bluuebunny/crossref_metadata_2025 huggingface dataset:
A two-stage robust generation expansion planning framework for regional integrated energy systems with carbon growth constraints
Authors: Nan Junpei , Feng Jieran , Deng Xu , Guan Li , Sun Ke , Zhou Hao
Published: February 2023

After proposing the carbon peaking and carbon neutrality target, China further proposed a series of specific carbon emission growth limit sub-targets. How to decarbonize the energy system to ensure the realization of the carbon growth limit sub-targets is a meaningful topic. At present, generation expansion planning of renewable energy in integrated energy systems has been well studied. However, few of the existing studies consider specific carbon emission growth targets. To address this research gap, a two-stage robust generation expansion planning framework for regional integrated energy systems with carbon growth constraints is proposed in this paper, which takes into account multiple uncertainties. In this framework, the objective function is to minimize the total operation cost and wind turbine investment cost. The first stage is the decision-making level of the wind turbine capacity configuration scheme. The second stage is the optimal economic dispatching in the worst-case scenario, which is a bi-level problem of max-min form. Thus, the two-stage robust optimization framework constitutes a problem of min-max-min form, which is pretty hard to solve directly with a commercial solver. Therefore, a nested column-and-constraint generation algorithm is adopted and nested iterations are performed to solve the complex problem. Finally, case studies are carried out on a regional electric-gas integrated energy system. The MATLAB/YALMIP simulation platform with the Gurobi solver is used to verify the effectiveness and superiority of the proposed framework. Compared with other four cases, 5,000 Monte Carlo scheduling tests demonstrate that the proposed framework can ensure the system carbon emission to be controlled within a certain limit even in the worst scenario. Due to the consideration of multiple uncertainties, the proposed framework planning results are both robust and economical for investment. This study can provide theoretical support for the actual regional integrated energy system to achieve a certain carbon growth target.
Case report: A reciprocal translocation-free and pathogenic DUOX2 mutation-free embryo selected by complicated preimplantation genetic testing resulted in a healthy live birth
Authors: Shi Biwei , Ye Yinghui
Published: February 2023

Preimplantation genetic testing (PGT) is an effective approach to improve clinical outcomes and prevent transmission of genetic imbalances by selecting embryos free of disease-causing genes and chromosome abnormalities. In this study, PGT was performed for a challenging case in which a couple simultaneously carried a maternal subchromosomal reciprocal translocation (RecT) revealed by fluorescence in situ hybridization involving the chromosome X (ChrX) and heterozygous mutations in dual oxidase 2 (DUOX2). Carriers of RecT are at increased risk for infertility, recurrent miscarriages, or having affected children due to the unbalanced gametes produced. DUOX2 mutation results in congenital hypothyroidism. Pedigree haplotypes for DUOX2 was constructed after the mutations were verified by Sanger sequencing. Since male carriers of X-autosome translocations may exhibit infertility or other abnormalities, pedigree haplotype for chromosomal translocation was also constructed to identify embryo with RecT. Three blastocysts were obtained by in vitro fertilization and underwent trophectoderm biopsy, whole genomic amplification, and next-generation sequencing (NGS). A blastocyst lacking copy number variants and RecT but carrying the paternal gene mutation in DUOX2, c.2654G>T (p.R885L) was used for embryo transfer, resulting in a healthy female infant whose genetic properties were confirmed by amniocentesis. Cases containing RecT and single gene disorder are rare. And the situation is more complicated when the subchromosomal RecT involving ChrX cannot be identified with routine karyotype analysis. This case report contributes significantly to the literature and the results have shown that the NGS-based PGT strategy may be broadly useful for complex pedigrees.
Exploration and identification of anoikis-related genes in polycythemia vera
Authors: Aini Wufuer , Xie Limin , Hu Wanyu , Tang Yuan , Peng Hongling , Zhang Guangsen , Deng Tuo
Published: February 2023

Background: Polycythemia Vera (PV) is a type of typical Myeloproliferative Neoplasms (MPNs) characterized with excessive erythropoiesis and thrombosis. Anoikis is a special programmed cell death mode induced by the adhesion disorder between cells and extracellular matrix (ECM) or adjacent cells facilitating cancer metastasis. However, few studies have focused on the role of anoikis in PV, especially on the development of PV.

Methods: The microarray and RNA-seq results were screened from the Gene Expression Omnibus (GEO) database and the anoikis-related genes (ARGs) were downloaded from Genecards. The functional enrichment analysis of intersecting differentially expressed genes (DEGs) and protein-protein interaction (PPI) network analysis were performed to discover hub genes. The hub genes expression was tested in the training (GSE136335) and validation cohort (GSE145802), and RT-qPCR was performed to verify the gene expression in PV mice.

Results: In the training GSE136335, a total of 1,195 DEGs was obtained from Myeloproliferative Neoplasm (MPN) patients compared with controls, among which 58 were anoikis-related DEGs. The significant enrichment of the apoptosis and cell adhesion pathways (i.e., cadherin binding) were shown in functional enrichment analysis. The PPI network was conducted to identify top five hub genes (CASP3, CYCS, HIF1A, IL1B, MCL1). The expression of CASP3 and IL1B were significantly upregulated both in validation cohort and PV mice and downregulated after treatment, suggesting that CASP3 and IL1B could be important indicators for disease surveillance.

