bluuebunny/crossref_metadata_2025 huggingface dataset:
HMG-CoA Lyase Deficiency: A Retrospective Study of 62 Saudi Patients
Authors: Alfadhel Majid , Abadel Basma , Almaghthawi Hind , Umair Muhammad , Rahbeeni Zuhair , Faqeih Eissa , Almannai Mohammed , Alasmari Ali , Saleh Mohammed , Eyaid Wafaa , Alfares Ahmed , Al Mutairi Fuad
Published: May 2022

3-Hydroxy-3-methylglutaryl-coenzyme A lyase deficiency (HMG-CoA lyase) is a rare inborn error of leucine degradation and ketone body synthesis, caused by homozygous or compound heterozygous disease-causing variants in HMGCL. To understand the natural history of this disease, we reviewed the biochemical, clinical, and molecular data of 62 patients from 54 different families with confirmed HMG-CoA lyase deficiency (HMGCLD) diagnosis from Saudi Arabia. The majority of the affected individuals were symptomatic. At initial diagnosis, 38 patients (61.29%) presented with hypoglycemia and 49 patients (79.03%) developed metabolic acidosis. In 27 patients (43.54%), the disorder manifested in the neonatal period, mostly within the first days of life, while 35 (56.45%) patients were diagnosed within the first year of life or beyond. All the patients were alive and developed long-term neurological complications during data collection, which may significantly influence their quality of life. Common neurological findings include seizures 17/62 (27.41%), hypotonic 3/62 (4.83%), speech delay 7/62 (11.29%), hyperactivity 4/62 (4.83%), developmental delay 6/62 (9.677%), learning disability 15/62 (24.14%), and ataxic gate 1/62 (1.612%). An MRI of the brain exhibited nonspecific periventricular and deep white matter hyperintense signal changes in 16 patients (25.80%) and cerebral atrophy was found in one (1/62; 1.612%) patient. We identified a founder variant [c.122G>A; p.(Arg41Gln)] in 48 affected individuals (77.41%) in the HMGCL gene. This is the largest cohort of HMGCLD patients reported from Saudi Arabia, signifying this disorder as a likely life-threatening disease, with a high prevalence in the region. Our findings suggest that diagnosis at an early stage with careful dietary management may avoid metabolic crises.
Endoscopic Submucosal Dissection of Deeply Invasive Colorectal Cancers Using the Pocket-Creation Method: Analysis of Vertical Margins
Authors: Morikawa Takaaki , Hayashi Yoshikazu , Fukuda Hisashi , Ishii Hiroaki , Nomura Tatsuma , Ikeda Eriko , Kitamura Masafumi , Kagaya Yuka , Okada Masahiro , Takezawa Takahito , Sunada Keijiro , Lefor Alan Kawarai , Fukushima Noriyoshi , Yamamoto Hironori
Published: May 2022

Background and aims

The standard treatment for stage T1b colorectal cancers with 1,000µm or greater submucosal invasion is surgical resection. However, the risk of lymph node metastases is only 1-2% when excluding risk factors for metastases other than depth of submucosal invasion. The number of elderly patients with significant comorbidities is increasing with societal aging in Japan. Therefore, local endoscopic resection of T1b colorectal cancers needs more consideration in the future. We previously showed that the pocket-creation method (PCM) for endoscopic submucosal dissection (ESD) is useful regardless of the morphology, including large sessile tumors with submucosal fibrosis, or location of the colorectal tumor. However, some T1b colorectal cancers have pathologically positive margins even when using the PCM. We retrospectively investigated the causes of failure to achieve negative vertical margins.

Methods

We retrospectively analyzed 953 colorectal tumors in 886 patients resected with the PCM. Finally, 65 pathological T1b colorectal cancers after en bloc resection were included in this study. ESD specimens and recorded procedure videos of T1b cancer resections with pathologically positive vertical margins were reviewed.

Results

The 65 cancers were divided into positive vertical margin (VM+ group) and negative vertical margin (VM- group) groups with 10 [10/65 (15%)] and 55 [55/65 (85%)] patients in each group, respectively. There was a significant difference in the rate of submucosal fibrosis (P=0.012) and dissection speed (P=0.044). There were no significant differences between the two groups in other regards. When verifying 8/10 available videos in the VM+ group, endoscopic technical factors led to positive vertical margins in five patients, and essential pathological factors of ESD led to positive vertical margins in the other three. Six of these eight patients underwent additional surgical resection. No residual tumor was identified in six T1b cancers. None of these six resected specimens contained lymph node metastases on pathological examination.

Conclusion

The PCM resulted in a high rate of negative-vertical-margin resections. The PCM resulted in complete resection of T1b cancers when examining additional surgical specimens. ESD using the PCM is a viable option for the endoscopic treatment of T1b colorectal cancers.
High-Frequency Notable HBV Mutations Identified in Blood Donors With Occult Hepatitis B Infection From Heyuan City of Southern China
Authors: Ye Xianlin , Liu Lihua , Chen Lina , Nie Xianghui , Huang Lu , Ye Denghuang , Zeng Jinfeng , Li Tong , Li Bin , Xu Min , Chen Limin
Published: May 2022

Background

All Chinese blood centers have implemented mini pool (MP) HBV nucleic acid testing (NAT) together with HBsAg ELISA in routine donor screening since 2015. The prevalence of occult hepatitis B virus infection (OBI) in donors from different regions varies, and the molecular characterization of the HBV DNA and clinical outcomes of these OBIs remain largely unexplored.

