bluuebunny/crossref_metadata_2025 huggingface dataset:
Study on wetting deformation model of coarse-grained materials based on P-Z model and BP neural network
Authors: Zhang Hongyang , Li Xuan , Liu Jianlong , Han Pengju , Yang Yige , Ding Zelin , Han Liwei , Zhang Xianqi , Wang Shunsheng
Published: April 2023

The wetting deformation of coarse-grained materials can seriously affect the safety of earth and rock dams during initial water storage. The wetting model formulas are expressed in various forms and have complex parameters. Only a small amount of test data is fitted by mathematical statistics, and the universality of the obtained wetting model is unknown. Duncan-Chang E-B constitutive model cannot accurately reflect the wetting deformation characteristics of coarse-grained materials. Through the double-line wetting test of coarse-grained materials, the wetting model proposed by predecessors was verified and analyzed. Based on the indoor wetting test data, the parameters of each wetting model were fitted to analyze the accuracy of each wetting model in describing the wetting deformation characteristics. According to the P-Z model in the elastic-plastic theory and the wetting model formula, the P-Z wetting model is established, and the BP artificial neural network is introduced to establish the artificial neural network wetting deformation prediction model based on the P-Z model. The results show that the relationship between wetting axial strain and wetting stress level is best expressed by the exponential function. The relationship between wetting volumetric strain and wetting stress level is best described by Cheng’s linear function. The relative errors between the predicted and experimental values of the proposed neural network prediction model are all within 6%. The relationship between wetting axial strain and wetting stress level is exponential function, and the relationship between wetting volumetric strain and wetting stress level is linear function. The P-Z wetting model proposed in this research can better reflect the wetting deformation characteristics of coarse-grained materials under complex stress paths. The artificial neural network prediction model based on P-Z wetting model is more reliable and accurate, which can meet the prediction requirements of actual engineering for wetting deformation of coarse-grained materials.
Cover-up or true? does CSR disclosure really contribute to corporate environmental performance?
Authors: Yun Feifei , Lan Tian , Chen Yu
Published: April 2023

Do companies disclose their environmental social responsibility to demonstrate their good environmental performance or to cover up their poor environmental performance? This study examines the relationship between the disclosure level of corporate environmental responsibility information and corporate environmental performance based on institutional pressure, using data from Chinese A-share listed companies between 2008 and 2021. The results showed a negative relationship between the two variables, indicating that many firms might disclose environmental information to cover up their poor environmental performance. This phenomenon was more evident among non-state-owned enterprises and the enterprises in the economically underdeveloped regions. This study provides a new theoretical perspective for relevant management institutions to study social responsibility reports and formulate environmental protection policies.
Population structure, genetic diversity and prolificacy in pishan red sheep under an extreme desert environment
Authors: Zhang Cheng-long , Zhang Jihu , Tuersuntuoheti Mirenisa , Chang Qianqian , Liu Shudong
Published: April 2023

Extreme environmental conditions are a major challenge for livestock production. Changes in climate conditions, especially those that lead to extreme weather, can reduce livestock production. The screening of genes and molecular markers is of great significance to explore the genetic mechanism of sheep prolificacy traits in Taklimakan Desert environment. We selected healthy adult Pishan Red Sheep (PRS) and Qira Black Sheep (QR) which live in Taklimakan Desert environment, collected blood from jugular vein, extracted DNA, and prepared Illumina Ovine SNP50 chip. For PRS, linkage disequilibrium (LD) was calculated using the ovine SNP50 Beadchip and the effective population size (Ne) was estimated using SMC++. The genetic characteristics of PRS were analyzed by integrated haplotype score (iHS) and fixation index (FST). The result showed that r2 of PRS was 0.233 ± 0.280 in the range of 0–10 Kb and decreased with increasing distances. SMC++ tested that the Ne of PRS remained at 236.99 in recent generations. 184 genes were screened out under iHS 1% threshold, and 1148 genes were screened out with FST under the 5% threshold, and 29 genes were obtained from the intersection of the two gene sets. In this study, the genetic characteristics of PRS and QR were compared by ovine genome chip, and the related excellent genes were searched, providing reference for the protection of sheep germplasm resources and molecular breeding in a desert environment.
Impact of endogenous glucocorticoid on response to immune checkpoint blockade in patients with advanced cancer
Authors: Cui Yu , Han Xinyue , Liu Hongtao , Xie Qi , Guan Yaping , Yin Beibei , Xiao Junjuan , Feng Dongfeng , Wang Xuan , Li Junwei , Chen Jinghua , Liu Xiaolin , Li Xingyu , Nie Weiwei , Ma Lin , Liu Hairong , Liang Jing , Li Yan , Wang Baocheng , Wang Jun
Published: April 2023

Background

Previous studies indicate that exogenous use of glucocorticoid (GC) affects immune checkpoint inhibitor (ICI) efficacy. However, there is a paucity of clinical data evaluating the direct impact of endogenous GC on the efficacy for cancer patients with immune checkpoint blockade.

Methods

We first compared the endogenous circulating GC levels in healthy individuals and patients with cancer. We next retrospectively reviewed patients with advanced cancer with PD-1/PD-L1 inhibitor alone or combination therapy in a single center. The effects of baseline circulating GC levels on objective response rate (ORR), durable clinical benefit (DCB), progression‐free survival (PFS), and overall survival (OS) were analyzed. The association of the endogenous GC levels with circulating lymphocytes, cytokines levels, and neutrophil to lymphocyte ratio, and tumor infiltrating immune cells, were systematically analyzed.