Conclusion: Our research revealed a relationship between anoikis and PV for the first time by combined analysis of gene level, protein interaction and functional enrichment, allowing novel insights into mechanisms of PV. Moreover, CASP3 and IL1B may become promising indicators of PV development and treatment.
Prospects and feasibility of synergistic therapy with radiotherapy, immunotherapy, and DNA methyltransferase inhibitors in non-small cell lung cancer
Authors: Jie Chen , Li Rumeng , Cheng Yajie , Wang Zhihao , Wu Qiuji , Xie Conghua
Published: February 2023

The morbidity and mortality of lung cancer are increasing, seriously threatening human health and life. Non-small cell lung cancer (NSCLC) has an insidious onset and is not easy to be diagnosed in its early stage. Distant metastasis often occurs and the prognosis is poor. Radiotherapy (RT) combined with immunotherapy, especially with immune checkpoint inhibitors (ICIs), has become the focus of research in NSCLC. The efficacy of immunoradiotherapy (iRT) is promising, but further optimization is necessary. DNA methylation has been involved in immune escape and radioresistance, and becomes a game changer in iRT. In this review, we focused on the regulation of DNA methylation on ICIs treatment resistance and radioresistance in NSCLC and elucidated the potential synergistic effects of DNA methyltransferases inhibitors (DNMTis) with iRT. Taken together, we outlined evidence suggesting that a combination of DNMTis, RT, and immunotherapy could be a promising treatment strategy to improve NSCLC outcomes.
Lymphoid stromal cells - potential implications for the pathogenesis of CVID
Authors: Cousin Victoria N. , Perez Guillermo F. , Payne Kathryn J. , Voll Reinhard E. , Rizzi Marta , Mueller Christopher G. , Warnatz Klaus
Published: February 2023

Non-hematopoietic lymphoid stromal cells (LSC) maintain lymph node architecture and form niches allowing the migration, activation, and survival of immune cells. Depending on their localization in the lymph node, these cells display heterogeneous properties and secrete various factors supporting the different activities of the adaptive immune response. LSCs participate in the transport of antigen from the afferent lymph as well as in its delivery into the T and B cell zones and organize cell migrationvianiche-specific chemokines. While marginal reticular cells (MRC) are equipped for initial B-cell priming and T zone reticular cells (TRC) provide the matrix for T cell-dendritic cell interactions within the paracortex, germinal centers (GC) only form when both T- and B cells successfully interact at the T-B border and migrate within the B-cell follicle containing the follicular dendritic cell (FDC) network. Unlike most other LSCs, FDCs are capable of presenting antigenviacomplement receptors to B cells, which then differentiate within this niche and in proximity to T follicular helper (TFH) cells into memory and plasma cells. LSCs are also implicated in maintenance of peripheral immune tolerance. In mice, TRCs induce the alternative induction of regulatory T cells instead of TFHcells by presenting tissue-restricted self-antigens to naïve CD4 T cellsviaMHC-II expression. This review explores potential implications of our current knowledge of LSC populations regarding the pathogenesis of humoral immunodeficiency and autoimmunity in patients with autoimmune disorders or common variable immunodeficiency (CVID), the most common form of primary immunodeficiency in humans.
Clinical efficacy of tetrandrine in artificial stone-associated silicosis: A retrospective cohort study
Authors: Wu Wen-hong , Feng Yong-hong , Min Chun-yan , Zhou Shao-wei , Chen Zi-dan , Huang Li-min , Yang Wen-lan , Yang Guang-hong , Li Jun , Shi Jin , Quan Hua , Mao Ling
Published: February 2023

Background

Outbreaks of silicosis have occurred among workers in the artificial stone (AS) industry, and there is currently no effective antifibrosis treatment for silicosis.

Design

A retrospective cohort study.

Methods

We retrospectively analyzed the clinical data of 89 artificial stone-associated silicosis patients treated in Shanghai Pulmonary Hospital (China). Patients who agreed to be administered tetrandrine entered the observation group and those who disagreed entered the control group. Changes in chest HRCT, pulmonary function, and clinical symptoms of patients in two groups were compared pre- and post-treatment.

Results

After treatment for 3–12 months, 56.5%–65.4% of patients in the observation group showed improvements in HRCT imaging, while there was no improvement in the control group (p < 0.05). Disease progression occurred in 0%–17.4% of patients in the observation group after 3–12 months of treatment compared with 44.4%–92.0% of patients in the control group (p < 0.05). After 3 months of treatment, the forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and diffusing capacity of the lung for carbon monoxide (DLco) in the observation group increased by 136.7 ± 189.2 mL (p < 0.05), 124.2 ± 169.9 mL (p < 0.05), and 1.4 ± 2.3 mL/min/mmHg (p > 0.05), respectively, while those in the control group decreased (145.8 ± 356.5; 107.5 ± 272.1; 1.9 ± 3.8). After 6 months of treatment, FVC, FEV1, and DLco in the observation group increased by 207.8 ± 372.2 mL (p > 0.05), 107.8 ± 295.2 mL (p > 0.05) and 0.7 ± 6.0 mL/min/mmHg (p > 0.05), respectively, while those of the control group decreased (383.3 ± 536.7; 215.6 ± 228.9; 1.4 ± 1.7). The incidences of clinical symptoms such as cough, expectoration, dyspnea, chest tightness, and chest pain in the observation group were decreased-after treatment (all p < 0.05), while the incidences of these symptoms increased in the control group, although the change was not statistically significant (all p > 0.05).