Methods

Blood donations from Heyuan city in Southern China were screened by HBsAg ELISA and HBV MP8 NAT. Donations with HBsAg-/HBV DNA+ were collected for this study. Molecular characterizations of HBV DNAs were further analyzed by various DNA amplification assays including quantitative PCR (qPCR) and nested PCR, amplifying the basic core and pre-core promoter regions (BCP/PC). The HBsAg (S) region from HBV DNA was isolated by high-volume nucleic acid extraction. Notable mutations were identified by comparison to the HBV reference sequences. The clinical outcomes of the donors with OBIs were further followed for nearly 3 years.

Results

Seventy OBIs from 44,592 donations (0.15%) that we identified and reported previously were enrolled for this current study. HBV sequences were obtained from 44/70 OBIs, and genotyping analysis showed that 42/44 (95.2%) OBIs were genotype B, and 2/44 (4.8%) were genotype C. Interestingly, mutation analysis revealed that various mutations including M133L/T, F134L, P142L, V168A, R169H, S174N, L175S, and V177A of HBV DNA affecting HBsAg detection were observed in genotype B OBIs. Two notable mutations, T47K and L53S, were identified in genotype C OBIs. Follow-up studies showed that 3/31 (9.7%) OBIs converted to HBsAg+ as chronic infections while 1/31 (3.2%) HBV DNA was undetectable (classified as recovery) and 27/31 (87.1%) remained as OBIs.

Conclusion

Various notable mutations affecting HBsAg detection were observed in blood donors with OBIs in Heyuan city of Southern China. Follow-up studies showed that most OBIs remained as OBIs with fluctuating or low viral loads. Higher sensitive HBV ID NAT is recommended for donor screening to further reduce the transmission risk of OBIs.
Cytosolic p53 Inhibits Parkin-Mediated Mitophagy and Promotes Acute Liver Injury Induced by Heat Stroke
Authors: Huang Wei , Xie Weidang , Zhong Hanhui , Cai Shumin , Huang Qiaobing , Liu Youtan , Zeng Zhenhua , Liu Yanan
Published: May 2022

Heat stroke (HS) is a severe condition characterized by increased morbidity and high mortality. Acute liver injury (ALI) is a well-documented complication of HS. The tumor suppressor p53 plays an important role in regulation of mitochondrial integrity and mitophagy in several forms of ALI. However, the role of p53-regulated mitophagy in HS-ALI remains unclear. In our study, we discovered the dynamic changes of mitophagy in hepatocytes and demonstrated the protective effects of mitophagy activation on HS-ALI. Pretreatment with 3-MA or Mdivi-1 significantly exacerbated ALI by inhibiting mitophagy in HS-ALI mice. Consistent with the animal HS-ALI model results, silencing Parkin aggravated mitochondrial damage and apoptosis by inhibiting mitophagy in HS-treated normal human liver cell line (LO2 cells). Moreover, we described an increase in the translocation of p53 from the nucleus to the cytoplasm, and cytosolic p53 binds to Parkin in LO2 cells following HS. p53 overexpression using a specific adenovirus or Tenovin-6 exacerbated HS-ALI through Parkin-dependent mitophagy both in vivo and in vitro, whereas inhibition of p53 using siRNA or PFT-α effectively reversed this process. Our results demonstrate that cytosolic p53 binds to Parkin and inhibits mitophagy by preventing Parkin’s translocation from the cytosol to the mitochondria, which decreases mitophagy activation and leads to hepatocyte apoptosis in HS-ALI. Overall, pharmacologic induction of mitophagy by inhibiting p53 may be a promising therapeutic approach for HS-ALI treatment.
Aminoacyl-tRNA Synthetases: On Anti-Synthetase Syndrome and Beyond
Authors: Galindo-Feria Angeles S. , Notarnicola Antonella , Lundberg Ingrid E. , Horuluoglu Begum
Published: May 2022

Anti-synthetase syndrome (ASSD) is an autoimmune disease characterized by the presence of autoantibodies targeting one of several aminoacyl t-RNA synthetases (aaRSs) along with clinical features including interstitial lung disease, myositis, Raynaud’s phenomenon, arthritis, mechanic’s hands, and fever. The family of aaRSs consists of highly conserved cytoplasmic and mitochondrial enzymes, one for each amino acid, which are essential for the RNA translation machinery and protein synthesis. Along with their main functions, aaRSs are involved in the development of immune responses, regulation of transcription, and gene-specific silencing of translation. During the last decade, these proteins have been associated with cancer, neurological disorders, infectious responses, and autoimmune diseases including ASSD. To date, several aaRSs have been described to be possible autoantigens in different diseases. The most commonly described are histidyl (HisRS), threonyl (ThrRS), alanyl (AlaRS), glycyl (GlyRS), isoleucyl (IleRS), asparaginyl (AsnRS), phenylalanyl (PheRS), tyrosyl (TyrRS), lysyl (LysRS), glutaminyl (GlnRS), tryptophanyl (TrpRS), and seryl (SerRS) tRNA synthetases. Autoantibodies against the first eight autoantigens listed above have been associated with ASSD while the rest have been associated with other diseases. This review will address what is known about the function of the aaRSs with a focus on their autoantigenic properties. We will also describe the anti-aaRSs autoantibodies and their association to specific clinical manifestations, and discuss their potential contribution to the pathogenesis of ASSD.
Multi-Scale Spatial Analysis of the Tumor Microenvironment Reveals Features of Cabozantinib and Nivolumab Efficacy in Hepatocellular Carcinoma
Authors: Mi Haoyang , Ho Won Jin , Yarchoan Mark , Popel Aleksander S.
Published: May 2022

Background

Concomitant inhibition of vascular endothelial growth factor (VEGF) and programmed cell death protein 1 (PD-1) or its ligand PD-L1 is a standard of care for patients with advanced hepatocellular carcinoma (HCC), but only a minority of patients respond, and responses are usually transient. Understanding the effects of therapies on the tumor microenvironment (TME) can provide insights into mechanisms of therapeutic resistance.

