to operate as an integrated turn-key system. In this study, we present the HEDscan, a 128-sensor OPM MEG system by FieldLine Medical, and evaluate its sensor performance with regard to bandwidth, linearity, and crosstalk. We report results from cross-validation studies with conventional cryogenic MEG, the Magnes 3,600 WH Biomagnetometer by 4-D Neuroimaging. Our results show high signal amplitudes captured by the OPM-MEG system during a standard auditory paradigm, where short tones at 1000 Hz were presented to the left ear of six healthy adult volunteers. We validate these findings through an event-related beamformer analysis, which is in line with existing literature results.
Insects as food and medicine: a sustainable solution for global health and environmental challenges
Authors: Aidoo Owusu Fordjour , Osei-Owusu Jonathan , Asante Kwasi , Dofuor Aboagye Kwarteng , Boateng Belinda Obenewa , Debrah Shadrack Kwaku , Ninsin Kodwo Dadzie , Siddiqui Shahida Anusha , Chia Shaphan Yong
Published: June 2023

Insects are a significant source of food for millions of people worldwide. Since ancient times, insects in medicine have been contributing to the treatment of diseases in humans and animals. Compared to conventional animal farming, the production of insects for food and feed generates significantly less greenhouse gas emissions and uses considerably less land. Edible insects provide many ecosystem services, including pollination, environmental health monitoring, and the decomposition of organic waste materials. Some wild edible insects are pests of cash crops. Thus, harvesting and consuming edible insect pests as food and utilizing them for therapeutic purposes could be a significant progress in the biological control of insect pests. Our review discusses the contribution of edible insects to food and nutritional security. It highlights therapeutic uses of insects and recommends ways to ensure a sustainable insect diet. We stress that the design and implementation of guidelines for producing, harvesting, processing, and consuming edible insects must be prioritized to ensure safe and sustainable use.
Risk assessment of dietary factors in global pattern of ischemic heart disease mortality and disability-adjusted life years over 30 years
Authors: Wang Fang , Mubarik Sumaira , Zhang Yu , Shi Wenqi , Yu Chuanhua
Published: June 2023

Objectives

The aim of this study was to investigate differences in the burden of ischemic heart disease (IHD)-related mortality and disability-adjusted life years (DALYs) caused by dietary factors, as well as the influencing factors with age, period, and cohort effects, in regions with different social-demographic status from 1990 to 2019.

Methods

We extracted data on IHD mortality, DALYs, and age-standardized rates (ASRs) related to dietary risks from 1990 to 2019 as IHD burden measures. Hierarchical age–period–cohort analysis was used to analyze age- and time-related trends and the interaction between different dietary factors on the risk of IHD mortality and DALYs.

Results

Globally, there were 9.2 million IHD deaths and 182 million DALYs in 2019. Both the ASRs of death and DALYs declined from 1990 to 2019 (percentage change: −30.8% and −28.6%, respectively), particularly in high and high-middle socio-demographic index (SDI) areas. Low-whole-grain, low-legume, and high-sodium diets were the three main dietary factors that increased the risk of IHD burden. Advanced age [RR (95%CI): 1.33 (1.27, 1.39)] and being male [1.11 (1.06, 1.16)] were independent risk factors for IHD mortality worldwide and in all SDI regions. After controlling for age effects, IHD risk showed a negative period effect overall. Poor diets were positively associated with increased risk of death but were not yet statistically significant. Interactions between dietary factors and advanced age were observed in all regions after adjusting for related variables. In people aged 55 and above, low intake of whole grains was associated with an increased risk of IHD death [1.28 (1.20, 1.36)]. DALY risks showed a similar but more obvious trend.

Conclusion

IHD burden remains high, with significant regional variations. The high IHD burden could be attributed to advanced age, sex (male), and dietary risk factors. Dietary habits in different SDI regions may have varying effects on the global burden of IHD. In areas with lower SDI, it is recommended to pay more attention to dietary problems, particularly in the elderly, and to consider how to improve dietary patterns in order to reduce modifiable risk factors.
Efficacy of apatinib 250 mg combined with chemotherapy in patients with pretreated advanced breast cancer in a real-world setting
Authors: Zhang Ruyan , Chen Yifei , Liu Xiaoran , Gui Xinyu , Zhu Anjie , Jiang Hanfang , Shao Bin , Liang Xu , Yan Ying , Zhang Jiayang , Song Guohong , Li Huiping
Published: June 2023

Objectives

This study evaluated the efficacy and safety of apatinib (an oral small-molecule tyrosine kinase inhibitor targeting VEGFR-2) 250 mg combined with chemotherapy in patients with pretreated metastatic breast cancer in a real-world setting.

Patients and methods

A database of patients with advanced breast cancer who received apatinib between December 2016 and December 2019 in our institution was reviewed, and patients who received apatinib combined with chemotherapy were included. Progression-free survival (PFS), overall survival (OS), the objective response rate (ORR), the disease control rate (DCR), and treatment-related toxicity were analyzed.

Results

In total, 52 evaluated patients with metastatic breast cancer previously exposed to anthracyclines or taxanes who received apatinib 250 mg combined with chemotherapy were enrolled in this study. Median PFS and OS were 4.8 (95% confidence interval [CI] = 3.2–6.4) and 15.4 months (95% CI = 9.2–21.6), respectively. The ORR and DCR were 25% and 86.5%, respectively. Median PFS for the previous line of treatment was 2.1 months (95% CI = 0.65–3.6), which was significantly shorter than that for the apatinib–chemotherapy combination (p < 0.001). No significant difference was identified in the ORR and PFS among the subgroups(subtypes, target lesion, combined regimens and treatment lines). The common toxicities related to apatinib were hypertension, hand-foot syndrome, proteinuria, and fatigue events.

Conclusion

Apatinib 250 mg combined with chemotherapy provided favorable efficacy in patients with pretreated metastatic breast cancer regardless of molecular types and treatment lines. The toxicities of the regimen were well tolerated and manageable. This regimen could be a potential treatment option in patients with refractory pretreated metastatic breast cancers.