bluuebunny/crossref_metadata_2025 huggingface dataset:
Spatiotemporal parameters for energy efficient kilohertz-frequency nerve block with low onset response
Authors: Peña Edgar , Pelot Nicole A. , Grill Warren M.
Published: June 2023

Background

Electrical nerve conduction block has great potential for treatment of disease through reversible and local inactivation of somatic and autonomic nerves. However, the relatively high energy requirements and the presence of undesired excitation at the onset of the kilohertz-frequency (KHF) signals used for block pose obstacles to effective translation. Frequency, electrode geometry, and waveform shape are known to influence block threshold and onset response, but available data provide a limited understanding of how to select these parameters to optimize nerve block.

Methods

We evaluated KHF nerve block in rat tibial nerve across frequencies (5–60 kHz), electrode geometries (monopolar, bipolar, and tripolar), and waveform shapes. We present a novel Fourier-based method for constructing composite signals that systematically sample the KHF waveform design space.

Results

The lowest frequencies capable of blocking (5–16 kHz) were not the most energy-efficient among the tested frequencies. Further, bipolar cuffs required the largest current and power to block, monopolar cuffs required the lowest current, and both tripolar and monopolar cuffs required the lowest power. Tripolar cuffs produced the smallest onset response across frequencies. Composite signals comprised of a first harmonic sinusoid at fundamental frequency (f0) superposed on a second harmonic sinusoid at 2f0could block at lower threshold and lower onset response compared to the constituent sinusoids alone. This effect was strongly dependent on the phase of the second harmonic and on the relative amplitudes of the first and second harmonics. This effect was also dependent on electrode geometry: monopolar and tripolar cuffs showed clear composite signal effects in most experiments; bipolar cuffs showed no clear effects in most experiments.

Conclusions

Our data provide novel information about block threshold and onset response at the boundary of frequencies that can block. Our results also show an interaction between spatial (cuff geometry) and temporal (frequency and waveform shape) parameters. Finally, while previous studies suggested that temporal parameters could reduce onset response only in exchange for increased block threshold (or vice versa), our results show that waveform shape influences KHF response in ways that can be exploited to reducebothenergy and onset responses.
Three-dimensional femur morphology analysis for the optimal location of subtrochanteric osteotomy with an implanted Wagner cone stem in total hip arthroplasty for Crowe type IV developmental dysplasia of the hip
Authors: Tao Kun , Wang Shi-Cheng , Ma Xiao-Ying , Shao Long , Di Zheng-Lin , Huang Zhe-Yu
Published: June 2023

Background

This study aimed to accurately evaluate the matching of proximal and distal femoral segments and fitting of the femur–femoral stem in patients with Crowe type IV developmental dysplasia of the hip (DDH) who have undergone subtrochanteric osteotomy at different locations with an implanted Wagner cone stem to improve the rate of the bone union at the osteotomy site.

Methods

Three-dimensional femur morphology of 40 patients with Crowe type IV DDH was evaluated at each cross-section to determine the femoral cortical bone area. This study focused on five osteotomy lengths (2.5, 3, 3.5, 4, and 4.5 cm). The overlapped area between the proximal and distal cortical bone segments was defined as the contact area (S, mm2), and the contact area to distal cortical bone area ratio was defined as the coincidence rate (R). Three indicators were used to evaluate the matching and fitting of the osteotomy sites with the implanted Wagner cone stems: (1) higher S and R between the proximal and distal segments; (2) the effective fixation length of the femoral stem at the distal segments being at least 1.5 cm; and (3) osteotomy did not involve the isthmus.

Results

In all groups, S significantly decreased in the two proximal levels above the 0.5 cm level below the lesser trochanter (LT) compared with those below this level. In comparison, at osteotomy lengths from 2.5 to 4 cm, R significantly decreased in the three proximal levels. The optimal osteotomy levels ranged from 1.5 and 2.5 cm below the LT for an appropriately sized stem.

Conclusions

Subtrochanteric osteotomy at the optimal level not only ensures fitting of the femur–femoral stem but also meets the requirements of a higher S and R to ensure adequate reduction and stabilization at the osteotomy site, which may contribute to the bone union. Although the optimal osteotomy level varies with the size of the femoral stem and the length of the subtrochanteric osteotomy, the optimal osteotomy levels for an appropriately sized Wagner cone femoral stem implantation range from 1.5 to 2.5 cm below the LT.
The role of peripheral inflammatory insults in Alzheimer’s disease: a review and research roadmap
Authors: Walker Keenan A. , Le Page Lydia M. , Terrando Niccolò , Duggan Michael R. , Heneka Michael T. , Bettcher Brianne M.
Published: June 2023

Peripheral inflammation, defined as inflammation that occurs outside the central nervous system, is an age-related phenomenon that has been identified as a risk factor for Alzheimer’s disease. While the role of chronic peripheral inflammation has been well characterized in the context of dementia and other age-related conditions, less is known about the neurologic contribution of acute inflammatory insults that take place outside the central nervous system. Herein, we define acute inflammatory insults as an immune challenge in the form of pathogen exposure (e.g., viral infection) or tissue damage (e.g., surgery) that causes a large, yet time-limited, inflammatory response. We provide an overview of the clinical and translational research that has examined the connection between acute inflammatory insults and Alzheimer’s disease, focusing on three categories of peripheral inflammatory insults that have received considerable attention in recent years: acute infection, critical illness, and surgery. Additionally, we review immune and neurobiological mechanisms which facilitate the neural response to acute inflammation and discuss the potential role of the blood–brain barrier and other components of the neuro-immune axis in Alzheimer’s disease. After highlighting the knowledge gaps in this area of research, we propose a roadmap to address methodological challenges, suboptimal study design, and paucity of transdisciplinary research efforts that have thus far limited our understanding of how pathogen- and damage-mediated inflammatory insults may contribute to Alzheimer’s disease. Finally, we discuss how therapeutic approaches designed to promote the resolution of inflammation may be used following acute inflammatory insults to preserve brain health and limit progression of neurodegenerative pathology.
Amino acid metabolism in immune cells: essential regulators of the effector functions, and promising opportunities to enhance cancer immunotherapy
Authors: Yang Luming , Chu Zhaole , Liu Meng , Zou Qiang , Li Jinyang , Liu Qin , Wang Yazhou , Wang Tao , Xiang Junyu , Wang Bin
Published: June 2023

