bluuebunny/crossref_metadata_2025 huggingface dataset:
Prediction of excessively low vault after implantable collamer lens implantation using iris morphology
Authors: Khan Muhammad Ahmad , Tan Qian , Sun Wei , Cai Wang , Zhao Libei , Lin Ding
Published: October 2022

Purpose

To identify the iris morphology-related factors for prediction of outcomes of excessively low vault (< 100 μm) after Implantable Collamer Lens V4c (ICL V4c; STAAR Surgical) implantation.

Methods

This retrospective case-control study included 81 eyes from 2,080 patients who underwent ICL implantation. Twenty-seven eyes of 27 patients with excessively low vault (< 100 μm) constituted the case group (excessively low vault group). Patients with vault (250 to 750 μm) were selected as the optimal vault group by matching anterior chamber depth, white-to-white distance and ICL size with cases with excessive low vault (< 100 μm) at a proportion of 1:2. The preoperative biometric parameters and postoperative vault were recorded. Multiple linear regression analysis was performed to assess the relationship between the postoperative vault and various variables. Conditional logistic regression analysis was used to estimate the risk factors for excessively low vault.

Results

The postoperative vault was associated with preoperative pupil diameter (PD), crystalline lens rise, iris concavity and the ratio of the iris concavity to chord length (P < 0.05). The larger iris concavity increased risk of excessively low postoperative vault (< 100 μm) (OR = 81.10; 95%CI = 2.87 to 2296.58; P = 0.01).

Conclusions

Eyes with obviously concave iris were associated with a higher rate of excessively low vault (< 100 μm). Evaluation of iris morphology may provide significant information for predicting excessive postoperative vault.
Case report: Severe non-pigmenting fixed drug eruption showing general symptoms caused by chondroitin sulfate sodium
Authors: Otsuka Haruhiko , Fukumoto Takeshi , Oka Masahiro , Nishigori Chikako
Published: October 2022

Non-pigmenting fixed drug eruption (NPFDE) is a subtype of fixed drug eruption (FDE) in which repeated eruptions occur at the same site. Clinically, NPFDE disappears without pigmentation changes; however, it sometimes causes fever or arthralgia. Its histopathological characteristics reportedly include infiltrations of CD8-positive T cells with a paucity of melanocytes as compared to FDE. We present the first case of severe NPFDE exhibiting general symptoms caused by chondroitin sulfate sodium. The patient was a 44-year-old man. Intravenous injection of chondroitin sulfate sodium caused erythema in the affected area. A histopathological examination of the biopsy tissue revealed infiltration of CD3-positive lymphocytes (both CD4-positive and CD8-positive lymphocytes) into the epidermis, minimal liquefaction degeneration in the basal layer of the epidermis, and few dermal melanophages, which may be responsible for non-pigmentation.
Association between cervical disorders and adverse obstetric outcomes: A retrospective cohort study
Authors: Sun Hanxiang , Su Xiujuan , Liu Yang , Huang Shijia , Liu Xiaosong , Li Guohua , Du Qiaoling
Published: October 2022

Objective

The purpose of this study was to explore the association of cervical disorders on obstetric outcomes of singleton pregnancies in China.

Methods

This hospital-based retrospective cohort study of women with live singleton births included 71,097 Chinese women. We compared the risk of adverse obstetric outcomes in different types of pregnancies with cervical disorders with those with normal cervix. Logistic regression model was used to estimate the association between cervical disorders and adverse obstetric outcomes.

Results

Women with cervical disorders had a higher risk of premature delivery (10.98 vs. 4.41%), preterm premature rupture of membranes (PPROM) (3.48 vs. 1.62%), low birth weight (LBW) (7.62 vs. 2.92%) and very low birth weight (VLBW) (2.01 vs. 0.28%) than women with normal cervix. After adjusting for confounding factors, compared with women with normal cervix, women with high-grade abnormal cervical cytology are at greater risk of premature birth (adjusted OR 1.971, 95% CI: 1.302–2.983), premature rupture of membranes (PROM) (adjusted OR 1.379, 95% CI: 1.047–1.815), LBW (adjusted OR 1.790, 95% CI: 1.059–3.025), and VLBW (adjusted OR 4.519, 95% CI: 1.662–12.292) than women with low-grade abnormal cervical cytology, and women with abnormal cervical cytology after treatment had a higher risk of premature birth (adjusted OR 2.060, 95% CI: 1.348–3.147), PROM (adjusted OR 1.381, 95% CI: 1.038–1.839), PPROM (adjusted OR 1.995, 95% CI: 1.022–3.892), LBW (adjusted OR 1.801, 95% CI: 1.046–3.102), and VLBW (adjusted OR 4.868, 95% CI: 1.788–13.255) than untreated women.

Conclusions

Our research showed that pregnant women with cervical disorders were more likely to have premature delivery, PPROM, LBW, and VLBW. Moreover, pregnant women with high-grade abnormal cervical cytology and abnormal cervical cytology after treatment had a higher risk of premature birth, PROM, LBW, and VLBW.
A study on the diagnosis of the Helicobacter pylori coccoid form with artificial intelligence technology
Authors: Zhong Zishao , Wang Xin , Li Jianmin , Zhang Beiping , Yan Lijuan , Xu Shuchang , Chen Guangxia , Gao Hengjun
Published: October 2022

Background

Helicobacter pylori (H. pylori) is an important pathogenic microorganism that causes gastric cancer, peptic ulcers and dyspepsia, and infects more than half of the world’s population. Eradicating H. pylori is the most effective means to prevent and treat these diseases. H. pylori coccoid form (HPCF) causes refractory H. pylori infection and should be given more attention in infection management. However, manual HPCF recognition on slides is time-consuming and labor-intensive and depends on experienced pathologists; thus, HPCF diagnosis is rarely performed and often overlooked. Therefore, simple HPCF diagnostic methods need to be developed.

