bluuebunny/crossref_metadata_2025 huggingface dataset:
The Correlation Between Immune Invasion and SARS-COV-2 Entry Protein ADAM17 in Cancer Patients by Bioinformatic Analysis
Authors: Wang Kai , Deng Haoyue , Song Binghui , He Jiayue , Liu Shuguang , Fu Jiewen , Zhang Lianmei , Li Dabing , Balaji Kyathegowdanadoddi Srinivasa , Mei Zhiqiang , Cheng Jingliang , Fu Junjiang
Published: June 2022

SARS-Cov-2 caused the COVID-19 pandemic worldwide. ADAM17 functions as a disintegrin and transmembrane metalloproteinase domain protein involved in the regulation of SARS-CoV-2 receptor ACE2. However, its impact on cancer patients infected with COVID-19 and its correlation with immune cell infiltration is unclear. This study compared ADAM17 expression between normal and tumor tissues based on GEPIA. The correlations between ADAM17 expression and immune cell infiltration and immunomodulators were investigated. Besides, treated drugs for targeting ADAM17 were searched in the TISDB database. We found that ADAM17 was highly conserved in many species and was mainly expressed in lung, brain, female tissues, bone marrow and lymphoid tissues. It was also highly expressed in respiratory epithelial cells of rhinitis and bronchus. ADAM17 expression in tumors was higher than that in several paired normal tissues and was negatively correlated with the prognosis of patients with malignant tumors. Interestingly, ADAM17 expression significantly correlated with immunomodulators and immune cell infiltration in normal and tumor tissues. Moreover, eight small molecules targeting ADAM17 only demonstrate therapeutic significance. These findings imply important implications for ADAM17 in cancer patients infected with COVID-19 and provide new clues for development strategy of anti-COVID-19.
Effects of Temperature on the Bioenergetics of the Marine Protozoans Gyrodinium dominans and Oxyrrhis marina
Authors: Calbet Albert , Martínez Rodrigo Andrés , Saiz Enric , Alcaraz Miquel
Published: June 2022

We exposed Gyrodinium dominans and two strains of Oxyrrhis marina to temperatures well above (25°C) and below (12°C) their maintenance temperature (18°C) to study the mechanisms controlling the overall physiological response to thermal stress. As variables, we measured growth, ingestion, and respiration rates (this latter with and without food). The growth rates of O. marina strains plotted as a function of temperature showed maximum values at the maintenance temperature, as expected in a typical unimodal functional response. However, G. dominans showed similar growth rates at 12 and 18°C, and even a marked decrease in growth rates at 25°C, happened to be not significant. G. dominans ingestion rates were not significantly different at all temperatures (although apparently decreased at 25°C), whereas both O. marina strains showed higher ingestion rates at 18°C. The respiration rates of G. dominans were unaffected by temperature, but those of O. marina strains increased with temperature. The specific dynamic action (respiration increase produced by feeding activity) ranged from 2 to 20% of the daily carbon ingestion for all organisms investigated. The calculated energetic budget indicated that the responses to temperature were diverse, even between in strains of the same species. G. dominans maintained similar growth at all temperatures by balancing metabolic gains and losses. In O. marina strains, on the other hand, the decrease in growth rates at the lowest temperature was driven mainly by reduced ingestion rates. However, increased respiration seemed the primary factor affecting the decrease in growth rates at the highest temperature. These results are discussed in the light of previous studies and on its suitability to understand the response of wild organisms to fluctuations in temperature.
Controlling Light to Optimize Growth and Added Value of the Green Macroalga Codium tomentosum
Authors: Marques Rúben , Moreira Anthony , Cruz Sónia , Calado Ricardo , Cartaxana Paulo
Published: June 2022

Codium tomentosumis a recently domesticated green macroalga, being currently cultured as an extractive species in integrated multi-trophic aquaculture (IMTA). Optimization of light requirements in outdoor systems must be achieved to increase the market value of cultivated algal biomass. The present study addresses the seasonal effects of light intensity and wavelength on productivity, pigment composition and epiphyte overgrowth inC. tomentosumcultured in a land-based IMTA system. Exposure to high light (non-filtered sun light) lead to higher net productivities in spring. However, non-filtered sun light caused significantly reduced productivities during summer when compared to filtered sun light (~ 4x lower irradiance levels). Furthermore, lower photosynthetic capacity (Fv/Fm) was observed in macroalgae cultured under high light during summer, indicating photoinhibition. Treatments with filtered sun light (low and red light) showed intermediate and more stable productivities. Epiphyte biomass was higher under high light and the lowest epiphyte overgrowth was recorded under red light. Concentrations of light-harvesting pigments were lower in summer than in spring, indicating a seasonal photoacclimation of macroalgae. An opposite seasonal trend was observed for accessory xanthophylls, as the main role of these pigments is photoprotection. Higher all-trans-neoxanthin and violaxanthin concentrations were found in high light than in low or red light treatments, confirming the important role of these biomolecules in the photoprotection ofC. tomentosum. This study underlines the importance of controlling light to optimize algal growth outdoors and enhance the production of high-value compounds (i.e., pigments). Additionally, this practice can also reduce epiphyte overgrowth, thus enhancing the valorization of macroalgal biomass derived fromC. tomentosumaquaculture.
Synthesis of Biochar From Lignocellulosic Biomass for Diverse Industrial Applications and Energy Harvesting: Effects of Pyrolysis Conditions on the Physicochemical Properties of Biochar
Authors: Mukherjee Alivia , Patra Biswa R. , Podder Jiban , Dalai Ajay K.
Published: June 2022

