bluuebunny/crossref_metadata_2025 huggingface dataset:
Hyaluronan breakdown by snake venom hyaluronidases: From toxins delivery to immunopathology
Authors: Silva de França Felipe , Tambourgi Denise V.
Published: March 2023

Snake venom enzymes have a broad range of molecular targets in plasma, tissues, and cells, among which hyaluronan (HA) is outstanding. HA is encountered in the extracellular matrix of diverse tissues and in the bloodstream, and its different chemical configurations dictate the diverse morphophysiological processes in which it participates. Hyaluronidases are highlighted among the enzymes involved in HA metabolism. This enzyme has been detected along the phylogenetic tree, suggesting that hyaluronidases exert multiple biological effects on different organisms. Hyaluronidases have been described in tissues, blood and snake venoms. Snake venom hyaluronidases (SVHYA) contribute to tissue destruction in envenomations and are called spreading factors since their action potentiates venom toxin delivery. Interestingly, SVHYA are clustered in Enzyme Class 3.2.1.35 together with mammalian hyaluronidases (HYAL). Both HYAL and SVHYA of Class 3.2.1.35 act upon HA, generating low molecular weight HA fragments (LMW-HA). LMW-HA generated by HYAL becomes a damage-associated molecular pattern that is recognized by Toll-like receptors 2 and 4, triggering cell signaling cascades culminating in innate and adaptive immune responses that are characterized by lipid mediator generation, interleukin production, chemokine upregulation, dendritic cell activation and T cell proliferation. In this review, aspects of the structures and functions of HA and hyaluronidases in both snake venoms and mammals are presented, and their activities are compared. In addition, the potential immunopathological consequences of HA degradation products generated after snakebite envenoming and their use as adjuvant to enhance venom toxin immunogenicity for antivenom production as well as envenomation prognostic biomarker are also discussed.
The role of iron metabolism in the pathogenesis and treatment of multiple sclerosis
Authors: Duarte-Silva Eduardo , Meuth Sven G. , Peixoto Christina Alves
Published: March 2023

Multiple sclerosis is a severe demyelinating disease mediated by cells of the innate and adaptive immune system, especially pathogenic T lymphocytes that produce the pro-inflammatory cytokine granulocyte-macrophage colony stimulating factor (GM-CSF). Although the factors and molecules that drive the genesis of these cells are not completely known, some were discovered and shown to promote the development of such cells, such as dietary factors. In this regard, iron, the most abundant chemical element on Earth, has been implicated in the development of pathogenic T lymphocytes and in MS development via its effects on neurons and glia. Therefore, the aim of this paper is to revise the state-of-art regarding the role of iron metabolism in cells of key importance to MS pathophysiology, such as pathogenic CD4+ T cells and CNS resident cells. Harnessing the knowledge of iron metabolism may aid in the discovery of new molecular targets and in the development of new drugs that tackle MS and other diseases that share similar pathophysiology.
Comparison of hematopoietic stem cell transplantation and immunosuppressive therapy as the first-line treatment option for patients with severe hepatitis−associated aplastic anemia
Authors: Zhang Xiaoyu , Yang Wenrui , Yang Donglin , Wei Jialin , Zhang Ping , Feng Sizhou , Jiang Erlie , Zhang Li , He Yi , Zhang Fengkui , Han Mingzhe
Published: March 2023

Hepatitis-associated aplastic anemia (HAAA) is a rare variant of acquired aplastic anemia characterized with a syndrome of bone marrow failure after hepatitis. We retrospectively analyzed the outcomes of consecutive severe HAAA patients who received immunosuppressive therapy (IST, n = 70), matched-sibling donor hematopoietic stem cell transplantation (MSD-HSCT, n = 26) or haploidentical-donor (HID) HSCT (n = 11) as the first-line treatment. In the IST group, the hematologic response (HR) rate was 55.71% at 6 months. In contrast, HSCT recipients exhibited significantly more rapid and sustained hematopoiesis (HR 76.92%, 96.15% and 96.15% at 3, 6 and 12months, respectively). The 5-year overall survival (OS) was not different among IST (83.7 ± 4.9%), MSD-HSCT (93.3 ± 6.4%) and HID-HSCT group (80.8 ± 12.3%). Compared with IST, MSD and HID-HSCT demonstrated a trend of superiority in the estimated 5-year failure-free survival rates (93.3 ± 6.4% vs 64.3 ± 6.0%, p = 0.05; 80.8 ± 12.3% vs 64.3 ± 6.0%, p = 0.57). In subsequent stratified analysis on age, we found that HID-HSCT showed its efficacy and safety among young patients. In sum, MSD-HSCT remains first-line treatment choice for HAAA, whereas HID-HSCT represents an alternative treatment choice in addition to IST for young patients (< 40 years) without a matched sibling donor.
Targeting myeloid-derived suppressor cells in tumor immunotherapy: Current, future and beyond
Authors: Zhao Yang , Du Junfeng , Shen Xiaofei
Published: March 2023