Methods

14 patients with HCC were treated with the combination of cabozantinib and nivolumab through the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center. Among them, 12 patients (5 responders + 7 non-responders) underwent successful margin negative resection and are subjects to tissue microarray (TMA) construction containing 37 representative tumor region cores. Using the TMAs, we performed imaging mass cytometry (IMC) with a panel of 27-cell lineage and functional markers. All multiplexed images were then segmented to generate a single-cell dataset that enables (1) tumor-immune compartment analysis and (2) cell community analysis based on graph-embedding methodology. Results from these hierarchies are merged into response-associated biological process patterns.

Results

Image processing on 37 multiplexed-images discriminated 59,453 cells and was then clustered into 17 cell types. Compartment analysis showed that at immune-tumor boundaries from NR, PD-L1 level on tumor cells is significantly higher than remote regions; however, Granzyme B expression shows the opposite pattern. We also identify that the close proximity of CD8+ T cells to arginase 1hi (Arg1hi) macrophages, rather than CD4+ T cells, is a salient feature of the TME in non-responders. Furthermore, cell community analysis extracted 8 types of cell-cell interaction networks termed cellular communities (CCs). We observed that in non-responders, macrophage-enriched CC (MCC) and lymphocyte-enriched CC (LCC) strongly communicate with tumor CC, whereas in responders, such communications were undermined by the engagement between MCC and LCC.

Conclusion

These results demonstrate the feasibility of a novel application of multiplexed image analysis that is broadly applicable to quantitative analysis of pathology specimens in immuno-oncology and provides further evidence that CD163-Arg1hi macrophages may be a therapeutic target in HCC. The results also provide critical information for the development of mechanistic quantitative systems pharmacology models aimed at predicting outcomes of clinical trials.
Assessment of the Safety and Efficacy of an Oral Probiotic-Based Vaccine Against Aspergillus Infection in Captive-Bred Humboldt Penguins (Spheniscus humboldti)
Authors: Thorel Milan , Mateos-Hernandez Lourdes , Mulot Baptiste , Azzouni Mouna Naila , Hodžić Adnan , Gaillot Hugues , Ruel Yannick , Desoubeaux Guillaume , Delaye Jean-Baptiste , Obregon Dasiel , Wu-Chuang Alejandra , de la Fuente José , Bermúdez-Humarán Luis G. , Risco-Castillo Veronica , Leclerc Antoine , Cabezas-Cruz Alejandro
Published: May 2022

Aspergillosis is a fungal infection caused mainly byAspergillus fumigatusthat often results in respiratory disease in birds. Aspergillosis is a major cause of morbidity and mortality in captive-bred penguin species. Currently, there is no registered vaccine to prevent aspergillosis. Recent research demonstrated that oral administration of gram-negative bacteria expressing high levels of galactose-α-1,3-galactose (α-Gal) modulates anti-α-Gal immunity and protects turkeys from clinical aspergillosis caused by experimentalA. fumigatusinfection. The role of anti-α-Gal immunity in penguins has not been studied. Here, we tested the distribution of α-1,3-galactosyltransferase (α1,3GT) genes in the fecal microbiome of Humboldt penguins (Spheniscus humboldti). The occurrence of natural anti-α-Gal antibodies (Abs) in sera and eggs of healthy Humboldt penguins was also assessed. A trial was then conducted to test whether oral administration ofEscherichia coliNissle, expressing high α-Gal levels, modulates anti-α-Gal immunity in a colony of Humboldt penguins. Animals in the vaccination and placebo groups were evaluated before the trial and followed for one year for aspergillosis detection using a diagnostic panel including computed tomography scans, capillary zone electrophoresis, 3-hydroxybutyrate levels, and anti-A. fumigatusAbs. Anti-α-Gal Abs were detected in sera (IgM and IgY) and eggs (IgY) of healthy penguins. Microbiota analysis and functional predictions revealed the presence of α1,3GT genes in the microbiota of Humboldt penguins and other penguin species. A strong decrease in anti-α-Gal IgM levels was observed in all animals in the placebo group three months after vaccination protocol. This decrease was not observed inE. coliNissle-treated penguins. After the vaccination protocol, we found a positive correlation between anti-E. coliIgY and anti-α-Gal IgY in theE. coliNissle group, suggesting a correlation between the presence of the bacteria and these Abs. During the study period, three penguins exhibited respiratory signs consistent with aspergillosis. Two were from the placebo group whose symptoms resolved with specific treatments, while a single vaccinated individual developed fatal respiratory aspergillosis eight months after the trial. We conclude thatE. coliNissle represents a safe potential probiotic with a protective effect against aspergillosis in Humboldt penguins that deserves to be further explored for therapeutic uses in these animals.
Role of Lectin in the Response of Aedes aegypti Against Bt Toxin
Authors: Alam Intikhab , Batool Khadija , Idris Aisha Lawan , Tan Weilong , Guan Xiong , Zhang Lingling
Published: May 2022

