bluuebunny/crossref_metadata_2025 huggingface dataset:
T cell perturbations persist for at least 6 months following hospitalization for COVID-19
Authors: Govender Melissa , Hopkins Francis R. , Göransson Robin , Svanberg Cecilia , Shankar Esaki M. , Hjorth Maria , Nilsdotter-Augustinsson Åsa , Sjöwall Johanna , Nyström Sofia , Larsson Marie
Published: August 2022

COVID-19 is being extensively studied, and much remains unknown regarding the long-term consequences of the disease on immune cells. The different arms of the immune system are interlinked, with humoral responses and the production of high-affinity antibodies being largely dependent on T cell immunity. Here, we longitudinally explored the effect COVID-19 has on T cell populations and the virus-specific T cells, as well as neutralizing antibody responses, for 6-7 months following hospitalization. The CD8+ TEMRA and exhausted CD57+ CD8+ T cells were markedly affected with elevated levels that lasted long into convalescence. Further, markers associated with T cell activation were upregulated at inclusion, and in the case of CD69+ CD4+ T cells this lasted all through the study duration. The levels of T cells expressing negative immune checkpoint molecules were increased in COVID-19 patients and sustained for a prolonged duration following recovery. Within 2-3 weeks after symptom onset, all COVID-19 patients developed anti-nucleocapsid IgG and spike-neutralizing IgG as well as SARS-CoV-2-specific T cell responses. In addition, we found alterations in follicular T helper (TFH) cell populations, such as enhanced TFH-TH2 following recovery from COVID-19. Our study revealed significant and long-term alterations in T cell populations and key events associated with COVID-19 pathogenesis.
Roles and functions of SARS-CoV-2 proteins in host immune evasion
Authors: Rashid Farooq , Xie Zhixun , Suleman Muhammad , Shah Abdullah , Khan Suliman , Luo Sisi
Published: August 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evades the host immune system through a variety of regulatory mechanisms. The genome of SARS-CoV-2 encodes 16 non-structural proteins (NSPs), four structural proteins, and nine accessory proteins that play indispensable roles to suppress the production and signaling of type I and III interferons (IFNs). In this review, we discussed the functions and the underlying mechanisms of different proteins of SARS-CoV-2 that evade the host immune system by suppressing the IFN-β production and TANK-binding kinase 1 (TBK1)/interferon regulatory factor 3 (IRF3)/signal transducer and activator of transcription (STAT)1 and STAT2 phosphorylation. We also described different viral proteins inhibiting the nuclear translocation of IRF3, nuclear factor-κB (NF-κB), and STATs. To date, the following proteins of SARS-CoV-2 including NSP1, NSP6, NSP8, NSP12, NSP13, NSP14, NSP15, open reading frame (ORF)3a, ORF6, ORF8, ORF9b, ORF10, and Membrane (M) protein have been well studied. However, the detailed mechanisms of immune evasion by NSP5, ORF3b, ORF9c, and Nucleocapsid (N) proteins are not well elucidated. Additionally, we also elaborated the perspectives of SARS-CoV-2 proteins.
A novel tumor mutational burden-based risk model predicts prognosis and correlates with immune infiltration in ovarian cancer
Authors: Wang Haoyu , Liu Jingchun , Yang Jiang , Wang Zhi , Zhang Zihui , Peng Jiaxin , Wang Ying , Hong Li
Published: August 2022

Tumor mutational burden (TMB) has been reported to determine the response to immunotherapy, thus affecting the patient’s prognosis in many cancers. However, it is unclear whether TMB or TMB-related signature could be used as prognostic indicators for ovarian cancer (OC), as its potential association with immune infiltration remains poorly understood. Therefore, this study aimed to develop a novel TMB-related risk model (TMBrisk) to predict the prognosis of OC patients on the basis of exploring TMB-related genes, and to explore the potential association between TMB/TMBrisk and immune infiltration. The mutational landscape, TMB scores, and correlations between TMB and clinical characteristics and immune infiltration were investigated in The Cancer Genome Atlas (TCGA)-OV cohort. Differentially expressed gene (DEG) analyses and weighted gene co-expression network analysis (WGCNA) were performed to derive TMB-related genes. TMBrisk was constructed by Cox regression and further validated in Gene Expression Omnibus (GEO) datasets. The mRNA and protein expression levels and biological functions of TMBrisk hub genes were verified through Gene Expression Profiling Interactive Analysis (GEPIA), GSCA Lite, the Human Protein Atlas (HPA) database, and RT-qPCR. TMBrisk-related biological phenotypes were analyzed in function enrichment and tumor immune infiltration signature. Potential therapeutic regimens were inferred utilizing the Genomics of Drug Sensitivity in Cancer (GDSC) database and connectivity map (CMap). According to our results, higher TMB was associated with better survival and higher CD8+ T cell, regulatory T cell, and NK cell infiltration. TMBrisk was developed based on CBWD1, ST7L, RFX5-AS1, C3orf38, LRFN1, LEMD1, and HMGB1. High TMBrisk was identified as a poor factor for prognosis in TCGA and GEO datasets; the high-TMBrisk group comprised more higher-grade (G2 and G3) and advanced clinical stage (stage III/IV) tumors. Meanwhile, higher TMBrisk was associated with an immunosuppressive phenotype, with less infiltration of a majority of immunocytes and less expression of several genes of the human leukocyte antigen (HLA) family. Moreover, a nomogram containing TMBrisk showed a strong predictive ability demonstrated by time-dependent ROC analysis. Overall, this novel TMB-related risk model (TMBrisk) could predict prognosis, evaluate immune infiltration, and discover new therapeutic regimens in OC, which is very promising in clinical promotion.
Effect of cellular aging on memory T-cell homeostasis
Authors: Swain Arpit C. , Borghans José A.M. , de Boer Rob J.
Published: August 2022