The excessive dependency on fossil fuel resources could be curtailed by the efficient conversion of lignocellulosic biomass. Biochar, a porous carbonaceous product synthesized exploiting thermochemical conversion pathway, could be an environment-friendly replacement of fossil fuel resources. Slow pyrolysis, a sub-class among various thermochemical conversion techniques, has gained immense popularity owing to its potential to convert biomass to biochar. Furthermore, biochar obtained as the by-product of slow pyrolysis has attracted enormous popularity due to its proven role and application in the multidisciplinary areas of engineering and environmental remediation applications. The physicochemical quality of biochar and its performance is significantly dependent on the feedstock type and pyrolysis process parameters. Therefore, further experimental research and investigations in terms of lignocellulose biomass type and pyrolytic process parameters (temperature, heating rate and reaction time) are essential to produce biochar with desired physicochemical features for effective utilization. This review presents an updated report on slow pyrolysis of lignocellulosic biomass, impact of different pyrolysis parameters and degradation pathway involved in the evolution properties of biomass. The influence of the feedstock type and lignocellulosic composition on the biochar properties are also discussed meticulously. The co-relationship between biochar yield at different pyrolysis temperatures and the development of textural properties provides valuable information for their effective utilization as a functional carbon material. Additionally, an extensive study was undertaken to collate and discuss the excellent physicochemical characteristics of biochar and summarizes the benefits of biochar application for diverse industrial purposes. Biochar is acknowledged for its excellent physicochemical properties owing to the thermal treatment and as a result its prospective diverse industrial applications such as for soil treatment, carbon sequestration, adsorbent (wastewater treatment or CO2 capture), producing activated carbon for gold recovery, energy storage and supercapacitor are summarized systematically in this review paper. For instance, biochar when applied in soil have shown improvement in soil respiration by 1.9 times. Furthermore, biochar when used to capture CO2 from flue gas stream under post-combustion scenario has demonstrated superior capture performance (2.8 mmol/g) compared to commercial activated carbon. This paper identified the knowledge gaps and outlooks in the field of the advancements of biochar from slow pyrolysis for targeted engineering applications mainly in the field of environmental remediation and energy harvesting.
A Comparative Study of CoNi-LDH/ZnO Film for Photocathodic Protection Applications in the Marine Environment
Authors: Zhang Xuan , Wang Yanhua , Zhang Dongmei , Tao Zhencheng
Published: June 2022

In this study, two kinds of Co–Ni-layer double hydroxide (LDH)/ZnO films were prepared with different morphologies by a simple electrochemical method. The properties of the films were investigated by SEM, XRD, UV–Vis DRS, XPS, and electrochemical techniques. It was found that Co–Ni-LDH-modified ZnO films exhibited excellent photocathodic properties in a scavenger-free environment. This is mainly due to the absorption of visible light by LDH, the formation ofp–nheterojunction, and the depletion of photo-generated holes by the cycling process of Co (II)/Co (III). Compared with CoNi-LDH/ZnO nanorods, CoNi-LDH/ZnO nanoclusters showed better photocathodic protection performance and physical barrier effect. Under illumination conditions, the rough surface of ZnO nanoclusters and the deposition of a large amount of LDH can provide more photoelectrochemical active sites, thus improving the light absorption capacity and photocathodic protection performance of CoNi-LDH/ZnO nanoclusters. Under dark conditions, the physical barrier effect of CoNi-LDH/ZnO nanoclusters was also enhanced by the dense ZnO nanoclusters and thick CoNi-LDH layers.
Ultra-Broadband Sound Absorbing Materials Based on Periodic Gradient Impedance Matching
Authors: Wu Fei , Zhang Xiao , Ju Zegang , Zhao Jiang , Hu Man , Gao Mingyuan , Luo Jun , Pu Huayan
Published: June 2022

Ultra-broadband sound absorption with periodic gradient impedance matching is of great concern in the research of acoustic materials. This study investigates the impedance matching of composite acoustic metamaterials comprising micro-perforated plates (MPPs) and subsequent Fabry–Pérot(FP) channels. Based on the impedance matching theory, ultra-broadband sound absorption has been realized through a design with 36 channels whose thickness is only 50 mm. Also, the average sound absorption coefficient of 88% and an absorption frequency bandwidth (490–4000 Hz) can be achieved by preserving the matching impedance. Furthermore, by changing the thickness of the perfect absorber being 100 mm, the average sound absorption coefficient can reach greater than 90% in the frequency range of 250–4500 Hz. The proposed structure is validated analytically and experimentally. This work can help with designing and improving the method of acoustic metasurfaces and especially have the potential in ultra-broadband sound absorber designs.
Study on Molecular Information Intelligent Diagnosis and Treatment of Bladder Cancer on Pathological Tissue Image
Authors: Bai Yanfeng , Wang Huogen , Wu Xuesong , Weng Menghan , Han Qingmei , Xu Liming , Zhang Han , Chang Chengdong , Jin Chaohui , Chen Ming , Luo Kunfeng , Teng Xiaodong
Published: June 2022

Background

Molecular information about bladder cancer is significant for treatment and prognosis. The immunohistochemistry (IHC) method is widely used to analyze the specific biomarkers to determine molecular subtypes. However, procedures in IHC and plenty of reagents are time and labor-consuming and expensive. This study established a computer-aid diagnosis system for predicting molecular subtypes, p53 status, and programmed death-ligand 1 (PD-L1) status of bladder cancer with pathological images.

