bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative transcriptomic analysis of PK15 cells infected with a PRV variant and the Bartha-K/61 vaccine strain
Authors: Zhang Hongliang , Duan Xiaoxiao , Liu Gang , Li Yingguang , Dong Shaoming , Lin Jiaxu , Zhang Ruihua , Cai Xiulei , Shan Hu
Published: May 2023

Introduction

Pseudorabies virus (PRV) is a herpesvirus that can infect domestic animals, such as pigs, cattle and sheep, and cause fever, itching (except pigs), and encephalomyelitis. In particular, the emergence of PRV variants in 2011 have resulted in serious economic losses to the Chinese pig industry. However, the signaling pathways mediated by PRV variants and their related mechanisms are not fully understood.

Methods

Here, we performed RNA-seq to compare the gene expression profiling between PRV virulent SD2017-infected PK15 cells and Bartha-K/61-infected PK15 cells.

Results

The results showed that 5,030 genes had significantly different expression levels, with 2,239 upregulated and 2,791 downregulated. GO enrichment analysis showed that SD2017 significantly up-regulated differentially expressed genes (DEGs) were mainly enriched in the binding of cell cycle, protein and chromatin, while down-regulated DEGs were mainly enriched in ribosomes. KEGG enrichment analysis revealed that the pathways most enriched for upregulated DEGs were pathways in cancer, cell cycle, microRNAs in cancer, mTOR signaling pathway and autophagy-animal. The most down-regulated pathways of DEGs enrichment were ribosome, oxidative phosphorylation, and thermogenesis. These KEGG pathways were involved in cell cycle, signal transduction, autophagy, and virus-host cell interactions.

Discussion

Our study provides a general overview of host cell responses to PRV virulent infection and lays a foundation for further study of the infection mechanism of PRV variant strain.
A functional metagenomics study of soil carbon and nitrogen degradation networks and limiting factors on the Tibetan plateau
Authors: Yang Chong , Zhang Hong , Zhao Xinquan , Liu Pan , Wang Lushan , Wang Wenying
Published: May 2023

Introduction

The Three-River Source Nature Reserve is located in the core area of the Qinghai-Tibetan Plateau, with the alpine swamp, meadow and steppe as the main ecosystem types. However, the microbial communities in these alpine ecosystems, and their carbon and nitrogen degrading metabolic networks and limiting factors remain unclear.

Methods

We sequenced the diversity of bacteria and fungi in alpine swamps, meadows, steppes, and their degraded and artificially restored ecosystems and analyzed soil environmental conditions.

Results

The results indicated that moisture content had a greater influence on soil microbial community structure compared to degradation and restoration. Proteobacteria dominated in high moisture alpine swamps and alpine meadows, while Actinobacteria dominated in low moisture alpine steppes and artificial grasslands. A metabolic network analysis of carbon and nitrogen degradation and transformation using metagenomic sequencing revealed that plateau microorganisms lacked comprehensive and efficient enzyme systems to degrade organic carbon, nitrogen, and other biological macromolecules, so that the short-term degradation of alpine vegetation had no effect on the basic composition of soil microbial community. Correlation analysis found that nitrogen fixation was strong in meadows with high moisture content, and their key nitrogen-fixing enzymes were significantly related to Sphingomonas. Denitrification metabolism was enhanced in water-deficient habitats, and the key enzyme, nitrous oxide reductase, was significantly related to Phycicoccus and accelerated the loss of nitrogen. Furthermore, Bacillus contained a large number of amylases (GH13 and GH15) and proteases (S8, S11, S26, and M24) which may promote the efficient degradation of organic carbon and nitrogen in artificially restored grasslands.