Aedes aegyptiis one of the world’s most dangerous mosquitoes, and a vector of diseases such as dengue fever, chikungunya virus, yellow fever, and Zika virus disease. Currently, a major global challenge is the scarcity of antiviral medicine and vaccine for arboviruses.Bacillus thuringiensisvar israelensis (Bti) toxins are used as biological mosquito control agents. Endotoxins, including Cry4Aa, Cry4Ba, Cry10Aa, Cry11Aa, and Cyt1Aa, are toxic to mosquitoes. Insect eradication by Cry toxin relies primarily on the interaction of cry toxins with key toxin receptors, such as aminopeptidase (APN), alkaline phosphatase (ALP), cadherin (CAD), and ATP-binding cassette transporters. The carbohydrate recognition domains (CRDs) of lectins and domains II and III of Cry toxins share similar structural folds, suggesting that midgut proteins, such as C-type lectins (CTLs), may interfere with interactions among Cry toxins and receptors by binding to both and alter Cry toxicity. In the present review, we summarize the functional role of C-type lectins inAe. aegyptimosquitoes and the mechanism underlying the alteration of Cry toxin activity by CTLs. Furthermore, we outline future research directions on elucidating theBtiresistance mechanism. This study provides a basis for understandingBtiresistance, which can be used to develop novel insecticides.
Influence of the Polysaccharide Capsule on the Bactericidal Activity of Indolicidin on Streptococcus pneumoniae
Authors: Waz Natalha T. , Oliveira Sheila , Girardello Raquel , Lincopan Nilton , Barazzone Giovana , Parisotto Thais , Hakansson Anders P. , Converso Thiago Rojas , Darrieux Michelle
Published: May 2022

Streptococcus pneumoniae is a pathogen responsible for high morbidity and mortality worldwide. The polysaccharide capsule confers protection against phagocytosis and influences many aspects of pneumococcal pathogenesis. The capsular polysaccharides (CPS) are highly immunogenic and exhibit great structural variability, with more than 100 serotypes described so far. Antimicrobial peptides (AMPs) are an important part of the innate defense mechanisms against many pathogens. Indolicidin is a cationic AMP produced by bovine neutrophils, with bactericidal effects against several bacteria. CPS has been shown to interfere with the ability of AMPs to kill pneumococci, but the effects of capsule variability on susceptibility to indolicidin have not been explored. The present work determined the effects of capsule on resistance to indolicidin in vitro. Using a bactericidal plate assay, we observed that different pneumococcal serotypes exhibited variable resistance to indolicidin, which correlated with the capsule net charge. Interestingly, the effect of capsule expression on resistance to indolicidin was dependent on the serotype; bacteria with lower zeta potential were more resistant to indolicidin when capsule was present, while those with less negative surface charge were more resistant in the absence of capsule. The addition of purified CPS partially rescued the bacteria from the bactericidal effects of indolicidin, while the addition of anticapsular antibodies accentuated the peptide’s bactericidal action, suggesting a possible new protective mechanism induced by polysaccharide-based pneumococcal vaccines.
Salt-Tolerant PGPR Confer Salt Tolerance to Maize Through Enhanced Soil Biological Health, Enzymatic Activities, Nutrient Uptake and Antioxidant Defense
Authors: Shabaan Muhammad , Asghar Hafiz Naeem , Zahir Zahir Ahmad , Zhang Xiu , Sardar Muhammad Fahad , Li Hongna
Published: May 2022

Salt-tolerant plant growth-promoting rhizobacteria (PGPR) can improve soil enzyme activities, which are indicators of the biological health of the soil, and can overcome the nutritional imbalance in plants. A pot trial was executed to evaluate the effect of inoculation of different salt-tolerant PGPR strains in improving soil enzyme activities. Three different salinity levels (original, 5, and 10 dS m–1) were used and maize seeds were coated with the freshly prepared inocula of ten different PGPR strains. Among different strains, inoculation of SUA-14 (Acinetobacter johnsonii) caused a maximum increment in urease (1.58-fold), acid (1.38-fold), and alkaline phosphatase (3.04-fold) and dehydrogenase (72%) activities as compared to their respective uninoculated control. Acid phosphatase activities were found to be positively correlated with P contents in maize straw (r= 0.96) and grains (r= 0.94). Similarly, a positive correlation was found between alkaline phosphatase activities and P contents in straw (r= 0.77) and grains (r= 0.75). In addition, urease activities also exhibited positive correlation with N contents in maize straw (r= 0.92) and grains (r= 0.91). Moreover, inoculation ofAcinetobacter johnsoniicaused a significant decline in catalase (39%), superoxide dismutase (26%) activities, and malondialdehyde contents (27%). The PGPR inoculation improved the soil’s biological health and increased the uptake of essential nutrients and conferred salinity tolerance in maize. We conclude that the inoculation of salt-tolerant PGPR improves soil enzyme activities and soil biological health, overcomes nutritional imbalance, and thereby improves nutrient acquisition by the plant under salt stress.
Production and Characterization of Exopolysaccharide From Newly Isolated Marine Probiotic Lactiplantibacillus plantarum EI6 With in vitro Wound Healing Activity
Authors: Zaghloul Eman H. , Ibrahim Mohamed I. A.
Published: May 2022