Amino acids are basic nutrients for immune cells during organ development, tissue homeostasis, and the immune response. Regarding metabolic reprogramming in the tumor microenvironment, dysregulation of amino acid consumption in immune cells is an important underlying mechanism leading to impaired anti-tumor immunity. Emerging studies have revealed that altered amino acid metabolism is tightly linked to tumor outgrowth, metastasis, and therapeutic resistance through governing the fate of various immune cells. During these processes, the concentration of free amino acids, their membrane bound transporters, key metabolic enzymes, and sensors such as mTOR and GCN2 play critical roles in controlling immune cell differentiation and function. As such, anti-cancer immune responses could be enhanced by supplement of specific essential amino acids, or targeting the metabolic enzymes or their sensors, thereby developing novel adjuvant immune therapeutic modalities. To further dissect metabolic regulation of anti-tumor immunity, this review summarizes the regulatory mechanisms governing reprogramming of amino acid metabolism and their effects on the phenotypes and functions of tumor-infiltrating immune cells to propose novel approaches that could be exploited to rewire amino acid metabolism and enhance cancer immunotherapy.
Immunotherapies targeting GPRC5D in relapsed or refractory multiple myeloma: latest updates from 2022 ASH Annual Meeting
Authors: Xia Jieyun , Li Zhenyu , Xu Kailin
Published: June 2023

B cell maturation antigen (BCMA)-targeted immunotherapy has shown unprecedented results in the treatment of relapsed or refractory (R/R) multiple myeloma (MM). However, disease progression remains an issue attributed to variable BCMA expression, BCMA downregulation, and heterogeneity of tumor antigens in MM. Therefore, additional treatment options with novel therapeutic targets are warranted. G protein-coupled receptor, class C group 5 member D (GPRC5D), an orphan receptor expressed on malignant plasma cells with limited expression in normal tissue, has emerged as a promising therapeutic target for R/R MM. GPRC5D-targeted chimeric antigen receptor (CAR)-T and CAR-NK cell therapy, as well as bispecific T cell engagers, offer remarkable anti-tumor activities. We summarized some latest reports on GPRC5D-targeted treatments for R/R MM from the 2022 ASH Annual Meeting (ASH 2022).
m6A-mediated upregulation of LINC01003 regulates cell migration by targeting the CAV1/FAK signaling pathway in glioma
Authors: Zhu Xiaolong , Wu Xingwei , Yang Hui , Xu Qiancheng , Zhang Mengying , Liu Xiaocen , Lv Kun
Published: June 2023

Background

Long non-coding RNAs (lncRNAs) play important roles in the progression of glioma. Here, we examined the potential functions of a lncRNA, LINC01003, in glioma and characterized the underlying molecular mechanisms.

Methods

The GEIPA2 and Chinese Glioma Genome Atlas (CCGA) databases were employed to analyze gene expression and the overall survival curve in patients with glioma. The functions of LINC01003 in glioma growth and migration were assessed by loss-of-function experiments in vitro and in vivo. RNA sequencing was used to determine the signaling pathways effected by LINC01003. Bioinformatics analysis and RNA immunoprecipitation (RIP) assays were used to explore the mechanism underlying the N6-methyladenine (m6A) modification-dependent upregulation of LINC01003 in glioma.

Results

LINC01003 expression was upregulated in glioma cell lines and tissues. Higher LINC01003 expression predicted shorter overall survival time in glioma patients. Functionally, LINC01003 knockdown inhibited the cell cycle and cell proliferation and migration in glioma cells. Mechanistically, RNA sequencing revealed that LINC01003 mediated the focal adhesion signaling pathway. Furthermore, LINC01003 upregulation is induced by m6A modification regulated by METTL3.

Conclusion

This study characterized LINC01003 as a lncRNA that contributes to tumorigenesis in glioma and demonstrated that the LINC01003-CAV1-FAK axis serves as a potential therapeutic target for glioma.
Effect of pelvic floor muscle training on reports of urinary incontinence in obese women undergoing a low-calorie diet before bariatric surgery — protocol of a randomized controlled trial
Authors: Mendes Pauliana C. S. , Fretta Tatiana B. , Camargo Milena F. C. , Driusso Patricia , Homsi Jorge Cristine
Published: June 2023

Background

Obesity represents a growing threat to health with multiple negative impacts including urinary incontinence. Pelvic floor muscle training (PFMT) is the first line of treatment for urinary incontinence. Both surgical and conservative weight loss results in improvement of urinary incontinence reports in obese women and we hypothesize that a low-calorie diet in combination with PFMT would result in additional beneficial effects to urinary symptoms in women with UI compared would with weight loss alone.

Objective

To assess the effect of a low-calorie diet plus PFMT protocol in obese women’s urinary incontinence reports.