Discussion

This study illustrated the irrecoverability of meadow degradation and offered fundamental information for altering microbial communities to restore alpine ecosystems.
Ralstonia chuxiongensis sp. nov., Ralstonia mojiangensis sp. nov., and Ralstonia soli sp. nov., isolated from tobacco fields, are three novel species in the family Burkholderiaceae
Authors: Lu Can-Hua , Zhang Ying-Ying , Jiang Ning , Chen Wei , Shao Xiaoli , Zhao Zhi-Ming , Lu Wen-Lin , Hu Xiaodong , Xi Yi-Xuan , Zou Si-Yuan , Wei Qiu-Ju , Lin Zhong-Long , Gong Li , Gai Xiao-Tong , Zhang Li-Qun , Li Jun-Ying , Jin Yan , Xia Zhen-Yuan
Published: May 2023

Eight Gram-negative, aerobic, motile with paired polar flagella and rod-shaped bacteria were isolated from six tobacco fields in Yunnan, PR China. 16S rRNA gene sequence analysis revealed that all the strains belonged to the genus Ralstonia. Among them, strain 22TCCZM03-6 had an identical 16S rRNA sequence to that of R. wenshanensis 56D2T, and the other strains were closely related to R. pickettii DSM 6297T (98.34–99.86%), R. wenshanensis 56D2T (98.70–99.64%), and R. insidiosa CCUG 46789T (97.34–98.56%). Genome sequencing yielded sizes ranging from 5.17 to 5.72 Mb, with overall G + C contents of 63.3–64.1%. Pairwise genome comparisons showed that strain 22TCCZM03-6 shared average nucleotide identity (ANI) and digital DNA–DNA hybridization (dDDH) values above the species cut-off with R. wenshanensis 56D2T, suggesting that strain 22TCCZM03-6 is a special strain of the R. wenshanensis. Five strains, including 21MJYT02-10T, 21LDWP02-16, 22TCJT01-1, 22TCCZM01-4, and 22TCJT01-2, had ANI values >95% and dDDH values >70% when compared with each other. These five strains had ANI values of 73.32–94.17% and dDDH of 22.0–55.20% with the type strains of the genus Ralstonia individually, supporting these five strains as a novel species in the genus Ralstonia. In addition, strains 21YRMH01-3T and 21MJYT02-11T represent two independent species. They both had ANI and dDDH values below the thresholds for species delineation when compared with the type species of the genus Ralstonia. In strains 21YRMH01-3T and 21MJYT02-10T, the main fatty acids were summed features 3, 8, and C16:0; however, strain 21MJYT02-11T contained C16:0, cyclo-C17:0, and summed features 3 as major fatty acids. The main polar lipids, including diphosphatidylglycerol, phosphatidylglycerol, and phosphatidylethanolamine, were identified from strains 21YRMH01-3T, 21MJYT02-10T, and 21MJYT02-11T. The ubiquinones Q-7 and Q-8 were also detected in these strains, with Q-8 being the predominant quinone. Based on the above data, we propose that the eight strains represent one known species and three novel species in the genus Ralstonia, for which the names Ralstonia chuxiongensis sp. nov., Ralstonia mojiangensis sp. nov., and Ralstonia soli sp. nov. are proposed. The type strains are 21YRMH01-3T (=GDMCC 1.3534T = JCM 35818T), 21MJYT02-10T (=GDMCC 1.3531T = JCM 35816T), and 21MJYT02-11T (=GDMCC 1.3532T = JCM 35817T), respectively.
Safety and efficacy of lecanemab for Alzheimer's disease: a systematic review and meta-analysis of randomized clinical trials
Authors: Qiao Yue , Chi Yuewei , Zhang Qingyuan , Ma Ying
Published: May 2023

Objective

We performed a systematic review and meta-analysis of the cognitive effectiveness and safety of lecanemab on subjects with Alzheimer's disease (AD).

Methods

We screened the literature published before February 2023 in PubMed, Embase, Web of Science, and Cochrane that were searched for randomized controlled trials testing lecanemab for the treatment of cognitive decline in patients with MCI or AD. Outcomes measured were CDR Sum of Boxes (CDR-SB), Alzheimer's Disease Composite Score (ADCOMS), AD Assessment Scale–Cognitive Subscale (ADAS-Cog), Clinical Dementia Rating (CDR), amyloid PET Standardized Uptake Volume Ratio (SUVr), amyloid burden on PET, and risks for adverse events.