Myeloid-derived suppressor cells (MDSCs) are one of the major negative regulators in tumor microenvironment (TME) due to their potent immunosuppressive capacity. MDSCs are the products of myeloid progenitor abnormal differentiation in bone marrow, which inhibits the immune response mediated by T cells, natural killer cells and dendritic cells; promotes the generation of regulatory T cells and tumor-associated macrophages; drives the immune escape; and finally leads to tumor progression and metastasis. In this review, we highlight key features of MDSCs biology in TME that are being explored as potential targets for tumor immunotherapy. We discuss the therapies and approaches that aim to reprogram TME from immunosuppressive to immunostimulatory circumstance, which prevents MDSC immunosuppression activity; promotes MDSC differentiation; and impacts MDSC recruitment and abundance in tumor site. We also summarize current advances in the identification of rational combinatorial strategies to improve clinical efficacy and outcomes of cancer patients, via deeply understanding and pursuing the mechanisms and characterization of MDSCs generation and suppression in TME.
Association of adenotonsillar disease and adenotonsillectomy with the development of vitiligo: A nationwide population-based cohort study
Authors: Kim Jong Seung , Lee Min Gyu , Lee Sang-Kyung , Yeom Sang-Woo , Kang Min-Gu , Lee Jong Hwan , Lee Il-Jae , Park Jin , Yun Seok-kweon , Nam Kyung-Hwa
Published: March 2023

Background

Vitiligo is a common acquired skin depigmentation disorder and is associated with various other autoimmune diseases which include thyroid disease and rheumatoid arthritis. Similarly, adenotonsillar disease (ATD) may induce inflammatory or autoimmune diseases in other organs which include the skin. However, the influence of ATD on the development of vitiligo has not been studied.

Objectives

To determine the association between ATD and adenotonsillectomy, and the development of vitiligo.

Design and methods

Using data from the National Health Insurance Service database, patients diagnosed with ATD between 2008 and 2010 were included in the study. We performed two rounds of 1:1 propensity score matching in the ATD and adenotonsillectomy groups. The ATD and non-ATD groups both included 206,514 individuals. Among the ATD group, the adenotonsillectomy and non-adenotonsillectomy groups both included 23,354 individuals. Each individual was monitored until 2019. The primary end point was the risk of vitiligo. Using the Cox Proportional Hazards model, the incidence of vitiligo and the hazard ratio (HR) were calculated.

Results

The incidence of vitiligo was 1.16-fold higher in the ATD group than in the non-ATD group [adjusted HR (aHR), 1.16; 95% confidence interval (CI), 1.09–1.24] and 0.82-fold lower in the adenotonsillectomy group than in the non-adenotonsillectomy group (aHR, 0.82; 95% CI, 0.68–0.99). Additionally, the other risk factors for developing vitiligo included thyroid disease (aHR, 1.48; 95% CI, 1.11–1.98), age younger than 30 years (aHR, 1.18; 95% CI, 1.09–1.27), and age over 60 years (aHR, 1.22; 95% CI, 1.06–1.41), whereas factors including rural residency (aHR, 0.91; 95% CI, 0.85–0.98) and low economic status (aHR 0.87; 95% CI, 0.82–0.93) were associated with decreased incidence of vitiligo.

Conclusion

In this study, ATD increases the risk of vitiligo and adenotonsillectomy attenuates its development. Clinicians should consider ATD as a pathogenic factor for vitiligo and the potential effect of adenotonsillectomy in its management.
The combination effect of meropenem/sulbactam/polymyxin-B on the pharmacodynamic parameters for mutant selection windows against carbapenem-resistant Acinetobacter baumannii
Authors: Zhang Jiayuan , Diao Shuo , Liu Yanfei , Wang Hongxiang , Liu Yuwei , Zhu Shixing , Feng Kun , Tang Xiaoqian , Oo Charles , Zhu Peijuan , Lv Zhihua , Yu Mingming , Sy Sherwin K. B. , Zhu Yuanqi
Published: March 2023

The objective of this study was to evaluate whether combinations of sulbactam, meropenem, and polymyxin-B could reduce or close the gap of mutant selection window (MSW) of individual antibiotics against Acinetobacter baumannii harboring OXA-23. MICs of three antimicrobials used alone and in combination (meropenem/polymyxin-B or meropenem/polymyxin-B/sulbactam) were obtained in 11 clinical isolates and mutant prevention concentrations were determined in 4 of the 11 isolates. All isolates were resistant to meropenem or polymyxin-B. Combining meropenem and polymyxin-B with or without sulbactam resulted in synergistic bactericidal activities. Pharmacokinetic (PK) simulations of drug concentrations in the blood and epithelial lining fluid coupled with pharmacodynamic (PD) evaluations revealed that the fractions of time over the 24-h in terms of free drug concentration within the MSW (fTMSW) and above the MPC (fT>MPC) were optimized by combination therapy. The resultant clinical regimens of meropenem, polymyxin-B, and sulbactam evaluated in the PK-PD analysis were 2 g q8h, 2.5 mg/kg loading dose followed by 1.5 mg/kg q12h, and 3 g q8h, respectively, in patients with normal renal function. Subsequent corresponding equivalent exposure regimens would depend on the extent of renal failure. The overall results indicate that combination antibiotics consisting of sulbactam/meropenem/polymyxin-B can confer potential efficacy against A. baumannii harboring OXA-23, and reduce the opportunity for bacteria to develop further resistance. This study provides a framework for pharmacodynamic evaluation of drug-resistant mutant suppression in an antimicrobial co-administration setting. The results thereby lay the groundwork for additional studies and future clinical confirmation is warranted.
Bacterial community structure in geothermal springs on the northern edge of Qinghai-Tibet plateau
Authors: Zhang Huai-sheng , Feng Qing-da , Zhang Ding-yue , Zhu Gui-lin , Yang Li
Published: March 2023

Introduction:

In order to reveal the composition of the subsurface hydrothermal bacterial community in the zones of magmatic tectonics and their response to heat storage environments.