Because of its safety, biological activities, and unique properties, exopolysaccharide (EPS) from lactic acid bacteria (LAB) has been developed as a potential biopolymer. A few studies have investigated the EPS produced by marine LAB. This study reports the wound healing activity of an EPS produced by a marine isolate identified asLactiplantibacillus plantarumEI6, in addition to assessingL. plantarumEI6's probiotic properties. EI6 demonstrated promising antimicrobial activity against different pathogenic bacteria, as well as the ability to withstand stomach pH 3, tolerate 0.3% bile salt concentration, and exhibit no signs of hemolysis. Furthermore, EI6 was able to produce 270 mg/L of EPS upon growth for 48 h at 37°C in an MRS medium enriched with 1.0% of sucrose. The chemical features of the novel EI6-EPS were investigated: the UV-vis estimated a high carbohydrate content of ~91.5%, and the FTIR emphasized its polysaccharide nature by the characteristic hydroxyl, amide I, II, & III, and glycosidic linkage regions. The GC-MS and NMR analyses revealed the existence of five monosaccharides, namely, rhamnose, galactose, mannose, glucose, and arabinose, existing mainly in the pyranose form and linked together by α- and β-glycosidic linkages. EI6-EPS was found to be safe (IC50 > 100 μg/ml) and induced human skin fibroblasts (HSF) proliferation and migration. These findings imply that EI6 can be used as a safe source of bioactive polymer in wound care.
Responses of Gut Microbial Community Composition and Function of the Freshwater Gastropod Bellamya aeruginosa to Cyanobacterial Bloom
Authors: Lyu Tianying , Zhu Jinyong , Yang Xianming , Yang Wen , Zheng Zhongming
Published: May 2022

Freshwater gastropods are widely distributed and play an important role in aquatic ecosystems. Symbiotic microorganisms represented by gut microbes can affect the physiological and biochemical activities of their hosts. However, few studies have investigated the response of the gut microbial community of snails to environmental stress. In this study, the dynamics of the gut microbiota of the gastropod Bellamya aeruginosa were tracked to explore their responses in terms of their composition and function to cyanobacterial bloom. Differences in gut microbial community structures during periods of non-cyanobacterial bloom and cyanobacterial bloom were determined. Results showed that the alpha diversity of the gut microbiota exposed to cyanobacterial bloom was lower than that of the gut microbiota exposed to non-cyanobacterial bloom. The main genera differentiating the two periods were Faecalibacterium, Subdoligranulum, Ralstonia, and Pelomonas. Microcystins (MCs) and water temperature (WT) were the primary factors influencing the gut microbial community of B. aeruginosa; between them, the influence of MCs was greater than that of WT. Fourteen pathways (level 2) were notably different between the two periods. The pathways of carbohydrate metabolism, immune system, environmental adaptation, and xenobiotics biodegradation and metabolism in these differential pathways exhibited a strong linear regression relationship with MCs and WT. Changes in the functions of the gut microbiota may help B. aeruginosa meet its immunity and energy needs during cyanobacterial bloom stress. These results provide key information for understanding the response pattern of freshwater snail intestinal flora to cyanobacterial blooms and reveal the underlying environmental adaptation mechanism of gastropods from the perspective of intestinal flora.
Shape and Rule Information Is Reflected in Different Local Field Potential Frequencies and Different Areas of the Primate Lateral Prefrontal Cortex
Authors: Sakamoto Kazuhiro , Kawaguchi Norihiko , Mushiake Hajime
Published: May 2022

The lateral prefrontal cortex (LFPC) plays a crucial role in executive function by adaptively storing behavior-relevant information as working memory. Neural mechanisms associated with local field potentials (LFPs) may underlie the adaptive properties of the LFPC. Here, we analyzed how LFPs recorded from the monkey LFPC are modulated by the crucial factors of a shape manipulation task. In this task, the test shape is transformed by manipulating a lever to match the size and orientation of the sample shape. The subject is required to temporarily memorize the rules such as the arm-movement-manipulation relationship and the sample shape to generate the sequential behavior of operations. In the present study, we focused on task variables about shape and rules, and examined among which aspects distinguish the ventral and dorsal sides of the LFPC. We found that the transformed shape in the sample period strongly affected the theta and delta waves in the delay period on the ventral side, while the arm-manipulation assignment influenced the gamma components on the dorsal side. These findings suggest that area- and frequency-selective LFP modulations are involved in dynamically recruiting different behavior-relevant information in the LFPC.
Culture Effects on the Chinese Version Boston Naming Test Performance and the Normative Data in the Native Chinese-Speaking Elders in Mainland China
Authors: Li Yan , Qiao Yuchen , Wang Fen , Wei Cuibai , Wang Rui , Jin Hongmei , Xie Bingxin , You Jing , Jia Jianping , Zhou Aihong
Published: May 2022

Background

The Chinese version of Boston Naming Test (BNT-C) is administered in China widely. However, the neuropsychological parameter of BNT-C in native Chinese-speaking elders in mainland China has not been explored systematically. The aim of this study was to explore cultural influences on BNT-C performance and establish norms among native Chinese-speaking elders in Beijing.

Methods

A total of 161 native, Chinese-speaking, cognitively normal elders aged ≥55 years were enrolled from various communities in Beijing. The BNT-C was conducted on all the participants. The internal consistency, participants' familiarity, and naming accuracy were analyzed and compared with data from Chinese areas outside the mainland and from American published previously. The influencing factors and stratified norms for BNT-C were established.

Results

The BNT-C showed good internal consistency (α = 0.738). Strong correlation between naming accuracy and object familiarity was found (r = 0.962, P < 0.001). Participants' familiarity and correct naming rate for many items were notably different between the Chinese-speaking elders and English-speaking elders in America. The difference in some items' correct naming rate also existed between Beijing, Taiwan, and Hongkong. Higher education was associated with higher scores, whereas age and gender had no effect on BNT-C performance. The recommended norms of total naming scores for elders with education ≤ 9 and >9 years were 16 and 23, respectively.