Results

A total of four randomized controlled trials were included, involving 3,108 AD patients (1,695 lecanemab groups and 1,413 placebo groups) to synthesize evidence. Baseline characteristics of the two groups were similar in all outcomes except that ApoE 4 status and higher MMSE score were observed in the lecanemab group. It is reported that lecanemab was beneficial to stabilize or slow down the decrease in CDR-SB (WMD: −0.45; 95% CI: −0.64, −0.25;p< 0.00001), ADCOMS (WMD: −0.05; 95% CI: −0.07, −0.03;p< 0.00001), ADAS-cog (WMD: −1.11; 95% CI: −1.64, −0.57;p< 0.0001), amyloid PET SUVr (WMD: −0.15; 95% CI: −0.48, 0.19;p= 0.38), amyloid burden on PET (WMD:−35.44; 95% CI: −65.22,−5.67;p= 0.02), adverse events (subjects with any TEAE) (OR: 0.73; 95% CI: 0.25, 2.15;p= 0.57), ARIA-E (OR:8.95; 95% CI: 5.36, 14.95;p< 0.00001), and ARIA-H (OR:2.00; 95% CI: 1.53, 2.62;p< 0.00001) in early AD patients.

Conclusion

Our analysis found that lecanemab showed significant positive statistical efficacy with respect to cognition, function, and behavior in patients with early AD though the actual clinical significance is yet to be established

Systematic review registration

https://www.crd.york.ac.uk/PROSPERO/#recordDetails, identifier: CRD42023393393.
Modeling inducible neuropathologies of the retina with differential phenotypes in organoids
Authors: Völkner Manuela , Wagner Felix , Kurth Thomas , Sykes Alex M. , Del Toro Runzer Claudia , Ebner Lynn J. A. , Kavak Cagri , Alexaki Vasileia Ismini , Cimalla Peter , Mehner Mirko , Koch Edmund , Karl Mike O.
Published: May 2023

Neurodegenerative diseases remain incompletely understood and therapies are needed. Stem cell-derived organoid models facilitate fundamental and translational medicine research. However, to which extent differential neuronal and glial pathologic processes can be reproduced in current systems is still unclear. Here, we tested 16 different chemical, physical, and cell functional manipulations in mouse retina organoids to further explore this. Some of the treatments induce differential phenotypes, indicating that organoids are competent to reproduce distinct pathologic processes. Notably, mouse retina organoids even reproduce a complex pathology phenotype with combined photoreceptor neurodegeneration and glial pathologies upon combined (not single) application of HBEGF and TNF, two factors previously associated with neurodegenerative diseases. Pharmacological inhibitors for MAPK signaling completely prevent photoreceptor and glial pathologies, while inhibitors for Rho/ROCK, NFkB, and CDK4 differentially affect them. In conclusion, mouse retina organoids facilitate reproduction of distinct and complex pathologies, mechanistic access, insights for further organoid optimization, and modeling of differential phenotypes for future applications in fundamental and translational medicine research.
Cortical superficial siderosis, hematoma volume, and outcomes after intracerebral hemorrhage: a mediation analysis
Authors: Jin Yu-jia , Li Jia-wen , Wu Jian , Huang Yu-hui , Yang Kai-cheng , An Hong-na , Yuan Chang-zheng , Gao Feng , Tong Lu-sha
Published: May 2023

Background

Previous studies have shown that cortical superficial siderosis (cSS) can increase hematoma volume and predict poor outcomes following primary intracerebral hemorrhage (ICH).

Objective

We aimed to determine whether a large hematoma volume was the essential factor contributing to worse outcomes of cSS.

Methods

Patients with spontaneous ICH underwent a CT scan within 48 h after ictus. Evaluation of cSS was performed using magnetic resonance imaging (MRI) within 7 days. The 90-day outcome was assessed using the modified Rankin Scale (mRS). In addition, we investigated the correlation between cSS, hematoma volume, and 90-day outcomes using multivariate regression and mediation analyses.