Conclusion

Tetrandrine can control and delay the progression of AS-associated silicosis fibrosis, with improved chest HRCT imaging and pulmonary function.
Pattern and trends of Helicobacter pylori genotypes in gastric cancer: A Kenyan 8-year study
Authors: Njenga Priscilla , Njau Allan , Moloo Zahir , Revathi Gunturu , Tshibangu Evariste , Yamaoka Yoshio
Published: February 2023

Background

Notable geographic and temporal variations in the prevalence and genotypes of Helicobacter pylori, in relation to gastric pathologies, have been observed; however, their significance and trends in African populations is scarcely described. The aim of this study, was to investigate the association of H. pylori and its respective CagA and vacuolating cytotoxin A (VacA) genotypes with gastric adenocarcinoma, and to describe the trends of H. pylori genotypes over an 8-year period (2012–2019).

Materials and methods

A total of 286 samples of gastric cancer cases and benign controls (one-to-one matching), from three main cities in Kenya, between 2012 and 2019 were included. Histologic evaluation, and CagA and VacA genotyping using PCR, was performed. Distribution of H. pylori genotypes was presented in proportions. To determine association, a univariate analysis was conducted using a Wilcoxon rank sum test for continuous variables, and a Chi-squared test or Fisher’s exact test for categorical data.

Results

The VacA s1m1 genotype was associated with gastric adenocarcinoma, {odds ratio (OR) = 2.68 [confidence interval (CI) of 95%: 0.83–8.65]; p = 0.108}, whilst VacA s2m2 was associated with a reduced probability of gastric adenocarcinoma [OR = 0.23 (CI 95%: 0.07–0.78); p = 0.031]. No association between cytotoxin associated gene A (CagA) and gastric adenocarcinoma was observed.

Conclusion

Over the study period, an increase in all genotypes of H. pylori was seen, and although no predominant genotype was noted, there was significant year-to-year variation, with VacA s1 and VacA s2 showing the greatest variation. VacA s1m1 and VacA s2m2 were associated with increased, and reduced risk of gastric cancer, respectively. Intestinal metaplasia and atrophic gastritis did not appear to be significant in this population.
Efficacy and safety of single-dose intravitreal dexamethasone implant in non-infectious uveitic macular edema: A systematic review and meta-analysis
Authors: Fan Shipei , Shi Xing-yu , Zhao Chao-fu , Chen Zhen , Ying Jia , Yu Song-ping , Li Jun , Li Xia
Published: February 2023

Purpose

We conducted a systematic review and meta-analysis to investigate the efficacy and safety of single-dose intravitreal dexamethasone (DEX) implant for treating non-infectious uveitic macular edema (UME).

Methods

Studies including clinical outcomes of the DEX implant in UME were comprehensively searched in PubMed, Embase, and Cochrane databases for potential studies from inception to July 2022. The primary outcomes were best corrected visual acuity (BCVA) and central macular thickness (CMT) during the follow-up period. Stata 12.0 was used to perform the statistical analyses.

Results

Six retrospective studies and one prospective investigation involving 201 eyes were ultimately included. Significantly improved BCVA was observed from baseline to 1 month (WMD = −0.15, 95%CI = −0.24, −0.06), 3 months (WMD = −0.22, 95%CI = −0.29, −0.15), and 6 months (WMD = −0.24, 95%CI = −0.35, −0.13), after single-dose DEX implant. When considering CMT, macular thickness of 1 month (WMD = −179.77, 95%CI = −223.45, −136.09), 3 months (WMD = −179.13, 95%CI = −232.63, −125.63), and 6 months (WMD = −140.25, 95%CI = −227.61, −52.88) decreased in comparison with baseline, with statistical significance.

Conclusion

Based on the current results, this meta-analysis confirmed favorable visual prognosis and anatomical improvement in patients with UME, after receiving the single-dose DEX implant. The most common adverse event is increased intraocular pressure, which could be controlled with topical medications.

Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022325969.
Challenges and concepts in the diagnosis and management of ocular graft-versus-host disease
Authors: Tappeiner Christoph , Heiligenhaus Arnd , Halter Joerg P. , Miserocchi Elisabetta , Bandello Francesco , Goldblum David
Published: February 2023

Graft-versus-host disease (GVHD) is characterized by tissue inflammation in the host following an allogeneic hematopoietic cell transplantation (HCT). The pathophysiology is complex and only incompletely understood yet. Donor lymphocyte interaction with the histocompatibility antigens of the host plays a crucial role in the pathogenesis of the disease. Inflammation may affect multiple organs and tissues, e.g., the gastrointestinal tract, liver, lung, fasciae, vaginal mucosa, and the eye. Subsequently, alloreactive donor-derived T and B lymphocytes may lead to severe inflammation of the ocular surface (i.e., cornea and conjunctiva) and the eyelids. Furthermore, fibrosis of the lacrimal gland may lead to severe dry eye. This review focuses on ocular GVHD (oGVHD) and provides an overview of current challenges and concepts in the diagnosis and management of oGVHD. Ophthalmic manifestations, diagnostic procedures, grading of severity and recommendations for ophthalmic examination intervals are provided. Management of ocular surface disease with lubricants, autologous serum eye drops, topical anti-inflammatory agents and systemic treatment options are described based on the current evidence. Ocular surface scarring and corneal perforation are severe complications of oGVHD. Therefore, ophthalmic screening and interdisciplinary treatment approaches are highly relevant to improve the quality of life of patients and to prevent potentially irreversible visual loss.
The NagY regulator: A member of the BglG/SacY antiterminator family conserved in Enterococcus faecalis and involved in virulence
Authors: Soussan Diane , Salze Marine , Ledormand Pierre , Sauvageot Nicolas , Boukerb Amine , Lesouhaitier Olivier , Fichant Gwennaele , Rincé Alain , Quentin Yves , Muller Cécile
Published: February 2023