The fact that T-cell numbers remain relatively stable throughout life, and that T-cell proliferation rates increase during lymphopenia, has led to the consensus that T-cell numbers are regulated in a density-dependent manner. Competition for resources among memory T cells has been proposed to underlie this ‘homeostatic’ regulation. We first review how two classic models of resource competition affect the T-cell receptor (TCR) diversity of the memory T-cell pool. First, ‘global’ competition for cytokines leads to a skewed repertoire that tends to be dominated by the very first immune response. Second, additional ‘cognate’ competition for specific antigens results in a very diverse and stable memory T-cell pool, allowing every antigen to be remembered, which we therefore define as the ‘gold-standard’. Because there is limited evidence that memory T cells of the same specificity compete more strongly with each other than with memory T cells of different specificities, i.e., for ‘cognate’ competition, we investigate whether cellular aging could account for a similar level of TCR diversity. We define cellular aging as a declining cellular fitness due to reduced proliferation. We find that the gradual erosion of previous T-cell memories due to cellular aging allows for better establishment of novel memories and for a much higher level of TCR diversity compared to global competition. A small continual source (either from stem-cell-like memory T-cells or from naive T-cells due to repeated antigen exposure) improves the diversity of the memory T-cell pool, but remarkably, only in the cellular aging model. We further show that the presence of a source keeps the inflation of chronic memory responses in check by maintaining the immune memories to non-chronic antigens. We conclude that cellular aging along with a small source provides a novel and immunologically realistic mechanism to achieve and maintain the ‘gold-standard’ level of TCR diversity in the memory T-cell pool.
Current therapeutic strategies and perspectives in refractory ITP: What have we learned recently?
Authors: Lv Yue , Shi Huiping , Liu Hong , Zhou Lu
Published: August 2022

Immune thrombocytopenia (ITP) is an acquired autoimmune bleeding disorder featured by increased platelet destruction and deficient megakaryocyte maturation. First-line treatments include corticosteroids, intravenous immunoglobulin and intravenous anti-D immunoglobulin. Second-line treatments consist of rituximab, thrombopoietin receptor agonists and splenectomy. Although most patients benefit from these treatments, an individualized treatment approach is warranted due to the large heterogeneity among ITP patients. In addition, ITP patients may relapse and there remains a subset of patients who become refractory to treatments. The management of these refractory patients is still a challenge. This review aims to summarize emerging therapeutic approaches for refractory ITP in several categories according to their different targets, including macrophages, platelets/megakaryocytes, T cells, B cells, and endothelial cells. Moreover, current management strategies and combination regimens of refractory ITP are also discussed.
Transcriptional patterns reveal tumor histologic heterogeneity and immunotherapy response in lung adenocarcinoma
Authors: Jiao Mengxue , Liu Hui , Liu Xuejun
Published: August 2022

Tumoral heterogeneity has proven to be a leading cause of difference in prognosis and acquired drug resistance. High intratumor heterogeneity often means poor clinical response and prognosis. Histopathological subtypes suggest tumor heterogeneity evolved during the progression of lung adenocarcinoma, but the exploration of its molecular mechanisms remains limited. In this work, we first verified that transcriptional patterns of a set of differentially expressed genes profoundly revealed the histologic progression of lung adenocarcinoma. Next, a predictive model based on the transcriptional patterns was established to accurately distinguish histologic subtypes. Two crucial genes were identified and used to construct a tumor heterogeneous scoring model (L2SITH) to stratify patients, and we found that patients with low heterogeneity score had better prognosis. Low L2SITH scores implied low tumor purity and beneficial tumor microenvironment. Moreover, L2SITH effectively identified cohorts with better responses to anti–PD-1 immunotherapy.
Colon metastasis from lung adenocarcinoma with BRAF V600E mutation: A case report
Authors: Luo Yuhao , Mou Kelin , Wang Jianmei , Luo Jing , Peng Lin , Ye Hua , Lin Sheng
Published: August 2022

Symptomatic colon metastasis from primary lung cancer is rare in clinical practice. We report the case of a 58-year-old patient with advanced lung adenocarcinoma who developed abdominal symptoms, including abdominal distention and difficulty defecating, after immunotherapy and chemotherapy. The patient was diagnosed with lung adenocarcinoma, and systemic positron emission tomography-computed tomography confirmed multiple lymph node, pleural, and adrenal metastases. Molecular detection indicated BRAF V600E mutation and high programmed death-ligand 1 (PD-L1) expression. After first-line anti-programmed cell death protein 1 immunotherapy combined with chemotherapy, the nodes in the chest remarkably diminished. However, it was followed by colon obstruction, incomplete ileus, and bone metastasis. Endoscopic histological examination confirmed adenocarcinoma but could not identify primary or secondary tumors due to insufficient tissue. We performed colon resection to remove the obstruction, and postoperative tissue pathological microscopy confirmed metastasis from the lung adenocarcinoma. We corroborated the BRAF V600E mutation and high PD-L1 expression and supported the molecular features of lung adenocarcinoma. During hospitalization, the patient presented with unbearable pain in the bone metastases, and palliative radiotherapy was administered. Then, the patient received dabrafenib plus trametinib as the second-line therapy. This report discusses the clinical characteristics, pathology, imaging, molecular profile assessments, and treatment of primary lung adenocarcinoma with colon metastasis.
Immune landscape of distinct subtypes in urothelial carcinoma based on immune gene profile
Authors: Peng Mou
Published: August 2022