Materials and Methods

We collected 119 muscle-invasive bladder cancer (MIBC) patients who underwent radical cystectomy from January 2016 to September 2018. All the pathological sections are scanned into digital whole slide images (WSIs), and the IHC results of adjacent sections were recorded as the label of the corresponding slide. The tumor areas are first segmented, then molecular subtypes, p53 status, and PD-L1 status of those tumor-positive areas would be identified by three independent convolutional neural networks (CNNs). We measured the performance of this system for predicting molecular subtypes, p53 status, and PD-L1 status of bladder cancer with accuracy, sensitivity, and specificity.

Results

For the recognition of molecular subtypes, the accuracy is 0.94, the sensitivity is 1.00, and the specificity is 0.909. For PD-L1 status recognition, the accuracy is 0.897, the sensitivity is 0.875, and the specificity is 0.913. For p53 status recognition, the accuracy is 0.846, the sensitivity is 0.857, and the specificity is 0.750.

Conclusion

Our computer-aided diagnosis system can provide a novel and simple assistant tool to obtain the molecular subtype, PD-L1 status, and p53 status. It can reduce the workload of pathologists and the medical cost.
Case Report: Metagenomic Next-Generation Sequencing Clinches the Diagnosis of Acute Q Fever and Verified by Indirect Immunofluorescence Assay
Authors: Yang Yide , Shi Qingmiao , Jin Qian , Yang Zhangnv , Li Wangfang , Han Jianfeng , Mao Juanjuan , Zheng Beiwen
Published: June 2022

Q fever is a zoonotic infectious disease caused by Coxiella burnetii. The clinical symptoms of acute Q fever are usually atypical, and routine serological tests of C. burnetii are not readily available, making the diagnosis of Q fever a challenge. In this case, we report a male patient who had repeated fevers and was administered empirical anti-infective treatment, but the effect was poor. After conducting relevant laboratory and imagological examinations, the etiology has not yet been confirmed. Subsequently, metagenomic next-generation sequencing (mNGS) identified the sequence reads of C. burnetii from the patient's peripheral blood within 48 h, and then the diagnosis of acute Q fever was established. Moreover, the serological test of indirect immunofluorescence assay (IFA) of the C. burnetii antibody was further performed in the Centers for Disease Control, certifying the result of mNGS. The patient was ultimately treated with doxycycline and recovered well. mNGS is an unbiased and comprehensive method in infrequent or culture-negative pathogen identification. To our knowledge, this is the first case of acute Q fever identified by mNGS and confirmed by IFA in Taizhou, China. A further large-scale prospective clinical cohort study is worth carrying out to compare the diagnostic efficiency of mNGS with traditional serological methods and PCR in acute Q fever.
Social Engagement in the Fight Against COVID-19 in the Urban and Peri-Urban Areas of Cotonou (Benin, Sub-saharan Africa): Acceptability of the Vaccination and Tracking Program
Authors: Maccaro Alessia , Piaggio Davide , Oronti Iyabosola Busola , Vignigbé Marius , Gbokli Antoinette , Houngnihin Roch , Pecchia Leandro
Published: June 2022

Introduction

This article aims at investigating social engagement in the fight against the COVID-19 pandemic in low-resource settings (LRSs). In particular, it focuses on Benin (Sub-Saharan Africa), and reports the results of a field study that investigated the local people's acceptance of the vaccine and the tracking program.

Methods

This project is the product of a collaboration between the ABSPIE (Applied Biomedical and Signal Processing E-Health) Lab of the University of Warwick (UK) and the LAMA (Laboratoire d'Antropologie Medical Appliqué) of the University of Abomey Calavi (Benin). This international multidisciplinary collaboration brought together engineers, sociologists, anthropologists, and bioethicists. In light of the aims of the project, a qualitative methodology was deemed appropriate. The research team prepared two questionnaires that provided the basis for semi-structured interviews that took place between June and August 2021.

Results

The research team interviewed 34 Beninese respondents, comprising people aged 60+ (with multiple comorbidities), who were primarily healthcare workers and/or traditional therapists. The results of this work highlight the fact that there is widespread reticence about the vaccination program in Benin, both due to local beliefs and uncertainty about governmental management. In this study, we uncovered several local reasons interfering with the involvement of the population in the vaccination campaign against COVID-19, e.g., the existence of traditional medical practices considered as valid alternatives to vaccines, and many beliefs showing a fear of neo-colonialism hidden in the pandemic threat. Yet, another hindrance can be traced to shortcomings in the management of the vaccination campaign which resulted in obstacles to the implementation of the program.

Conclusions

This work does not intend to denounce any governmental effort or foster a regressive mindset, but shows how the overall confusion (defined by the World Health Organization as infodemic) linked to the pandemic and its management has caused even more dramatic consequences in LRSs. In addition, the paper proposes a specific framework for the interpretation and management of bioethical and biomedical issues in LRSs that the authors are validating in their current research.
Acupuncture to Improve Patient Discomfort During Upper Gastrointestinal Endoscopy: Systematic Review and Meta-Analysis
Authors: Gao Ning , Chen Huan , Wang Yang , Guo Yufeng , Liu Zhishun , Wang Weiming
Published: June 2022

Background and Aims

Severe discomfort during an upper gastrointestinal endoscopy (UGE) is often a stressful experience for patients undergoing the procedure. An increasing number of studies have shown that acupuncture may reduce discomfort during UGE. A systematic review in 2004 investigated the effect of acupuncture for gastrointestinal endoscopy, but these data have not been recently reviewed. Therefore, this study was conducted to evaluate the current evidence and provide up-to-date knowledge for clinical decision-making.