Materials and methods

We manually labeled 4,547 images from anonymized paraffin-embedded samples in the China Center for H. pylori Molecular Medicine (CCHpMM, Shanghai), followed by training and optimizing the Faster R-CNN and YOLO v5 models to identify HPCF. Mean average precision (mAP) was applied to evaluate and select the model. The artificial intelligence (AI) model interpretation results were compared with those of the pathologists with senior, intermediate, and junior experience levels, using the mean absolute error (MAE) of the coccoid rate as an evaluation metric.

Results

For the HPCF detection task, the YOLO v5 model was superior to the Faster R-CNN model (0.688 vs. 0.568, mean average precision, mAP); the optimized YOLO v5 model had a better performance (0.803 mAP). The MAE of the optimized YOLO v5 model (3.25 MAE) was superior to that of junior pathologists (4.14 MAE, p < 0.05), no worse than intermediate pathologists (3.40 MAE, p > 0.05), and equivalent to a senior pathologist (3.07 MAE, p > 0.05).

Conclusion

HPCF identification using AI has the advantage of high accuracy and efficiency with the potential to assist or replace pathologists in clinical practice for HPCF identification.
Quorum sensing regulates heteroresistance in Pseudomonas aeruginosa
Authors: Lu Yang , Liu Yuyang , Zhou Chenxu , Liu Yaqin , Long Yifei , Lin Dongling , Xiong Rui , Xiao Qian , Huang Bin , Chen Cha
Published: October 2022

The prevalence and genetic mechanism of antibiotic heteroresistance (HR) have attracted significant research attention recently. However, non-genetic mechanism of HR has not been adequately explored. The present study aimed to evaluate the role of quorum sensing (QS), an important mechanism of behavioral coordination in different subpopulations and consequent heteroresistance. First, the prevalence of HR to 7 antibiotics was investigated in 170 clinical isolates of P. aeruginosa using population analysis profiles. The results showed that P. aeruginosa was significantly heteroresistant to meropenem (MEM), amikacin (AMK), ciprofloxacin (CIP), and ceftazidime (CAZ). The observed HR was correlated with down-regulation of QS associated genes lasI and rhlI. Further, loss-of-function analysis results showed that reduced expression of lasI and rhlI enhanced HR of P. aeruginosa to MEM, AMK, CIP, and CAZ. Conversely, overexpression of these genes or treatment with 3-oxo-C12-HSL/C4-HSL lowered HR of P. aeruginosa to the four antibiotics. Additionally, although downregulation of oprD and upregulation of efflux-associated genes was evident in heteroresistant subpopulations, their expression was not regulated by LasI and RhlI. Moreover, fitness cost measurements disclosed higher growth rates of PAO1ΔlasI and PAO1ΔrhlI in the presence of sub-MIC antibiotic as compared with that of wild-type PAO1. Our data suggest that under temporary antibiotic pressure, downregulation of QS might result in less fitness cost and promote HR of P. aeruginosa.
Mutagenesis and functional analysis of SotB: A multidrug transporter of the major facilitator superfamily from Escherichia coli
Authors: Zhai Guoqing , Zhang Zhengyu , Dong Changjiang
Published: October 2022

Dysfunction of the major facilitator superfamily multidrug (MFS Mdr) transporters can lead to a variety of serious diseases in human. In bacteria, such membrane proteins are often associated with bacterial resistance. However, as one of the MFS Mdr transporters, the physiological function of SotB from Escherichia coli is poorly understood to date. To better understand the function and mechanism of SotB, a systematic study on this MFS Mdr transporter was carried out. In this study, SotB was found to directly efflux L-arabinose in E. coli by overexpressing sotB gene combined with cell based radiotracer uptake assay. Besides, the surface plasmon resonance (SPR) studies, the L-arabinose inhibition assays, together with precise molecular docking analysis, reveal the following: (i) the functional importance of E29 (protonation), H115/N343 (substrate recognition), and W119/S339 (substrate efflux) in the SotB mediated export of L-arabinose, and (ii) for the first time find that D-xylose, an isomer of L-arabinose, likely hinders the binding of L-arabinose with SotB as a competitive inhibitor. Finally, by analyzing the structure of SotB2 (shares 62.8% sequence similarity with SotB) predicted by AlphaFold 2, the different molecular mechanism of substrate recognition between SotB and SotB2 is explained. To our knowledge, this is the first systematic study of MFS Mdr transporter SotB. The structural information, together with the biochemical inspections in this study, provide a valuable framework for further deciphering the functional mechanisms of the physiologically important L-arabinose transporter SotB and its family.
Polyphasic evaluation and cytotoxic investigation of isolated cyanobacteria with an emphasis on potent activities of a Scytonema strain
Authors: Ngo Trang T. , Nguyen Bich-Loan T. , Duong Tuan A. , Nguyen Thu-Huyen T. , Nguyen Thanh L. , Kieu Kien T. , Do Minh-Hanh T. , Nguyen Sang V. , Thang Nguyen Dinh , Pham Hang T. L.
Published: October 2022