Immune checkpoint blockade (ICB) has become a promising therapy for multiple cancers. However, only a small proportion of patients display a limited antitumor response. The present study aimed to classify distinct immune subtypes and investigate the tumor microenvironment (TME) of urothelial carcinoma, which may help to understand treatment failure and improve the immunotherapy response. RNA-seq data and clinical parameters were obtained from TCGA-BLCA, E-MTAB-4321, and IMVigor210 datasets. A consensus cluster method was used to distinguish different immune subtypes of patients. Infiltrating immune cells, TME signatures, immune checkpoints, and immunogenic cell death modulators were evaluated in distinct immune subtypes. Dimension reduction analysis was performed to visualize the immune status of urothelial carcinoma based on graph learning. Weighted gene co-expression network analysis (WGCNA) was performed to obtain hub genes to predict responses after immunotherapy. Patients with urothelial carcinoma were classified into four distinct immune subtypes (C1, C2, C3 and C4) with various types of molecular expression, immune cell infiltration, and clinical characteristics. Patients with the C3 immune subtype displayed abundant immune cell infiltrations in the tumor microenvironment and were typically identified as “hot” tumor phenotypes, whereas those with the C4 immune subtype with few immune cell infiltrations were identified as “cold” tumor phenotypes. The immune-related and metastasis-related signaling pathways were enriched in the C3 subtype compared to the C4 subtype. In addition, tumor mutation burden, inhibitory immune checkpoints, and immunogenic cell death modulators were highly expressed in the C3 subtype. Furthermore, patients with the C4 subtype had a better probability of overall survival than patients with the C3 subtype in TCGA-BLCA and E-MTAB-4321 cohorts. Patients with the C1 subtype had the best prognosis when undergoing anti-PD-L1 antibody treatment. Finally, the immune landscape of urothelial carcinoma showed the immune status in each patient, and TGFB3 was identified as a potential biomarker for the prediction of immunotherapy resistance after anti-PD-L1 monoclonal antibody treatment. The present study provided a bioinformatics basis for understanding the immune landscape of the tumor microenvironment of urothelial carcinoma.
Governing factors of the record-breaking marine heatwave over the mid-latitude western North Pacific in the summer of 2021
Authors: Pak Gyundo , Noh Joocheul , Park Young-Gyu , Jin Hyunkeun , Park Jae-Hyoung
Published: August 2022

During July of 2021, the sea surface temperature of the mid-latitude western North Pacific had increased by five degrees over 10 days. This high temperature was maintained for approximately a month before it disappeared rapidly in approximately five days. The underlying mechanisms of this unprecedented marine heatwave event have not yet been researched through a quantitative approach. The development and decay processes of the marine heatwave event were investigated using heat budget analysis and one-dimensional modeling. In mid-July, an anomalous high-pressure atmospheric circulation, affecting to the reduced cloud coverage and increased solar radiation, anchored where the marine heatwave occurred. The increased solar radiation accompanied by the weakened wind reduced the vertical mixing and resulted in a thinner mixed-layer, which accelerated the sea surface warming. The impact of reduced mixing is as important as the increase in solar radiation. In mid-August, typhoon-induced entrainment mainly caused sea surface cooling. The wind-driven mechanical mixing between warm surface water and cooler subsurface water lowered the SST. Additionally, evaporative cooling by strong winds, which drives buoyancy-driven vertical mixing, contributed to the decay of the MHW. The effect of mechanical mixing on cooling is comparable to that of buoyancy-driven mixing.
Metabolic response of the sea cucumber Apostichopus japonicus during the estivation-arousal cycles
Authors: Zhao Ye , Wang Haona , Wang Han , Pi Yongrui , Chen Muyan
Published: August 2022

Estivation is a widespread survival strategy for dealing with adverse environmental conditions such as high temperature, low oxygen and lack of water or food, which has been reported across multiple vertebrate and invertebrate species. The sea cucumber Apostichopus japonicus is an excellent model organism to investigate the adaptive mechanism of estivation in marine invertebrates. In this study, a metabolomics approach based on ultraperformance liquid chromatography coupled with electrospray ionization time-of-flight mass spectrometry (UPLC-ESI-Q-TOF/MS) was performed to reveal the metabolic response of intestines from adult A. japonicus over the annual estivation-arousal cycle: nonestivation (NA), deep-estivation (DA) and arousal from estivation (AA). A total of 424 metabolites were identified, and among them, 243, 238 and 37 significant differentially metabolites (DMs) were further screened in the comparisons of DA vs. NA, AA vs. DA, and AA vs. NA. Specifically, the levels of metabolites involved in glycolysis and the tricarboxylic acid cycle were significantly decreased, while higher amounts of long-chain fatty acids, phospholipids and free amino acids were found in A. japonicus during estivation, implying that sea cucumbers might reorganize metabolic priorities for ATP production by depressing carbohydrate metabolism and promoting lipid and amino acid catabolism. Interestingly, elevated relative carbon flow entry into the pentose phosphate pathway and accumulation of various nonenzymatic antioxidant molecules (e.g., tocotrienols, folic acid, catechin, genistein and resveratrol) were observed in estivating sea cucumbers, which suggested that enhancement of the reactive oxygen species defense system might promote long-term viability in the hypometabolic state in an energy-efficient manner. Thus, this research provides new insights into the adaptation mechanisms of marine invertebrates to estivation at the metabolic level.
Docosahexaenoic acid (DHA) production by Aurantiochytrium limacinum using cassava pulp hydrolysate as an alternative low-cost carbon source
Authors: Aini Uyun Nurul , Lunprom Siriporn , Reungsang Alissara , Salakkam Apilak
Published: August 2022