Results

Among the 673 patients with ICH [mean (SD) age, 61 (13) years; 237 female subjects (35.2%); median (IQR) hematoma volume, 9.0 (3.0–17.6) ml], 131 (19.5%) had cSS. There was an association between cSS and larger hematoma volume (β = 4.449, 95% CI 1.890–7.009, p < 0.001) independent of hematoma location and was also related to worse 90-day mRS (β = 0.333, 95% CI 0.008–0.659, p = 0.045) in multivariable regression. In addition, mediation analyses revealed that hematoma volume was an essential factor mediating the effect of cSS on unfavorable 90-day outcomes (proportion mediated:66.04%, p = 0.01).

Conclusion

Large hematoma volume was the major charge of directing cSS to worse outcomes in patients with mild to moderate ICH, and cSS was related to a larger hematoma in both lobar and non-lobar areas.

Clinical trial registration

https://clinicaltrials.gov/ct2/show/NCT04803292, identifier: NCT04803292.
Multi-tensor diffusion abnormalities of gray matter in an animal model of cortical dysplasia
Authors: Villaseñor Paulina J. , Cortés-Servín David , Pérez-Moriel Aylín , Aquiles Ana , Luna-Munguía Hiram , Ramirez-Manzanares Alonso , Coronado-Leija Ricardo , Larriva-Sahd Jorge , Concha Luis
Published: May 2023

Focal cortical dysplasias are a type of malformations of cortical development that are a common cause of drug-resistant focal epilepsy. Surgical treatment is a viable option for some of these patients, with their outcome being highly related to complete surgical resection of lesions visible in magnetic resonance imaging (MRI). However, subtle lesions often go undetected on conventional imaging. Several methods to analyze MRI have been proposed, with the common goal of rendering subtle cortical lesions visible. However, most image-processing methods are targeted to detect the macroscopic characteristics of cortical dysplasias, which do not always correspond to the microstructural disarrangement of these cortical malformations. Quantitative analysis of diffusion-weighted MRI (dMRI) enables the inference of tissue characteristics, and novel methods provide valuable microstructural features of complex tissue, including gray matter. We investigated the ability of advanced dMRI descriptors to detect diffusion abnormalities in an animal model of cortical dysplasia. For this purpose, we induced cortical dysplasia in 18 animals that were scanned at 30 postnatal days (along with 19 control animals). We obtained multi-shell dMRI, to which we fitted single and multi-tensor representations. Quantitative dMRI parameters derived from these methods were queried using a curvilinear coordinate system to sample the cortical mantle, providing inter-subject anatomical correspondence. We found region- and layer-specific diffusion abnormalities in experimental animals. Moreover, we were able to distinguish diffusion abnormalities related to altered intra-cortical tangential fibers from those associated with radial cortical fibers. Histological examinations revealed myelo-architectural abnormalities that explain the alterations observed through dMRI. The methods for dMRI acquisition and analysis used here are available in clinical settings and our work shows their clinical relevance to detect subtle cortical dysplasias through analysis of their microstructural properties.
EMAGINE–Study protocol of a randomized controlled trial for determining the efficacy of a frequency tuned electromagnetic field treatment in facilitating recovery within the subacute phase following ischemic stroke
Authors: Saver Jeffrey L. , Duncan Pamela W. , Stein Joel , Cramer Steven C. , Eng Janice J. , Lifshitz Assaf , Hochberg Arielle , Bornstein Natan M.
Published: May 2023

Stroke is a leading cause of disability with limited effective interventions that improve recovery in the subacute phase. This protocol aims to evaluate the safety and efficacy of a non-invasive, extremely low-frequency, low-intensity, frequency-tuned electromagnetic field treatment [Electromagnetic Network Targeting Field (ENTF) therapy] in reducing disability and promoting recovery in people with subacute ischemic stroke (IS) with moderate-severe disability and upper extremity (UE) motor impairment. Following a sample-size adaptive design with a single interim analysis, at least 150 and up to 344 participants will be recruited to detect a 0.5-point (with a minimum of 0.33 points) difference on the modified Rankin Scale (mRS) between groups with 80% power at a 5% significance level. This ElectroMAGnetic field Ischemic stroke–Novel subacutE treatment (EMAGINE) trial is a multicenter, double-blind, randomized, sham-controlled, parallel two-arm study to be conducted at approximately 20 United States sites, and enroll participants with subacute IS and moderate-severe disability with UE motor impairment. Participants will be assigned to active (ENTF) or sham treatment, initiated 4–21 days after stroke onset. The intervention, applied to the central nervous system, is designed for suitability in multiple clinical settings and at home. Primary endpoint is change in mRS score from baseline to 90 days post-stroke. Secondary endpoints: change from baseline to 90 days post-stroke on the Fugl-Meyer Assessment - UE (lead secondary endpoint), Box and Block Test, 10-Meter Walk, and others, to be analyzed in a hierarchical manner. EMAGINE will evaluate whether ENTF therapy is safe and effective at reducing disability following subacute IS.