Methods

Nine databases were searched from inception to June 2021. Eligible randomized controlled trials (RCTs) were included. The outcome data were synthesized where necessary, and risks of bias of included studies were assessed using RevMan V.5.3.

Results

Twenty-three eligible RCTs with 3,349 patients were identified. It was found that acupuncture plus topical pharyngeal anesthesia with lidocaine hydrochloride (TPALH) resulted in greater improvements regarding visual analog scale (VAS) scores and the incidence of nausea and vomiting (INV) when compared with TPALH alone. These results were consistent among studies of manual acupuncture, electroacupuncture, auricular-plaster, superficial needle (SFN) and acupressure. In the meta-analysis, SFN plus TPALH showed significant improvement of VAS scores compared to sham SFN plus TPALH (MD −1.11, 95% CI −1.52 to −0.70, P < 0.00001). Most of included studies did not report any side effects in their findings, and were of medium-to-high risk of bias.

Conclusion

Acupuncture, as adjunctive therapy to TPA, may result in less patient discomfort than TPA alone. Findings from this review should be interpreted with caution due to the high heterogeneity identified. There is low-quality evidence supporting the use of acupuncture over sham. More rigorously designed RCTs are needed to inform clinical decision-making.

Systematic Review Registration

PROSPERO [CRD42014008966].
Diagnostic and Therapeutic Approach in ANCA-Associated Glomerulonephritis: A Review on Management Strategies
Authors: Molnár Adél , Studinger Péter , Ledó Nóra
Published: June 2022

Anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis is a destructive small vessel vasculitis affecting multiple organs. Renal involvement often leads to end-stage renal disease and increases mortality. Prompt diagnosis and initiation of adequate immunosuppressive therapy are critical for the best patient and kidney outcomes. However, considerable heterogeneity in symptoms and severity across the patients frequently hinder the diagnosis and management. The objective of this review is to emphasize the heterogeneity of the ANCA-associated vasculitis, facilitate the recognition and give guidance to the therapeutical possibilities. We present epidemiologic and risk factors, pathogenesis, and provide comprehensive clinical features of the disease. This article also focuses on the currently available therapeutic options and emerging cellular and molecular targets for the management of systemic and especially renal disease. We conducted extensive literature research published on PubMed and Google Scholar. We systematically reviewed, analyzed, and assembled databases, covering a broad spectrum of aspects of the disease. We compared and summarized the recommendations of two recent guidelines on ANCA-associated vasculitis. The incidence of ANCA-associated vasculitis, hence glomerulonephritis shows a steady increase. Familiarity with the presenting symptoms and laboratory abnormalities are necessary for rapid diagnosis. Early initiation of treatment is the key aspect for favorable patient and renal outcomes. A better understanding of the pathogenesis constantly leads to more targeted and therefore more efficient and less toxic treatment.
The HIDDEN Protocol: An Australian Prospective Cohort Study to Determine the Utility of Whole Genome Sequencing in Kidney Failure of Unknown Aetiology
Authors: Soraru Jacqueline , Jahan Sadia , Quinlan Catherine , Simons Cas , Wardrop Louise , O’Shea Rosie , Wood Alasdair , Mallawaarachchi Amali , Patel Chirag , Stark Zornitza , Mallett Andrew John
Published: June 2022

Early identification of genetic kidney disease allows personalised management, clarification of risk for relatives, and guidance for family planning. Genetic disease is underdiagnosed, and recognition of genetic disease is particularly challenging in patients with kidney failure without distinguishing diagnostic features. To address this challenge, the primary aim of this study is to determine the proportion of genetic diagnoses amongst patients with kidney failure of unknown aetiology, using whole genome sequencing (WGS). A cohort of up to 100 Australian patients with kidney failure of unknown aetiology, with onset <50 years old and approved by a panel of study investigators will be recruited via 18 centres nationally. Clinically accredited WGS will be undertaken with analysis targeted to a priority list of ∼388 genes associated with genetic kidney disease. The primary outcome will be the proportion of patients who receive a molecular diagnosis (diagnostic rate) via WGS compared with usual -care (no further diagnostic investigation). Participant surveys will be undertaken at consent, after test result return and 1 year subsequently. Where there is no or an uncertain diagnosis, future research genomics will be considered to identify candidate genes and new pathogenic variants in known genes. All results will be relayed to participants via the recruiting clinician and/or kidney genetics clinic. The study is ethically approved (HREC/16/MH/251) with local site governance approvals in place. The future results of this study will be disseminated and inform practical understanding of the potential monogenic contribution to kidney failure of unknown aetiology. These findings are anticipated to impact clinical practice and healthcare policy.