Cost of nutrients is one of the major contributors to the production cost of docosahexaenoic acid (DHA) by thraustochytrids, and this remains the main challenge for economical and sustainable production of DHA. In the present study, cassava pulp (CP) was investigated as an alternative low-cost carbon source for DHA production by Aurantiochytrium limacinum SR21. Cultivation conditions, i.e., salinity level, type of nitrogen source, and concentrations of glucose and nitrogen sources, as well as pH, were optimized for cell growth. CP was enzymatically hydrolyzed, and used as the base medium, supplemented with artificial seawater salts, for DHA production under fed-batch cultivation. A. limacinum grew well at 18 g/L of NaCl (equivalent to 50% salinity level), and initial glucose concentration of 64 g/L, initial yeast extract concentration of 5 g/L, and pH 7.5 were optimum for cell growth. Fed-batch cultivation, with dissolved oxygen (DO) controlled at 10%, using CP-based medium as the carbon source gave a final cell dry mass of 26.3 ± 2.0 g/L, with 15.5 ± 0.1 g/L of lipid. DHA content in the lipid was 37.4 ± 1.5%, equivalent to 5.8 ± 0.3 g/L, and DHA productivity was 960 mg/(L·d). Medium-based economic analysis showed that an economic yield (EY) of this process was 0.86, which was higher than the 0.81 obtained using glucose as the substrate, assuming the same process and conditions. Overall, the results reveal that CP is a highly feasible feedstock for DHA production by A. limacinum SR21.
Tunable Topological Phase Transition in Two-Dimensional Ternary Transition Metal Halides TiXI (X = P and As)
Authors: Chen Peng-Jen
Published: August 2022

With first-principles calculations we predict tunable topological phase transition in two-dimensional (2D) ternary transition metal halides α-TiXI (X = P and As) via strain engineering. Besides, changing the number of stacking layers or van der Waals interlayer spacing can also result in topological phase transition in few-layer TiXI. The on-site Coulomb U of Ti atoms is neither tunable nor empirical in this work. Instead, it is evaluated by the density functional perturbation theory and hence the results are more accurate. The tunable topological phase of 2D α-TiXI via strain engineering makes them promising in spintronics devices that exploit quantum spin Hall effect. Furthermore, the topological edge states of the single-layer TiAsI exhibit interesting feature. They do not cross at the time-reversal invariant momenta (TRIM) where the band inversion occurs. Instead, they extend over the whole one-dimensional Brillouin zone and cross at the other TRIM. While all requirements of Z2 topological phase are fulfilled, it is rare especially for those with direct gap. The linear bulk bands around and at Γ point may be the reason for the unusual crossing.
Structure design study of vacuum magnetic fluid seal
Authors: Liu Sijia , Li Decai , He Xinzhi , Zhang Zhili
Published: August 2022

In response to the requirement of high vacuum and leakage rate of a small-diameter low-speed device of an enterprise, a double magnet multistage magnetic fluid sealing device is designed by analyzing the advantages and disadvantages of four different vacuum magnetic fluid sealing devices. The Ansys simulation software is used to analyze and calculate the magnetic field strength and distribution of this magnetic fluid sealing device, discuss the influence of the number of intermediate section pole teeth and the seal gap size on the pressure resistance of the magnetic fluid seal, and summarize the law. The proposed structure of the double magnet multistage magnetic fluid sealing device is optimized and determined by the influence law of structural parameters. Compared with traditional sealing forms, the advantages of the sealing device proposed in this article can be summarized as low processing difficulty, good reliability, and high pressure resistance. The reliability and rationality of this magnetic fluid sealing device are demonstrated by Ansys simulation results, which provide a reference for the structural design and analysis of small-diameter low-speed vacuum magnetic fluid sealing devices.
Relationship between high intra-abdominal pressure and compliance of the pelvic floor support system in women without pelvic organ prolapse: A finite element analysis
Authors: Liu Xiaode , Rong Qiguo , Liu Yanan , Wang Jianliu , Xie Bing , Ren Shuang
Published: August 2022