Methods:

In this study, we performed hydrochemical analysis and regional sequencing of the 16S rRNA microbial V4-V5 region in 7 Pleistocene and Lower Neogene hot water samples from the Gonghe basin.

Results:

Two geothermal hot spring reservoirs in the study area were found to be alkaline reducing environments with a mean temperature of 24.83°C and 69.28°C, respectively, and the major type of hydrochemistry was SO4-Cl·Na. The composition and structure of microorganisms in both types of geologic thermal storage were primarily controlled by temperature, reducing environment intensity, and hydrogeochemical processes. Only 195 ASVs were shared across different temperature environments, and the dominant bacterial genera in recent samples from temperate hot springs were Thermus and Hydrogenobacter, with both genera being typical of thermophiles. The correlation analysis showed that the overall level of relative abundance of the subsurface hot spring relied on a high temperature and a slightly alkaline reducing environment. Nearly all of the top 4 species in the abundance level (53.99% of total abundance) were positively correlated with temperature and pH, whereas they were negatively correlated with ORP (oxidation–reduction potential), nitrate, and bromine ions.

Discussion:

In general, the composition of bacteria in the groundwater in the study area was sensitive to the response of the thermal storage environment and also showed a relationship with geochemical processes, such as gypsum dissolution, mineral oxidation, etc.
Geo-epidemiology of animal tuberculosis and Mycobacterium bovis genotypes in livestock in a small, high-incidence area in Sicily, Italy
Authors: Marianelli Cinzia , Verrubbi Vladimiro , Pruiti Ciarello Flavia , Ippolito Dorotea , Pacciarini Maria Lodovica , Di Marco Lo Presti Vincenzo
Published: March 2023

Introduction

The persistence of animal tuberculosis (TB) in livestock is a major concern in Sicily, Italy. The objective of this study was to elucidate the transmission dynamics of M. bovis infection in a highly circumscribed, and at the same time geographically diverse, high-risk area of the island through an in-depth geo-epidemiological investigation of TB in cattle and black pigs raised in small-scale extensive farms across the district of Caronia.

Methods

We used genotype analysis coupled with geographic information system (GIS) technology and phylogenetic inference to characterize the spatial distribution of TB and M. bovis genotypes in livestock and the genetic relationships between M. bovis isolates. A total of 589 M. bovis isolates collected from slaughtered cattle (n = 527) and Sicilian black pigs (n = 62) over a 5-year period (2014–2018) were included in the study.

Results

TB was widespread throughout the district and was most frequent in the north-central area of the district, especially along one of the district’s streams. We identified a total of 62 M. bovis genotypes. Identical genetic profiles were isolated from both neighboring and non-neighburing herds. The 10 most frequent genotypes, accounting for 82% of M. bovis isolates, showed geographic specificities in that they tended to cluster in specific spatial niches. The landscape structure of these niches—i.e. steep slopes, rocky ridges, meadows and streams—is likely to have had a significant influence on the distribution of TB among livestock in Caronia. Higher concentrations of TB were observed along streams and in open meadows, while rocky ridges and slopes appeared to have hampered the spread of TB.

Discussion

The geographical distribution of TB cases among livestock in Caronia is consistent with several epidemiological scenarios (e.g., high density of infected herds along the streams or in hilly plateau where livestock share pastures). Landscape structure is likely to play an important role in the transmission and persistence of M. bovis infection across the district. Additional potential risk factors, such as livestock trading and extensive breeding methods, are also discussed. Our results will contribute to the improvement of surveillance, control and eradication activities of TB in Sicily by the implementation of ad hoc TB control measures, especially in farms located along streams, sharing common pastures or with mixed animal species.
Chromosome 1 trisomy confers resistance to aureobasidin A in Candida albicans
Authors: Zheng Lijun , Xu Yi , Dong Yubo , Ma Xiaowen , Wang Chen , Yang Feng , Guo Liangsheng
Published: March 2023

Introduction

Candida albicans is a prevalent opportunistic human fungal pathogen. However, there are currently very few antifungal treatments available. Inositol phosphoryl ceramide synthase is an essential and fungal-specific protein that also provides a novel and promising antifungal target. Aureobasidin A is a widely used inhibitor of inositol phosphoryl ceramide synthase, however the mechanism of resistance to aureobasidin A is largely unknown in pathogenic fungi.

Methods

Here we investigated how C. albicans adapted to low and high concentrations of aureobasidin A.