Cyanobacteria are phototrophic organisms widely found in most types of natural habitats in the tropical regions of the world. In this study, we isolated and identified cyanobacterial strains from paddy soil in Hanoi (Vietnam) and investigated their cytotoxic activities. Five isolated cyanobacterial strains showed distinctive profiles of gene sequences (rRNA 16S and rbcL), phylogenetic placements, and morphological characteristics. Based on the polyphasic evaluation, they were classified as Scytonema bilaspurense NK13, Hapalosiphon welwitschii MD2411, Aulosira sp. XN1103, Desikacharya sp. NS2000, and Desmonostoc sp. NK1813. The cytotoxic screening revealed that the extract of strain Scytonema bilaspurense NK13 exhibited potent cytotoxic activities against four human cell lines of HeLa cells, OVCAR-8 cells, HaCaT cells, and HEK-293T cells, with IC50 values of 3.8, 34.2, 21.6, and 0.6 μg/mL, respectively. This is the first time a well-classified Scytonema strain from tropical habitat in Southeast Asia has been recognized as a potential producer of cytotoxic compounds.
Immunogenicity of the recombinant adenovirus fusion-expressing E0-E2 gene of the classical swine fever virus
Authors: Zhang Heng , Yin Dehua , Qin Huairui , Zhang Ke , Li Zhaoyang , Cui Guangchao , Ma Guangbin , Sun Peng , Cao Zhi
Published: October 2022

Adenovirus vector vaccines have been the mainstream research direction of CSF vaccines, due to the replication deficiency of adenovirus vectors, achieving double effects with the safety of inactivated vaccines and the efficacy of live vaccines. Therefore, the E0 and E2 genes were expressed by an adenovirus vector, a recombinant adenovirus E0-E2 (rAd-E0-E2) vaccine was constructed, and the minimum immunization dose and immune duration period were determined in this study. Forty healthy piglets were randomly divided into 8 groups (n = 5). Groups 1 ~ 5 were used to determine the minimum immunization dose, and 5 groups were inoculated with rAd-E0-E2 at different immune doses. Serum was collected at 7 d and 14 d after immunization to detect CSFV antibodies by ELISA, and piglets were challenged at 7 d post immunization. Groups 6 ~ 8 were immunized with 1 dose of rAd-E0-E2, the CSFV live attenuated vaccine C strain and saline to identify the immune duration period. Serum was collected at different time points after immunization, CSFV antibodies were detected by ELISA, and piglets were challenged at 8 months post immunization. Meanwhile, temperature, clinical symptoms and pathology were observed. The results of groups 1 ~ 5 showed that 1 piglet was protected after challenge, and 4 piglets exhibited high fever retention, typical CSFV symptoms and tissue lesions in the 1/50 dose group, whereas no clinical symptoms were observed in the 1/10 dose, 1/5 dose or 1 dose groups with 5/5 protection after challenge. The minimum dose was determined as 1/10 dose. The results of groups 6 ~ 8 showed that all piglets survived after challenge, but the antibody level of the rAd-E0-E2 strain was higher than that of the C strain at 8 months post immunization, and all piglets in the negative group developed the disease process after challenge. Overall, the minimum immunization dose of rAd-E0-E2 was 1/10 dose (3.16 × 106.0 IFU) and the minimum immune dose was determined to be 1 dose (3.16 × 107.0 IFU) to achieve the expected effects. The immune duration period of piglets immunized with 1 dose of rAd-E0-E2 was at least 8 months.
Nationwide and long-term molecular epidemiologic studies of mumps viruses that circulated in Japan between 1986 and 2017
Authors: Kidokoro Minoru , Shiino Teiichiro , Yamaguchi Tomohiro , Nariai Eri , Kodama Hiroe , Nakata Keiko , Sano Takako , Gotou Keiko , Kisu Tomoko , Maruyama Tomomi , Kuba Yumani , Sakata Wakako , Higashi Teruaki , Kiyota Naoko , Sakai Takashi , Yahiro Shunsuke , Nagita Akira , Watanabe Kaori , Hirokawa Chika , Hamabata Hirotsune , Fujii Yoshiki , Yamamoto Miwako , Yokoi Hajime , Sakamoto Misako , Saito Hiroyuki , Shibata Chihiro , Inada Machi , Fujitani Misako , Minagawa Hiroko , Ito Miyabi , Shima Akari , Murano Keiko , Katoh Hiroshi , Kato Fumihiro , Takeda Makoto , Suga Shigeru ,   The Surveillance Team for Mumps Virus in Japan
Published: October 2022

In Japan, major mumps outbreaks still occur every 4–5 years because of low mumps vaccine coverage (30–40%) owing to the voluntary immunization program. Herein, to prepare for a regular immunization program, we aimed to reveal the nationwide and long-term molecular epidemiological trends of the mumps virus (MuV) in Japan. Additionally, we performed whole-genome sequencing (WGS) using next-generation sequencing to assess results from conventional genotyping using MuV sequences of the small-hydrophobic (SH) gene. We analyzed 1,064 SH gene sequences from mumps clinical samples and MuV isolates collected from 25 prefectures from 1986 to 2017. The results showed that six genotypes, namely B (110), F (1), G (900), H (3), J (41), and L (9) were identified, and the dominant genotypes changed every decade in Japan since the 1980s. Genotype G has been exclusively circulating since the early 2000s. Seven clades were identified for genotype G using SH sequence-based classification. To verify the results, we performed WGS on 77 representative isolates of genotype G using NGS and phylogenetically analyzed them. Five clades were identified with high bootstrap values and designated as Japanese clade (JPC)-1, -2, -3, -4, -5. JPC-1 and -3 accounted for over 80% of the total genotype G isolates (68.3 and 13.8%, respectively). Of these, JPC-2 and -5, were newly identified clades in Japan through this study. This is the first report describing the nationwide and long-term molecular epidemiology of MuV in Japan. The results provide information about Japanese domestic genotypes, which is essential for evaluating the mumps elimination progress in Japan after the forthcoming introduction of the mumps vaccine into Japan’s regular immunization program. Furthermore, the study shows that WGS analysis using NGS is more accurate than results obtained from conventional SH sequence-based classification and is a powerful tool for accurate molecular epidemiology studies.
A Case Report of Two Kala-Azar Cases in China Diagnosed by Metagenomic Next-Generation Sequencing
Authors: Gao Hongguang , Wang Jing , Zhang Shu , Li Tian
Published: October 2022