Trial registration

www.ClinicalTrials.gov, NCT05044507 (14 September 2021).
Case report: binaural beats music assessment experiment
Authors: Krasnoff Elizabeth , Chevalier Gaétan
Published: May 2023

We recruited subjects with the focus on people who were stressed and needed a break to experience relaxation. The study used inaudible binaural beats (BB) to measure the ability of BB to induce a relaxed state. We found through measuring brain wave activity that in fact BB seem to objectively induce a state of relaxation. We were able to see this across several scores, F3/F4 Alpha Assessment and CZ Theta Beta, calculated from EEG readings, that indicated an increase in positive outlook and a relaxing brain, respectively, and scalp topography maps. Most subjects also showed an improvement in Menlascan measurements of microcirculation or cardiovascular score, although the Menlascan scores and Big Five character assessment results were less conclusive. BB seem to have profound effects on the physiology of subjects and since the beats were not audible, these effects could not be attributed to the placebo effect. These results are encouraging in terms of developing musical products incorporating BB to affect human neural rhythms and corollary states of consciousness and warrant further research with more subjects and different frequencies of BB and different music tracks.
Metformin inhibits spontaneous excitatory postsynaptic currents in spinal dorsal cord neurons from paclitaxel-treated rats
Authors: Liu Ting-Ting , Qiu Chun-Yu , Hu Wang-Ping
Published: May 2023

Introduction

Cancer patients treated with paclitaxel often develop chemotherapy-induced peripheral neuropathy, which has not been effectively treated with drugs. The anti-diabetic drug metformin is effective in the treatment of neuropathic pain. The aim of this study was to elucidate effect of metformin on paclitaxel-induced neuropathic pain and spinal synaptic transmission.

Methods

Electrophysiological experiments on rat spinal slices were performed in vitro and mechanical allodynia quantified in vitro.

Results

The present data demonstrated that intraperitoneal injection of paclitaxel produced mechanical allodynia and potentiated spinal synaptic transmission. Intrathecal injection of metformin significantly reversed the established mechanical allodynia induced by paclitaxel in rats. Either spinal or systemic administration of metformin significantly inhibited the increased frequency of spontaneous excitatory postsynaptic currents (sEPSCs) in spinal dorsal horn neurons from paclitaxel-treated rats. We found that 1 h incubation of metformin also reduced the frequency rather than the amplitude of sEPSCs in the spinal slices from paclitaxel-treated rats.

Discussion

These results suggested that metformin was able to depress the potentiated spinal synaptic transmission, which may contribute to alleviating the paclitaxel-induced neuropathic pain.
A disynaptic basal ganglia connection to the inferior olive: potential for basal ganglia influence on cerebellar learning
Authors: Ruigrok Tom J. H. , Wang Xiaolu , Sabel-Goedknegt Erika , Coulon Patrice , Gao Zhenyu
Published: May 2023