Enterococcus faecalis is a commensal bacterium of the gastrointestinal tract but also a major nosocomial pathogen. This bacterium uses regulators like BglG/SacY family of transcriptional antiterminators to adapt its metabolism during host colonization. In this report, we investigated the role of the BglG/SacY family antiterminator NagY in the regulation of the nagY-nagE operon in presence of N-acetylglucosamine, with nagE encoding a transporter of this carbohydrate, as well as the expression of the virulence factor HylA. We showed that this last protein is involved in biofilm formation and glycosaminoglycans degradation that are important features in bacterial infection, confirmed in the Galleria mellonella model. In order to elucidate the evolution of these actors, we performed phylogenomic analyses on E. faecalis and Enterococcaceae genomes, identified orthologous sequences of NagY, NagE, and HylA, and we report their taxonomic distribution. The study of the conservation of the upstream region of nagY and hylA genes showed that the molecular mechanism of NagY regulation involves ribonucleic antiterminator sequence overlapping a rho-independent terminator, suggesting a regulation conforming to the canonical model of BglG/SacY family antiterminators. In the perspective of opportunism understanding, we offer new insights into the mechanism of host sensing thanks to the NagY antiterminator and its targets expression.
Transfection of clMagR/clCry4 imparts MR-T2 imaging contrast properties to living organisms (E. coli) in the presence of Fe3+ by endogenous formation of iron oxide nanoparticles
Authors: Li Nuan , Xue Le , Mai Xiaoli , Wang Peng , Zhu Chenzhuo , Han Xiaofeng , Xie Yuanyuan , Wang Bin , Ge Yuqing , Zhang Yewei , Sun Jianfei
Published: February 2023

Rapid development of medical imaging, such as cellular tracking, has increased the demand for “live” contrast agents. This study provides the first experimental evidence demonstrating that transfection of the clMagR/clCry4 gene can impart magnetic resonance imaging (MRI) T2-contrast properties to living prokaryotic Escherichia coli (E. coli) in the presence of Fe3+ through the endogenous formation of iron oxide nanoparticles. The transfected clMagR/clCry4 gene markedly promoted uptake of exogenous iron by E. coli, achieving an intracellular co-precipitation condition and formation of iron oxide nanoparticles. This study will stimulate further exploration of the biological applications of clMagR/clCry4 in imaging studies.
Presenilin 1 deficiency impairs Aβ42-to-Aβ40- and angiotensin-converting activities of ACE
Authors: Gao Yuan , Sun Yang , Islam Sadequl , Nakamura Tomohisa , Tomita Taisuke , Zou Kun , Michikawa Makoto
Published: February 2023

Introduction

Alzheimer’s disease (AD) is associated with amyloid β-protein 1-42 (Aβ42) accumulation in the brain. Aβ42 and Aβ40 are the major two species generated from amyloid precursor protein. We found that angiotensin-converting enzyme (ACE) converts neurotoxic Aβ42 to neuroprotective Aβ40 in an ACE domain– and glycosylation-dependent manner. Presenilin 1 (PS1) mutations account for most of cases of familial AD and lead to an increased Aβ42/40 ratio. However, the mechanism by which PSEN1 mutations induce a higher Aβ42/40 ratio is unclear.

Methods

We over expressed human ACE in mouse wild-type and PS1-deficient fibroblasts. The purified ACE protein was used to analysis the Aβ42-to-Aβ40- and angiotensin-converting activities. The distribution of ACE was determined by Immunofluorescence staining.

Result

We found that ACE purified from PS1-deficient fibroblasts exhibited altered glycosylation and significantly reduced Aβ42-to-Aβ40- and angiotensin-converting activities compared with ACE from wild-type fibroblasts. Overexpression of wild-type PS1 in PS1-deficient fibroblasts restored the Aβ42-to-Aβ40- and angiotensin-converting activities of ACE. Interestingly, PS1 mutants completely restored the angiotensin-converting activity in PS1-deficient fibroblasts, but some PS1 mutants did not restore the Aβ42-to-Aβ40-converting activity. We also found that the glycosylation of ACE in adult mouse brain differed from that of embryonic brain and that the Aβ42-to-Aβ40-converting activity in adult mouse brain was lower than that in embryonic brain.

Conclusion

PS1 deficiency altered ACE glycosylation and impaired its Aβ42-to-Aβ40- and angiotensin-converting activities. Our findings suggest that PS1 deficiency and PSEN1 mutations increase the Aβ42/40 ratio by reducing the Aβ42-to-Aβ40-converting activity of ACE.
SMN post-translational modifications in spinal muscular atrophy
Authors: Riboldi Giulietta M. , Faravelli Irene , Rinchetti Paola , Lotti Francesco
Published: February 2023