Study Registration

[https://dora.health.qld.gov.au], identifier [HREC/16/MH/251].
Using Artificial Intelligence to Establish Chest X-Ray Image Recognition Model to Assist Crucial Diagnosis in Elder Patients With Dyspnea
Authors: Liong-Rung Liu , Hung-Wen Chiu , Ming-Yuan Huang , Shu-Tien Huang , Ming-Feng Tsai , Chia-Yu Chang , Kuo-Song Chang
Published: June 2022

Pneumonia and pulmonary edema are the most common causes of acute respiratory failure in emergency and intensive care. Airway maintenance and heart function preservation are two foundations for resuscitation. Laboratory examinations have been utilized for clinicians to early differentiate pneumonia and pulmonary edema; however, none can provide results as prompt as radiology examinations, such as portable chest X-ray (CXR), which can quickly deliver results without mobilizing patients. However, similar features between pneumonia and pulmonary edema are found in CXR. It remains challenging for Emergency Department (ED) physicians to make immediate decisions as radiologists cannot be on-site all the time and provide support. Thus, Accurate interpretation of images remains challenging in the emergency setting. References have shown that deep convolutional neural networks (CNN) have a high sensitivity in CXR readings. In this retrospective study, we collected the CXR images of patients over 65 hospitalized with pneumonia or pulmonary edema diagnosis between 2016 and 2020. After using the ICD-10 codes to select qualified patient records and removing the duplicated ones, we used keywords to label the image reports found in the electronic medical record (EMR) system. After that, we categorized their CXR images into five categories: positive correlation, negative correlation, no correlation, low correlation, and high correlation. Subcategorization was also performed to better differentiate characteristics. We applied six experiments includes the crop interference and non-interference categories by GoogLeNet and applied three times of validations. In our best model, the F1 scores for pneumonia and pulmonary edema are 0.835 and 0.829, respectively; accuracy rate: 83.2%, Recall rate: 83.2%, positive predictive value: 83.3%, and F1 Score: 0.832. After the validation, the best accuracy rate of our model can reach up to 73%. The model has a high negative predictive value of excluding pulmonary edema, meaning the CXR shows no sign of pulmonary edema. At the time, there was a high positive predictive value in pneumonia. In that way, we could use it as a clinical decision support (CDS) system to rule out pulmonary edema and rule in pneumonia contributing to the critical care of the elderly.
Would Chinese Men Who Have Sex With Men Take Up Human Papillomavirus (HPV) Screening as an Alternative Prevention Strategy to HPV Vaccination?
Authors: Chan Paul Shing-fong , Fang Yuan , Chidgey Andrew , Fong Francois , Ip Mary , Wang Zixin
Published: June 2022

Background

Men who have sex with men (MSM) are at high risk for human papillomavirus (HPV) infection. A community-based organization (CBO)-private clinic service model promoting HPV vaccination among MSM was implemented in Hong Kong. The aim of this study was to evaluate the effectiveness of this service model in increasing HPV screening among MSM.

Methods

This was a secondary analysis of the CBO-private clinic service model in increasing HPV screening among MSM. Participants were Hong Kong Chinese-speaking MSM aged 18–45 years who had never received HPV vaccination. All participants completed a telephone survey at baseline before receiving online intervention promoting HPV vaccination and completed another telephone survey 12 months afterward.

Results

A total of 350 participants completed a baseline telephone survey and received interventions promoting HPV vaccination. Among 274 participants being followed up at Month 12, 33 (12.0%) received any type of HPV screening during the study period. Such uptake rate was similar to the prevalence of HPV screening in the past year measured at baseline (12.0 vs. 9.9%, p = 0.43). More MSM preferred HPV vaccination or HPV vaccination plus HPV screening, and very few preferred HPV screening alone. After adjusting for significant baseline characteristics, higher perceived susceptibility to HPV (adjusted odds ratio (AOR): 1.16, 95% confidence interval (CI): 1.00–1.34) and receiving HPV vaccination during the study period (AOR: 7.03, 95% CI: 3.07–16.13) were significantly associated with higher HPV screening uptake.

Conclusions

The CBO-private clinic service model promoting HPV vaccination had limited impact in increasing HPV screening among MSM in Hong Kong. MSM in Hong Kong may not use HPV screening as an alternative prevention strategy to HPV vaccination. Future programs preventing HPV-related diseases among MSM in Hong Kong should focus on HPV vaccination promotion.
Comparison of the Gut Microbiota in Healthy Infants With Different Delivery Modes and Feeding Types: A Cohort Study
Authors: Ma Jingran , Li Zhenghong , Zhang Wenjuan , Zhang Chunli , Zhang Yuheng , Mei Hua , Zhuo Na , Wang Hongyun , Wu Dan
Published: June 2022