Background

Leishmaniasis being a local disease, as kala-azar this particular form is a visceral form. It is transmitted by sandflies, and is a parasitic disease involving the reticuloendothelial system of mononuclear macrophages. Due to its poor prognosis and high fatality rate, the fatality rate of patients without effective treatment can exceed 95%. Thereby, early diagnosis and treatment can significantly improve its prognosis. The metagenomic next-generation sequencing (mNGS) has the advantage of being able to find pathogens that cannot be detected by traditional methods. More importantly, it can conduct nucleic acid detection of pathogens covering a wide range in a short time. For infectious diseases like kala-azar, which is clinically complicated and difficult, mNGS detection provides a basis for accurate etiological diagnosis.

Case Report

We report 2 cases of kala-azar in West China Hospital, Chengdu, China. The first case is a 47-year-old male patient who had recurrent fever for 4 months, accompanied by reduction of red blood cell, white blood cell, and blood platelet. He was detected by mNGS and clinically diagnosed as kala-azar (Leishmania detection), finally died of multiple organ failure. The second patient was a 15-year-old male who had fever for more than 10 days. He was detected by mNGS and clinically diagnosed as kala-azar (Leishmania detection). He recovered and discharged quickly after treatment with sodium stibogluconate.

Conclusion

Efforts should be made to improve early etiological diagnosis in order to improve patient prognosis. mNGS detection is beneficial to the diagnosis and treatment of infectious diseases with unknown causes in the early stage of emergency treatment.
A buffalo rumen-derived probiotic (SN-6) could effectively increase simmental growth performance by regulating fecal microbiota and metabolism
Authors: Yang Shumin , Luo Ji , Chen Yingying , Wu Rui , Liu Huazhen , Zhou Zutao , Akhtar Muhammad , Xiao Yuncai , Shi Deshi
Published: October 2022

Microorganisms play a key role in ruminal digestion, some of which can be used as probiotics to promote growth in ruminants. However, which potential bacteria are responsible for ruminant growth and how they potentiate the basic mechanism is unclear. In this study, three bacterial strains, Bacillus pumilus (SN-3), Bacillus paralicheniformis (SN-6), and Bacillus altitudinis (SN-20) with multiple digestive enzymes were isolated from the rumen of healthy buffaloes. Among these strains, SN-6 secreted cellulase, laccase, and amylase, and significantly inhibited Staphylococcus aureus ATCC25923 and Escherichia coli K99 in vitro. In addition, SN-6 exhibited strong tolerance to artificial gastric juice, intestinal juice, and high temperature. Antibiotic resistance test, virulence gene test, and mouse toxicity test confirmed the safety of SN-6. Further, SN-6 significantly increased the body weight (p < 0.01), affects the intestinal microbiota structure, and alters the metabolomic patterns of Simmental. There was a remarkable difference in the β diversity of fecal microflora between SN-6 and control groups (p < 0.05). Furthermore, SN-6 significantly increased the abundance of Clostridium_sensu_stricto_1, Bifidobacterium, Blautia, and Cellulolyticum, decreased the relative abundance of Monoglobus and norank_f_Ruminococcacea. Moreover, SN-6 feeding significantly enriched intestinal metabolites (i.e., 3-indoleacrylic acid, kynurenic acid) to maintain intestinal homeostasis. Finally, the microbial and metabolic functional analysis indicated that SN-6 could enhance amino acid metabolism (mainly tryptophan metabolism) and lipid metabolism pathways. Overall, these findings indicated that SN-6 could be used as a probiotic in ruminants.
Inflammasomes and their roles in arthritic disease pathogenesis
Authors: Yang Gabsik , Kang Han Chang , Cho Yong-Yeon , Lee Hye Suk , Lee Joo Young
Published: October 2022

The inflammasome is a molecular platform that is created in the cytosolic compartment to mediate the host immunological response to cellular injury and infection. Caspase-1 may be activated by the inflammasome, which leads to the generation of the inflammatory cytokines interleukin-1β (IL-1β) and IL-18 and the beginning of pyroptosis, which is a type of proinflammatory cell death. Scientists have identified a number of different inflammasomes in the last 2 decades. The NLRP3 inflammasome has been studied the most, and its activity may be triggered by a broad range of different inducers. However, activation of the NLRP3 inflammasome in a manner that is not properly controlled is also a factor in the etiology of many human illnesses. Accumulating evidence indicates that the NLRP3 inflammasome plays a significant role in the innate and adaptive immune systems and the development of various arthritic illnesses, such as rheumatoid arthritis, ankylosing spondylitis, and gout. The present review provides a concise summary of the biological properties of the NLRP3 inflammasome and presents the fundamental processes behind its activation and control. We discuss the role of the inflammasome in the pathogenesis of arthritic diseases, such as rheumatoid arthritis, ankylosing spondylitis, and gout, and the potential of newly developed therapies that specifically target the inflammasome or its products for the treatment of inflammatory diseases, with a particular emphasis on treatment and clinical application.
APOE alleles modulate associations of plasma metabolites with variants from multiple genes on chromosome 19q13.3
Authors: Nazarian Alireza , Loiko Elena , Yassine Hussein N. , Finch Caleb E. , Kulminski Alexander M.
Published: October 2022