Since its first identification as the gene responsible for spinal muscular atrophy (SMA), the range of survival motor neuron (SMN) protein functions has increasingly expanded. This multimeric complex plays a crucial role in a variety of RNA processing pathways. While its most characterized function is in the biogenesis of ribonucleoproteins, several studies have highlighted the SMN complex as an important contributor to mRNA trafficking and translation, axonal transport, endocytosis, and mitochondria metabolism. All these multiple functions need to be selectively and finely modulated to maintain cellular homeostasis. SMN has distinct functional domains that play a crucial role in complex stability, function, and subcellular distribution. Many different processes were reported as modulators of the SMN complex activities, although their contribution to SMN biology still needs to be elucidated. Recent evidence has identified post-translational modifications (PTMs) as a way to regulate the pleiotropic functions of the SMN complex. These modifications include phosphorylation, methylation, ubiquitination, acetylation, sumoylation, and many other types. PTMs can broaden the range of protein functions by binding chemical moieties to specific amino acids, thus modulating several cellular processes. Here, we provide an overview of the main PTMs involved in the regulation of the SMN complex with a major focus on the functions that have been linked to SMA pathogenesis.
Deficiency of the RNA-binding protein ELAVL1/HuR leads to the failure of endogenous and exogenous neuroprotection of retinal ganglion cells
Authors: Pacwa Anna , Machowicz Joanna , Akhtar Saeed , Rodak Piotr , Liu Xiaonan , Pietrucha-Dutczak Marita , Lewin-Kowalik Joanna , Amadio Marialaura , Smedowski Adrian
Published: February 2023

Introduction

ELAVL1/HuR is a keystone regulator of gene expression at the posttranscriptional level, including stress response and homeostasis maintenance. The aim of this study was to evaluate the impact of hur silencing on the age-related degeneration of retinal ganglion cells (RGC), which potentially describes the efficiency of endogenous neuroprotection mechanisms, as well as to assess the exogenous neuroprotection capacity of hur-silenced RGC in the rat glaucoma model.

Methods

The study consisted of in vitro and in vivo approaches. In vitro, we used rat B-35 cells to investigate, whether AAV-shRNA-HuR delivery affects survival and oxidative stress markers under temperature and excitotoxic insults. In vivo approach consisted of two different settings. In first one, 35 eight-week-old rats received intravitreal injection of AAV-shRNA-HuR or AAV-shRNA scramble control. Animals underwent electroretinography tests and were sacrificed 2, 4 or 6 months after injection. Retinas and optic nerves were collected and processed for immunostainings, electron microscopy and stereology. For the second approach, animals received similar gene constructs. To induce chronic glaucoma, 8 weeks after AAV injection, unilateral episcleral vein cauterization was performed. Animals from each group received intravitreal injection of metallothionein II. Animals underwent electroretinography tests and were sacrificed 8 weeks later. Retinas and optic nerves were collected and processed for immunostainings, electron microscopy and stereology.

Results

Silencing of hur induced apoptosis and increased oxidative stress markers in B-35 cells. Additionally, shRNA treatment impaired the cellular stress response to temperature and excitotoxic insults. In vivo, RGC count was decreased by 39% in shRNA-HuR group 6 months after injection, when compared to shRNA scramble control group. In neuroprotection study, the average loss of RGCs was 35% in animals with glaucoma treated with metallothionein and shRNA-HuR and 11.4% in animals with glaucoma treated with metallothionein and the scramble control shRNA. An alteration in HuR cellular content resulted in diminished photopic negative responses in the electroretinogram.

Conclusions

Based on our findings, we conclude that HuR is essential for the survival and efficient neuroprotection of RGC and that the induced alteration in HuR content accelerates both the age-related and glaucoma-induced decline in RGC number and function, further confirming HuR’s key role in maintaining cell homeostasis and its possible involvement in the pathogenesis of glaucoma.
Human subthalamic nucleus neurons differentially encode speech and limb movement
Authors: Johari Karim , Kelley Ryan M. , Tjaden Kris , Patterson Charity G. , Rohl Andrea H. , Berger Joel I. , Corcos Daniel M. , Greenlee Jeremy D. W.
Published: February 2023

Deep brain stimulation (DBS) of the subthalamic nucleus (STN), which consistently improves limb motor functions, shows mixed effects on speech functions in Parkinson’s disease (PD). One possible explanation for this discrepancy is that STN neurons may differentially encode speech and limb movement. However, this hypothesis has not yet been tested. We examined how STN is modulated by limb movement and speech by recording 69 single- and multi-unit neuronal clusters in 12 intraoperative PD patients. Our findings indicated: (1) diverse patterns of modulation in neuronal firing rates in STN for speech and limb movement; (2) a higher number of STN neurons were modulated by speech vs. limb movement; (3) an overall increase in neuronal firing rates for speech vs. limb movement; and (4) participants with longer disease duration had higher firing rates. These data provide new insights into the role of STN neurons in speech and limb movement.
Alleviation of cognitive deficits in a rat model of glutamate-induced excitotoxicity, using an N-type voltage-gated calcium channel ligand, extracted from Agelena labyrinthica crude venom
Authors: Keimasi Mohammad , Salehifard Kowsar , Keimasi Mohammadjavad , Amirsadri Mohammadreza , Esfahani Noushin Mirshah Jafar , Moradmand Majid , Esmaeili Fariba , Mofid Mohammad Reza
Published: February 2023