Results

The endogenous GC levels in advanced cancer patients were higher than those in early-stage cancer patients as well as healthy people. In the advanced cancer cohort with immune checkpoint blockade (n=130), patients with high baseline endogenous GC levels (n=80) had a significantly reduced ORR (10.0% vs 40.0%; p<0.0001) and DCB (35.0% vs 73.5%, p=0.001) compared to those with low endogenous GC levels (n=50). The increased GC levels was significantly associated with reduced PFS (HR 2.023; p=0.0008) and OS (HR 2.809; p=0.0005). Moreover, statistically significant differences regarding PFS, and OS were also detected after propensity score matching. In a multivariable model, the endogenous GC was identified as an independent indicator for predicting PFS (HR 1.779; p=0.012) and OS (HR 2.468; p=0.013). High endogenous GC levels were significantly associated with reduced lymphocytes (p=0.019), increased neutrophil to lymphocyte ratio (p=0.0009), and increased interleukin-6 levels (p=0.025). Patients with high levels of endogenous GC had low numbers of tumor infiltrating CD3+ (p=0.001), CD8+ T (p=0.059), and CD4+ T (p=0.002) cells, and the numbers of circulating PD-1+ NK cells (p=0.012), and the ratio of CD8+PD-1+ to CD4+PD-1+ (p=0.031) were higher in patients with high levels of endogenous GC compared to low levels of endogenous GC.

Conclusion

Baseline endogenous GC increase executes a comprehensive negative effect on immunosurveillance and response to immunotherapy in real-world cancer patients accompanied with cancer progression.
Construction of a novel molecular typing and scoring system for anoikis distinguishes between different prognostic risks and treatment responsiveness in low-grade glioma
Authors: Zhang Ganghua , Chen Aiyan , Fang Jianing , Wu Anshan , Chen Guanjun , Tai Panpan , Chen Haotian , Chen Xinyu , Cao Ke
Published: April 2023

Background

The main factors responsible for low-grade glioma (LGG)s’ poor prognosis and treatment effectiveness include recurrence and malignant progression. A specific type of programmed cell death, known as anoikis, which is crucial for tumor invasion and metastasis, however, has not yet been investigated in LGGs.

Methods

We downloaded data of 509 samples from the TCGA-LGG cohort, carried out cluster analysis for typing twice on the basis of 19 anoikis-associated genes, and the subtypes were evaluated the differences in clinicopathological and biological features. ESTIMATE and single-sample gene set enrichment analysis were employed to examine the immunological milieu of LGGs, and enrichment analysis was used to look into the underlying biological mechanisms in LGGs. Cox regression analysis and the Least Absolute Shrinkage and Selection Operator regression algorithm were used to create a prediction scoring system. The scoring system was used for classifying LGG into high- and low- anoikis riskscore (anoiS) groups. The impact of the anoiS on the prognosis, standard treatment, and immunotherapy of patients with LGG was assessed using survival analysis and drug sensitivity analysis. Cell experiments were employed for the verification of the differential expression between LGG cells and normal cells of the anoikis gene team that regard CCT5 as the core.

Results

Based on the expression profiles of the 19 anoikis-associated genes, all individuals with LGG were classified into four subtypes and two macrosubtypes. The different macrosubtypes had significantly different biological characteristics, and the anoirgclusterBD subtype manifested a significantly bad prognosis and a high immune level of infiltration. And subsequent secondary genotyping also showed good prognostic discrimination. We further constructed an anoikis scoring system, anoiS. LGG patients having a high anoiS had a worse prognosis in comparison to those having a low anoiS. The high anoiS group exhibited larger levels of immune infiltration and superior immunotherapy efficacy than the low anoiS group. The high anoiS group was also more susceptible to temozolomide (TMZ) than the low anoiS group, according to a drug sensitivity analysis of TMZ.

Conclusion

This study constructed a scoring system for predicting the prognosis of patients with LGG and their responsive to TMZ and immunotherapy.
Echovirus induces autophagy to promote viral replication via regulating mTOR/ULK1 signaling pathway
Authors: Wu Chunchen , Zeng Luzhi , Yi Wenfu , Miao Yuanjiu , Liu Yihan , Wang Qiming , Liu Shi , Peng Guoping , Zheng Zhenhua , Xia Jianbo
Published: April 2023

Among enteroviruses, echovirus can cause severe illnesses in neonates or infants, with high morbidity and mortality. Autophagy, a central component of host defense mechanisms, can function against diverse infections. In the present study, we investigated the interplay between echovirus and autophagy. We demonstrated that echovirus infection increases LC3-II expression dose-dependently, accompanied by an increased intracellular LC3 puncta level. In addition, echovirus infection induces the formation of autophagosome. These results suggest that echovirus infection induces autophagy machinery. Furthermore, phosphorylated mTOR and ULK1 were both decreased upon echovirus infection. In contrast, both levels of the vacuolar protein sorting 34 (VPS34) and Beclin-1, the downstream molecules which play essential roles in promoting the formation of autophagic vesicles, increased upon virus infection. These results imply that the signaling pathways involved in autophagosome formation were activated by echovirus infection. Moreover, induction of autophagy promotes echovirus replication and viral protein VP1 expression, while inhibition of autophagy impairs VP1 expression. Our findings suggest that autophagy can be induced by echovirus infection via regulating mTOR/ULK1 signaling pathway and exhibits a proviral function, revealing the potential role of autophagy in echovirus infection.
Risk factors for hospital outcomes in pulmonary embolism: A retrospective cohort study
Authors: Lüthi-Corridori Giorgia , Giezendanner Stéphanie , Kueng Cedrine , Boesing Maria , Leuppi-Taegtmeyer Anne B. , Mbata Munachimso Kizito , Schuetz Philipp , Leuppi Joerg D.
Published: April 2023

Background

Pulmonary embolism (PE) is not only a life-threatening disease but also a public health issue with significant economic burden. The aim of the study was to identify factors—including the role of primary care—that predict length of hospital stay (LOHS), mortality and re-hospitalization within 6 months of patients admitted for PE.