To compare the gut microbiota of healthy infants based on specific interactions of delivery modes and feeding types, we recruited 62 healthy babies who were followed up for 2 years from our previous cohort study of 91 infants (the rest were lost to follow-up). They were exclusively fed breast milk or specific formulas for more than 4 months after birth. The fecal bacterial composition was tested at 40 days, 3 months, and 6 months of age. Solid foods were introduced from 4 to 6 months of age and thus did not affect the microbiota before 4 months of age. According to the different delivery modes (i.e., vaginal delivery, VD, or cesarean section delivery, CS) and feeding types (i.e., breast-fed, br, or formula-fed, fo), the infants were assigned to four different groups, namely, the VD-br, VD-fo, CS-br, and CS-fo groups. We found that at 40 days of age, the α diversity (reported as the Shannon index) was lower in the br infants than in the fo infants. At 3 months of age, the α diversity was significantly lower in the CS-br group, although significant differences were not observed after solid food introduction. Bifidobacterium represented the most predominant genus in all groups at all time points, followed by Enterobacteriaceae. At 40 days of age, the abundance of Bifidobacterium was much higher in the CS-br group than in the CS-fo group but did not differ between the VD-br and VD-fo groups. The differences in Bifidobacterium disappeared at 3 and 6 months of age among the different groups. At 40 days of age, the abundance of Streptococcus and Enterococcus was much lower in the br infants than in the CS-fo group. At 3 months of age, Enterococcus was significantly lower in the CS-br group than in the fo infants, although for infants delivered by VD, the difference between feeding types was not significant. The specific interaction of delivery modes and feeding types has a large impact on the infants' gut microbiota. Breastfeeding and VD may decrease the potential adverse effects of formula feeding or CS delivery on gut microbiota, thus leading to a more stable and beneficial gut environment for infants.
Inhibiting UCH-L5: Rational Design of a Cyclic Ubiquitin-Based Peptide Inhibitor
Authors: Hameed Dharjath S. , Ovaa Huib , van der Heden van Noort Gerbrand J. , Sapmaz Aysegul
Published: June 2022

The ubiquitin-proteasome system is an essential regulator of many cellular processes including controlling protein homeostasis. The degradation of proteins by the multi-subunit proteasome complex is tightly regulated through a series of checkpoints, amongst which are a set of deubiquitinating proteases (DUBs). The proteasome-associated DUBs, UCH-L5 (Ubiquitin carboxyl-terminal hydrolase isozyme L5) and USP14 (Ubiquitin-specific protease 14), and the integral-DUB in the proteasome, Rpn11, is known to regulate proteasomal degradation by deubiquitination of distinct substrates. Although selective inhibitors for USP14 and Rpn11 have been recently developed, there are no known inhibitors that selectively bind to UCH-L5. The X-ray structure of the Ubiquitin (Ub) bound to UCH-L5 shows a β-sheet hairpin in Ub that contains a crucial hydrophobic patch involved in the interaction with UCH-L5. Herein, we designed and developed both a Ub sequence-based linear- and cyclic- β-sheet hairpin peptide that was found to preferably inhibit UCH-L5. We show that these peptides have low micromolar IC50values and the cyclic peptide competes with the activity-based UbVME (Ubiquitin-Vinyl-Methyl-Ester) probe for UCH-L5, binding in a concentration-dependent manner. We further establish the selectivity profile of the cyclic peptide for UCH-L5 compared to other members of the UCH-DUB family and other cysteine DUBs in cell lysate. Furthermore, the cyclic peptide infiltrated cells resulting in the accumulation of polyUb chains, and was found to be non-toxic at the concentrations used here. Taken together, our data suggest that the cyclic peptide permeates the cell membrane, inhibits UCH-L5 by possibly blocking its deubiquitinating function, and contributes to the accumulation of polyubiquitinated substrates. The implications of inhibiting UCH-L5 in the context of the 26S proteasome render it an attractive candidate for further development as a potential selective inhibitor for therapeutic purposes.
Effects of Moxa Cone Moxibustion Therapy on Cognitive Function and Brain Metabolic Changes in MCI Patients: A Pilot 1H-MRS Study
Authors: Mai Wei , Zhang Aizhen , Liu Qiang , Tang Liying , Wei Yichen , Su Jiahui , Duan Gaoxiong , Teng Jinlong , Nong Xiucheng , Yu Bihan , Li Chong , Shao Lijuan , Deng Demao , Chen Shangjie , Zhao Lihua
Published: June 2022

Objective

To explore the effect of moxa cone moxibustion on N-acetyl aspartate/total creatinine (NAA/tCr) and choline/total creatinine (Cho/tCr) in the bilateral hippocampus (HIP) and bilateral posterior cingulate gyrus (PCG) in patients with mild cognitive impairment (MCI) using hydrogen proton magnetic resonance spectroscopy (1H-MRS) and to provide imaging basis for moxa cone moxibustion treatment for MCI.

Methods

One hundred eight patients with MCI were served as the MCI group, and 67 age-matched subjects were enrolled as the normal control group. The MCI group was randomized and allocated into acupoint group, drug group, and sham acupoint group, with 36 cases in each group. Some patients in each group withdrew. Finally, 25 cases were included in the acupoint group, 24 cases in the drug group, and 20 cases in the sham acupoint group. The drug group was treated with oral donepezil hydrochloride. The acupoint group and sham acupoint group received moxa cone moxibustion treatment. Mini-mental state exam (MMSE) and Montreal cognitive assessment (MoCA) scores were recorded before intervention, at the end of the first and the second months of intervention, and in the 5th month of follow-up. The NAA/tCr and Cho/tCr ratios in the HIP and PCG were bilaterally measured by 1H-MRS before and after intervention.

Results

Before intervention, compared with the normal control group, the MMSE and MoCA scores, the Cho/tCr ratio in the right HIP, the NAA/tCr ratio in the bilateral HIP, and the NAA/tCr ratio in the left PCG in the three treatment groups decreased significantly (both p < 0.01), and the NAA/tCr ratio in the right PCG significantly reduced in the acupoint and drug groups (p < 0.05). After two months of treatment, compared with the normal control group, there were no differences in the MoCA scores, the NAA/tCr, and Cho/tCr ratios in the bilateral PCG and bilateral HIP in the three treatment groups (p > 0.05). However, the MMSE scores in the drug group decreased when compared with the acupoint group and normal control group (p < 0.05, p < 0.01). The scores of MMSE and MoCA in the acupoint group and sham acupoint group at all time points were better than those in the drug group, which were similar to those in the normal control group.