Conclusion

The participants' familiarity with BNT items differed between different cultures, which further affected the naming accuracy and total scores. The education stratified norms established here are helpful for the better application of BNT-C in mainland China.
Knockdown of NRSF Alleviates Ischemic Brain Injury and Microvasculature Defects in Diabetic MCAO Mice
Authors: He Cheng-Feng , Xue Wen-Jiao , Xu Xiao-Die , Wang Jian-Tao , Wang Xin-Ru , Feng Yi , Zhou Hou-Guang , Guo Jing-Chun
Published: May 2022

Diabetes is one of the well-established risk factors of stroke and is associated with a poor outcome in patients with stroke. Previous studies have shown that the expression of neuron restrictive silencer factor (NRSF) is elevated in diabetes as well as ischemic stroke. However, the role of NRSF in regulating an outcome of diabetic ischemic stroke has not been completely understood. Here, we hypothesized that diabetes-induced NRSF elevation can aggravate brain injury and cognition impairment in ischemic stroke. The diabetic ischemic stroke mice model was established by 8 weeks of high-fat-diet feeding and 5 days of streptozotocin injection followed by 30 min of middle cerebral artery occlusion (MCAO). We found that diabetes enhanced the MCAO-induced elevation of NRSF in the hippocampus in accompany with an elevation of its corepressors, HDAC1, and mSin3A, and decrease of β-TrCP. By using histological/immunofluorescence staining and neurobehavioral testing, our results showed that the brain damage and learning/memory impairment were aggravated in diabetic ischemic mice but significantly attenuated after stereotaxic injection of NRSF-shRNA. Meanwhile, by performing whole-brain clearing with PEGASOS, microvascular reconstruction, western blotting, and ELISA, we found that NRSF-shRNA markedly alleviated the vasculature disorders and rescued the suppression of NRP-1, VEGF, and VEGFR2 in the hippocampus of diabetic ischemic mice. Therefore, our results demonstrated for the first time that the elevation of hippocampal NRSF plays an important role in alleviating brain injury and cognitive disabilities in diabetic ischemic mice, potentially via the reduction of NRP-1/VEGF signaling.
Advancing Prediction of Risk of Intraoperative Massive Blood Transfusion in Liver Transplantation With Machine Learning Models. A Multicenter Retrospective Study
Authors: Chen Sai , Liu Le-ping , Wang Yong-jun , Zhou Xiong-hui , Dong Hang , Chen Zi-wei , Wu Jiang , Gui Rong , Zhao Qin-yu
Published: May 2022

Background

Liver transplantation surgery is often accompanied by massive blood loss and massive transfusion (MT), while MT can cause many serious complications related to high mortality. Therefore, there is an urgent need for a model that can predict the demand for MT to reduce the waste of blood resources and improve the prognosis of patients.

Objective

To develop a model for predicting intraoperative massive blood transfusion in liver transplantation surgery based on machine learning algorithms.

Methods

A total of 1,239 patients who underwent liver transplantation surgery in three large grade lll-A general hospitals of China from March 2014 to November 2021 were included and analyzed. A total of 1193 cases were randomly divided into the training set (70%) and test set (30%), and 46 cases were prospectively collected as a validation set. The outcome of this study was an intraoperative massive blood transfusion. A total of 27 candidate risk factors were collected, and recursive feature elimination (RFE) was used to select key features based on the Categorical Boosting (CatBoost) model. A total of ten machine learning models were built, among which the three best performing models and the traditional logistic regression (LR) method were prospectively verified in the validation set. The Area Under the Receiver Operating Characteristic Curve (AUROC) was used for model performance evaluation. The Shapley additive explanation value was applied to explain the complex ensemble learning models.

Results

Fifteen key variables were screened out, including age, weight, hemoglobin, platelets, white blood cells count, activated partial thromboplastin time, prothrombin time, thrombin time, direct bilirubin, aspartate aminotransferase, total protein, albumin, globulin, creatinine, urea. Among all algorithms, the predictive performance of the CatBoost model (AUROC: 0.810) was the best. In the prospective validation cohort, LR performed far less well than other algorithms.

Conclusion

A prediction model for massive blood transfusion in liver transplantation surgery was successfully established based on the CatBoost algorithm, and a certain degree of generalization verification is carried out in the validation set. The model may be superior to the traditional LR model and other algorithms, and it can more accurately predict the risk of massive blood transfusions and guide clinical decision-making.
The Effect of Bangerter Filters on Visual Acuity and Contrast Sensitivity With External Noise
Authors: Zhang Pan , Wang Hanlin , Ren Weicong , Guo Huanhuan , Yang Jiayi , Tao Jiayu , Yang Zhijie , Li Ying , Chen Lijun , Zhang Yajing , Wu Di
Published: May 2022

It is critical to address the relationship between density label of Bangerter filters and expected visual acuity, and how filters modulate contrast sensitivity (CS) at different spatial frequency and external noise levels. In the current study, the monocular visual acuity and CS at ten spatial frequencies and three noise levels were measured in normal subjects wearing no filters, 0.8, 0.4, or 0.2 Bangerter filters. Compared with the baseline condition (no filter worn), Bangerter filters degraded both visual acuity and contrast sensitivity function (CSF) in zero-noise conditions, but the reduction of both visual functions did not correlate with each other at any filter level. In addition, the stronger the filter was, the worse both visual functions became. In contrast, when external noise was present, filters improved the contrast sensitivity at low frequencies but deteriorated it at intermediate and high spatial frequencies. The perceptual template model was used to reveal the corresponding mechanism accounted for filter-induced visual function changes. Although the internal process in visual system should not be affected by the filters, the measurement of parameters was biased. To be specific, (1) the internal additive noise was elevated at all frequencies; (2) the perceptual template was improved at low spatial frequencies but impaired at intermediate spatial frequencies; and (3) the changes in both factors were highly dependent on filter intensity. We conclude that Bangerter filters influence visual acuity and contrast sensitivity differently and that their effect on contrast sensitivity depends on spatial frequency and noise.
The Potential Circular RNAs Biomarker Panel and Regulatory Networks of Parkinson’s Disease
Authors: Xiao Yousheng , Chen Hongchang , Liao Jiajia , Zhang Qinxin , He Honghu , Lei Jiang , Huang Jinjun , Ouyang Qiang , Shen Yuefei , Wang Jin
Published: May 2022