Results and discussions

We identified trisomy of chromosome 1 as the predominant mechanism of rapid adaptation. Resistance to aureobasidin A was unstable because of the inherent instability of aneuploids. Importantly, chromosome 1 trisomy simultaneously regulated genes which were associated with aureobasidin A resistance that are on this aneuploid chromosome as well as on other chromosomes. Furthermore, the pleiotropic effect of aneuploidy caused altered resistance not only to aureobasidin A but also to other antifungal drugs including caspofungin and 5-flucytosine. We posit aneuploidy provides a rapid and reversible mechanism of development of drug resistance and cross resistance in C. albicans.
Field ponding water exacerbates the dissemination of manure-derived antibiotic resistance genes from paddy soil to surrounding waterbodies
Authors: Zhang Ming-Sha , Liang Si-Zhou , Zhang Wei-Guo , Chang Ya-Jun , Lei Zhongfang , Li Wen , Zhang Guo-Liang , Gao Yan
Published: March 2023

Farmlands fertilized with livestock manure-derived amendments have become a hot topic in the dissemination of antibiotic resistance genes (ARGs). Field ponding water connects rice paddies with surrounding water bodies, such as reservoirs, rivers, and lakes. However, there is a knowledge gap in understanding whether and how manure-borne ARGs can be transferred from paddy soil into field ponding water. Our studies suggest that the manure-derived ARGs aadA1, bla1, catA1, cmlA1-01, cmx(A), ermB, mepA and tetPB-01 can easily be transferred into field ponding water from paddy soil. The bacterial phyla Crenarchaeota, Verrucomicrobia, Cyanobacteria, Choloroflexi, Acidobacteria, Firmicutes, Bacteroidetes, and Actinobacteria are potential hosts of ARGs. Opportunistic pathogens detected in both paddy soil and field ponding water showed robust correlations with ARGs. Network co-occurrence analysis showed that mobile genetic elements (MGEs) were strongly correlated with ARGs. Our findings highlight that manure-borne ARGs and antibiotic-resistant bacteria in paddy fields can conveniently disseminate to the surrounding waterbodies through field ponding water, posing a threat to public health. This study provides a new perspective for comprehensively assessing the risk posed by ARGs in paddy ecosystems.
Response to HIV-1 gp160-carrying recombinant virus HSV-1 and HIV-1 VLP combined vaccine in BALB/c mice
Authors: Zhang Beibei , Mao Hongyan , Zhu Hongjuan , Guo Jingxia , Zhou Paul , Ma Zhenghai
Published: March 2023

Human immunodeficiency virus (HIV) induced AIDS causes a large number of infections and deaths worldwide every year, still no vaccines are available to prevent infection. Recombinant herpes simplex virus type 1 (HSV-1) vector-based vaccines coding the target proteins of other pathogens have been widely used for disease control. Here, a recombinant virus with HIV-1 gp160 gene integration into the internal reverse (IR) region-deleted HSV-1 vector (HSV-BAC), was obtained by bacterial artificial chromosome (BAC) technology, and its immunogenicity investigated in BALB/c mice. The result showed similar replication ability of the HSV-BAC-based recombinant virus and wild type. Furthermore, humoral and cellular immune response showed superiority of intraperitoneal (IP) administration, compared to intranasally (IN), subcutaneous (SC) and intramuscularly (IM), that evidenced by production of significant antibody and T cell responses. More importantly, in a prime-boost combination study murine model, the recombinant viruses prime followed by HIV-1 VLP boost induced stronger and broader immune responses than single virus or protein vaccination in a similar vaccination regimen. Antibody production was sufficient with huge potential for viral clearance, along with efficient T-cell activation, which were evaluated by the enzyme-linked immunosorbent assay (ELISA) and flow cytometry (FC). Overall, these findings expose the value of combining different vaccine vectors and modalities to improve immunogenicity and breadth against different HIV-1 antigens.
The longitudinal relationship between hearing loss and cognitive decline in tonal language-speaking older adults in China
Authors: Fu Xinxing , Eikelboom Robert H. , Liu Bo , Wang Shuo , Jayakody Dona M. P.
Published: March 2023

Introduction

Previous longitudinal studies indicate that hearing loss and cognitive impairment are associated in non-tonal language-speaking older adults. This study aimed to investigate whether there is a longitudinal association between hearing loss and cognitive decline in older adults who speak a tonal language.

Methods

Chinese-speaking older adults aged 60 years and above were recruited for baseline and 12 month follow-up measurements. All participants completed a pure tone audiometric hearing test, Hearing Impaired-Montreal Cognitive Assessment Test (HI-MoCA), and a Computerized Neuropsychological Test Battery (CANTAB). The De Jong Gierveld Loneliness Scale was used to measure loneliness, and the 21-item Depression Anxiety Stress Scale (DASS-21) was used to measure aspects of mental health. Associations between baseline hearing loss and various cognitive, mental and psychosocial measures were evaluated using logistic regression.

Results

A total of 71 (29.6%) of the participants had normal hearing, 70 (29.2%) had mild hearing loss, and 99 (41.2%) had moderate or severe hearing loss at baseline, based on mean hearing thresholds in the better ear. After adjusting for demographic and other factors, baseline moderate/severe audiometric hearing loss was associated with an increased risk of cognitive impairment at follow-up (OR: 2.20, 95% CI: 1.06, 4.50). When pure-tone average (PTA) was modeled continuously, an average difference of 0.24 in HI-MoCA scores for every 10 dB increase in BE4FA existed, and an average difference of 0.07 in the change of HI-MoCA scores in a 12 month period.