Previous studies mainly focused on the relationship between the size of the prolapse and injury to the supporting tissues, but the strain and stress distributions of the supporting tissues as well as high-risk areas of injury are still unknown. To further investigate the effect of supporting tissues on organs and the interactions between organs, this study focused on the relationship between high intra-abdominal pressure and the compliance of the pelvic floor support system in a normal woman without pelvic organ prolapse (POP), using a finite element model of the whole pelvic support system. A healthy female volunteer (55 years old) was scanned using magnetic resonance imaging (MRI) during rest and Valsalva maneuver. According to the pelvic structure contours traced by a gynecologist and anatomic details measured from dynamic MRI, a finite element model of the whole pelvic support system was established, including the uterus, vagina with cavity, cardinal and uterosacral ligaments, levator ani muscle, rectum, bladder, perineal body, pelvis, and obturator internus and coccygeal muscles. This model was imported into ANSYS software, and an implicit iterative method was employed to simulate the biomechanical response with increasing intra-abdominal pressure. Stress and strain distributions of the vaginal wall showed that the posterior wall was more stable than the anterior wall under high intra-abdominal pressure. Displacement at the top of the vagina was larger than that at the bottom, especially in the anterior–posterior direction. These results imply potential injury areas with high intra-abdominal pressure in non-prolapsed women, and provide insight into clinical managements for the prevention and surgical repair plans of POP.
Applications of natural language processing in ophthalmology: present and future
Authors: Chen Jimmy S. , Baxter Sally L.
Published: August 2022

Advances in technology, including novel ophthalmic imaging devices and adoption of the electronic health record (EHR), have resulted in significantly increased data available for both clinical use and research in ophthalmology. While artificial intelligence (AI) algorithms have the potential to utilize these data to transform clinical care, current applications of AI in ophthalmology have focused mostly on image-based deep learning. Unstructured free-text in the EHR represents a tremendous amount of underutilized data in big data analyses and predictive AI. Natural language processing (NLP) is a type of AI involved in processing human language that can be used to develop automated algorithms using these vast quantities of available text data. The purpose of this review was to introduce ophthalmologists to NLP by (1) reviewing current applications of NLP in ophthalmology and (2) exploring potential applications of NLP. We reviewed current literature published in Pubmed and Google Scholar for articles related to NLP and ophthalmology, and used ancestor search to expand our references. Overall, we found 19 published studies of NLP in ophthalmology. The majority of these publications (16) focused on extracting specific text such as visual acuity from free-text notes for the purposes of quantitative analysis. Other applications included: domain embedding, predictive modeling, and topic modeling. Future ophthalmic applications of NLP may also focus on developing search engines for data within free-text notes, cleaning notes, automated question-answering, and translating ophthalmology notes for other specialties or for patients, especially with a growing interest in open notes. As medicine becomes more data-oriented, NLP offers increasing opportunities to augment our ability to harness free-text data and drive innovations in healthcare delivery and treatment of ophthalmic conditions.
High-flow nasal oxygen reduces the incidence of hypoxia in sedated hysteroscopy for assisted reproduction
Authors: Tang Ying , Huang Ping , Chai Di , Zhang Xiao , Zhang Xiaoyi , Chen Shaoyi , Su Diansan , Huang Yonglei
Published: August 2022

Backgrounds and aims

Pain is the main reason for hysteroscopy failure. In day-surgical settings, hysteroscopy procedures are commonly performed with the patient under sedation. Hypoxia is the most common adverse event during sedation and can lead to severe adverse events. This study aimed to compare the incidence of hypoxia when using high-flow nasal oxygen (HFNO) with that when using regular nasal oxygen in patients undergoing hysteroscopy with sedation.

Materials and methods

In this single-center, prospective, randomized, single-blinded study, 960 female patients undergoing elective diagnostic or operative hysteroscopy were randomly enrolled into the following two groups: the regular nasal group [O2 (3–6 L/min) covered by an HFNO] and the HFNO group [O2 (30–60 L/min)] from September 2021 to December 2021. All women were sedated with propofol (1.5 mg/kg) and remifentanil (1.5 μg/kg) in the operating room. The primary outcome was the incidence of hypoxia (75% ≤ SpO2 < 90%, < 60 s).

Results

HFNO decreased the incidence of hypoxia (75% ≤ SpO2 < 90%, < 60 s), subclinical respiratory depression (90% ≤ SpO2 < 95%) and severe hypoxia (SpO2 < 75% for any duration or 75% ≤ SpO2 < 90% for ≥ 60 s) from 24.38 to 0.83%, from 11.25 to 1.46% and from 3.75 to 0%, respectively (P < 0.001).

Conclusion

In procedures conducted to treat female infertility, HFNO can reduce hypoxia during hysteroscopy in patients sedated with propofol, and it can prevent the occurrence of subclinical respiratory depression and severe hypoxia.
Perinatal maternal characteristics predict a high risk of neonatal asphyxia: A multi-center retrospective cohort study in China
Authors: Yu Yi , Gao Jinsong , Liu Juntao , Tang Yabing , Zhong Mei , He Jing , Liao Shixiu , Wang Xietong , Liu Xinghui , Cao Yinli , Liu Caixia , Sun Jingxia
Published: August 2022

Objective

This study aimed to identify various perinatal maternal characteristics that contributed to neonatal asphyxia (NA) in term and late-preterm newborns based on the data obtained from a Chinese birth registry cohort and to establish an effective model for predicting a high risk of asphyxia.

Method

We retrospectively reviewed and analyzed the birth database from July 1, 2016, to June 30, 2017, in the main economically developed regions of China. Asphyxia was defined as an Apgar score <7 at 5 min post-delivery with umbilical cord arterial blood pH < 7.2 in the infant born after 34weeks. We compared the perinatal maternal characteristics of the newborns who developed asphyxia (NA group, n = 1,152) and those who did not (no NA group, n = 86,393). Candidate predictors of NA were analyzed using multivariable logistic regression. Subsequently, a prediction model was developed and validated by an independent test group.