Parkinson’s disease (PD) is a progressive neurodegenerative disease. It has been reported that circular RNAs (circRNAs) play important roles in several neurological diseases. However, the role and regulatory networks of circRNAs in PD are still largely unclear. In this study, we first compared the global expression level of circRNAs from patients with PD and controls using microarray, then the candidate circRNAs were validated in another PD cohort. The possible functions of these candidate circRNAs were analyzed using Gene Ontology (GO) analyses and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, and the regulatory networks of these candidate circRNAs were constructed through circRNA–miRNA–mRNA regulatory networks, protein–protein interaction (PPI) networks, and transcription factor-circRNA networks. The results indicated that hsa_circRNA_101275, hsa_circRNA_103730, and hsa_circRNA_038416 were significantly more highly expressed in patients with PD, while hsa_circRNA_102850 was lower expressed in patients with PD when compared with controls. A circRNA panel combining the four differentially expressed circRNA showed a high diagnostic ability to distinguish patients with PD from controls (AUC = 0.938). Furthermore, GO and KEGG analysis showed these candidate circRNAs were enriched in PI3K–Akt and MAPK signaling pathways. We established circRNA–miRNA–mRNA regulatory networks and identified 10 hub genes (ESR1, PTEN, SHC1, IGF1R, SMAD2, KRAS, MDM2, HIF1A, BMP4, and ACVR2B) were closely related to PD by using PPI network analysis. Besides, these circRNAs were predicted to be regulated through tyrosine hydroxylase (TH)-relevant transcription factors such as GATA2 and GATA3. In conclusion, our results suggest that the circRNA panel and the established circRNA–miRNA–mRNA regulation networks might provide potential novel biomarkers and therapeutic targets for PD.
Research Hotspots and Frontiers in Post Stroke Pain: A Bibliometric Analysis Study
Authors: Li Chong , Shu Xiaoyi , Liu Xiangyun
Published: May 2022

Background

Pain is a common complication after stroke with a high incidence and mortality rate. Many studies in the field of pain after stroke have been published in various journals. However, bibliometric analysis in the domain of pain after stroke is still lacking. This study aimed to deliver a visual analysis to analyze the global trends in research on the comorbidity of pain after stroke in the last 12 years.

Methods

The publications from the Web of Science (WoS) in the last 12 years (from 2010 to 2021) were collected and retrieved. CiteSpace software was used to analyze the relationship of publication year with countries, institutions, journals, authors, references, and keywords.

Results

A total of 322 publications were included in the analysis. A continuous but unstable growth in the number of articles published on pain after stroke was observed over the last 12 years. The Peoples' R China (65), Chang Gung University (10), and Topic in Stroke Rehabilitation (16) were the country, institution, and journal with the highest number of publications, respectively. Analysis of keywords showed that shoulder pain after stroke and central post-stroke pain were the research development trends and focus in this research field.

Conclusion

This study provides a visual analysis method for the trend and frontiers of pain research after stroke. In the future, large sample, randomized controlled trials are needed to identify the potential treatments and pathophysiology for pain after stroke.
Novel Cerebello-Amygdala Connections Provide Missing Link Between Cerebellum and Limbic System
Authors: Jung Se Jung , Vlasov Ksenia , D’Ambra Alexa F. , Parigi Abhijna , Baya Mihir , Frez Edbertt Paul , Villalobos Jacqueline , Fernandez-Frentzel Marina , Anguiano Maribel , Ideguchi Yoichiro , Antzoulatos Evan G. , Fioravante Diasynou
Published: May 2022

The cerebellum is emerging as a powerful regulator of cognitive and affective processing and memory in both humans and animals and has been implicated in affective disorders. How the cerebellum supports affective function remains poorly understood. The short-latency (just a few milliseconds) functional connections that were identified between the cerebellum and amygdala—a structure crucial for the processing of emotion and valence—more than four decades ago raise the exciting, yet untested, possibility that a cerebellum-amygdala pathway communicates information important for emotion. The major hurdle in rigorously testing this possibility is the lack of knowledge about the anatomy and functional connectivity of this pathway. Our initial anatomical tracing studies in mice excluded the existence of a direct monosynaptic connection between the cerebellum and amygdala. Using transneuronal tracing techniques, we have identified a novel disynaptic circuit between the cerebellar output nuclei and the basolateral amygdala. This circuit recruits the understudied intralaminar thalamus as a node. Using ex vivo optophysiology and super-resolution microscopy, we provide the first evidence for the functionality of the pathway, thus offering a missing mechanistic link between the cerebellum and amygdala. This discovery provides a connectivity blueprint between the cerebellum and a key structure of the limbic system. As such, it is the requisite first step toward obtaining new knowledge about cerebellar function in emotion, thus fundamentally advancing understanding of the neurobiology of emotion, which is perturbed in mental and autism spectrum disorders.
Association of Serum Retinol Concentrations With Metabolic Syndrome Components in Iranian Children and Adolescents: The CASPIAN-V Study
Authors: Qorbani Mostafa , Seif Ehsan , Heshmat Ramin , Ghonbalani Zahra Nouri , Basiry Pouria , Kazemian Elham , Kelishadi Roya
Published: May 2022

Background

As a fat-soluble vitamin, vitamin A plays a crucial role in adipogenesis, lipolysis, insulin resistance, and obesity. However, it is still unclear whether they are associated with cardiometabolic risk factors in children and adolescents. The current study aimed to determine the association between serum retinol concentration and the cluster of metabolic syndrome components among children and adolescents.