Recent studies have shown that the cerebellum and the basal ganglia are interconnected at subcortical levels. However, a subcortical basal ganglia connection to the inferior olive (IO), being the source of the olivocerebellar climbing fiber system, is not known. We have used classical tracing with CTb, retrograde transneuronal infection with wildtype rabies virus, conditional tracing with genetically modified rabies virus, and examination of material made available by the Allen Brain Institute, to study potential basal ganglia connections to the inferior olive in rats and mice. We show in both species that parvalbumin-positive, and therefore GABAergic, neurons in the entopeduncular nucleus, representing the rodent equivalent of the internal part of the globus pallidus, innervate a group of cells that surrounds the fasciculus retroflexus and that are collectively known as the area parafascicularis prerubralis. As these neurons supply a direct excitatory input to large parts of the inferior olivary complex, we propose that the entopeduncular nucleus, as a main output station of the basal ganglia, provides an inhibitory influence on olivary excitability. As such, this connection may influence olivary involvement in cerebellar learning and/or could be involved in transmission of reward properties that have recently been established for olivocerebellar signaling.
Neutrophil-to-high-density-lipoprotein-cholesterol ratio and mortality among patients with hepatocellular carcinoma
Authors: Shi Ke , Hou Jie , Zhang Qun , Bi Yufei , Zeng Xuanwei , Wang Xianbo
Published: May 2023

Background

Inflammatory responses and lipid metabolism disorders contribute to the development and prognosis of hepatocellular carcinoma (HCC). This study aimed to investigate the prognostic value of lipid-related inflammatory parameters in patients with HCC.

Methods

From January 2010 to June 2017, we enrolled 1,639 patients with HCC at Beijing Ditan Hospital. Multivariate Cox regression analysis and area under the receiver operating characteristic (AUC) analysis were used to evaluate and compare the predictability and reliability of high-density lipoprotein cholesterol (HDL-C), neutrophil-to-HDL-C ratio (NHR), monocyte-to-HDL-C ratio (MHR), and lymphocyte-to-HDL-C ratio (LHR) values. A restricted cubic spline was used to explore the association between the NHR and 3-year mortality in patients with HCC. Differences in survival rates were estimated using the Kaplan–Meier method and compared using the log-rank test. The results were validated in an internal cohort between July 2017 and October 2019 (n = 373).

Results

After adjusting for confounding variables, NHR was independently associated with 3-year mortality, both as a continuous and categorical variable (both p < 0.05). The correlation between the mortality and the MHR and LHR was not statistically significant. The NHR showed a suitable prognostic value (AUC at 3 years: 0.740), similar to that of the Model for End-stage Liver Disease (MELD) (AUC at 3 years: 0.761). In the validation cohort, the AUC of the NHR was 0.734 at 3 years. The optimal cut-off values of NHR and MELD were 3.5 and 9, respectively. The 3-year survival rates in the low- (NHR < 3.5 and MELD <9) and high-risk (NHR ≥ 3.5 and MELD ≥9) groups were 81.8 and 19.4%, respectively, in the training cohort, and 84.6 and 27.5%, respectively, in the validation cohort.

Conclusion

Baseline NHR is a promising prognostic parameter for mortality in patients with HCC and patients with NHR ≥ 3.5 and MELD ≥9 have a high mortality rate.
Exploring the potential of cold plasma treatment followed by zinc-priming for biofortification of buckwheat sprouts
Authors: Starič Pia , Remic Lucija , Vogel-Mikuš Katarina , Junkar Ita , Vavpetič Primož , Kelemen Mitja , Pongrac Paula
Published: May 2023

Increasing the concentration of an element in edible produce (i.e., biofortification) can mitigate the element deficiency in humans. Sprouts are small but popular part of healthy diets providing vitamins and essential elements throughout the year. Element composition of sprouts can easily be amended, e.g., by soaking the grains in element-rich solution before germination (grain-priming). In addition, pre-treatment of grains to improve element translocation from the solution into the grain may further enhance the element concentration in the sprout. Cold plasma technique could provide such solution, as it increases wettability and water uptake of grains. Grains of common buckwheat (Fogopyrum esculentum Moench) were pre-treated/ untreated with cold plasma and soaked in ZnCl2 solution/pure water. Germination tests, α-amylase activity, grain hydrophilic properties and water uptake were assessed. Element composition of grain tissues and of sprouts was assessed by micro-particle-induced-X-ray emission and X-ray fluorescence spectroscopy, respectively. Grain-priming increased Zn concentration in shoots of common buckwheat sprouts more than five-times, namely from 79 to 423 mg Zn kg−1 dry weight. Cold plasma treatment increased grain wettability and water uptake into the grain. However, cold plasma pre-treatment followed by grain-priming with ZnCl2 did not increase Zn concentration in different grain tissues or in the sprouts more than the priming alone, but rather decreased the Zn concentration in sprout shoots (average ± standard error: 216 ± 6.13 and 174 ± 7.57 mg Zn kg−1 dry weight, respectively). When the fresh weight portion of whole sprouts (i.e., of roots and shoots) was considered, comparable average requirements of Zn, namely 24.5 % and 35 % for adult men and women would be satisfied by consuming cold plasma pre-treated and not pre-treated grains. Potential advantages of cold plasma pre-treatment need to be tested further, mainly to optimize the duration of soaking required to produce Zn-enriched sprouts.
Dynapenic abdominal obesity and susceptibility to fall: a prospective analysis of the Osteoarthritis Initiative
Authors: Veronese Nicola , Koyanagi Ai , Soysal Pinar , Bolzetta Francesco , Dominguez Ligia J. , Barbagallo Mario , Sabico Shaun , Al-Daghri Nasser M. , Smith Lee
Published: May 2023