Excitotoxicity is a common pathological process in Alzheimer’s disease (AD) which is caused by the over-activity of N-Methyl-D-Aspartate receptors (NMDARs). The release of neurotransmitters depends on the activity of voltage-gated calcium channels (VGCCs). Hyper-stimulation of NMDARs can enhance the releasement of neurotransmitters through the VGCCs. This malfunction of channels can be blocked by selective and potent N-type VGCCs ligand. Under excitotoxicity condition, glutamate has negative effects on the pyramidal cells of the hippocampus, which ends in synaptic loss and elimination of these cells. These events leads to learning and memory elimination through the hippocampus circuit’s dysfunction. A suitable ligand has a high affinity to receptor or channel and is selective for its target. The bioactive small proteins of venom have these characteristics. Therefore, peptides and small proteins of animal venom are precious sources for pharmacological applications. The omega-agatoxin-Aa2a was purified, and identified from Agelena labyrinthica specimens, as an N-type VGCCs ligand for this study. The effect of the omega-agatoxin-Aa2a on the glutamate-induced excitotoxicity in rats was evaluated through behavioral tests including Morris Water Maze, and Passive avoidance. The syntaxin1A (SY1A), synaptotagmin1 (SYT1), and synaptophysin (SYN) genes expression were measured via Real-Time PCR. The local expression of synaptosomal-associated protein, 25 k Da (SNAP-25) was visualized using an immunofluorescence assay for synaptic quantification. Electrophysiological amplitude of field excitatory postsynaptic potentials (fEPSPs) in the input–output and LTP curves of mossy fiber were recorded. The cresyl violet staining of hippocampus sections was performed for the groups. Our results demonstrated that the omega-agatoxin-Aa2a treatment could recover the learning, and memory impairment caused by NMDA-induced excitotoxicity in rat hippocampus.
MRI radiomics and potential applications to glioblastoma
Authors: Hooper Grayson W. , Ginat Daniel T.
Published: February 2023

MRI plays an important role in the evaluation of glioblastoma, both at initial diagnosis and follow up after treatment. Quantitative analysis via radiomics can augment the interpretation of MRI in terms of providing insights regarding the differential diagnosis, genotype, treatment response, and prognosis. The various MRI radiomic features of glioblastoma are reviewed in this article.
Comparison of three clinical scoring tools for bronchiolitis to predict the need for respiratory support and length of stay in neonates and infants up to three months of age
Authors: De Rose Domenico Umberto , Maddaloni Chiara , Martini Ludovica , Braguglia Annabella , Dotta Andrea , Auriti Cinzia
Published: February 2023

Background

Bronchiolitis severity can be assessed using different clinical scores. Some of the most used are the Wang Bronchiolitis Severity Score (WBSS), the Kristjansson Respiratory Score (KRS), and the Global Respiratory Severity Score (GRSS), calculated on the vital parameters and the clinical conditions.

Objective

To assess which of the three clinical scores better predicts the need for respiratory support and length of hospital stay in neonates and infants younger than three months, admitted to neonatal units for bronchiolitis.

Methods

Neonates and infants younger than three months admitted to neonatal units from October 2021 to March 2022 were included in this retrospective study. The scores were calculated in all patients soon after admission.

Results

Ninety-six patients (of whom 61 neonates) admitted for bronchiolitis were included in the analysis. Median WBSS at admission was 4.00 (interquartile range, IQR 3.00–6.00), median KRS was 4.00 (IQR 3.00–5.00), and median GRSS 4.90 (IQR 3.89–6.10). We found significant differences in all three scores between infants who needed respiratory support (72.9%) and those who did not (27.1%) (p < 0.001). A value >3 for WBSS, > 3 for KRS, and >3.8 for GRSS were accurate in predicting the need for respiratory support, with a sensitivity of 85.71%, 75.71%, and 93.75% and a specificity of 80.77%, 92.31%, and 88.24%, respectively. The three infants who required mechanical ventilation had a median WBSS of 6.00 (IQR 5.00–6.50), a KRS of 7.00 (IQR 5.00–7.00), and a GRSS of 7.38 (IQR 5.59–7.39). The median length of stay was 5 days (IQR 4–8). All three scores were significantly correlated with the length of stay, although with a low correlation coefficient: WBSS with an r2 of 0.139 (p < 0.001), KRS with an r2 of 0.137 (p < 0.001), and GRSS with an r2 of 0.170 (p < 0.001).

Conclusion

Clinical scores WBSS, KRS, and GRSS calculated on admission accurately predict the need for respiratory support and the length of hospital stay in neonates and infants younger than three months with bronchiolitis. The GRSS score seems to better discriminate the need for respiratory support than the others.
Efficacy of traditional Chinese medicine injection for diabetic kidney disease: A network meta analysis and systematic review
Authors: Long Caiyi , Feng Haoyue , Liu Zheng , Li Zihan , Liu Jun , Jiang Yayi , Yue Rensong
Published: February 2023

Background: Diabetic kidney disease (DKD) is an important public health problem worldwide that increases the mortality of patients and incurs high medical costs. Traditional Chinese Medicine injections (TCMIs) are widely used in clinical practice. However, their efficacy is unknown owing to a lack of definitive evidence. This study conducted a network meta-analysis (NMA) to evaluate the efficacy and safety of traditional Chinese medicine injections in the treatment of DKD to provide a reference for clinical treatment.

Methods: Total 7 databases had been searched, which included PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), Chinese scientific journal database (VIP), WanFang, and SinoMed. Only randomised controlled trials (RCT) had been included for analysis. The retrieval time limit was from the establishment of the database until 20 July 2022. Cochrane Risk of Bias 2.0 tool was used to evaluate the quality of the studies. Network meta-analyses, and Trial Sequential Analyses (TSA) were used to analysis the effectiveness of the included RCTs for DKD. The Stata 15.1 and R 4.0.4 were used to perform the network meta-analysis. Sensitivity analysis was used to assess the robustness of the findings. The effect of the intervention evidence are summarized on the basis of the minimum background framework.