Method

A retrospective cohort study was conducted with patients presenting to a Swiss public hospital with PE diagnosed at the hospital between November 2018 and October 2020. Multivariable logistic and zero-truncated negative binomial regression analyses were performed to assess risk factors for mortality, re-hospitalization and LOHS. Primary care variables encompassed whether patients were sent by their general practitioner (GP) to the emergency department and whether a GP follow-up assessment after discharge was recommended. Further analyzed variables were pulmonary embolism severity index (PESI) score, laboratory values, comorbidities, and medical history.

Results

A total of 248 patients were analyzed (median 73 years and 51.6% females). On average patients were hospitalized for 5 days (IQR 3–8). Altogether, 5.6% of these patients died in hospital, and 1.6% died within 30 days (all-cause mortality), 21.8% were re-hospitalized within 6 months. In addition to high PESI scores, we detected that, patients with an elevated serum troponin, as well as with diabetes had a significantly longer hospital stay. Significant risk factors for mortality were elevated NT-proBNP and PESI scores. Further, high PESI score and LOHS were associated with re-hospitalization within 6 months. PE patients who were sent to the emergency department by their GPs did not show improved outcomes. Follow-up with GPs did not have a significant effect on re-hospitalization.

Conclusion

Defining the factors that are associated with LOHS in patients with PE has clinical implications and may help clinicians to allocate adequate resources in the management of these patients. Serum troponin and diabetes in addition to PESI score might be of prognostic use for LOHS. In this single-center cohort study, PESI score was not only a valid predictive tool for mortality but also for long-term outcomes such as re-hospitalization within 6 months.
Burnout and job stress of anesthesiologists in the tertiary class A hospitals in Northwest China: A cross-sectional design
Authors: Yang Guang , Pan Lin-yuan , Fu Xiao-li , Qing Zhong , Dong Bu-huai , Ye Jiu-min
Published: April 2023

Purpose

Our purpose was to assess job stress and burnout among anesthesiologists in the tertiary class A hospitals in Northwest China, analyze the possible causes and adverse consequences of increased job stress and burnout of anesthesiologists in this region, and put forward suggestions in combination with the current national policies.

Methods

We sent 500 electronic questionnaires to all anesthesiologists practicing in the tertiary class A hospitals in Northwest China from 1960 to 2017 on April 2020. A total of 336 (67.2%) questionnaires were returned and could be used for analysis. Burnout and job stress were assessed by using the modified Maslach Burnout Inventory—Human Services Survey and Chinese Perceived Stress Scale, respectively.

Results

First, as for emotional exhaustion, the situations of anesthesiologists with different working years and workloads are different with statistical significance (P < 0.05). Second, as for depersonalization, the situations of anesthesiologists with different ages, professional titles, working years, physical health status, and workload are different (P < 0.05). Third, as for personal accomplishment, the situations of anesthesiologists with different physical health status are different (P < 0.05). Finally, the regression results showed that the longer the fatigue working years and the worse the physical health of anesthesiologists in Northwest China, the more likely these two factors were to cause burnout (P < 0.05), as for job stress, there was a negative correlation between job stress and physical health status (P < 0.05).

Conclusion

Burnout and high job pressure are common among anesthesiologists in tertiary class A hospitals in Northwest China. We should focus on the allocation of labor intensity, pay attention to the physical and mental health of employees, establish targeted incentive mechanism, and improve the system of promotion and income rises for grassroots doctors. This may be not only conducive to the quality of medical care for patients but also conducive to the development of anesthesiology in China.

Trial registration

Identifier: ChiCTR2000031316.
Hinokitiol inhibits Aspergillus fumigatus by interfering with the cell membrane and cell wall
Authors: Meng Fanyue , Liu Xing , Li Cui , Peng Xudong , Wang Qian , Xu Qiang , Sui Jialin , Zhao Guiqiu , Lin Jing
Published: April 2023

Hinokitiol (β-thujaplicin) is an important component of the essential oil extracted from Chamaecyparis obtuse, which prevents the decay and decomposition of temple and shrine buildings in Japan. Hinokiol has been shown to have a detrimental effect on various fungi such as Candida albicans and saprophytic fungi. However how hinokitiol works against Aspergillus fumigatus (A. fumigatus) has not been claimed. This study aims to investigate the adverse effects of hinokitiol on the disruption of the cell wall and cell membrane of A. fumigatus and to explore possible potential mechanisms or pathways. According to our results, hinokitiol negatively altered mycelium morphology, growth density, and cell plasma composition content. When incubated with human corneal epithelial cells (HCECs), hinokitiol saw a safe effect with concentrations below 12 μg/ml. Hinokitiol was shown to increase the cell membrane’s permeability by decreasing the cell membrane’s ergosterol content. The integrity of the cell wall was disrupted, as well as a significant increase in chitin degradation and chitinase activity. As determined by RNA-seq results, subsequent analysis, and qRT-PCR, altered transcript levels of cell walls and cell membranes-related genes (such as eglC) illustrated how hinokitiol affected the genetic profile of A. fumigatus. With this study, we recommend hinokitiol as an effective anti-A. fumigatus agent by reducing the amounts of key components in the cell wall and membrane by preventing production and accelerating breakdown.
Aneuploidy enables cross-tolerance to unrelated antifungal drugs in Candida parapsilosis
Authors: Sun Liu-liu , Li Hao , Yan Tian-hua , Cao Yong-bing , Jiang Yuan-ying , Yang Feng
Published: April 2023