Conclusion

Our findings suggest that moxibustion could improve the cognitive function of patients with MCI. The mechanism may be related to the improvement of abnormal brain metabolism in HIP and PCG.
Long Term Cognitive Function After Cardiac Arrest: A Mini-Review
Authors: Hagberg Guri , Ihle-Hansen Håkon , Sandset Else Charlotte , Jacobsen Dag , Wimmer Henning , Ihle-Hansen Hege
Published: June 2022

Out-of-hospital cardiac arrest (OHCA) is a leading cause of mortality worldwide. With better pre- and inhospital treatment, including cardiopulmonary resuscitation (CPR) as an integrated part of public education and more public-access defibrillators available, OHCA survival has increased over the last decade. There are concerns, after successful resuscitation, of cerebral hypoxia and degrees of potential acquired brain injury with resulting poor cognitive functioning. Cognitive function is not routinely assessed in OHCA survivors, and there is a lack of consensus on screening methods for cognitive changes. This narrative mini-review, explores available evidence on hypoxic brain injury and long-term cognitive function in cardiac arrest survivors and highlights remaining knowledge deficits.
Integrated Analyses of Microbiomics and Metabolomics Explore the Effect of Gut Microbiota Transplantation on Diabetes-Associated Cognitive Decline in Zucker Diabetic Fatty Rats
Authors: Bi Tingting , Zhang Lijing , Zhan Libin , Feng Ruiqi , Zhao Tian , Ren Weiming , Hang Tianyi , Zhou Wen , Lu Xiaoguang
Published: June 2022

Diabetes-associated cognitive decline (DACD), one of the complications of type 2 diabetes (T2DM), correlates significantly with the disorder in glycolipid metabolism, insulin/leptin resistance, and accumulation of β-amyloid (Aβ). Although gut microbiota transplantation (GMT), a novel non-invasive physiotherapy strategy, has been a promising intervention to alleviate the symptoms of T2DM, its protective effect on progressive cognitive decline remains elusive. Here, we transplanted the gut microbiota of healthy or cognitive decline donor rats into ZDF or LZ rats, and integrated microbiomics and metabolomics to evaluate the directional effect of the gut microbiota on the recipient rats. The basal metabolism phenotype changed in ZDF rats instead of in LZ rats. One possible mechanism is that the microbiota and metabolites alter the structure of the intestinal tract, stimulate the brain insulin and leptin signaling pathways, and regulate the deposition of Aβ in the brain. It is worth noting that 10 species of genera, such as Parabacteroides, Blautia, and Lactobacillus, can regulate 20 kinds of metabolites, such as propanoic acid, acetic acid, and citramalic acid, and having a significant improvement on the cognitive behavior of ZDF rats. In addition, the correlation analysis indicated the gut microbiota and metabolites are highly associated with host phenotypes affected by GMT. In summary, our study indicates that altering the microbiota-gut-brain axis by reshaping the composition of gut microbiota is a viable strategy that has great potential for improving cognitive function and combatting DACD.
Phenotyping Young GluA1 Deficient Mice – A Behavioral Characterization in a Genetic Loss-of-Function Model
Authors: Reiber Maria , Stirling Helen , Sprengel Rolf , Gass Peter , Palme Rupert , Potschka Heidrun
Published: June 2022

Alterations of glutamatergic neurotransmission have been implicated in neurodevelopmental and neuropsychiatric disorders. Mice lacking the GluA1 AMPA receptor subunit, encoded by the Gria1 gene, display multiple phenotypical features associated with glutamatergic dysfunction. While the phenotype of adult GluA1 deficient (Gria1–/–) mice has been studied comprehensively, there are relevant gaps in knowledge about the course and the onset of behavioral alterations in the Gria1 knockout mouse model during post-weaning development. Based on former investigations in young wild-type mice, we exposed female and male adolescent Gria1–/– mice to a behavioral home-cage based testing battery designed for the purpose of severity assessment. Data obtained from mice with a constitutive loss of GluA1 were compared with those from wild-type littermates. We identified several genotype-dependent behavioral alterations in young Gria1–/– mice. While the preference for sweetness was not affected by genotype during adolescence, Gria1–/– mice displayed limited burrowing performance, and reached lower nest complexity scores. Analysis of home-cage based voluntary wheel running performance failed to confirm genotype-dependent differences. In contrast, when exposed to the open field test, Gria1–/– mice showed pronounced hyperlocomotion in early and late adolescence, and female Gria1–/– mice exhibited thigmotaxis when prepubescent. We found increased corticosterone metabolite levels in fecal samples of adolescent Gria1–/– mice with females exhibiting increased adrenocortical activity already in prepubescence. Considering the course of behavioral modifications in early and late adolescence, the results do not support a persistent level of distress associated with GluA1 deficiency in the line. In contrast, the laboratory-specific readouts indicate transient, mild impairments of behavioral patterns relevant to animal welfare, and suggest a mild overall burden of the line.
Mesenchymal Stromal Cell Therapy in Spinal Cord Injury: Mechanisms and Prospects
Authors: Xie Ji-Le , Wang Xing-Ran , Li Mei-Mei , Tao Zi-Han , Teng Wen-Wen , Saijilafu
Published: June 2022