Result

Of the maternal characteristics, duration of PROM ≥ 48 h, a gestational week at birth <37, prolonged duration of labor, hypertensive disorder, nuchal cord, and birth weight <2,500 or ≥4,000 g, abnormal fetal heart rate, meconium-stained amniotic fluid, and placenta previa were included in the predicting model, which presented a good performance in external validation (c-statistic of 0.731).

Conclusion

Our model relied heavily on clinical predictors that may be determined before or during birth, and pregnant women at high risk of NA might be recognized earlier in pregnancy and childbirth using this methodology, allowing them to avoid being neglected and delayed. Future studies should be conducted to assess its usefulness.
Advances in the pharmacological treatment of hepatic alveolar echinococcosis: From laboratory to clinic
Authors: Xu Xiaolei , Qian Xinye , Gao Cancan , Pang Yuan , Zhou Hu , Zhu Lizhen , Wang Zhan , Pang Mingquan , Wu Defang , Yu Wenhao , Kong Fanyu , Shi Dalin , Guo Yuting , Su Xiaoxia , Hu Wang , Yan Jun , Feng Xiaobin , Fan Haining
Published: August 2022

Hepatic alveolar echinococcosis (HAE) is a zoonotic parasitic disease caused by the larvae ofEchinococcus multilocularis. Because of its characteristics of diffuse infiltration and growth similar to tumors, the disability rate and mortality rate are high among patients. Although surgery (including hepatectomy, liver transplantation, and autologous liver transplantation) is the first choice for the treatment of hepatic alveolar echinococcosis in clinic, drug treatment still plays an important and irreplaceable role in patients with end-stage echinococcosis, including patients with multiple organ metastasis, patients with inferior vena cava invasion, or patients with surgical contraindications, etc. However, Albendazole is the only recommended clinical drug which could exhibit a parasitostatic rather than a parasitocidal effect. Novel drugs are needed but few investment was made in the field because the rarity of the cases. Drug repurposing might be a solution. In this review, FDA-approved drugs that have a potential curative effect on hepatic alveolar echinococcosis in animal models are summarized. Further, nano drug delivery systems boosting the therapeutic effect on hepatic alveolar echinococcosis are also reviewed. Taken together, these might contribute to the development of novel strategy for advanced hepatic alveolar echinococcosis.
Hepatitis of unknown etiology in children: What we know and what we can do?
Authors: Zhu Mingyu , Chen Li
Published: August 2022

Recently, acute hepatitis of unknown etiology in children has gained great concern since March 2022. The disease was first reported by Public Health Scotland. Cases increased rapidly and are now reported in 33 countries worldwide. All cases are predominantly aged under 5 years old. Most patients presented with jaundice, and remarkably, some cases progress to acute liver failure. Until now, the etiology is not fully elucidated, and the investigations are ongoing. Adenovirus infection seems to be an important factor. Several hypotheses on the etiology have been proposed. This review aims to summarize current research progress and put forward some suggestions.
Endosymbiotic bacteria of the boar louse Haematopinus apri (Insecta: Phthiraptera: Anoplura)
Authors: Nishide Yudai , Oguchi Kohei , Murakami Maria , Moriyama Minoru , Koga Ryuichi , Fukatsu Takema
Published: August 2022

Insects exclusively feeding on vertebrate blood are usually dependent on symbiotic bacteria for provisioning of B vitamins. Among them, sucking lice are prominent in that their symbiotic bacteria as well as their symbiotic organs exhibit striking diversity. Here we investigated the bacterial diversity associated with the boar louse Haematopinus apri in comparison with the hog louse Haematopinus suis. Amplicon sequencing analysis identified the primary endosymbiont predominantly detected from all populations of H. apri with some minor secondary bacterial associates. Sequencing and phylogenetic analysis of bacterial 16S rRNA gene confirmed that the endosymbionts of the boar louse H. apri, the hog louse H. suis and the cattle louse Haematopinus eurysternus form a distinct clade in the Gammaproteobacteria. The endosymbiont clade of Haematopinus spp. was phylogenetically distinct from the primary endosymbionts of other louse lineages. Fluorescence in situ hybridization visualized the endosymbiont localization within midgut epithelium, ovarial ampulla and posterior oocyte of H. apri, which were substantially the same as the endosymbiont localization previously described in H. suis and H. eurysternus. Mitochondrial haplotype analysis revealed that, although the domestic pig was derived from the wild boar over the past 8,000 years of human history, the populations of H. apri constituted a distinct sister clade to the populations of H. suis. Based on these results, we discussed possible evolutionary trajectories of the boar louse, the hog louse and their endosymbionts in the context of swine domestication. We proposed ‘Candidatus Haematopinicola symbiotica’ for the distinct clade of the endosymbionts of Haematopinus spp.
A preliminary investigation into bacterial viability using scanning electron microscopy–energy-dispersive X-ray analysis: The case of antibiotics
Authors: Haddad Gabriel , Takakura Tatsuki , Bellali Sara , Fontanini Anthony , Ominami Yusuke , Khalil Jacques Bou , Raoult Didier
Published: August 2022