Candida parapsilosis is an emerging major human fungal pathogen. Echinocandins are first-line antifungal drugs for the treatment of invasive Candida infections. In clinical isolates, tolerance to echinocandins in Candida species is mostly due to point mutations of FKS genes, which encode the target protein of echinocandins. However, here, we found chromosome 5 trisomy was the major mechanism of adaptation to the echinocandin drug caspofungin, and FKS mutations were rare events. Chromosome 5 trisomy conferred tolerance to echinocandin drugs caspofungin and micafungin and cross-tolerance to 5-flucytosine, another class of antifungal drugs. The inherent instability of aneuploidy caused unstable drug tolerance. Tolerance to echinocandins might be due to increased copy number and expression of CHS7, which encodes chitin synthase. Although copy number of chitinase genes CHT3 and CHT4 was also increased to the trisomic level, the expression was buffered to the disomic level. Tolerance to 5-flucytosine might be due to the decreased expression of FUR1. Therefore, the pleiotropic effect of aneuploidy on antifungal tolerance was due to the simultaneous regulation of genes on the aneuploid chromosome and genes on euploid chromosomes. In summary, aneuploidy provides a rapid and reversible mechanism of drug tolerance and cross-tolerance in C. parapsilosis.
Quorum sensing improves the plant growth-promoting ability of Stenotrophomonas rhizophila under saline-alkaline stress by enhancing its environmental adaptability
Authors: Zhuang Xuliang , Liu Ying , Fang Na , Bai Zhihui , Gao Jie
Published: April 2023

Quorum sensing (QS) system has an essential function in plant growth-promoting rhizobacteria (PGPR) response to environmental stress and PGPR induction of plant tolerance to saline-alkaline stress. Nevertheless, there is a lack of understanding about how QS influences the growth-promoting effects of PGPR on plants. Stenotrophomonas rhizophila DSM14405T is a PGPR with a QS system, which can secrete diffusible signal factor (DSF), one of the QS signal molecules. In this study, we used the S. rhizophila wild type (WT) and an incompetent DSF production rpfF-knockout mutant strain to explore whether DSF-QS could affect the growth-promoting ability of PGPR in Brassica napus L. By measuring the seed germination rate, plant fresh weight, biomass, the total antioxidant capacity (T-AOC) level, and the content of chlorophyll in leaves, we found that DSF was unable to enhance the growth-promoting capacity of ΔrpfF and did not directly assist the plants in tolerating saline-alkaline stress. However, DSF aided S. rhizophila ΔrpfF in resisting stress during its effective period, and QS represents a continuous and precise regulatory mechanism. Altogether, our results show that DSF is helpful to improve the environmental adaptability and survival rate of S. rhizophila, thus indirectly improving the germination rate of seeds and helping plants grow under saline-alkaline stress. In this study, the mechanism of QS enhancing the environmental adaptability of PGPR was studied, which provided a theoretical basis for improving the application of PGPR to help plants better cope with saline-alkaline stress.
Identification and characterization of new proteins crucial for bacterial spore resistance and germination
Authors: Yu Benjamin , Kanaan Julia , Shames Hannah , Wicander James , Aryal Makunda , Li Yunfeng , Korza George , Brul Stanley , Kramer Gertjan , Li Yong-qing , Nichols Frank C. , Hao Bing , Setlow Peter
Published: April 2023

2Duf, named after the presence of a transmembrane (TM) Duf421 domain and a small Duf1657 domain in its sequence, is likely located in the inner membrane (IM) of spores in some Bacillus species carrying a transposon with an operon termed spoVA2mob. These spores are known for their extreme resistance to wet heat, and 2Duf is believed to be the primary contributor to this trait. In this study, we found that the absence of YetF or YdfS, both Duf421 domain-containing proteins and found only in wild-type (wt) B. subtilis spores with YetF more abundant, leads to decreased resistance to wet heat and agents that can damage spore core components. The IM phospholipid compositions and core water and calcium-dipicolinic acid levels of YetF-deficient spores are similar to those of wt spores, but the deficiency could be restored by ectopic insertion of yetF, and overexpression of YetF increased wt spore resistance to wet heat. In addition, yetF and ydfS spores have decreased germination rates as individuals and populations with germinant receptor-dependent germinants and increased sensitivity to wet heat during germination, potentially due to damage to IM proteins. These data are consistent with a model in which YetF, YdfS and their homologs modify IM structure to reduce IM permeability and stabilize IM proteins against wet heat damage. Multiple yetF homologs are also present in other spore forming Bacilli and Clostridia, and even some asporogenous Firmicutes, but fewer in asporogenous species. The crystal structure of a YetF tetramer lacking the TM helices has been reported and features two distinct globular subdomains in each monomer. Sequence alignment and structure prediction suggest this fold is likely shared by other Duf421-containing proteins, including 2Duf. We have also identified naturally occurring 2duf homologs in some Bacilli and Clostridia species and in wt Bacillus cereus spores, but not in wt B. subtilis. Notably, the genomic organization around the 2duf gene in most of these species is similar to that in spoVA2mob, suggesting that one of these species was the source of the genes on this operon in the extremely wet heat resistant spore formers.
The performance of patients with cerebral microbleeds in different cognitive tests: A cross-sectional study
Authors: Li Xuanting , Yang Shuna , Li Yue , Qin Wei , Yang Lei , Yuan Junliang , Hu Wenli
Published: April 2023

Background

The clinical features and pathological process of cerebral microbleed (CMB)-related cognitive impairment are hot topics of cerebral small vessel disease (CSVD). However, how to choose a more suitable cognitive assessment battery for CMB patients is still an urgent issue to be solved. This study aimed to analyze the performance of CMB patients on different cognitive tests.