The APOE ε2, ε3, and ε4 alleles differentially impact various complex diseases and traits. We examined whether these alleles modulated associations of 94 single-nucleotide polymorphisms (SNPs) harbored by 26 genes in 19q13.3 region with 217 plasma metabolites using Framingham Heart Study data. The analyses were performed in the E2 (ε2ε2 or ε2ε3 genotype), E3 (ε3ε3 genotype), and E4 (ε3ε4 or ε4ε4 genotype) groups separately. We identified 31, 17, and 22 polymorphism-metabolite associations in the E2, E3, and E4 groups, respectively, at a false discovery rate PFDR < 0.05. These entailed 51 and 19 associations with 20 lipid and 12 polar analytes. Contrasting the effect sizes between the analyzed groups showed 20 associations with group-specific effects at Bonferroni-adjusted P < 7.14E−04. Three associations with glutamic acid or dimethylglycine had significantly larger effects in the E2 than E3 group and 12 associations with triacylglycerol 56:5, lysophosphatidylethanolamines 16:0, 18:0, 20:4, or phosphatidylcholine 38:6 had significantly larger effects in the E2 than E4 group. Two associations with isocitrate or propionate and three associations with phosphatidylcholines 32:0, 32:1, or 34:0 had significantly larger effects in the E4 than E3 group. Nine of 70 SNP-metabolite associations identified in either E2, E3, or E4 groups attained PFDR < 0.05 in the pooled sample of these groups. However, none of them were among the 20 group-specific associations. Consistent with the evolutionary history of the APOE alleles, plasma metabolites showed higher APOE-cluster-related variations in the E4 than E2 and E3 groups. Pathway enrichment mainly highlighted lipids and amino acids metabolism and citrate cycle, which can be differentially impacted by the APOE alleles. These novel findings expand insights into the genetic heterogeneity of plasma metabolites and highlight the importance of the APOE-allele-stratified genetic analyses of the APOE-related diseases and traits.
Forsythoside B ameliorates diabetic cognitive dysfunction by inhibiting hippocampal neuroinflammation and reducing synaptic dysfunction in ovariectomized mice
Authors: Nan Xinyu , Sun Qi , Xu Xiaoyu , Yang Ying , Zhen Yanfeng , Zhang Yameng , Zhou Haixia , Fang Hui
Published: October 2022

Background

Diabetes-associated cognitive impairment (DACI) is a common complication of diabetes, and studies have shown that DACI is more severe in postmenopausal patients with diabetes. Forsythoside B (FTS⋅B) can inhibit inflammation and reduce synaptic dysfunction, which can improve cognitive function. However, it has not been confirmed whether FTS⋅B has a reversing or retarding effect on postmenopausal diabetic encephalopathy.

Methods

Seven days after bilateral ovariectomy (OVX) or sham surgery, adult female C57 mice (n = 15/group) received intraperitoneal injection of streptozotocin (60 mg/kg/day/L) and citrate buffer for 5 consecutive days to induce diabetes mellitus (DM). Fourteen days later, ovariectomized diabetic mice were given intraperitoneal injection of FTS⋅B (100, 150 mg/kg/day/L) and subcutaneous injection of 17β-estradiol (1 mg/kg) for 8 weeks [OVX + DM + low-FTS⋅B group (L-F), OVX + DM + high-FTS⋅B group (H-F), and OVX + DM + 17β-estradiol (ER)]. In addition, the following control groups were defined: Sham, OVX, DM, and OVX + DM (O + D). Fasting plasma glucose, body weight and blood insulin levels were determined in each group of mice. Next, their cognitive function was tested through behavioral experiments. Hematoxylin & eosin (H&E) and Nissl staining were used to detect the morphological changes in the hippocampus. The aggregation of amyloid beta (Aβ) and the hyperaggregation of p-tau were assessed by immunohistochemistry. Interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), brain-derived neurotrophic factor (BDNF), post-synaptic density-95 (PSD-95), synaptophysin, and synapsin-1 expression in the hippocampus was detected by real-time polymerase chain reaction (RT-PCR) and western blot analysis.

Results

FTS⋅B can decrease fasting glucose and blood insulin level. Behavioral results showed that cognitive decline was the most severe in the O + D group, and the ER, L-F, and H-F groups revised the cognitive decline. Compared to the O + D group, more normal morphology, which has obvious nucleoli and clear nuclear membrane, was observed by H&E and Nissl staining in the ER, L-F, and H-F groups. FTS⋅B alleviated DACI by reducing the aggregation of Aβ and the hyperaggregation of p-tau in the hippocampus. Moreover, the protein and mRNA expression showed that FTS⋅B not only inhibited inflammation by decreasing IL-1β, IL-6, and TNF-α but also modulated synaptic plasticity by increasing BDNF, PSD-95, synaptophysin, and synapsin-1.

Conclusion

These results suggest that FTS⋅B may be a novel therapeutic target for postmenopausal diabetic encephalopathy treatment.
Experience of tinnitus in adults who have severe-to-profound hearing loss: A scoping review
Authors: Alzahrani Lama , Sereda Magdalena , Chamouton Carla Salles , Haider Háula , Dewey Rebecca Susan , Hoare Derek J.
Published: October 2022

Background

Tinnitus is defined as the subjective perception of sound in the absence of an external stimulus, and tinnitus disorder becomes relevant when it is associated with emotional distress, cognitive dysfunction, and/or autonomic arousal. Hearing loss is recognized as the main risk factor for the pathogenesis of tinnitus. However, clinical guidelines for tinnitus disorder provide little direction for those who have severe-to-profound hearing loss including those who are pre-lingually Deaf. The aim of this scoping review was to catalogue what is known from the existing literature regarding the experience and management of tinnitus in adults who have a severe-to-profound hearing loss.