The metabolic stages of bacterial development and viability under different stress conditions induced by disinfection, chemical treatments, temperature, or atmospheric changes have been thoroughly investigated. Here, we aim to evaluate early metabolic modifications in bacteria following induced stress, resulting in alterations to bacterial metabolism. A protocol was optimized for bacterial preparation using energy-dispersive X-ray (EDX) microanalysis coupled with scanning electron microscopy (SEM), followed by optimizing EDX data acquisition and analysis. We investigated different preparation methods aiming to detect modifications in the bacterial chemical composition at different states. We first investigated Escherichia coli, acquiring data from fresh bacteria, after heat shock, and after contact with 70% ethanol, in order to prove the feasibility of this new strategy. We then applied the new method to different bacterial species following 1 h of incubation with increasing doses of antibiotics used as a stress-inducing agent. Among the different materials tested aiming to avoiding interaction with bacterial metabolites, phosphorous-doped silicon wafers were selected for the slide preparation. The 15 kV acceleration voltage ensured all the chemical elements of interest were excited. A thick layer of bacterial culture was deposited on the silicon wafer providing information from multiple cells and intra-cellular composition. The EDX spectra of fresh, heat-killed, and alcohol-killed E. coli revealed important modifications in magnesium, potassium, and sodium. Those same alterations were detected when applying this strategy to bacteria exposed to antibiotics. Tests based on SEM–EDX acquisition systems would provide early predictions of the bacterial viability state in different conditions, yielding earlier results than culture.
Structural Analysis and Conformational Dynamics of Short Helical Hyperphosphorylated Segments of Tau Protein (Sequence 254–290) in Alzheimer’s Disease: A Molecular Dynamics Simulation Study
Authors: Alipour Mozhgan , Motavaf Mahsa , Abdolmaleki Parviz , Zali Alireza , Ashrafi Farzad , Safari Saeid , Hajipour-Verdom Behnam
Published: August 2022

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder whose early diagnosis leads to a chance for successful treatment and decreases the side effects. Hyperphosphorylation of tau proteins is a pathological hallmark of AD that causes it to lose its attachment ability to the microtubules. Alteration of tau structure due to its hyperphosphorylation is an exciting challenge regarding AD treatments. Here, we aimed to examine the structural alterations of short helical segments of tau protein with one to three phosphorylated sites by molecular dynamics simulation. Results indicated that the interaction of two similar segments with three phosphorylated sites (P-Ser262, 285, and 289) formed a compact and more stable structure than the one phosphorylated site complex (P-Ser262). Moreover, due to the high dynamics of the P-Ser262 complex, several structures were made with different conformational dynamics, but there was only one stable cluster of the P-Ser262, 285, and 289 complex during simulation. It seems that the P-Ser262, 285, and 289 complex plays an important role in the formation of paired helical filaments (PHFs) by forming a stable dimer. Generally, it is important to identify how structural features of segments in tau protein change when the phosphorylated sites increase from one to three sites and their effects on the formation of PHFs for drug design and diagnostic biomarkers.
Olfactory dysfunction is associated with mild cognitive impairment in community-dwelling older adults
Authors: Yap Ai Che , Mahendran Rathi , Kua Ee Heok , Zhou Weibiao , Wang De Yun
Published: August 2022

Background

Olfactory impairment is aging related and is associated with cognitive decline in older adults. However, it remains unclear if an olfactory impairment is associated with mild cognitive impairment (MCI) and the degree of impairment in the MCI subtypes.

Materials and methods

In a cohort of community-living older adults aged 60 years and above, 670 participants were recruited from the Community Health and Intergenerational (CHI) Study. Olfactory function was assessed using a locally developed nine-item smell test in association with neurocognitive assessments. Analysis of covariance (ANCOVA) was used to examine the association of smell identification score and clinical cognitive status while considering demographic, clinical, and neuropsychological factors with Bonferroni correction for group comparisons.

Results

Age-related smell detection between normal aging (NA) and MCI participants had no significant difference. The overall mean smell identification score in older adults was negatively correlated with age. The mean smell identification score of MCI participants was also not significantly different as compared with NA, but an amnestic MCI multiple domain (aMCI_MD) subgroup had significantly lower (impaired) mean smell identification scores compared with the NA and MCI single domain (amnestic and non-amnestic) group.

Conclusion

This study demonstrated that olfactory identification impairment is a comorbidity in older adults with amnestic MCI (aMCI) and is a potential marker associated with an early stage of a neurocognitive disorder. The smell test could act as a screening tool to help in the early detection of smell impairment for heterogeneous syndromes of MCI among community-dwelling older adults. Clinicians and researchers could benefit from utilizing the locally developed smell test to screen their patients or research participants before the initiation of an appropriate health intervention or in a clinical trial.
N-acylethanolamide metabolizing enzymes are upregulated in human neural progenitor-derived neurons exposed to sub-lethal oxidative stress
Authors: Duncan R. Scott , Riordan Sean M. , Hall Conner W. , Payne Andrew J. , Chapman Kent D. , Koulen Peter
Published: August 2022