Methods

This study was designed as a cross-sectional study. The five main markers of CSVD (including the CMB, white matter hyperintensities, perivascular spaces, lacunes and brain atrophy) were assessed according to magnetic resonance imaging. The burden of CMB was categorized into four grades based on the total number of lesions. Cognitive function was assessed by Mini-Mental State Examination (MMSE), Trail-Making Test (TMT, Part A and Part B), Stroop color-word test (Stroop test, Part A, B and C), Verbal Fluency Test (VF, animal), Digit-Symbol Substitution Test (DSST), Digit Cancellation Test (DCT) and Maze. Multiple linear regression analysis was conducted to analyze the association between CMB and cognitive findings.

Results

A total of 563 participants (median age of 69 years) were enrolled in this study, including 218 (38.7%) CMB patients. CMB patients showed worse performance than non-CMB subjects in each cognitive test. Correlation analysis indicated the total number of CMB lesions had positive correlations with the time of TMT, Maze and Stroop test, and negative correlations with the performance of MMSE, VF, DSST, and DCT. After the adjustment for all the potential confounders by linear regression, the CMB burden grade was correlated with the performance of VF, Stroop test C, Maze and DCT.

Conclusion

The presence of CMB lesions was associated with much worse cognitive performances. In VF, Stroop test C, Maze and DCT, the correlations between CMB severity and assessment results were more significant. Our study further confirmed that the attention/executive function domain was the most commonly evaluated in CMB, which provided a picture of the most utilized tools to analyze the prognostic and diagnostic value in CMB.
On the other end of the line: Extracellular vesicle-mediated communication in glaucoma
Authors: Lucci Cristiano , De Groef Lies
Published: April 2023

In the last decade, extracellular vesicles (EVs) have emerged as a promising field of research due to their ability to participate in cell-to-cell communication via the transfer of their very diverse and complex cargo. The latter reflects the nature and physiological state of the cell of origin and, as such, EVs may not only play a pivotal role in the cellular events that culminate into disease, but also hold great potential as drug delivery vehicles and biomarkers. Yet, their role in glaucoma, the leading cause of irreversible blindness worldwide, has not been fully studied. Here, we provide an overview of the different EV subtypes along with their biogenesis and content. We elaborate on how EVs released by different cell types can exert a specific function in the context of glaucoma. Finally, we discuss how these EVs provide opportunities to be used as biomarkers for diagnosis and monitoring of disease.
Early identification of NORSE and transfer to care setting with appropriate supports: A proposed algorithm
Authors: Vinette Sarah A. , Young Gordon Bryan , Khosravani Houman
Published: April 2023

New-onset refractory status epilepticus (NORSE) is a clinical presentation where an individual develops refractory status epilepticus without active epilepsy, or related neurological conditions. A subset of these individuals has a preceding fever and would be diagnosed with febrile infection-related epilepsy syndrome (FIRES). The underlying etiology of this condition varies and includes autoimmune and viral encephalitides. These conditions require multiple specialized health care teams working collaboratively and specific resources for investigation of the underlying etiology and management to provide optimal patient care. In this paper, we provide: (1) recommendations upon early recognition of NORSE and FIRES, (2) guidance on the resources needed to optimally provide care, and (3) guidance on considerations to initiate transfer of patients to a more specialized medical center. Additional recommendations for resource-austere centers without the ability to transfer such patients are also discussed. These recommendations are only for adult patients with NORSE as pediatric patients may require additional special considerations.
Negative relationship between brain-derived neurotrophic factor (BDNF) and attention: A possible elevation in BDNF level among high-altitude migrants
Authors: Fan Jing , Chen Dongmei , Wang Niannian , Su Rui , Li Hao , Ma Hailin , Gao Fei
Published: April 2023

Objective

Brain-derived neurotrophic factor (BDNF), a member of the neurotrophic family that plays a vital role in regulating neuronal activity and synaptic plasticity in the brain, affects attention. However, studies investigating the association between BDNF and attention in long-term high-altitude (HA) migrants are limited in the literature. As HA affects both BDNF and attention, the relationship between these factors becomes more complex. Therefore, this study aimed to evaluate the relationship between peripheral blood concentrations of BDNF and the three attentional networks in both behavioral and electrical aspects of the brain in long-term HA migrants.

Materials and methods

Ninety-eight Han adults (mean age: 34.74 ± 3.48 years, 51 females and 47 males, all have lived at Lhasa for 11.30 ± 3.82 years) were recruited in this study. For all participants, the serum BDNF levels were assessed using enzyme-linked immunosorbent assay; event-related potentials (N1, P1, and P3) were recorded during the Attentional Networks Test, which was used as the measure of three attentional networks.