Results: NMA showed that the total effective rate of SMI, DCI, DHI, HQI, and SKI combined with alprostadil injection (PGE1) was better than PGE1 single used. Based on the surface under the cumulative ranking curve values, PGE1+DHI was the most effective for urinary albumin excretion rate and 24 h urinary albumin, PGE1+HQI was the most effective for the total response rate and β2-MG, and PGE1+SKI was the most effective for serum creatinine and blood urea nitrogen. Cluster analysis found that PGE1+HQI and PGE1+SKI could be the best treatments in terms of primary outcome measures. PGE1+SKI was found to be most effective on glomerular filtration function. PGE1+DHI was most effective for urinary protein-related indices.

Conclusion: The efficacy of TCMI combined with PGE1 was higher than PGE1 single used. PGE1+HQI and PGE1+SKI were the most effective treatments. The safety of TCMI treatment should be investigated further. This study needs to be validated using large-sample, double-blind, multicentre RCTs.

Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=348333], identifier [CRD42022348333].
AC power analysis for second-order memory elements
Authors: Liu Yue , Liu Fang , Luo Wanbo , Wu Aoyun , Li Hui
Published: February 2023

As the product of a circuit’s voltage and current, apparent power (S) is of paramount necessity and importance in electrical utilities, electronics, communication, and neural network systems. Based on the existing AC power analysis on the two-terminal passive elements (i.e., R, L, and C), some in-depth research on AC apparent power calculations for second-order memory elements and memristive systems is introduced to help with revealing their complex and unique non-linear phenomena. This paper derives the forms of real power, reactive power, and apparent power for the proposed second-order memory elements (i.e., MR, MC, and ML) and reveals the difference between ideal memory elements and traditional passive ones (i.e., R, C, and L). For all involved memory elements, harmonic values and an extra term occur in the expression of powers to represent their memory characteristics. Especially, the real power is a function of a circuit’s dissipative elements (usually resistances R), but not exactly the memristor (MR). Then, the corresponding curves could be depicted, which demonstrate the differences between R/C/L and MR/MC/ML and verified that harmonic values existed in SMR/SMC/SML, meaning that it would perpetually supply energy when operated with an alternating current.
Measurement of extracellular volume fraction using magnetic resonance-based conductivity tensor imaging
Authors: Choi Bup Kyung , Katoch Nitish , Park Ji Ae , Kim Jin Woong , Oh Tong In , Kim Hyung Joong , Woo Eung Je
Published: February 2023

Conductivity tensor imaging (CTI) using MRI is an advanced method that can non-invasively measure the electrical properties of living tissues. The contrast of CTI is based on underlying hypothesis about the proportionality between the mobility and diffusivity of ions and water molecules inside tissues. The experimental validation of CTI in both in vitro and in vivo settings is required as a reliable tool to assess tissue conditions. The changes in extracellular space can be indicators for disease progression, such as fibrosis, edema, and cell swelling. In this study, we conducted a phantom imaging experiment to test the feasibility of CTI for measuring the extracellular volume fraction in biological tissue. To mimic tissue conditions with different extracellular volume fractions, four chambers of giant vesicle suspension (GVS) with different vesicle densities were included in the phantom. The reconstructed CTI images of the phantom were compared with the separately-measured conductivity spectra of the four chambers using an impedance analyzer. Moreover, the values of the estimated extracellular volume fraction in each chamber were compared with those measured by a spectrophotometer. As the vesicle density increased, we found that the extracellular volume fraction, extracellular diffusion coefficient, and low-frequency conductivity decreased, while the intracellular diffusion coefficient slightly increased. On the other hand, the high-frequency conductivity could not clearly distinguish the four chambers. The extracellular volume fraction measured by the spectrophotometer and CTI method in each chamber were quite comparable, i.e., (1.00, 0.98 ± 0.01), (0.59, 0.63 ± 0.02), (0.40, 0.40 ± 0.05), and (0.16, 0.18 ± 0.02). The prominent factor influencing the low-frequency conductivity at different GVS densities was the extracellular volume fraction. Further studies are needed to validate the CTI method as a tool to measure the extracellular volume fractions in living tissues with different intracellular and extracellular compartments.
Abscisic acid plays a key role in the regulation of date palm fruit ripening
Authors: Elbar Saar , Maytal Yochai , David Itzhak , Carmeli-Weissberg Mira , Shaya Felix , Barnea-Danino Yaara , Bustan Amnon , Harpaz-Saad Smadar
Published: February 2023

The date palm (Phoenix dactylifera L.) fruit is of major importance for the nutrition of broad populations in the world’s desert strip; yet it is sorely understudied. Understanding the mechanism regulating date fruit development and ripening is essential to customise date crop to the climatic change, which elaborates yield losses due to often too early occurring wet season. This study aimed to uncover the mechanism regulating date fruit ripening. To that end, we followed the natural process of date fruit development and the effects of exogenous hormone application on fruit ripening in the elite cultivar ‘Medjool’. The results of the current study indicate that the onset of fruit ripening occurre once the seed had reached maximum dry weight. From this point, fruit pericarp endogenous abscisic acid (ABA) levels consistently increased until fruit harvest. The final stage in fruit ripening, the yellow-to-brown transition, was preceded by an arrest of xylem-mediated water transport into the fruit. Exogenous ABA application enhanced fruit ripening when applied just before the green-to-yellow fruit color transition. Repeated ABA applications hastened various fruit ripening processes, resulting in earlier fruit harvest. The data presented supports a pivotal role for ABA in the regulation of date fruit ripening.
Phylotranscriptomics and evolution of key genes for terpene biosynthesis in Pinaceae
Authors: Jiang Kaibin , Du Chengju , Huang Linwang , Luo Jiexian , Liu Tianyi , Huang Shaowei
Published: February 2023