Discussion

The results revealed a significant longitudinal relationship between age-related hearing loss and cognitive decline in this cohort of tonal language-speaking older adults. Steps should also be taken to incorporate hearing assessment and cognitive screening in clinical protocols for older adults 60 years and above in both hearing and memory clinics.
Biological networks and complexity in early-onset motor neuron diseases
Authors: Butchbach Matthew E. R. , Scott Rod C.
Published: March 2023

Motor neuron diseases (MNDs) are neuromuscular disorders where the spinal motor neurons–either the cell bodies themselves or their axons–are the primary cells affected. To date, there are 120 different genes that are lost or mutated in pediatric-onset MNDs. Most of these childhood-onset disorders, aside from spinal muscular atrophy (SMA), lack viable therapeutic options. Previous research on MNDs has focused on understanding the pathobiology of a single, specific gene mutation and targeting therapies to that pathobiology. This reductionist approach has yielded therapeutic options for a specific disorder, in this case SMA. Unfortunately, therapies specific for SMA have not been effective against other pediatric-onset MNDs. Pursuing the same approach for the other defined MNDs would require development of at least 120 independent treatments raising feasibility issues. We propose an alternative to this this type of reductionist approach by conceptualizing MNDs in a complex adaptive systems framework that will allow identification of common molecular and cellular pathways which form biological networks that are adversely affected in early-onset MNDs and thus MNDs with similar phenotypes despite diverse genotypes. This systems biology approach highlights the complexity and self-organization of the motor system as well as the ways in which it can be affected by these genetic disorders. Using this integrated approach to understand early-onset MNDs, we would be better poised to expand the therapeutic repertoire for multiple MNDs.
Clinical effect of short-term spinal cord stimulation in the treatment of patients with primary brainstem hemorrhage-induced disorders of consciousness
Authors: Huang Weilong , Chen Qiang , Liu Lin , Tang Jianhong , Zhou Hua , Tang Zhiji , Jiang Qing , Li Tao , Liu Jianwu , Wang Dong
Published: March 2023

Objective

Recently, short-term spinal cord stimulation (st-SCS) has been used in neurorehabilitation and consciousness recovery. However, little is known about its effects on primary brainstem hemorrhage (PBSH)-induced disorders of consciousness (DOC). In this study, we examined the therapeutic effects of st-SCS in patients with PBSH-induced DOC.

Methods

Fourteen patients received a 2-week st-SCS therapy. Each patient's state of consciousness was evaluated using the Coma Recovery Scale-Revised (CRS-R). CRS-R evaluation scores were recorded at the baseline (before SCS implantation) and 14 days later.

Results

Over 70% (10/14) of the patients (CRS-R score increased to ≥2 points) responded to the SCS stimulation after 14 days of st-SCS treatment. All items included in the CRS-R exhibited a significant increase post-treatment compared with pretreatment. After 2 weeks of st-SCS treatment, seven patients showed diagnostic improvement, resulting in a 50% (7/14) overall effective rate. Approximately 75% (3/4) of patients with minimally conscious state plus (MCS+) improved to emergence from MCS (eMCS), and 50% (1/2) of patients with vegetative state or unresponsive wakefulness syndrome (VS/UWS) improved to MCS+.

Conclusion

In PBSH-induced DOC, st-SCS is a safe and effective treatment. The clinical behavior of the patients improved significantly following the st-SCS intervention, and their CRS-R scores markedly increased. This was most effective for MCS+.
BCI-activated electrical stimulation in children with perinatal stroke and hemiparesis: A pilot study
Authors: Jadavji Zeanna , Kirton Adam , Metzler Megan J. , Zewdie Ephrem
Published: March 2023

Background

Perinatal stroke (PS) causes most hemiparetic cerebral palsy (CP) and results in lifelong disability. Children with severe hemiparesis have limited rehabilitation options. Brain computer interface- activated functional electrical stimulation (BCI-FES) of target muscles may enhance upper extremity function in hemiparetic adults. We conducted a pilot clinical trial to assess the safety and feasibility of BCI-FES in children with hemiparetic CP.

Methods

Thirteen participants (mean age = 12.2 years, 31% female) were recruited from a population-based cohort. Inclusion criteria were: (1) MRI-confirmed PS, (2) disabling hemiparetic CP, (3) age 6–18 years, (4) informed consent/assent. Those with neurological comorbidities or unstable epilepsy were excluded. Participants attended two BCI sessions: training and rehabilitation. They wore an EEG-BCI headset and two forearm extensor stimulation electrodes. Participants’ imagination of wrist extension was classified on EEG, after which muscle stimulation and visual feedback were provided when the correct visualization was detected.

Results

No serious adverse events or dropouts occurred. The most common complaints were mild headache, headset discomfort and muscle fatigue. Children ranked the experience as comparable to a long car ride and none reported as unpleasant. Sessions lasted a mean of 87 min with 33 min of stimulation delivered. Mean classification accuracies were (M = 78.78%, SD = 9.97) for training and (M = 73.48, SD = 12.41) for rehabilitation. Mean Cohen’s Kappa across rehabilitation trials was M = 0.43, SD = 0.29, range = 0.019–1.00, suggesting BCI competency.

Conclusion

Brain computer interface-FES was well -tolerated and feasible in children with hemiparesis. This paves the way for clinical trials to optimize approaches and test efficacy.
Increased spontaneous activity of the superior frontal gyrus with reduced functional connectivity to visual attention areas and cerebellum in male smokers
Authors: Niu Xiaoyu , Gao Xinyu , Lv Qingqing , Zhang Mengzhe , Dang Jinghan , Sun Jieping , Wang Weijian , Wei Yarui , Cheng Jingliang , Han Shaoqiang , Zhang Yong
Published: March 2023

Background

Chronic smokers have abnormal spontaneous regional activity and disrupted functional connectivity as revealed by previous neuroimaging studies. Combining different dimensions of resting-state functional indicators may help us learn more about the neuropathological mechanisms of smoking.