A scoping review was conducted following the Preferred Reporting Item for Systematic Reviews and Meta-analysis extension for Scoping Reviews. Records were included if they reported an evaluation of tinnitus in adults who had severe-to-profound hearing loss. The online databases Ovid (MEDLINE, EMBASE and PsycINFO), CINAHL, ProQuest, Scopus, and Google Scholar were searched using the search terms ‘tinnitus’ (as a MESH term) and ‘deaf’ OR ‘profound hearing loss. Thirty-five records met the inclusion criteria for this review and were cataloged according to three major themes: Impact of tinnitus in deaf adults; Primary treatment of tinnitus in deaf adults; and Cochlear implant studies where tinnitus was a secondary outcome. Tinnitus symptom severity was assessed before and after intervention using tinnitus validated questionnaires in 29 records, with six further records using other assessment tools to measure tinnitus severity. Participants using cochlear implants were included in 30 studies. Medication, repetitive transcranial magnetic stimulation (rTMS), electrical promontory stimulation, and behavioral self-control therapy were each reported in single records.

Key messages

This scoping review cataloged the experience, assessment, and treatment of tinnitus in adults who have severe-to-profound hearing loss. It is shown that there is very limited research reported in this field. Although this review included many records, most focused on the provision of cochlear implants for severe-to-profound hearing loss, with assessment and measurement of tinnitus as a baseline or secondary outcome. Largely missing in the literature are empirical studies that seek firstly to understand the nature of the experience of tinnitus by people with no or little residual access to external sound.
Burden of illness in people with medically refractory epilepsy who suffer from daily to weekly seizures: 12-month follow-up of participants in the EPISODE study
Authors: van Hezik-Wester Valérie , de Groot Saskia , Kanters Tim , Versteegh Matthijs , Wagner Louis , Ardesch Jacqueline , Brouwer Werner , van Exel Job
Published: October 2022

Background

A small group of people with epilepsy suffers from frequent seizures despite the available pharmacological and non-pharmacological interventions. The impact of epilepsy on these people extends beyond health-related quality of life (HRQoL), impacting a person's broader well-being and ability to participate in society. This study describes the burden of medically refractory epilepsy in people who suffer from daily to weekly seizures, in terms of HRQoL, well-being, and societal costs.

Methods

Data from the EPISODE study on (cost-) effectiveness of seizure dogs for adults with severe medically refractory epilepsy were used, collected in 25 patients during the first 12 months before they were partnered with a certified seizure dog. Data comprised seizure diaries covering 365 days and five three-monthly surveys, including the EQ-5D-5L, QOLIE-31-P, and ICECAP-A to measure HRQoL and well-being. A societal perspective was applied to estimate costs using the iMCQ and iPCQ questionnaires about healthcare use, informal care, and productivity losses.

Results

Daily seizure frequency and survey data were collected in 25 patients. A minimum of 114 observations was available for each instrument included in the survey. A total of 80% of participants experienced seizures on three or more days per week, with a median ranging from 1 to 17 seizures per seizure day. The mean EQ-5D-5L utility score was 0.682 (SD 0.235), which is considerably lower than the age-adjusted general population average. The mean QOLIE-31-P and ICECAP-A scores were 55.8 (SD 14.0) and 0.746 (SD 0.172), respectively. The average annual total cost amounted to €39,956 (range €3,804–€132,64). Informal care accounted for the largest share of costs (50%); those who received informal care reported, on average, 26 h per week (SD 30).

Conclusions

Severe medically refractory epilepsy is associated with a considerable burden of illness at the patient and societal level. People with this condition have significantly reduced HRQoL and well-being and are limited in their ability to work while having substantial medical costs and a strong dependency on informal care.
A novel risk score to predict deep vein thrombosis after spontaneous intracerebral hemorrhage
Authors: Ji Ruijun , Wang Linlin , Liu Xinyu , Liu Yanfang , Wang Dandan , Wang Wenjuan , Zhang Runhua , Jiang Ruixuan , Jia Jiaokun , Feng Hao , Ding Zeyu , Ju Yi , Lu Jingjing , Liu Gaifen , Wang Yongjun , Zhao Xingquan ,   Beijing Registration of Intracerebral Hemorrhage investigators
Published: October 2022

Background and purpose

Studies showed that patients with hemorrhagic stroke are at a higher risk of developing deep vein thrombosis (DVT) than those with ischemic stroke. We aimed to develop a risk score (intracerebral hemorrhage-associated deep vein thrombosis score, ICH-DVT) for predicting in-hospital DVT after ICH.

Methods

The ICH-DVT was developed based on the Beijing Registration of Intracerebral Hemorrhage, in which eligible patients were randomly divided into derivation (60%) and internal validation cohorts (40%). External validation was performed using the iMCAS study (In-hospital Medical Complication after Acute Stroke). Independent predictors of in-hospital DVT after ICH were obtained using multivariable logistic regression, and β-coefficients were used to generate a scoring system of the ICH-DVT. The area under the receiver operating characteristic curve (AUROC) and the Hosmer–Lemeshow goodness-of-fit test were used to assess model discrimination and calibration, respectively.