Background

The prediction of the risk of falling remains a challenge in geriatric medicine and the identification of new potential reversible risk factors is a public health priority. In this study, we aim to investigate the association between DAO (dynapenic abdominal obesity) and incident falls in a large sample of people with knee OA (osteoarthritis) or at high risk for this condition, over 8 years of follow-up.

Methods

DAO was defined using a waist circumference more than 102 cm in men and 88 cm in women and a concomitant presence of dynapenia, defined as a time over 15 s in the five times chair stands time. Falls, during follow-up, were recorded using self-reported information in the previous year. A logistic binary regression analysis was run, adjusted for potential confounders at the baseline, reporting the data as odds ratios (ORs) with their 95% confidence intervals (CIs).

Results

Overall, 3,844 subjects were included, majority of whom had abdominal obesity. Across the 8 years of follow-up, 2,695 participants fell vs. 1,149 not reporting any fall. Taking those without DAO as reference, the presence of only dynapenia was not associated with risk of falls (OR = 1.18;95%CI: 0.73–1.91; p = 0.50), whilst the presence of abdominal obesity (OR = 1.30; 95%CI: 1.09–1.56; p = 0.004) and DAO (OR = 1.31; 95%CI:1.01–1.73; p = 0.04) were significantly associated with a higher risk of incident falls.

Conclusion

DAO significantly increased risk of falls as well as the presence of abdominal obesity.
Proton therapy for pediatric diencephalic tumors
Authors: Grippin Adam J. , McGovern Susan L.
Published: May 2023

Diencephalic tumors tend to be low grade tumors located near several critical structures, including the optic nerves, optic chiasm, pituitary, hypothalamus, Circle of Willis, and hippocampi. In children, damage to these structures can impact physical and cognitive development over time. Thus, the goal of radiotherapy is to maximize long term survival while minimizing late effects, including endocrine disruption leading to precocious puberty, height loss, hypogonadotropic hypogonadism, and primary amenorrhea; visual disruption including blindness; and vascular damage resulting in cerebral vasculopathy. Compared to photon therapy, proton therapy offers the potential to decrease unnecessary dose to these critical structures while maintaining adequate dose to the tumor. In this article, we review the acute and chronic toxicities associated with radiation for pediatric diencephalic tumors, focusing on the use of proton therapy to minimize treatment-related morbidity. Emerging strategies to further reduce radiation dose to critical structures will also be considered.
Incidence, mortality and survival trends of penile cancer in Lithuania 1998–2017
Authors: Drevinskaite Mingaile , Patasius Ausvydas , Kincius Marius , Jonušas Justinas , Ladukas Adomas , Jievaltas Mindaugas , Kairevice Laura , Smailyte Giedre
Published: May 2023

Background and objectives

The aim of this study was to analyse trends in penile cancer incidence, mortality, and relative survival in Lithuania during the period of 1998–2017.

Materials and methods

The study was based on all cases of penile cancer reported to the Lithuanian Cancer Registry between 1998 and 2017. Age-specific rates standardized rates were calculated, using the direct method (World standard population). The Joinpoint regression model was used to provide estimated average annual percentage change (AAPC). One-year and five-year relative survival estimates were calculated using period analysis. Relative survival was calculated as the ratio of the observed survival of cancer patients and the expected survival of the underlying general population.