Methods

This is a protocol for a randomized controlled trial that will include obese women reporting UI and being able to contract their pelvic floor muscles. The participants will be randomly allocated in two groups: group 1 will participate in a 12-week protocol of low-calorie diet delivered by a multi-professional team at a tertiary hospital; group II will receive the same low-calorie diet protocol during 12 weeks and will additionally participate in 6 group sessions of supervised PFMT delivered by a physiotherapist. The primary outcome of the study is self-reported UI, and severity and impact of UI on women’s quality of life will be assessed by the ICIQ-SF score. The secondary outcomes will be adherence to the protocols assessed using a home diary, pelvic floor muscle function assessed by bidigital vaginal palpation and the modified Oxford grading scale, and women’s self-perception of their PFM contraction using a questionnaire. Satisfaction with treatments will be assessed using a visual analog scale. The statistical analysis will be performed by intention to treat and multivariate analysis of mixed effects will be used to compare outcomes. The complier average causal effects (CACE) method will be used to assess adherence. There is an urgent need for a high-quality RCT to investigate if the association of a low-calorie diet and PFMT can provide a larger effect in the improvement of urinary incontinence reports in women with obesity.

Trial registration

Clinical Trials NCT04159467. Registered on 08/28/2021.
Synthesis and drag reduction properties of a hydrophobically associative polymer containing ultra-long side chains
Authors: Jing Xianwu , Liu Youquan , Zhao Wanwei , Pu Junhong
Published: June 2023

Different from common hydrophobic associative polymers, a new hydrophobic associative polyacrylamide (HAPAM) with ultra-long side chains was synthesized and aimed to be used as drag reducer in this work. Firstly, a water-soluble hydrophobic monomer (named AT114) was obtained by alcoholysis reaction with acryloyl chloride and triton 114, then the drag reducer was obtained by radical copolymerization of AM, AMPS and AT114. The structures of AT114 and drag reducer were characterized by IR and NMR. Slick water was obtained by dissolving a small amount drag reducer in water. Although the viscosity of slick water varied greatly in fresh water and brine, the drag reduction rate always remained at a high level when flowing in pipelines. When the concentration of the drag reducer was 0.03% in fresh water, drag reduction rate can be up to 76.7%, while in high concentration brine, still as high as 76.2%. It shows that salt has no obvious negative impact on the drag reduction rate. That is also to say, in the case of low viscosity, the viscosity change has no obvious impact on drag reduction rate. From the Cryo-TEM observation, it can be concluded that the drag reducer forms sparse network structures in water, which is the direct reason for drag reducing effect. This finding provides knowledge regarding the development of new drag reducers.
Epidemiological characteristics and risk factors for cystic and alveolar echinococcosis in China: an analysis of a national population-based field survey
Authors: Ma Tian , Wang Qian , Hao Mengmeng , Xue Chuizhao , Wang Xu , Han Shuai , Wang Qian , Zhao Jiangshan , Ma Xiao , Wu Xianglin , Jiang Xiaofeng , Cao Lei , Yang Yaming , Feng Yu , Gongsang Quzhen , Scheffran Jürgen , Fang Liqun , Maude Richard James , Zheng Canjun , Ding Fangyu , Wu Weiping , Jiang Dong
Published: June 2023

Background

Human cystic and alveolar echinococcosis are neglected tropical diseases that WHO has prioritized for control in recent years. Both diseases impose substantial burdens on public health and the socio-economy in China. In this study, which is based on the national echinococcosis survey from 2012 to 2016, we aim to describe the spatial prevalence and demographic characteristics of cystic and alveolar echinococcosis infections in humans and assess the impact of environmental, biological and social factors on both types of the disease.

Methods

We computed the sex-, age group-, occupation- and education level-specific prevalences of cystic and alveolar echinococcosis at national and sub-national levels. We mapped the geographical distribution of echinococcosis prevalence at the province, city and county levels. Finally, by analyzing the county-level echinococcosis cases combined with a range of associated environmental, biological and social factors, we identified and quantified the potential risk factors for echinococcosis using a generalized linear model.

Results

A total of 1,150,723 residents were selected and included in the national echinococcosis survey between 2012 and 2016, of whom 4161 and 1055 tested positive for cystic and alveolar echinococcosis, respectively. Female gender, older age, occupation at herdsman, occupation as religious worker and illiteracy were identified as risk factors for both types of echinococcosis. The prevalence of echinococcosis was found to vary geographically, with areas of high endemicity observed in the Tibetan Plateau region. Cystic echinococcosis prevalence was positively correlated with cattle density, cattle prevalence, dog density, dog prevalence, number of livestock slaughtered, elevation and grass area, and negatively associated with temperature and gross domestic product (GDP). Alveolar echinococcosis prevalence was positively correlated with precipitation, level of awareness, elevation, rodent density and rodent prevalence, and negatively correlated with forest area, temperature and GDP. Our results also implied that drinking water sources are significantly associated with both diseases.

Conclusions

The results of this study provide a comprehensive understanding of geographical patterns, demographic characteristics and risk factors of cystic and alveolar echinococcosis in China. This important information will contribute towards developing targeted prevention measures and controlling diseases from the public health perspective.