Methods

The amplitude of low frequency fluctuations (ALFF) of 86 male smokers and 56 male non-smokers were first calculated. Brain regions that displayed significant differences in ALFF between two groups were selected as seeds for further functional connectivity analysis. Besides, we examined correlations between brain areas with abnormal activity and smoking measurements.

Results

Increased ALFF in left superior frontal gyrus (SFG), left medial superior frontal gyrus (mSFG) and middle frontal gyrus (MFG) as well as decreased ALFF in right calcarine sulcus were observed in smokers compared with non-smokers. In the seed-based functional connectivity analysis, smokers showed attenuated functional connectivity with left SFG in left precuneus, left fusiform gyrus, left lingual gyrus, left cerebellum 4 5 and cerebellum 6 as well as lower functional connectivity with left mSGF in left fusiform gyrus, left lingual gyrus, left parahippocampal gyrus (PHG), left calcarine sulcus, left cerebellum 4 5, cerebellum 6 and cerebellum 8 (GRF corrected, Pvoxel < 0.005, Pcluster<0.05). Furthermore, attenuated functional connectivity with left mSGF in left lingual gyrus and PHG displayed a negative correlation with FTND scores (r= −0.308,p= 0.004;r= −0.326,p= 0.002 Bonferroni corrected).

Conclusion

Our findings of increased ALFF in SFG with reduced functional connectivity to visual attention areas and cerebellum subregions may shed new light on the pathophysiology of smoking.
Neural circuit regulation by identified modulatory projection neurons
Authors: Blitz Dawn M.
Published: March 2023

Rhythmic behaviors (e.g., walking, breathing, and chewing) are produced by central pattern generator (CPG) circuits. These circuits are highly dynamic due to a multitude of input they receive from hormones, sensory neurons, and modulatory projection neurons. Such inputs not only turn CPG circuits on and off, but they adjust their synaptic and cellular properties to select behaviorally relevant outputs that last from seconds to hours. Similar to the contributions of fully identified connectomes to establishing general principles of circuit function and flexibility, identified modulatory neurons have enabled key insights into neural circuit modulation. For instance, while bath-applying neuromodulators continues to be an important approach to studying neural circuit modulation, this approach does not always mimic the neural circuit response to neuronal release of the same modulator. There is additional complexity in the actions of neuronally-released modulators due to: (1) the prevalence of co-transmitters, (2) local- and long-distance feedback regulating the timing of (co-)release, and (3) differential regulation of co-transmitter release. Identifying the physiological stimuli (e.g., identified sensory neurons) that activate modulatory projection neurons has demonstrated multiple “modulatory codes” for selecting particular circuit outputs. In some cases, population coding occurs, and in others circuit output is determined by the firing pattern and rate of the modulatory projection neurons. The ability to perform electrophysiological recordings and manipulations of small populations of identified neurons at multiple levels of rhythmic motor systems remains an important approach for determining the cellular and synaptic mechanisms underlying the rapid adaptability of rhythmic neural circuits.
L-shaped association between dietary zinc intake and the risk of developing cardiovascular disease in Chinese adults: A cohort study
Authors: Zhang Huanxiang , Wang Shanjie , Gu Xia , Qiu Hongbin , Zhang Yiying
Published: March 2023

Background

Although the association of zinc (Zn) with cardiovascular disease (CVD) has been studied, no consensus has been reached on this relationship, particularly dietary Zn intake. The purpose of this study was to assess the effect of dietary Zn intake on the risk of CVD and to analyze whether this effect varied according to zinc consumption using representative data from China.

Methods

11,470 adults from the China Health and Nutrition Survey (CHNS) were eventually enrolled. The dietary information was collected by the 3 day 24-h dietary recalls combined with dietary weighting method. CVD was defined as participants with self-reported physician-diagnosed apoplexy and/or myocardial infarction during the follow-up. Cox regression was used to calculate the hazard ratios (HRs) of CVD with 95% confidence intervals. Restricted cubic spline function plus Cox regression was used to visualize the influence trend of dietary Zn intake on new-onset CVD and to test whether this trend is linear. 2-segment Cox regression was established to address the nonlinear trend.

Results

431 participants developed CVD, including 262 strokes and 197 myocardial infarctions. Compared with the lowest quintile (Q1), the adjusted hazard ratios and 95% confidence interval (CI) of CVD in Q2 to Q5 of dietary Zn intake were 0.72 (0.54, 0.97), 0.59 (0.42, 0.81), 0.50 (0.34, 0.72) and 0.44 (0.27, 0.71), respectively. The influence trend of dietary Zn intake on new-onset CVD was nonlinear and L-shaped. When dietary Zn intake <13.66 mg/day, increased dietary Zn intake was significantly associated with decreased risk of developing CVD (HR = 0.87, 95% CI: 0.82–0.92, p-value <0.0001).

Conclusion

An L-shaped trend was observed between dietary Zn intake and the risk of developing CVD, indicating that dietary Zn intake should be improved moderately, but not excessively, for the benefit of cardiovascular disease.
Global and regional prevalence of vitamin D deficiency in population-based studies from 2000 to 2022: A pooled analysis of 7.9 million participants
Authors: Cui Aiyong , Zhang Tiansong , Xiao Peilong , Fan Zhiqiang , Wang Hu , Zhuang Yan
Published: March 2023

Background

Vitamin D deficiency causes the bone hypomineralization disorder osteomalacia in humans and is associated with many non-skeletal disorders. We aim to estimate the global and regional prevalence of vitamin D deficiency in people aged 1 year or older from 2000 to 2022.