N-acyl amides (NAAs) are a class of lipids that consist of an acyl group N-linked to an amino acid, neurotransmitter, taurine or ethanolamide group (N-acylethanolamines or NAEs) and include some endocannabinoids (eCB) such as anandamide. These lipids are synthesized in a wide variety of organisms and in multiple cell types, including neurons. NAEs are involved in numerous cellular and physiological processes and their concentrations are elevated in response to ischemia and physical trauma to play a role in neuroprotection. The neuroprotective properties of eCB NAEs make the protein targets of these compounds attractive targets for clinical intervention for a variety of conditions. The most promising of these targets include cannabinoid receptor type 1 (CB1), cannabinoid receptor type 2 (CB2), fatty acid amide hydrolase (FAAH), N-acylethanolamine acid amidase (NAAA), and N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD). Further characterization of these targets in a more contemporary model system of neurodegeneration and neuroprotection will allow us to fully describe their role and mechanism of action in neuroprotection against oxidative stress leading to better utilization in the clinical setting. Human stem cell-derived or human neural progenitor cell-derived cells, such as ReN cells, have become more utilized for the study of human neuronal development and neurodegenerative diseases. ReN cells can be easily differentiated thereby circumventing the need for using transformed cell lines and primary neurons as cell model systems. In this study, we determined whether ReN cells, a superior cell model system for studying neurodevelopment, differentiation, and neuroprotection, express proteins involved in canonical eCB NAE signaling and whether oxidative stress can induce their expression. We determined that sublethal oxidative stress upregulates the expression of all eCB proteins tested. In addition, we determined that oxidative stress increases the nuclear localization of FAAH, and to a lesser extent, NAAA and NAPE-PLD. This study is a first step toward determining how oxidative stress affects CB1, CB2, FAAH, NAAA, and NAPE-PLD expression and their potential defense against oxidative stress. As such, our data is important for further determining the role of eCB metabolizing proteins and eCB receptors against oxidative stress.
Glial cells in anorexia
Authors: Reyes-Haro Daniel
Published: August 2022

Anorexia is a loss of appetite or an inability to eat and is often associated with eating disorders. However, animal anorexia is physiologically regulated as a part of the life cycle; for instance, during hibernation, migration or incubation. Anorexia nervosa (AN), on the other hand, is a common eating disorder among adolescent females that experience an intense fear of gaining weight due to body image distortion that results in voluntary avoidance of food intake and, thus, severe weight loss. It has been shown that the neurobiology of feeding extends beyond the hypothalamus. The prefrontal cortex (PFC) is involved in food choice and body image perception, both relevant in AN. However, little is known about the neurobiology of AN, and the lack of effective treatments justifies the use of animal models. Glial cells, the dominant population of nerve cells in the central nervous system, are key in maintaining brain homeostasis. Accordingly, recent studies suggest that glial function may be compromised by anorexia. In this review, we summarize recent findings about anorexia and glial cells.
Learning multisensory cue integration: A computational model of crossmodal synaptic plasticity enables reliability-based cue weighting by capturing stimulus statistics
Authors: Shaikh Danish
Published: August 2022

The brain forms unified, coherent, and accurate percepts of events occurring in the environment by integrating information from multiple senses through the process of multisensory integration. The neural mechanisms underlying this process, its development and its maturation in a multisensory environment are yet to be properly understood. Numerous psychophysical studies suggest that the multisensory cue integration process follows the principle of Bayesian estimation, where the contributions of individual sensory modalities are proportional to the relative reliabilities of the different sensory stimuli. In this article I hypothesize that experience dependent crossmodal synaptic plasticity may be a plausible mechanism underlying development of multisensory cue integration. I test this hypothesisviaa computational model that implements Bayesian multisensory cue integration using reliability-based cue weighting. The model uses crossmodal synaptic plasticity to capture stimulus statistics within synaptic weights that are adapted to reflect the relative reliabilities of the participating stimuli. The model is embodied in a simulated robotic agent that learns to localize an audio-visual target by integrating spatial location cues extracted from of auditory and visual sensory modalities. Results of multiple randomized target localization trials in simulation indicate that the model is able to learn modality-specific synaptic weights proportional to the relative reliabilities of the auditory and visual stimuli. The proposed model with learned synaptic weights is also compared with a maximum-likelihood estimation model for cue integrationviaregression analysis. Results indicate that the proposed model reflects maximum-likelihood estimation.
Disorder and the Neural Representation of Complex Odors
Authors: Krishnamurthy Kamesh , Hermundstad Ann M. , Mora Thierry , Walczak Aleksandra M. , Balasubramanian Vijay
Published: August 2022

Animals smelling in the real world use a small number of receptors to sense a vast number of natural molecular mixtures, and proceed to learn arbitrary associations between odors and valences. Here, we propose how the architecture of olfactory circuits leverages disorder, diffuse sensing and redundancy in representation to meet these immense complementary challenges. First, the diffuse and disordered binding of receptors to many molecules compresses a vast but sparsely-structured odor space into a small receptor space, yielding an odor code that preserves similarity in a precise sense. Introducing any order/structure in the sensing degrades similarity preservation. Next, lateral interactions further reduce the correlation present in the low-dimensional receptor code. Finally, expansive disordered projections from the periphery to the central brain reconfigure the densely packed information into a high-dimensional representation, which contains multiple redundant subsets from which downstream neurons can learn flexible associations and valences. Moreover, introducing any order in the expansive projections degrades the ability to recall the learned associations in the presence of noise. We test our theory empirically using data from Drosophila. Our theory suggests that the neural processing of sparse but high-dimensional olfactory information differs from the other senses in its fundamental use of disorder.