Graphical Abstract
Identifying primary and secondary MLH1 epimutation carriers displaying low-level constitutional MLH1 methylation using droplet digital PCR and genome-wide DNA methylation profiling of colorectal cancers
Authors: Joo Jihoon E. , Mahmood Khalid , Walker Romy , Georgeson Peter , Candiloro Ida , Clendenning Mark , Como Julia , Joseland Sharelle , Preston Susan , Graversen Lise , Wilding Mathilda , Field Michael , Lemon Michelle , Wakeling Janette , Marfan Helen , Susman Rachel , Isbister Joanne , Edwards Emma , Bowman Michelle , Kirk Judy , Ip Emilia , McKay Lynne , Antill Yoland , Hopper John L. , Boussioutas Alex , Macrae Finlay A. , Dobrovic Alexander , Jenkins Mark A. , Rosty Christophe , Winship Ingrid M. , Buchanan Daniel D.
Published: June 2023

Background

MLH1 epimutation is characterised by constitutional monoallelic MLH1 promoter hypermethylation, which can cause colorectal cancer (CRC). Tumour molecular profiles of MLH1 epimutation CRCs were used to classify germline MLH1 promoter variants of uncertain significance and MLH1 methylated early-onset CRCs (EOCRCs). Genome-wide DNA methylation and somatic mutational profiles of tumours from two germline MLH1: c.-11C > T and one MLH1: c.-[28A > G; 7C > T] carriers and three MLH1 methylated EOCRCs (< 45 years) were compared with 38 reference CRCs. Methylation-sensitive droplet digital PCR (ddPCR) was used to detect mosaic MLH1 methylation in blood, normal mucosa and buccal DNA.

Results

Genome-wide methylation-based Consensus Clustering identified four clusters where the tumour methylation profiles of germline MLH1: c.-11C > T carriers and MLH1 methylated EOCRCs clustered with the constitutional MLH1 epimutation CRCs but not with the sporadic MLH1 methylated CRCs. Furthermore, monoallelic MLH1 methylation and APC promoter hypermethylation in tumour were observed in both MLH1 epimutation and germline MLH1: c.-11C > T carriers and MLH1 methylated EOCRCs. Mosaic constitutional MLH1 methylation in MLH1: c.-11C > T carriers and 1 of 3 MLH1 methylated EOCRCs was identified by methylation-sensitive ddPCR.

Conclusions

Mosaic MLH1 epimutation underlies the CRC aetiology in MLH1: c.-11C > T germline carriers and a subset of MLH1 methylated EOCRCs. Tumour profiling and ultra-sensitive ddPCR methylation testing can be used to identify mosaic MLH1 epimutation carriers.
Novel insights into systemic sclerosis using a sensitive computational method to analyze whole-genome bisulfite sequencing data
Authors: Yu Jeffrey C. Y. , Zeng Yixiao , Zhao Kaiqiong , Lu Tianyuan , Oros Klein Kathleen , Colmegna Inés , Lora Maximilien , Bhatnagar Sahir R. , Leask Andrew , Greenwood Celia M. T. , Hudson Marie
Published: June 2023

Background

Abnormal DNA methylation is thought to contribute to the onset and progression of systemic sclerosis. Currently, the most comprehensive assay for profiling DNA methylation is whole-genome bisulfite sequencing (WGBS), but its precision depends on read depth and it may be subject to sequencing errors. SOMNiBUS, a method for regional analysis, attempts to overcome some of these limitations. Using SOMNiBUS, we re-analyzed WGBS data previously analyzed using bumphunter, an approach that initially fits single CpG associations, to contrast DNA methylation estimates by both methods.

Methods

Purified CD4+ T lymphocytes of 9 SSc and 4 control females were sequenced using WGBS. We separated the resulting sequencing data into regions with dense CpG data, and differentially methylated regions (DMRs) were inferred with the SOMNiBUS region-level test, adjusted for age. Pathway enrichment analysis was performed with ingenuity pathway analysis (IPA). We compared the results obtained by SOMNiBUS and bumphunter.

Results

Of 8268 CpG regions of ≥ 60 CpGs eligible for analysis with SOMNiBUS, we identified 131 DMRs and 125 differentially methylated genes (DMGs; p-values less than Bonferroni-corrected threshold of 6.05–06 controlling family-wise error rate at 0.05; 1.6% of the regions). In comparison, bumphunter identified 821,929 CpG regions, 599 DMRs (of which none had ≥ 60 CpGs) and 340 DMGs (q-value of 0.05; 0.04% of all regions). The top ranked gene identified by SOMNiBUS was FLT4, a lymphangiogenic orchestrator, and the top ranked gene on chromosome X was CHST7, known to catalyze the sulfation of glycosaminoglycans in the extracellular matrix. The top networks identified by IPA included connective tissue disorders.

Conclusions

SOMNiBUS is a complementary method of analyzing WGBS data that enhances biological insights into SSc and provides novel avenues of investigation into its pathogenesis.
APOE4 carrier status determines association between white matter disease and grey matter atrophy in early-stage dementia
Authors: Vipin Ashwati , Kumar Dilip , Soo See Ann , Zailan Fatin Zahra , Leow Yi Jin , Koh Chen Ling , Ng Adeline Su Lyn , Ng Kok Pin , Kandiah Nagaendran
Published: June 2023

Background

White matter hyperintensities, a neuroimaging marker of small-vessel cerebrovascular disease and apolipoprotein ε4 (APOE4) allele, are important dementia risk factors. However, APOE4 as a key effect modifier in the relationship between white matter hyperintensities and grey matter volume needs further exploration.

Methods

One hundred ninety-two early-stage dementia (including mild cognitive impairment and mild dementia) and 259 cognitively unimpaired participants from a neurocognitive research cohort with neuroimaging data, APOE genotyping, and neuropsychological assessments were studied. We investigated independent and interactive effects of white matter hyperintensities and APOE4 on whole-brain voxel-wise grey matter volume using voxel-based morphometry (uncorrectedp < 0.001; minimum cluster size = 100 voxels). We further assessed interactive effects between APOE4 and white matter hyperintensities on global cognition, memory, and executive function in early-stage dementia and cognitively unimpaired participants.