Results

Executive control scores were negatively correlated with P3 amplitude (r = −0.20, p = 0.044), and serum BDNF levels were positively correlated with executive control scores (r = 0.24, p = 0.019) and negatively correlated with P3 amplitude (r = −0.22, p = 0.027). Through grouping of BDNF levels and three attentional networks, executive control was found to be significantly higher in the high BDNF group than in the low BDNF group (p = 0.010). Different BDNF levels were associated with both orienting scores (χ2 = 6.99, p = 0.030) and executive control scores (χ2 = 9.03, p = 0.011). The higher the BDNF level, the worse was the executive function and the lower was the average P3 amplitude and vice versa. Females were found to have higher alerting scores than males (p = 0.023).

Conclusion

This study presented the relationship between BDNF and attention under HA. The higher the BDNF level, the worse was the executive control, suggesting that after long-term exposure to HA, hypoxia injury of the brain may occur in individuals with relatively higher BDNF levels, and this higher BDNF level may be the result of self-rehabilitation tackling the adverse effects brought by the HA environment.
Innovative vision rehabilitation method for hemianopsia: Comparing pre- and post audio-luminous biofeedback training for ocular motility improving visual functions and quality of life
Authors: Misawa Mariana , Pyatova Yulia , Sen Atri , Markowitz Michelle , Markowitz Samuel N. , Reber Michael , Daibert-Nido Monica
Published: April 2023

Background

Homonymous hemianopsia (HH) corresponds to vision loss in one hemi-field secondary to retro-chiasmal injury. Patients with HH experience difficulties in scanning and orientation in their environment. Near vision daily activities such as reading can also be impaired. There is an unmet need for standardized vision rehabilitation protocols for HH. We investigated the effectiveness of biofeedback training (BT), used for vision rehabilitation in patients with central vision loss, in individuals with HH.

Methods

In this prospective pilot pre/post study, 12 participants, with HH consecutive to brain injury, performed 5 weekly BT sessions for 20 min each under supervision using the Macular Integrity Assessment microperimeter. BT consisted of relocation of the retinal locus 1–4° toward the blind hemi-field. Outcomes measured post-BT were paracentral retinal sensitivity, visual acuity (near vision), fixation stability, contrast sensitivity, reading speed, and visual functioning questionnaire. Statistical analysis was performed using Bayesian paired t-tests.

Results

Paracentral retinal sensitivity significantly increased by 2.7 ± 0.9 dB in the treated eye in 9/11 of the participants. Significant improvements with medium-to-large effect size were observed for fixation stability (8/12 participants), contrast sensitivity (6/12 participants) and near vision visual acuity (10/12 participants). Reading speed increased by 32.5 ± 32.4 words per minute in 10/11 participants. Quality of vision scores improved significantly with large effect size for visual ability, visual information and mobility.

Conclusion

BT led to encouraging improvements in visual functions and functional vision in individuals with HH. Further confirmation with larger trials is required.
Brain motion networks predict head motion during rest- and task-fMRI
Authors: Tomasi Dardo , Volkow Nora D.
Published: April 2023

Introduction

The capacity to stay still during scanning, which is necessary to avoid motion confounds while imaging, varies markedly between people.

Methods

Here we investigated the effect of head motion on functional connectivity using connectome-based predictive modeling (CPM) and publicly available brain functional magnetic resonance imaging (fMRI) data from 414 individuals with low frame-to-frame motion (Δd < 0.18 mm). Leave-one-out was used for internal cross-validation of head motion prediction in 207 participants, and twofold cross-validation was used in an independent sample (n = 207).

Results and Discussion

Parametric testing, as well as CPM-based permutations for null hypothesis testing, revealed strong linear associations between observed and predicted values of head motion. Motion prediction accuracy was higher for task- than for rest-fMRI, and for absolute head motion (d) than for Δd. Denoising attenuated the predictability of head motion, but stricter framewise displacement threshold (FD = 0.2 mm) for motion censoring did not alter the accuracy of the predictions obtained with lenient censoring (FD = 0.5 mm). For rest-fMRI, prediction accuracy was lower for individuals with low motion (mean Δd < 0.02 mm; n = 200) than for those with moderate motion (Δd < 0.04 mm; n = 414). The cerebellum and default-mode network (DMN) regions that forecasted individual differences in d and Δd during six different tasks- and two rest-fMRI sessions were consistently prone to the deleterious effect of head motion. However, these findings generalized to a novel group of 1,422 individuals but not to simulated datasets without neurobiological contributions, suggesting that cerebellar and DMN connectivity could partially reflect functional signals pertaining to inhibitory motor control during fMRI.
In-vivo characterization of macro- and microstructural injury of the subventricular zone in relapsing-remitting and progressive multiple sclerosis
Authors: Cellerino Maria , Schiavi Simona , Lapucci Caterina , Sbragia Elvira , Boffa Giacomo , Rolla-Bigliani Claudia , Tonelli Serena , Boccia Daniele , Bruschi Nicolò , Tazza Francesco , Franciotta Diego , Inglese Matilde
Published: April 2023

Introduction

The subventricular zone (SVZ) represents one of the main adult brain neurogenesis niche. In-vivo imaging of SVZ is very challenging and little is known about MRI correlates of SVZ macro- and micro-structural injury in multiple sclerosis (MS) patients.