Methods

This nationwide cross-sectional study was performed on 2,518 students aged 7–18 years from the Childhood and Adolescence Surveillance and Prevention of Adult Non- communicable disease (CASPIAN-V) study. Students were selected via multistage cluster sampling method from 30 provinces of Iran in 2015. Multivariable logistic regression was used to assess the association of serum retinol concentration with metabolic syndrome (MetS) components.

Results

Overall, the mean (SD) age of study participants was 12.16 (3.04) years, and 44.9% (n = 1,166) of them were girls. The mean serum retinol concentration was 1.48 ± 1.55 μmol/L and vitamin A deficiency was observed among 19.7% (95% CI: 18.2–21.3) of study subjects. The results of the logistic regression analysis showed that increasing serum retinol concentrations were associated with an increased likelihood of developing obesity (OR: 1.12, 95% CI: 1.04, 1.20), abdominal obesity (OR: 1.07, 95% CI: 1.01, 1.14), low high-density lipoprotein cholesterol (HDL-C) (OR: 1.10, 95% CI: 1.04, 1.16) and high fasting blood glucose (FBG) (OR: 1.21, 95% CI: 1.10, 1.35), whereas it was associated with a decreased odds of developing high blood pressure (OR: 0.82, 95% CI: 0.73, 0.93). Nevertheless, there was no statistically significant association between metabolic syndrome itself and retinol concentration (OR: 1.02, 95% CI: 0.88, 1.18).

Conclusion

We found that serum retinol concentration was positively associated with metabolic syndrome components such as obesity, low HDL-C, and high FBG, but not with metabolic syndrome itself.
Evaluation of the Major Seed Storage Proteins, the Conglutins, Across Genetically Diverse Narrow-Leafed Lupin Varieties
Authors: Tahmasian Arineh , Juhász Angéla , Broadbent James A. , Nye-Wood Mitchell G. , Le Thao T. , Colgrave Michelle L.
Published: May 2022

Lupin seeds have an excellent nutritional profile, including a high proportion of protein and dietary fiber. These qualities make lupin seeds an ideal candidate to help meet the growing global demand for complementary sources of protein. Of consequence to this application, there are nutritional and antinutritional properties assigned to the major lupin seed storage proteins—referred to as α-, β-, δ- and γ-conglutins The variation in the abundance of these protein families can impact the nutritional and bioactive properties of different lupin varieties. Hence, exploring the conglutin protein profiles across a diverse range of lupin varieties will yield knowledge that can facilitate the selection of superior genotypes for food applications or lupin crop improvement. To support this knowledge generation, discovery proteomics was applied for the identification of the 16 known conglutin subfamilies from 46 domestic and wild narrow-leafed lupin (NLL) genotypes. Consequently, the diversity of abundance of these proteins was evaluated using liquid chromatography–multiple reaction monitoring-mass spectrometry (LC–MRM-MS). This comparative study revealed a larger variability for the β- and δ-conglutin content across the lines under study. The absence/lower abundance of the β2- to β6-conglutin subfamilies in a subset of the domesticated cultivars led to substantially lower overall levels of the allergenic β-conglutin content in these NLLs, for which the elevation of the other conglutin families were observed. The diversity of the conglutin profiles revealed through this study—and the identification of potential hypoallergenic genotypes—will have great significance for lupin allergic consumers, food manufactures as well as grain breeders through the future development of lupin varieties with higher levels of desirable bioactive proteins and lower allergen content.
Less Sugar and More Whole Grains in Infant Cereals: A Sensory Acceptability Experiment With Infants and Their Parents
Authors: Sanchez-Siles Luisma , Román Sergio , Haro-Vicente Juan F. , Bernal Maria Jose , Klerks Michelle , Ros Gaspar , Gil Ángel
Published: May 2022

There is an urgent need to reduce sugar intake in early childhood. Commercial infant cereals are among the first solid foods introduced to infants at the beginning of the complementary feeding period in most countries. The aim of this study was to examine infants’ overall acceptability of low-sugar complementary cereals. To do so, a between-subjects experimental study with 165 parents and their infants aged 6–24 months was conducted where one group tested a high-sugar refined cereal (21 g/100 g), and the other a low-sugar cereal (<1 g/100 g) with 50% of whole grain, which represented a 95.2% decrease in sugar content. We found no significant differences between the two groups in terms of infants’ overall acceptability (infant’s reaction, estimated intake and relative intake). Importantly, infants’ reactions to high- and low-sugar cereals were not influenced by the time that infants had been consuming sweet cereals (15–25% sugar) before the experiment took place. In addition, parent’s overall liking and sensory evaluation (sweetness, color, taste, texture, and aroma) was positive and very similar in both groups. Overall, our findings show that it is feasible to reduce sugar content in infant cereals without sacrificing its sensory acceptability by infants and their parents. This represents a good opportunity for the infant food industry to adhere to current healthy and sustainable demands of lowering the sugar intake leading to important benefits in infants’ health, without compromising competitiveness in the market.