Results

Independent of APOE4 status, higher white matter hyperintensity load was associated with greater grey matter atrophy across frontal, parietal, temporal, and occipital lobes in cognitively unimpaired and early-stage dementia subjects. However, interaction analyses and independent sample analyses revealed that APOE4 non-carriers demonstrated greater white matter hyperintensity-associated grey matter atrophy compared to APOE4 carriers in both cognitively unimpaired and early-stage dementia groups. Additional confirmatory analyses among APOE4 non-carriers demonstrated that white matter hyperintensities resulted in widespread grey matter loss. Analyses of cognitive function demonstrated that higher white matter hyperintensity load was associated with worse global (Mini-Mental State Examination, Montreal Cognitive Assessment) and executive function (Color Trails 2) in APOE4 non-carriers compared to APOE4 carriers in early-stage dementia but not cognitively unimpaired participants.

Conclusions

The association between white matter hyperintensities and grey matter loss is more pronounced in APOE4 non-carriers than APOE4 carriers in the cognitively unimpaired and early-stage dementia stages. Furthermore, white matter hyperintensity presence results in poorer executive function in APOE4 non-carriers compared to APOE4 carriers. This finding may have significant impact on the design of clinical trials with disease modifying therapies.
Endogenous and viral microRNAs in nasal secretions of water buffaloes (Bubalus bubalis) after Bubaline alphaherpesvirus 1 (BuHV-1) challenge infection
Authors: Lecchi Cristina , Ceciliani Fabrizio , Petrini Stefano , Cappelli Giovanna , Grassi Carlo , Balestrieri Anna , Galiero Giorgio , DeCarlo Ester , Salvi Gaspare , Panzeri Filippo , Gini Chiara , Cafiso Alessandra , Agazzi Alessandro , Martucciello Alessandra
Published: June 2023

Bubaline alphaherpesvirus 1 (BuHV-1) is a pathogen of water buffaloes responsible for economic loss worldwide. MicroRNAs (miRNAs) regulate gene expression produced by alphaherpesviruses and hosts. This study aimed at (a) unravelling the ability of BuHV-1 to produce miRNAs, including hv1-miR-B6, hv1-miR-B8, hv1-miR-B9; (b) measuring the host immune-related miRNAs associated to herpesvirus infection, including miR-210-3p, miR-490-3p, miR-17-5p, miR-148a-3p, miR-338-3p, miR-370-3p, by RT-qPCR; (c) identifying candidate markers of infection by receiver-operating characteristic (ROC) curves; (d) exploiting the biological functions by pathway enrichment analyses. Five water buffaloes BuHV-1 and Bovine alphaherpesvirus 1 (BoHV-1) free were immunized against Infectious Bovine Rhinotracheitis (IBR). Five additional water buffaloes served as negative controls. All animals were challenged with a virulent wild-type (wt) BuHV-1 via the intranasal route 120 days after the first vaccination. Nasal swabs were obtained at days (d) 0, 2, 4, 7, 10, 15, 30, and 63 post-challenge (pc). The animals of both groups shed wt BuHV-1 up to d7 pc. Results demonstrated that (a) miRNAs produced by the host and BuHV-1 could be efficiently quantified in the nasal secretion up to d63 and d15 pc, respectively; b) the levels of host and BuHV-1 miRNAs are different between vaccinated and control buffaloes; c) miR-370-3p discriminated vaccinated and control animals; d) host immune-related miRNAs may modulate genes involved in the cell adhesion pathway of the neuronal and immune system. Overall, the present study provides evidence that miRNAs can be detected in nasal secretions of water buffaloes and that their expression is modulated by BuHV-1.
Amelioration of olfactory dysfunction in a mouse model of Parkinson’s disease via enhancing GABAergic signaling
Authors: Liu Xing-Yang , Wang Ke , Deng Xian-Hua , Wei Yi-Hua , Guo Rui , Liu Sui-Feng , Zhu Yi-Fan , Zhong Jia-Jun , Zheng Jing-Yuan , Wang Meng-Dan , Ye Qiu-Hong , He Jian-Quan , Guo Kai-Hang , Zhu Jun-Rong , Huang Shu-Qiong , Chen Ze-Xu , Lv Chong-Shan , Wen Lei
Published: June 2023

Background

Olfactory dysfunction is among the earliest non-motor symptoms of Parkinson’s disease (PD). As the foremost pathological hallmark, α-synuclein initiates the pathology in the olfactory pathway at the early stage of PD, particularly in the olfactory epithelium (OE) and olfactory bulb (OB). However, the local neural microcircuit mechanisms underlying olfactory dysfunction between OE and OB in early PD remain unknown.

Results

We observed that odor detection and discrimination were impaired in 6-month-old SNCA-A53T mice, while their motor ability remained unaffected. It was confirmed that α-synuclein increased and accumulated in OB but not in OE. Notably, the hyperactivity of mitral/tufted cells and the excitation/inhibition imbalance in OB were found in 6-month-old SNCA-A53T mice, which was attributed to the impaired GABAergic transmission and aberrant expression of GABA transporter 1 and vesicular GABA transporter in OB. We further showed that tiagabine, a potent and selective GABA reuptake inhibitor, could reverse the impaired olfactory function and GABAergic signaling in OB of SNCA-A53T mice.