Methods

The aim of the present study is to evaluate differences in terms of volume and microstructural changes [as assessed with the novel Spherical Mean Technique (SMT) model, evaluating: Neurite Signal fraction (INTRA); Extra-neurite transverse (EXTRATRANS) and mean diffusivity (EXTRAMD)] in SVZ between relapsing-remitting (RR) or progressive (P) MS patients and healthy controls (HC). We are also going to explore whether SVZ microstructural injury correlate with caudate (a nucleus that is in the vicinity of the SVZ) or thalamus (another well-defined grey matter area which is further from SVZ than caudate) volume and clinical disability. Clinical and brain MRI data were prospectively acquired from 20 HC, 101 RRMS, and 50 PMS patients. Structural and diffusion metrics inside the global SVZ, normal appearing (NA-) SVZ, caudate and thalamus were collected.

Results

We found a statistically significant difference between groups in terms of NA-SVZ EXTRAMD (PMS>RRMS>HC; p = 0.002), EXTRATRANS (PMS>RRMS>HC; p<0.0001), and INTRA (HC>RRMS>PMS; p = 0.009). Multivariable models showed that NA-SVZ metrics significantly predicted caudate (R2 = 0.21, p < 0.0001), but not thalamus, atrophy. A statistically significant correlation between EXTRAMD and EXTRATRANS of the NA-SVZ and EDSS (r=0.25, p=0.003 and r=0.24, p = 0.003, respectively) was found. These findings were confirmed in analyses restricted to RRMS, but not to PMS patients.

Discussion

In conclusion, the microstructural damage we observed within the NA-SVZ of MS patients – reflecting higher free water content (higher EXTRAMD), cytoarchitecture disruption and astrogliosis (higher EXTRATRANS and lower INTRA) - was more evident in the progressive as compared to the relapsing phases of MS. These abnormalities were significantly associated with a more pronounced caudate atrophy and higher clinical disability scores. Our findings may support the neuroprotective role of SVZ in MS patients.
Associations between dairy consumption, physical activity, and blood pressure in Chinese young women
Authors: Lu Yining , Wiltshire Huw D. , Baker Julien S. , Wang Qiaojun , Ying Shanshan
Published: April 2023

Introduction

The prevalence of hypertension (HTN) has been increasing in young adults. A healthy dietary pattern and increasing physical activity (PA) are commonly recommended as lifestyle modifications needed to manage blood pressure (BP). However, little is known about the relationship between dairy intake, PA, and BP in Chinese young women. The aim of this study was to examine whether BP was associated with dairy intake, moderate-to-vigorous intensity physical activity (MVPA) and total physical activity (TPA) in a sample of Chinese young women.

Methods

A total of 122 women (20.4 ± 1.4) who had complete data sets from the Physical Fitness in Campus (PFIC) study were included in this cross-sectional analysis. Data related to dairy intake and PA was collected using a food frequency questionnaire and an accelerometer. BP was measured following standardized procedures. The association between BP with dairy intake and PA was examined using multivariable linear regression models.

Results

After controlling for potential covariables, we observed a significant and independent relationship only between systolic BP with dairy intake [standardized beta (b) = −0.275, p < 0.001], MVPA (b = −0.167, p = 0.027), and TPA (b = −0.233, p = 0.002). Furthermore, we found a decrease of 5.82 ± 2.94, 1.13 ± 1.01, and 1.10 ± 0.60 mm Hg in systolic BP for daily additional servings of dairy, 10 min of MVPA, and 100 counts per minute of TPA, respectively.

Conclusion

Our results suggested that the higher amount of dairy consumption or PA was associated with lower level of SBP in Chinese young women.
Dynamic gut microbiota changes in patients with advanced malignancies experiencing secondary resistance to immune checkpoint inhibitors and immune-related adverse events
Authors: Zeng Yanlin , Shi Qingya , Liu Xinyu , Tang Hao , Lu Bo , Zhou Qingyang , Xu Yan , Chen Minjiang , Zhao Jing , Li Yue , Qian Jiaming , Wang Mengzhao , Tan Bei
Published: April 2023

Background

Immune checkpoint inhibitors (ICIs) have been a breakthrough in cancer immunotherapy, but secondary resistance (SR) and immune-related adverse events (irAEs) are significant clinical dilemmas. Although the gut microbiota is associated with ICI efficacy and irAEs, the knowledge of longitudinal gut microbiota dynamics during SR and irAE development is still quite limited.

Methods

This was a prospective observational cohort study of cancer patients initially receiving anti-programmed cell death-1 (PD-1) treatment between May 2020 and October 2022. Clinical information was collected to evaluate therapy response and AEs. Patients were divided into a secondary resistance (SR) group, a non-secondary resistance (NSR) group, and an irAE group. Fecal samples were longitudinally obtained from baseline across multiple timepoints and analyzed with 16S rRNA sequencing.

Results

Thirty-five patients were enrolled, and 29 were evaluable. After a median follow-up of 13.3 months, NSR patients had a favorable progression-free survival (PFS) compared with SR (457.9 IQR 241.0-674.0 days vs. 141.2 IQR 116.9-165.4 days, P=0.003) and irAE patients (457.9 IQR 241.0-674.0 days vs. 269.9, IQR 103.2-436.5 days, P=0.053). There were no significant differences in the microbiota between groups at baseline. Several previously reported beneficial microbiomes for ICI efficacy including Lachnospiraceae, Ruminococcaceae, Agathobacter, and Faecalibacterium showed decreasing trends as secondary resistance developed, yet not achieved significance (P>0.05). Significant changes in butyrate-producing bacteria were also presented in the SR cohort (P=0.043) with a decreasing trend upon secondary resistance occurrence (P=0.078). While the abundance of IgA-coated bacteria was stable in the SR cohort, there was a temporary decrease upon ICI treatment initiation and reestablishment after continuation of ICI treatment in the NSR cohort (primary ICI response: 0.06, IQR 0.04-0.10; durable ICI response: 0.11, IQR 0.07-0.14; P=0.042). Bacteroides contributed most to the difference between baseline and irAE occurrence, which decreased after irAE occurrence (Baseline: 0.10 IQR 0.07-0.36; irAE occurrence: 0.08 IQR 0.06-0.12) and was restored upon irAE remission to a comparable level as baseline (irAE remission: 0.10 IQR 0.09-0.18).