Methods

We systematically searched Web of Science, PubMed (MEDLINE), Embase, Scopus, and Google databases on December 31, 2021, and updated them on August 20, 2022, without language and time restrictions. Meanwhile, we identified references of relevant system reviews and eligible articles and included the latest and unpublished data from the National Health and Nutrition Examination Survey (NHANES, 2015–2016 and 2017–2018) database. The studies investigating the prevalence of vitamin D deficiency in population-based studies were included. A standardized data extraction form was used to collect information from eligible studies. We used a random-effects meta-analysis to estimate the global and regional prevalence of vitamin D deficiency. We stratified meta-analyses by latitude, season, six WHO regions, the World Bank income groups, gender, and age groups. This study was registered with PROSPERO (CRD42021292586).

Findings

Out of 67,340 records searched, 308 studies with 7,947,359 participants from 81 countries were eligible for this study, 202 (7,634,261 participants), 284 (1,475,339 participants), and 165 (561,978 participants) studies for the prevalence of serum 25(OH)D <30, <50, and <75 nmol/L, respectively. We found that globally, 15.7% (95% CrI 13.7–17.8), 47.9% (95% CrI 44.9–50.9), and 76·6% (95% CrI 74.0–79.1) of participants had serum 25-hydroxyvitamin D levels less than 30, 50, and 75 nmol/l, respectively; the prevalence slightly decreased from 2000–2010 to 2011–2022, but it was still at a high level; people living in high latitude areas had a higher prevalence; the prevalence in winter-spring was 1.7 (95% CrI 1.4–2.0) times that in summer-autumn; the Eastern Mediterranean region and Lower-middle-income countries had a higher prevalence; females were vulnerable to vitamin D deficiency; gender, sampling frame, detection assays, sampling region, time of data collection, season, and other factors contributed to heterogeneity between the included studies.

Interpretation

Globally, vitamin D deficiency remained prevalent from 2000 to 2022. The high prevalence of vitamin D deficiency would increase the global burden of disease. Therefore, governments, policymakers, health workers, and individuals should attach importance to the high prevalence of vitamin D deficiency and take its prevention as a public health priority.

Systematic review registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021292586, PROSPERO CRD42021292586.
Estimating the dietary and health impact of implementing front-of-pack nutrition labeling in Canada: A macrosimulation modeling study
Authors: Flexner Nadia , Ng Alena P. , Ahmed Mavra , Khandpur Neha , Acton Rachel B. , Lee Jennifer J. , L’Abbe Mary R.
Published: March 2023

Background

Front-of-pack labeling (FOPL) has been identified as a cost-effective policy to promote healthy diets. Health Canada has recently published FOPL regulations that will require food and beverages that meet or exceed set thresholds for sodium, sugars, or saturated fat to display a ‘high in’ symbol on the front of the package. Although a promising measure, its potential impact on dietary intakes and health have not yet been estimated in Canada.

Objective

This study aims to estimate (1) the potential dietary impact of implementing a mandatory FOPL among Canadian adults; and (2) the number of diet-related non-communicable disease (NCD) deaths that could be averted or delayed due to these estimated dietary changes.

Methods

Baseline and counterfactual usual intakes of sodium, total sugars, saturated fats, and calories were estimated among Canadian adults (n = 11,992) using both available days of 24 h recalls from the 2015 Canadian Community Health Survey-Nutrition. The National Cancer Institute method was used to estimate usual intakes, and adjusted for age, sex, misreporting status, weekend/weekday, and sequence of recall. Estimated counterfactual dietary intakes were modeled from reductions observed in experimental and observational studies that examined changes in sodium, sugars, saturated fat, and calorie content of food purchases in the presence of a ‘high in’ FOPL (four counterfactual scenarios). The Preventable Risk Integrated ModEl was used to estimate potential health impacts.

Results

Estimated mean dietary reductions were between 31 and 212 mg/day of sodium, 2.3 and 8.7 g/day of total sugars, 0.8 and 3.7 g/day of saturated fats, and 16 and 59 kcal/day of calories. Between 2,183 (95% UI 2,008–2,361) and 8,907 (95% UI 8,095–9,667) deaths due to diet-related NCDs, mostly from cardiovascular diseases (~70%), could potentially be averted or delayed by implementing a ‘high in’ FOPL in Canada. This estimation represents between 2.4 and 9.6% of the total number of diet-related NCD deaths in Canada.

Conclusion

Results suggest that implementing a FOPL could significantly reduce sodium, total sugar, and saturated fat intakes among Canadian adults and subsequently prevent or postpone a substantial number of diet-related NCD deaths in Canada. These results provide critical evidence to inform policy decisions related to implementing FOPL in Canada.
Pulsed electric fields-assisted extraction of valuable compounds from red grape pomace: Process optimization using response surface methodology
Authors: Carpentieri Serena , Ferrari Giovanna , Pataro Gianpiero
Published: March 2023

Background

The application of Pulsed electric fields as a mild and easily scalable electrotechnology represents an effective approach to selectively intensify the extractability of bioactive compounds from grape pomace, one of the most abundant residues generated during the winemaking process.

Objective

This study addressed the optimization of the pulsed electric fields (PEF)-assisted extraction to enhance the extraction yields of bioactive compounds from red grape pomace using response surface methodology (RSM).