Conclusions

Taken together, our findings demonstrate potential synaptic mechanisms of local neural microcircuit underlying olfactory dysfunction at the early stage of PD. These results highlight the critical role of aberrant GABAergic signaling of OB in early diagnosis and provide a potential therapeutic strategy for early-stage PD.
The fear in desire: linking desire thinking and fear of missing out in the social media context
Authors: Brandtner Annika , Wegmann Elisa
Published: June 2023

According to the Elaborated Intrusion Theory of Desire, desire thinking and an associated deficit are fundamental factors to the emergence of craving. In the special case of problematic social networking sites (SNS) use, this experienced deficit could be constituted of an online-specific fear of missing out (FoMO). To test the interaction of these cognitions and their influence on problematic SNS use, we tested a serial mediation model on a sample of N = 193 individuals who use SNS (73% female, Mage = 28.3, SD = 9.29). We found that desire thinking predicted FoMO and both variables were only significant predictors of problematic SNS use when considered in interplay with craving. Ad hoc analyses revealed that the verbal subcomponent of desire thinking is more strongly associated with FoMO than imaginal prefiguration. Our results highlight that neither desire thinking nor FoMO are inherently dysfunctional but become problematic when they increase craving for potentially problematic SNS use.
Forecasting returns volatility of cryptocurrency by applying various deep learning algorithms
Authors: Khan Farman Ullah , Khan Faridoon , Shaikh Parvez Ahmed
Published: June 2023

The study aims at forecasting the return volatility of the cryptocurrencies using several machine learning algorithms, like neural network autoregressive (NNETAR), cubic smoothing spline (CSS), and group method of data handling neural network (GMDH-NN) algorithm. The data used in this study is spanning from April 14, 2017, to October 30, 2020, covering 1296 observations. We predict the volatility of four cryptocurrencies, namely Bitcoin, Ethereum, XRP, and Tether, and compare their predictive power in terms of forecasting accuracy. The predictive capabilities of CSS, NNETAR, and GMDH-NN are compared and evaluated by mean absolute error (MAE) and root-mean-square error (RMSE). Regarding the return volatility of Bitcoin and XRP markets, the forecasted results remarkably suggest that in contrast to rival approaches, the CSS can be an effective model to boost the predicting accuracy in the sense that it has the lowest forecast errors. Considering the Ethereum markets’ volatility, the MAE and RMSE associated with NNETAR are smaller than the MAE and RMSE of CSS and GMDH-NN algorithm, which ensures the effectiveness of NNETAR as compared to competing approaches. Similarly, in case of Tether markets’ volatility, the corresponding MAE and RMSE reveal that the GMDH-NN algorithm is an efficient technique to enhance the forecasting performance. We notice that no single tool performed uniformly for all cryptocurrency markets. The policymakers can adopt the model for forecasting cryptocurrency volatility accordingly.
Psychiatry in Dissent: Anthony Clare's critique, defence and reinvigoration of psychiatry
Authors: Kelly Brendan D.
Published: June 2023

Psychiatry in Dissent: Controversial Issues in Thought and Practice was published in 1976. In the book, Irish psychiatrist Anthony Clare (1942–2007) both defended and critiqued contemporary psychiatry. He demystified the field, analysed its problems and argued that psychiatry, for all its flaws, offered a reasoned and reasonable path forward. His arguments remain fiercely relevant today, sometimes eerily so.
The World Psychiatry Exchange Program in Iran: a unique academic and personal experience
Authors: Ben Said Cyrine , Ben Abid Hela , Shalbafan Mohammadreza , Pinto da Costa Mariana
Published: June 2023

The World Psychiatry Exchange Program in Iran is an academic experience we are delighted to share. As two participating early career psychiatrists, a local psychiatry faculty member manager, and the lead founder and international coordinator of the programme, we focus in this article on the unfolding of this new learning experience, the difficulties we encountered and the main lessons learned by the participants: commonalities and differences in training and practice in general adult psychiatry and child psychiatry in Tunisia and Iran, as well as in idioms of distress between the Arab and Persian cultures.
XMoSiN2 (X = S, Se, Te): A novel 2D Janus semiconductor with ultra-high carrier mobility and excellent thermoelectric performance
Authors: Ding Chang-Hao , Duan Zhi-Fu , Ding Zhong-Ke , Pan Hui , Wang Jue , Xiao Wei-Hua , Liu Wang-Ping , Li Qiu-Qiu , Luo Nan-Nan , Zeng Jiang , Ren Wei , Tang Li-Ming , Chen Ke-Qiu
Published: June 2023

Two-dimensional (2D) semiconductor

is a potential candidate for thermoelectric materials due to its high Seebeck coefficient. However, its high lattice thermal conductivity limits its applications in the field of thermoelectric materials. Here, we constructed an unsymmetrical 2D Janus semiconductor XMoSiN2(X = S, Se, Te) based on

to significantly reduce the lattice thermal conductivity to only one-sixth that of

at 300 K. We found that XMoSiN2 had an ultra-high carrier mobility up to 4640 cm2V−1s−1 leading to a metal-like electrical conductivity. Meanwhile, XMoSiN2 reserved the high Seebeck coefficient of

. The lower lattice thermal conductivity and metal-like electrical conductivity resulted in excellent thermoelectric performance.

possessed a record-high ZT value of 3.57 at 900 K. We believed that other materials with a similar structure to XMoSiN2 can also be potential candidates for high-performance thermoelectric materials. Our work provides valuable insights into designing novel high-performance thermoelectric materials.
Long-term Course of Cognitive Functioning After Aneurysmal and Angiographically Negative Subarachnoid Hemorrhage
Authors: Khosdelazad Sara , Jorna Lieke S. , Rakers Sandra E. , Koffijberg Ralf , Groen Rob J. M. , Spikman Jacoba M. , Buunk Anne M.
Published: June 2023

BACKGROUND AND OBJECTIVES:

Cognitive impairment is a common consequence of subarachnoid hemorrhage (SAH), negatively affecting everyday functioning. This study is the first to investigate the long-term course of cognitive functioning after SAH and its associations with long-term well-being (ie, anxiety and depression), cognitive complaints, and return to work, separately for patients with aneurysmal SAH (aSAH) and angiographically negative SAH (anSAH) in a longitudinal design.