Results

The overall in-hospital DVT after ICH was 6.3%, 6.0%, and 5.7% in the derivation (n= 1,309), internal validation (n= 655), and external validation (n= 314) cohorts, respectively. A 31-point ICH-DVT was developed from the set of independent predictors including age, hematoma volume, subarachnoid extension, pneumonia, gastrointestinal bleeding, and length of hospitalization. The ICH-DVT showed good discrimination (AUROC) in the derivation (0.81; 95%CI = 0.79–0.83), internal validation (0.83, 95%CI = 0.80–0.86), and external validation (0.88; 95%CI = 0.84–0.92) cohorts. The ICH-DVT was well calibrated (Hosmer–Lemeshow test) in the derivation (P= 0.53), internal validation (P= 0.38), and external validation (P= 0.06) cohorts.

Conclusion

The ICH-DVT is a valid grading scale for predicting in-hospital DVT after ICH. Further studies on the effect of the ICH-DVT on clinical outcomes after ICH are warranted.
The relationship between motor pathway damage and flexion-extension patterns of muscle co-excitation during walking
Authors: Srivastava Shraddha , Seamon Bryant A. , Marebwa Barbara K. , Wilmskoetter Janina , Bowden Mark G. , Gregory Chris M. , Seo Na Jin , Hanlon Colleen A. , Bonilha Leonardo , Brown Truman R. , Neptune Richard R. , Kautz Steven A.
Published: October 2022

Background

Mass flexion-extension co-excitation patterns during walking are often seen as a consequence of stroke, but there is limited understanding of the specific contributions of different descending motor pathways toward their control. The corticospinal tract is a major descending motor pathway influencing the production of normal sequential muscle coactivation patterns for skilled movements. However, control of walking is also influenced by non-corticospinal pathways such as the corticoreticulospinal pathway that possibly contribute toward mass flexion-extension co-excitation patterns during walking. The current study sought to investigate the associations between damage to corticospinal (CST) and corticoreticular (CRP) motor pathways following stroke and the presence of mass flexion-extension patterns during walking as evaluated using module analysis.

Methods

Seventeen healthy controls and 44 stroke survivors were included in the study. We used non-negative matrix factorization for module analysis of paretic leg electromyographic activity. We typically have observed four modules during walking in healthy individuals. Stroke survivors often have less independently timed modules, for example two-modules presented as mass flexion-extension pattern. We used diffusion tensor imaging-based analysis where streamlines connecting regions of interest between the cortex and brainstem were computed to evaluate CST and CRP integrity. We also used a coarse classification tree analysis to evaluate the relative CST and CRP contribution toward module control.

Results

Interhemispheric CST asymmetry was associated with worse lower extremity Fugl-Meyer score (p= 0.023), propulsion symmetry (p= 0.016), and fewer modules (p= 0.028). Interhemispheric CRP asymmetry was associated with worse lower extremity Fugl-Meyer score (p= 0.009), Dynamic gait index (p= 0.035), Six-minute walk test (p= 0.020), Berg balance scale (p= 0.048), self-selected walking speed (p= 0.041), and propulsion symmetry (p= 0.001). The classification tree model reveled that substantial ipsilesional CRP or CST damage leads to a two-module pattern and poor walking ability with a trend toward increased compensatory contralesional CRP based control.

Conclusion

Both CST and CRP are involved with control of modules during walking and damage to both may lead to greater reliance on the contralesional CRP, which may contribute to a two-module pattern and be associated with worse walking performance.
Clinical use of color Doppler ultrasonography to predict and evaluate the collateral development of two common revascularizations in patients with moyamoya disease
Authors: Wang Jing-Zhe , Mu Jie , Zhang Dong , Zheng Shuai , Zhu Xun , Wei Xi
Published: October 2022

Objective

To explore the value of color Doppler ultrasonography (CDU) to predict preoperatively and evaluate postoperatively the collateral development of two common revascularizations in patients with moyamoya disease (MMD).

Methods

We prospectively enrolled 49 patients with MMD who underwent unilateral superficial temporal artery (STA) -middle cerebral artery (MCA) anastomosis or encephalo-duro-arterio-synangiosis (EDAS). The parameters of the extracranial arteries, including STA, internal carotid artery (ICA), external carotid artery (ECA), and vertebral artery (VA), were performed before and at 3–6 months after surgery. DSA results were used to assess surgical collateral development.

Results

To predict good collateral development before STA-MCA anastomosis, the preoperative D > 1.75 mm in the STA had the highest area under the Receiver Operating Characteristic curve (AUC). To predict good collateral development before EDAS, the preoperative EDV > 12.00 cm/s in the STA had the highest AUC. To evaluate the good collateral development after STA-MCA anastomosis, the postoperative EDV > 16.50 cm/s in the STA had the highest AUC. To evaluate the good collateral development after EDAS, an increase of D of 0.15 mm in the STA had the highest AUC. Logistic regression analysis showed that the preoperative RI and EDV in the STA were highly correlated with collateral development. Besides, the preoperative RI was an independent risk factor for collateral development.