Conclusions

The development of SR and irAEs is related to the longitudinal dynamics of the intestinal microbiota. The investigation into the preventative and protective effects of enteric microbe manipulation strategies is further required.
Inflammatory markers in children with obstructive sleep apnea syndrome
Authors: Wang Yingge , Chen Ying , Lin Wei , Huang Min , Xu Yuanteng , Chen Guohao
Published: April 2023

Objective

To evaluate serum inflammatory markers of YKL-40, Interleukin-6 (IL-6), Interleukin-8(IL-8), Interleukin-10(IL-10), TNF-α(tumor necrosis factor-α), and CRP (C-reactive protein) in children with and without OSAS.

Methods

The ELISA technique has been used to identify the concentration of inflammatory markers such as YKL-40, IL-6, IL-8, IL-10, TNF-α, and CRP in the serum of 83 children with OSAS and 83 children without OSAS.

Results

Serum levels of YKL-40, IL-6, IL-8, and IL-10 were found to be increased in children with OSAS. YKL-40 was found to be positively correlated with IL-6 and IL-8, and negatively correlated with IL-10. At the same time,YKL-40 was also found to be positively correlated with OAHI and LoSpO2% in OSAS group. IL-8 was positively correlated with OAHI whereas IL-10 was positively correlated with LoSpO2.

Conclusion

Children with OSAS are in a systemic inflammatory state. YKL-40 together with IL-8 may act as serum inflammatory markers and provide an indication for the diagnosis of children with OSAS.
A Chinese family with cat eye syndrome and abnormality of eye movement: First case report
Authors: Lu Yang , Shen Liping , Zheng Yue , Zhang Haichen , Liu Yanbo , Qi Ming , Huang Shangzhi , Shen Bo
Published: April 2023

Background

Cat eye syndrome (CES) is a rare disease with a wide spectrum of phenotypic variability that is observed in 1:150,000 newborns. CES is characterized clinically by the combination of iris coloboma, anal atresia, and preauricular tags and/or pits. Many eye malformations have been reported to be associated with CES, such as iris and chorioretinal coloboma. However, an abnormality of eye movement has not been previously reported.

Case presentation

We report on a Chinese family carrying a 22q11.1-q11.21 duplication of 1.7Mb tetrasomy (chr22:16,500,000–18,200,000, hg38) in two generations. Based on the proband and her father’s clinical manifestations, including ophthalmological examination, cytogenetic analysis, FISH, CNV-seq, and WES, the diagnosis of CES with an abnormality of eye movement was made.

Conclusion

Our findings broadened the symptom spectrum of CES syndrome and laid the foundation for pathogenesis, diagnostic targets, and drug research on the abnormality of eye movement, and were helpful for early diagnosis and intervention of CES.
Utility of fetal cardiovascular magnetic resonance imaging in assessing the fetuses with complete vascular ring
Authors: Zhang Xia , Zhu Ming , Dong Su-Zhen
Published: April 2023

Objective

This study aimed to report our experience in qualitative and quantitative evaluation of fetal complete vascular ring (CVR) using fetal cardiovascular magnetic resonance imaging (MRI) to improve prenatal diagnosis and make early postnatal management possible.

Methods

A retrospective case-control study was performed on cases of CVR diagnosed using fetal cardiovascular MRI, and confirmed by postnatal imaging diagnosis. Associated abnormalities were recorded. The diameters of aortic arch isthmus (AoI) and ductus arteriosus (DA), and tracheal diameters in fetuses with tracheal compression were measured and compared with those of the control group.

Results

All fetal CVR cases in this study included right aortic arch (RAA) with aberrant left subclavian artery (ALSA) and left DA (n = 93), double aortic arch (DAA) (n = 29), RAA with mirror-image branching and retroesophageal left ductus arteriosus (RLDA) (n = 8). Compared with the control group, the diameters of AoI in fetuses with DAA were decreased (p < 0.001), and the diameters of DA in fetuses with RAA with ALSA and left DA were increased (p < 0.001). The diameters of AoI and DA were positively correlated with gestational age (GA) in the normal control group (both p < 0.001); The diameters of AoI and DA were also positively correlated with GA in RAA with ALSA and left DA subgroup (both p < 0.001) and RAA with mirror-image branching and RLDA subgroup (AoI: p = 0.003; DA: p = 0.002); The diameters of DA were positively associated with GA in DAA subgroup (p < 0.001), however, there was no linear tendency between the diameters of AoI and GA in the DAA subgroup (p = 0.074). There were CVR fetuses with associated intracardiac malformation (n = 13), especially ventricular septal defect rather than complex heart disease, and extracardiac malformation (n = 14). Sixteen fetuses were shown the airway compression whose tracheal diameters were smaller than the normal (p < 0.001).

Conclusions

The altered diameters of AoI and DA can be detected and measured in CVR fetuses using fetal cardiovascular MRI. Fetal CVR can occur alone or with intracardiac and extracardiac malformation. Fetal CVR can be associated with prenatal airway compression.