METHODS:

Cognitive functioning was measured at 2 time points (T1: 3-6 months post-SAH; T2: 2-4 years post-SAH) in 58 patients with aSAH and 22 patients with anSAH with neuropsychological tests for (working) memory, psychomotor speed, and attention/executive functioning. Questionnaires were used to measure cognitive complaints and well-being at T1 and T2 and return to work at T2.

RESULTS:

At T2, patients with aSAH only showed improvements in memory and on an executive functioning and psychomotor speed subtest, whereas in contrast, patients with anSAH had significantly poorer scores on tests for psychomotor speed. A significant amount of patients with aSAH and anSAH still reported cognitive complaints, anxiety, and depression in the chronic stage. Cognitive functioning was not significantly associated with cognitive complaints in both SAH groups. On the other hand, cognitive complaints were related to well-being at the long-term in both SAH groups. More cognitive complaints were also associated with more difficulties in return to work in patients with aSAH.

CONCLUSION:

Patients with aSAH and anSAH have cognitive impairments at the subacute stage post-SAH, and these impairments persist into the chronic stage. Moreover, both SAH groups still reported decreased well-being in the chronic stage post-SAH, related to cognitive complaints but not to cognitive impairment. For clinical practice, an early neuropsychological assessment will already provide relevant information to estimate long-term cognitive impairment, but in addition, it is important to pay attention to psychological distress at the long-term.
Aquaporin regulates cell rounding through vacuole formation during endothelial-to-hematopoietic transition
Authors: Sato Yuki , Shigematsu Mugiho , Shibata-Kanno Maria , Maejima Sho , Tamura Chie , Sakamoto Hirotaka
Published: June 2023

Endothelial-to-hematopoietic transition (EHT) is crucial for hematopoietic stem cell (HSC) generation. During EHT, the morphology of hemogenic endothelial cells (HECs) changes from flat and adherent to spherical hematopoietic cells, which detach from the dorsal aorta. HECs attain a rounded shape in a mitosis-independent manner before cell adhesion termination, suggesting an atypical cell-rounding mechanism. However, the direct mechanisms underlying this change in cell morphology during EHT remain unclear. Here, we show that large vacuoles were transiently formed in avian HECs, and that aquaporin 1 (AQP1) was localized in the vacuole and plasma membranes. Overexpression of AQP1 in non-HECs induced ectopic vacuole expansion, cell rounding and subsequent cell detachment from the endothelium into the bloodstream, mimicking EHT. Loss of redundant AQP functions by CRISPR/Cas9 gene editing in HECs impeded the morphological EHT. Our findings provide the first evidence to indicate that morphological segregation of hematopoietic cells from endothelial cells is regulated by water influx into vacuoles. These findings provide important insights for further exploration of the mechanisms underlying cell/tissue morphogenesis through water-adoptive cellular responses.
Endocytosis in Dictyostelium discoideum amoebae: Inhibition by cyclohexlmide and other inhibitors of protein synthesis
Authors: Gonzalez Carlos , Satre Michel
Published: June 2023

Cycloheximide, an inhibitor of protein synthesis, inhibited endocytosis pathways in the vegetative amoebae of the cellular slime mold Dictyostelium discoideum. Half-maximal inhibition of fluid-phase pinocytosis in nutrient medium or in buffer occurred at 0.08 mM or 0.35 mM cycloheximide, respectively. Other inhibitors of eucaryotic protein synthesis inhibited fluid-phase pinocytosis, with the following IC50 in nutrient medium: 0.15 mM anisomycin, ImM emetine, 0.25 mM puromycin. Kinetic studies showed that the inhibitory effects of cycloheximide occurred rapidly, with a half-time of less than 10 min, and were fully reversible upon removal of the drug. Both fluid-phase pinocytic influx and efflux were inhibited by cycloheximide, which furthermore prevented the vanadate-induced efflux of fluorescein-labeled dextran, the fluid-phase marker used in these experiments. The massive secretion of lysosomal enzymes: acid phosphatase, N-acetylhexosaminidase or α-mannosidase, which follows overloading of the endosomal compartment by sucrose, was also inhibited by cycloheximide. All these phenomena were unimpaired by cycloheximide in the cycloheximide-resistant (cycAl) mutant strain X6.
Bidirectional Approach with PIPAC and Systemic Chemotherapy for Patients with Synchronous Gastric Cancer Peritoneal Metastases (GCPM)
Authors: Casella Francesco , Bencivenga Maria , Brancato Giorgio , Torroni Lorena , Ridolfi Cecilia , Puccio Carmelo , Alloggio Mariella , Meloni Francesca , Fusario Daniele , Marrelli Daniele , Giacopuzzi Simone , Roviello Franco , de Manzoni Giovanni
Published: June 2023

Background

This study evaluated the efficacy of pressurized intraperitoneal aerosol chemotherapy (PIPAC) with systemic chemotherapy as a bidirectional approach for gastric cancer (GC) patients with synchronous peritoneal metastases (SPM).