Conclusion

CDU could predict preoperatively and evaluate postoperatively the collateral development of STA-MCA anastomosis and EDAS surgery postoperatively by detecting ultrasound parameters of the STA.
Do we parse the background into separate streams in the cocktail party?
Authors: Szalárdy Orsolya , Tóth Brigitta , Farkas Dávid , Orosz Gábor , Winkler István
Published: October 2022

In the cocktail party situation, people with normal hearing usually follow a single speaker among multiple concurrent ones. However, there is no agreement in the literature as to whether the background is segregated into multiple streams/speakers. The current study varied the number of concurrent speech streams and investigated target detection and memory for the contents of a target stream as well as the processing of distractors. A male-voiced target stream was either presented alone (single-speech), together with one male-voiced distractor (one-distractor), or a male- and a female-voiced distractor (two-distractor). Behavioral measures of target detection and content tracking performance as well as target- and distractor detection related event-related brain potentials (ERPs) were assessed. We found that the N2 amplitude decreased whereas the P3 amplitude increased from the single-speech to the concurrent speech streams conditions. Importantly, the behavioral effect of distractors differed between the conditions with one vs. two distractor speech streams and the non-zero voltages in the N2 time window for distractor numerals and in the P3 time window for syntactic violations appearing in the non-target speech stream significantly differed between the one- and two-distractor conditions for the same (male) speaker. These results support the notion that the two background speech streams are segregated, as they show that distractors and syntactic violations appearing in the non-target streams are processed even when two speech non-target speech streams are delivered together with the target stream.
Placental transcriptional signatures associated with cerebral white matter damage in the neonate
Authors: Marable Carmen Amelia , Roell Kyle , Kuban Karl , O’Shea T. Michael , Fry Rebecca C.
Published: October 2022

Cerebral white matter is the most common anatomic location of neonatal brain injury in preterm newborns. Factors that predispose preterm newborns to white matter damage are understudied. In relation to studies of the placenta-brain-axis, dysregulated placental gene expression may play a role in preterm brain damage given its implication in programming early life origins of disease, including neurological disorders. There is a critical need to investigate the relationships between the placental transcriptome and white matter damage in the neonate. In a cohort of extremely low gestational age newborns (ELGANs), we aimed to investigate the relationship between the placental transcriptome and white matter damage as assessed by neonatal cranial ultrasound studies (echolucency and/or ventriculomegaly). We hypothesized that genes involved in inflammatory processes would be more highly expressed in placentas of ELGANs who developed ultrasound-defined indicators of white matter damage. Relative to either form of white matter damage, 659 placental genes displayed altered transcriptional profiles. Of these white matter damage-associated genes, largely distinct patterns of gene expression were observed in the study (n = 415/659 genes). Specifically, 381 genes were unique to echolucency and 34 genes were unique to ventriculomegaly. Pathways involved in hormone disruption and metabolism were identified among the unique echolucency or ventriculomegaly genes. Interestingly, a common set of 244 genes or 37% of all genes was similarly dysregulated in the placenta relative to both echolucency and ventriculomegaly. For this common set of white matter damage-related genes, pathways involved in inflammation, immune response and apoptosis, were enriched. Among the white matter damage-associated genes are genes known to be involved in Autism Spectrum Disorder (ASD) and endocrine system disorders. These data highlight differential mRNA expression patterning in the placenta and provide insight into potential etiologic factors that may predispose preterm newborns to white matter damage. Future studies will build upon this work to include functional measures of neurodevelopment as well as measures of brain volume later in life.
Inferring miRNA sponge modules across major neuropsychiatric disorders
Authors: Balasubramanian Rami , Vinod P. K.
Published: October 2022

The role of non-coding RNAs in neuropsychiatric disorders (NPDs) is an emerging field of study. The long non-coding RNAs (lncRNAs) are shown to sponge the microRNAs (miRNAs) from interacting with their target mRNAs. Investigating the sponge activity of lncRNAs in NPDs will provide further insights into biological mechanisms and help identify disease biomarkers. In this study, a large-scale inference of the lncRNA-related miRNA sponge network of pan-neuropsychiatric disorders, including autism spectrum disorder (ASD), schizophrenia (SCZ), and bipolar disorder (BD), was carried out using brain transcriptomic (RNA-Seq) data. The candidate miRNA sponge modules were identified based on the co-expression pattern of non-coding RNAs, sharing of miRNA binding sites, and sensitivity canonical correlation. miRNA sponge modules are associated with chemical synaptic transmission, nervous system development, metabolism, immune system response, ribosomes, and pathways in cancer. The identified modules showed similar and distinct gene expression patterns depending on the neuropsychiatric condition. The preservation of miRNA sponge modules was shown in the independent brain and blood-transcriptomic datasets of NPDs. We also identified miRNA sponging lncRNAs that may be potential diagnostic biomarkers for NPDs. Our study provides a comprehensive resource on miRNA sponging in NPDs.
Neocortical layer 5 subclasses: From cellular properties to roles in behavior
Authors: Moberg Sara , Takahashi Naoya
Published: October 2022

Layer 5 (L5) serves as the main output layer of cortical structures, where long-range projecting pyramidal neurons broadcast the columnar output to other cortical and extracortical regions of the brain. L5 pyramidal neurons are grouped into two subclasses based on their projection targets; while intratelencephalic (IT) neurons project to cortical areas and the striatum, extratelencephalic (ET) neurons project to subcortical areas such as the thalamus, midbrain, and brainstem. Each L5 subclass possesses distinct morphological and electrophysiological properties and is incorporated into a unique synaptic network. Thanks to recent advances in genetic tools and methodologies, it has now become possible to distinguish between the two subclasses in the living brain. There is increasing evidence indicating that each subclass plays a unique role in sensory processing, decision-making, and learning. This review first summarizes the anatomical and physiological properties as well as the neuromodulation of IT and ET neurons in the rodent neocortex, and then reviews recent literature on their roles in sensory processing and rodent behavior. Our ultimate goal is to provide a comprehensive understanding of the role of each subclass in cortical function by examining their operational regimes based on their cellular properties.