Pinaceae is the largest family of conifers, dominating forest ecosystems and serving as the backbone of northern, temperate and mountain forests. The terpenoid metabolism of conifers is responsive to pests, diseases, and environmental stress. Determining the phylogeny and evolution of terpene synthase genes in Pinaceae may shed light on early adaptive evolution. We used different inference methods and datasets to reconstruct the Pinaceae phylogeny based on our assembled transcriptomes. We identified the final species tree of Pinaceae by comparing and summarizing different phylogenetic trees. The genes encoding terpene synthase (TPS) and cytochrome P450 proteins in Pinaceae showed a trend of expansion compared with those in Cycas. Gene family analysis revealed that the number of TPS genes decreased while the number of P450 genes increased in loblolly pine. Expression profiles showed that TPSs and P450s were mainly expressed in leaf buds and needles, which may be the result of long-term evolution to protect these two vulnerable tissues. Our research provides insights into the phylogeny and evolution of terpene synthase genes in Pinaceae and offers some useful references for the investigation of terpenoids in conifers.
Starting university during the pandemic: First-year international students’ complex transitions under online and hybrid-learning conditions
Authors: Wang Lizhou
Published: February 2023

International education activities suddenly halted due to the COVID-19 pandemic, severely disrupting student mobility and academic learning. Many educational institutions have delivered programs to students through digital devices globally rather than in situ. Such a shift presents a unique opportunity to assess the impact of online and hybrid education for international students. This qualitative study interviewed 30 international students who had arrived on campus and shared their first-year university transition experiences during the pandemic. The analysis shows that spatial and temporal circumstances created two scenarios and thus resulted in different first-year university experiences. Although all students were dissatisfied with online learning, studying at a distance in different time zones was particularly detrimental to international students’ mental and physical health. The (im)mobile environments led to mismatches in expectations, roles, activities, and realities, negatively affecting student learning and adjustment. This study highlights the complex international transition issues and offers implications for sustainable online and hybrid-learning practices in the educational system.
A risk-based decision framework for policy analysis of societal pandemic effects
Authors: Danielson Mats , Ekenberg Love , Komendantova Nadejda , Mihai Adriana
Published: February 2023

Introduction

In this article, we summarize our findings from an EU-supported project for policy analyses applied to pandemics such as Covid-19 (with the potential to be applied as well to other, similar hazards) while considering various mitigation levels and consequence sets under several criteria.

Methods

It is based on our former development for handling imprecise information in risk trees and multi-criteria hierarchies using intervals and qualitative estimates. We shortly present the theoretical background and demonstrate how it can be used for systematic policy analyses. In our model, we use decision trees and multi-criteria hierarchies extended by belief distributions for weights, probabilities and values as well as combination rules to aggregate the background information in an extended expected value model, taking into criteria weights as well as probabilities and outcome values. We used the computer-supported tool DecideIT for the aggregate decision analysis under uncertainty.

Results

The framework has been applied in three countries: Botswana, Romania and Jordan, and extended for scenario-building during the third wave of the pandemic in Sweden, proving its feasibility in real-time policy-making for pandemic mitigation measures.

Discussion

This work resulted in a more fine-grained model for policy decision that is much more aligned to the societal needs in the future, either if the Covid-19 pandemic prevails or for the next pandemic or other society-wide hazardous emergencies.
The epidemic of HIV and syphilis and the correlation with substance abuse among men who have sex with men in China: A systematic review and meta-analysis
Authors: Zhao Tian , Chen Guohong , Sun Chengqing , Gong Xiangdong , Li Huiyong , Fu Gengfeng
Published: February 2023

Background

In China, the HIV/AIDS epidemic among men who have sex with men (MSM) has been expanding in recent years. Substance abuse in MSM was not well studied as the independent risk factor for HIV and syphilis infection and other sexually transmitted diseases. The present review aimed to determine the correlation between HIV/Syphilis infections and substance abuse and other sexual risk behaviors among MSM.

Methods

We conducted a comprehensive search of PubMed, Web of Science, Embase, Scopus, Chinese National Knowledge Infrastructure, Chinese Wanfang Data, and VIP Chinese Journal Database for relevant articles of quantitative studies published between 2010 and May 31, 2022. Meta-analysis was performed using R software. Pooled estimated of the association-odds ratio, with 95% confidence intervals were calculated using random-effects models stratified by study design. Q statistics and I2 were used to measure the heterogeneity.

Results

Our meta-analysis included 61,719 Chinese MSM from 52 eligible studies. The pooled HIV prevalence rate among substance-abusing MSM was 10.0% (95% CI = 0.08–0.13). Substance abusers were more likely to have a higher prevalence of HIV (OR = 1.59) and syphilis (OR = 1.48) infections than non-substance abusers. Substance abusers were also more likely to seek sexual partners through the internet or social media applications (OR = 1.63), engage in unprotected anal intercourse (UAI) (OR = 1.69), group sex (OR = 2.78), and engage in commercial intercourse (OR = 2.04) compared to non-users. Regarding testing behaviors, substance abusers had a higher proportion of HIV or STI testing in their lifetime (OR = 1.70) compared with non-substance abusers (p < 0.05). They were also more likely to have had more sexual partners (≥2; OR = 2.31) and more likely to have consumed alcohol (OR = 1.49) in the past 6 months.

Conclusions

Our study shows the correlation between substance abuse and HIV/Syphilis infection. Eliminating disparities in HIV/Syphilis infection among substance abusing men who have sex with men (MSM) can be achieved if the Chinese government and public health sectors could provide targeted knowledge popularization and diagnosis interventions among high-risk populations.