Methods

A retrospective analysis of a prospective PIPAC database was queried for patients who underwent a bidirectional approach between October 2019 and April 2022 at two high-volume GC surgery units in Italy (Verona and Siena). Surgical and oncological outcomes were analyzed.

Results

Between October 2019 and April 2022, 74 PIPAC procedures in 42 consecutive patients with Eastern Cooperative Oncology Group performance status ≤2 were performed—32 patients treated in Verona and 10 in Siena. Twenty-seven patients (64%) were female and median age at first PIPAC was 60.5 years (I–III quartiles: 49–68 years). Median Peritoneal Cancer Index (PCI) was 16 (I–III quartiles: 8–26) and 25 patients (59%) had at least two PIPAC procedures. Major complications according to the Common Terminology Criteria for Adverse Events (CTCAE; 3 and 4) occurred in three (4%) procedures, and, according to the Clavien–Dindo classification (>3a), one (1%) severe complication occurred. There were no reoperations or deaths within 30 days. Median overall survival (mOS) from diagnosis was 19.6 months (range 14–24), and mOS from first PIPAC was 10.5 months (range 7–13). Excluding cases with very heavy metastatic peritoneal burden, with PCI from 2 to 26, treated with more than one PIPAC, mOS from diagnosis was 22 months (range 14–39). Eleven patients (26%) underwent curative-intent surgery after a bidirectional approach. R0 was achieved in nine (82%) patients and complete pathological response was obtained in three (27%) cases.

Conclusions

Patient selection is associated with bidirectional approach efficacy and feasibility for SPM GC treatment, which may allow potentially curative surgical radicalization in highly selected cases.
How Experiments with Children Inform Economics
Authors: List John A. , Petrie Ragan , Samek Anya
Published: June 2023

In the past several decades, the experimental method has lent deep insights into economics. One area that has contributed is the experimental study of children, where advances as varied as the evolution of human behaviors that shape markets and institutions to how early life influences shape later life outcomes, have been explored. We first develop a framework for economic preference measurement that provides a lens into how to interpret data from experiments with children. Next, we survey work that provides general empirical insights within our framework and provide a comprehensive summary of experimental methods used with children. Finally, we provide 10 tips for pulling off experiments with children, including factors such as taking into account child competencies, causal identification, and logistical issues related to recruitment and implementation. We envision the experimental study of children as a high-growth research area in the coming decades as social scientists begin to more fully appreciate that children are active participants in markets who (might) respond predictably to economic incentives. (JEL C90, D11, D83, D91, J13, J16, Z13)
From Micro to Macro Development
Authors: Buera Francisco J. , Kaboski Joseph P. , Townsend Robert M.
Published: June 2023

Macroeconomic development remains an important policy goal because of its ability to lift entire populations out of poverty. In our review of the literature, we emphasize that the best way to achieve this objective is to embrace a synthesis of methods and ideas, with the science of experiments as a unifying feature. Randomized controlled trials need representative data and structural modeling, and macro models need to be designed and disciplined to the realities and data of developing-country economies. Macroeconomic models have key lessons for gathering and analyzing micro evidence and for moving to an evaluation of macro policy. Resource constraints, heterogeneity, general equilibrium effects, obstacles to trade, dynamics, and returns to scale can all play key roles. A synthesis for macro development is well under way. (JEL C93, D00, E00, O10, O11, O12)
Fluorescent labeling of RNA and DNA on the Hoogsteen edge using sulfinate chemistry
Authors: Bassi Tiziano , Hirlinger Anastassia , Grayson Leah , Vantourout Julien , Toor Navtej
Published: June 2023

We have devised a single pot, low-cost method to add azide groups to unmodified nucleic acids without the need for enzymes or chemically modified nucleoside triphosphates. This involves reacting an azide-containing sulfinate salt with the nucleic acid, leading to replacement of C–H bonds on the nucleobase aromatic rings with C–R, where R is the azide-containing linker derived from the original sulfinate salt. With the addition of azide functional groups, the modified nucleic acid can easily be reacted with any alkyne-labeled compound of interest, including fluorescent dyes as shown in this work. This methodology enables the fluorescent labeling of a wide variety of nucleic acids, including natively folded RNAs, under mild conditions with minimal effects upon biochemical function and ribozyme catalysis. To demonstrate this, we show that a pair of labeled complementary ssDNA oligonucleotides (oligos) can hybridize to form dsDNA, even when labeled with multiple fluorophores per oligo. In addition, we also demonstrate that two different group II introns can splice when prelabeled internally with fluorophores, using our method. Broadly, this demonstrates that sulfinate modification of RNA is compatible with ribozyme function and Watson–Crick pairing, while preserving the labile backbone.
La construcción de los derechos menstruales como derecho fundamental en el sistema jurídico colombiano
Authors: Ariza García Laura Sofía , Puentes Villota Juliana del Pilar
Published: June 2023

El presente artículo busca abordar la equidad de género abriendo una discusión alrededor de los derechos menstruales, haciendo énfasis en el reconocimiento legal de los derechos menstruales como derechos fundamentales. A través de la metodología cualitativa se realizó una revisión sistemática de normativa, jurisprudencia nacional e internacional, informes de ONG’s y doctrina, para profundizar en las causas que permiten el detrimento en distintos aspectos de la vida de las personas menstruantes. Una vez realizado el análisis propuesto, se concluye que los derechos menstruales se categorizan como fundamentales debido a su conexión intrínseca al ejercicio de la dignidad humana, vida e integridad personal de quienes menstrúan, ya que se trata de un proceso natural.