Spinal cord injury (SCI) often leads to severe motor, sensory, and autonomic dysfunction in patients and imposes a huge economic cost to individuals and society. Due to its complicated pathophysiological mechanism, there is not yet an optimal treatment available for SCI. Mesenchymal stromal cells (MSCs) are promising candidate transplant cells for use in SCI treatment. The multipotency of MSCs, as well as their rich trophic and immunomodulatory abilities through paracrine signaling, are expected to play an important role in neural repair. At the same time, the simplicity of MSCs isolation and culture and the bypassing of ethical barriers to stem cell transplantation make them more attractive. However, the MSCs concept has evolved in a specific research context to encompass different populations of cells with a variety of biological characteristics, and failure to understand this can undermine the quality of research in the field. Here, we review the development of the concept of MSCs in order to clarify misconceptions and discuss the controversy in MSCs neural differentiation. We also summarize a potential role of MSCs in SCI treatment, including their migration and trophic and immunomodulatory effects, and their ability to relieve neuropathic pain, and we also highlight directions for future research.
Microrchidia CW-Type Zinc Finger 2, a Chromatin Modifier in a Spectrum of Peripheral Neuropathies
Authors: Jacquier Arnaud , Roubille Simon , Lomonte Patrick , Schaeffer Laurent
Published: June 2022

Microrchidia CW-type zinc finger 2 (MORC2) gene encodes a protein expressed in all tissues and enriched in the brain. MORC2 protein is composed of a catalytic ATPase domain, three coil-coiled domains allowing dimerization or protein complex interaction, a zinc-finger CW domain allowing DNA interaction, and a CHROMO-like (CHRromatin Organization Modifier) domain. Recently, de novo or dominantly inherited heterozygous mutations have been associated with a spectrum of disorders affecting the peripheral nervous system such as the Charcot-Marie-Tooth disease, spinal muscular atrophy-like phenotype disorder, or a neurodevelopmental syndrome associated with developmental delay, impaired growth, dysmorphic facies, and axonal neuropathy (DIGFAN). In this review, we detail the various mutations of MORC2 and their consequences on clinical manifestations. Possible genotype-phenotype correlations as well as intra and inter-family variability are discussed. MORC2 molecular functions such as transcriptional modulation, DNA damage repair, and lipid metabolism are then reviewed. We further discuss the impact of MORC2 mutations on the epigenetic landscape in the neuromuscular system and hypothesize probable pathophysiological mechanisms underlying the phenotypic variability observed.
Microglia in a Dish—Which Techniques Are on the Menu for Functional Studies?
Authors: Aktories Philipp , Petry Philippe , Kierdorf Katrin
Published: June 2022

Microglia build the first line of defense in the central nervous system (CNS) and play central roles during development and homeostasis. Indeed, they serve a plethora of diverse functions in the CNS of which many are not yet fully described and more are still to be discovered. Research of the last decades unraveled an implication of microglia in nearly every neurodegenerative and neuroinflammatory disease, making it even more challenging to elucidate molecular mechanisms behind microglial functions and to modulate aberrant microglial behavior. To understand microglial functions and the underlying signaling machinery, many attempts were made to employ functional in vitro studies of microglia. However, the range of available cell culture models is wide and they come with different advantages and disadvantages for functional assays. Here we aim to provide a condensed summary of common microglia in vitro systems and discuss their potentials and shortcomings for functional studies in vitro.
Mechanoreceptor Piezo1 Is Downregulated in Multiple Sclerosis Brain and Is Involved in the Maturation and Migration of Oligodendrocytes in vitro
Authors: Velasco-Estevez Maria , Koch Nina , Klejbor Ilona , Caratis Fionä , Rutkowska Aleksandra
Published: June 2022

Mechanical properties of the brain such as intracranial pressure or stiffness of the matrix play an important role in the brain’s normal physiology and pathophysiology. The physical properties are sensed by the cells through mechanoreceptors and translated into ion currents which activate multiple biochemical cascades allowing the cells to adapt and respond to changes in their microenvironment. Piezo1 is one of the first identified mechanoreceptors. It modulates various central nervous system functions such as axonal growth or activation of astrocytes. Piezo1 signaling was also shown to play a role in the pathophysiology of Alzheimer’s disease. Here, we explore the expression of the mechanoreceptor Piezo1 in human MO3.13 oligodendrocytes and human MS/non-MS patients’ brains and investigate its putative effects on oligodendrocyte proliferation, maturation, and migration. We found that Piezo1 is expressed in human oligodendrocytes and oligodendrocyte progenitor cells in the human brain and that its inhibition with GsMTx4 leads to an increment in proliferation and migration of MO3.13 oligodendrocytes. Activation of Piezo1 with Yoda-1 induced opposite effects. Further, we observed that expression of Piezo1 decreased with MO3.13 maturation in vitro. Differences in expression were also observed between healthy and multiple sclerosis brains. Remarkably, the data showed significantly lower expression of Piezo1 in the white matter in multiple sclerosis brains compared to its expression in the white matter in healthy controls. There were no differences in Piezo1 expression between the white matter plaque and healthy-appearing white matter in the multiple sclerosis brain. Taken together, we here show that Piezo1-induced signaling can be used to modulate oligodendrocyte function and that it may be an important player in the pathophysiology of multiple sclerosis.