Methods

The cell disintegration index (Zp) was identified as response variable to determine the optimal PEF processing conditions in terms of field strength (E = 0.5–5 kV/cm) and energy input (WT = 1–20 kJ/kg). For the solid-liquid extraction (SLE) process the effects of temperature (20–50°C), time (30–300min), and solvent concentration (0–50% ethanol in water) on total phenolic content (TPC), flavonoid content (FC), total anthocyanin content (TAC), tannin content (TC), and antioxidant activity (FRAP) of the extracts from untreated and PEF-treated plant tissues were assessed. The phenolic composition of the obtained extracts was determined via HPLC-PDA.

Results

Results demonstrated that the application of PEF at the optimal processing conditions (E = 4.6 kV/cm, WT = 20 kJ/kg) significantly enhanced the permeabilization degree of cell membrane of grape pomace tissues, thus intensifying the subsequent extractability of TPC (15%), FC (60%), TAC (23%), TC (42%), and FRAP values (31%) concerning the control extraction. HPLC-PDA analyses showed that, regardless of the application of PEF, the most abundant phenolic compounds were epicatechin, p-coumaric acid, and peonidin 3-O-glucoside, and no degradation of the specific compounds occurred upon PEF application.

Conclusion

The optimization of the PEF-assisted extraction process allowed to significantly enhance the extraction yields of high-value-added compounds from red grape pomace, supporting further investigations of this process at a larger scale.
Analysis of risk factors for lymph node metastasis and prognosis study in patients with early gastric cancer: A SEER data-based study
Authors: Li Jinzhou , Cui Ting , Huang Zeping , Mu Yanxi , Yao Yalong , Xu Wei , Chen Kang , Liu Haipeng , Wang Wenjie , Chen Xiao
Published: March 2023

Background

Lymph node status is an important factor in determining the prognosis of patients with early gastric cancer (EGC) and preoperative diagnosis of lymph node metastasis (LNM) has some limitations. This study explored the risk factors and independent prognostic factors of LNM in EGC patients and constructed a clinical prediction model to predict LNM.

Methods

Clinicopathological data of EGC patients was collected from the public Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate logistic regression was used to identify risk factors for LNM in EGC patients. The performance of the LNM model was evaluated by C-index, calibration curve, receiver operating characteristic (ROC) curve, decision curve analysis (DCA) curve, and clinical impact curve (CIC) based on the results of multivariate regression to develop a nomogram. An independent data set was obtained from China for external validation. The Kaplan-Meier method and Cox regression model were used to identify potential prognostic factors for overall survival (OS) in EGC patients.

Results

A total of 3993 EGC patients were randomly allocated to a training cohort (n=2797) and a validation cohort (n=1196). An external cohort of 106 patients from the Second Hospital of Lanzhou University was used for external validation. Univariate and multivariate logistic regression showed that age, tumor size, differentiation, and examined lymph nodes count (ELNC) were independent risk factors for LNM. Nomogram for predicting LNM in EGC patients was developed and validated. The predictive model had a good discriminatory performance with a concordance index (C-index) of 0.702 (95% CI: 0.679-0.725). The calibration plots showed that the predicted LNM probabilities were the same as the actual observations in both the internal validation cohort and external validation cohort. The AUC values for the training cohort, internal validation cohort and external validation cohort were 0.702 (95% CI: 0.679-0.725), 0.709 (95% CI: 0.674-0.744) and 0.750(95% CI: 0.607-0.892), respectively, and the DCA curves and CIC showed good clinical applicability. The Cox regression model identified age, sex, race, primary site, size, pathological type, LNM, distant metastasis, and ELNC were prognostic factors for OS in EGC patients, while a year at diagnosis, grade, marital status, radiotherapy, and chemotherapy were not independent prognostic factors.

Conclusion

In this study, we identified risk factors and independent prognostic factors for the development of LNM in EGC patients, and developed a relatively accurate model to predict the development of LNM in EGC patients.
Area-level socioeconomic status is positively correlated with glioblastoma incidence and prognosis in the United States
Authors: Gorenflo Maria P. , Shen Alan , Murphy Erin S. , Cullen Jennifer , Yu Jennifer S.
Published: March 2023

In the United States, an individual’s access to resources, insurance status, and wealth are critical social determinants that affect both the risk and outcomes of many diseases. One disease for which the correlation with socioeconomic status (SES) is less well-characterized is glioblastoma (GBM), a devastating brain malignancy. The aim of this study was to review the current literature characterizing the relationship between area-level SES and both GBM incidence and prognosis in the United States. A query of multiple databases was performed to identify the existing data on SES and GBM incidence or prognosis. Papers were filtered by relevant terms and topics. A narrative review was then constructed to summarize the current body of knowledge on this topic. We obtained a total of three papers that analyze SES and GBM incidence, which all report a positive correlation between area-level SES and GBM incidence. In addition, we found 14 papers that focus on SES and GBM prognosis, either overall survival or GBM-specific survival. Those studies that analyze data from greater than 1,530 patients report a positive correlation between area-level SES and individual prognosis, while those with smaller study populations report no significant relationship. Our report underlines the strong association between SES and GBM incidence and highlights the need for large study populations to assess SES and GBM prognosis to ideally guide interventions that improve outcomes. Further studies are needed to determine underlying socio-economic stresses on GBM risk and outcomes to identify opportunities for intervention.