Results

During the study period, the age-standardized incidence rate of penile cancer varied between 0.72 and 1.64 per 100 000, with AAPC 0.9% (95% CI -0.8–2.7). The mortality rate of penile cancer in Lithuania during this period varied from 0.18 to 0.69 per 100 000, with AAPC of -2.6% (95% CI -5.3–0.3). Relative one-year survival of patients, diagnosed with penile cancer improved over the time from 75.84% in period 1998–2001 to 89.33% in period 2014–2017. Relative five-year survival rate of patients, diagnosed with penile cancer changed from 55.44% in period 1998-2001 to 72.90% in period 2014–2017.

Conclusions

The incidence rates of penile cancer showed an increasing trend, while mortality rates were decreasing in Lithuania during 1998-2017. One-year and five-year relative survival increased, however, it does not reach the highest scores of Northern European countries.
Identification and validation of a novel signature based on cell-cell communication in head and neck squamous cell carcinoma by integrated analysis of single-cell transcriptome and bulk RNA-sequencing
Authors: Wang Jian , Sun Hong-Cun , Cao Cheng , Hu Jian-Dao , Qian Jing , Jiang Tao , Jiang Wen-Bo , Zhou Shao , Qiu Xiao-Wen , Wang Hong-Li
Published: May 2023

Background

The heterogeneous crosstalk between tumor cells and other cells in their microenvironment means a notable difference in clinical outcomes of head and neck squamous cell carcinoma (HNSCC). CD8+ T cells and macrophages are effector factors of the immune system, which have direct killing and phagocytosis effects on tumor cells. How the evolution of their role in the tumor microenvironment influences patients clinically remains a mystery. This study aims to investigate the complex communication networks in the HNSCC tumor immune microenvironment, elucidate the interactions between immune cells and tumors, and establish prognostic risk model.

Methods

20 HNSCC samples single-cell rna sequencing (scRNA-seq) data and bulk rna-seq data were derived from public databases. The “cellchat” R package was used to identify cell-to-cell communication networks and prognostic related genes, and then cell-cell communication (ccc) molecular subtypes were constructed by unsupervised clustering. Kaplan-Meier(K-M) survival analysis, clinical characteristics analysis, immune microenvironment analysis, immune cell infiltration analysis and CD8+T cell differentiation correlation analysis were performed. Finally, the ccc gene signature including APP, ALCAM, IL6, IL10 and CD6 was constructed based on univariate Cox analysis and multivariate Cox regression. Kaplan-Meier analysis and time-dependent receiver operating characteristic (ROC) analysis were used to evaluate the model in the train group and the validation group, respectively.

Results

With CD8+T cells from naive to exhaustion state, significantly decreased expression of protective factor (CD6 gene) is associated with poorer prognosis in patients with HNSCC. The role of macrophages in the tumor microenvironment has been identified as tumor-associated macrophage (TAM), which can promote tumor proliferation and help tumor cells provide more nutrients and channels to facilitate tumor cell invasion and metastasis. In addition, based on the strength of all ccc in the tumor microenvironment, we identified five prognostic ccc gene signatures (cccgs), which were identified as independent prognostic factors by univariate and multivariate analysis. The predictive power of cccgs was well demonstrated in different clinical groups in train and test cohorts.

Conclusion

Our study highlights the propensity for crosstalk between tumors and other cells and developed a novel signature on the basis of a strong association gene for cell communication that has a powerful ability to predict prognosis and immunotherapy response in patients with HNSCC. This may provide some guidance for developing diagnostic biomarkers for risk stratification and therapeutic targets for new therapeutic strategies.
Novel infusion strategy reduces severe adverse events caused by the anti-GD2 monoclonal antibody naxitamab
Authors: Varo Amalia , Castañeda Alicia , Chamorro Saray , Muñoz Juan Pablo , Gorostegui Maite , Celma Mónica S. , Lopez Sandra , Simao Margarida , Perez-Jaume Sara , Mora Jaume
Published: May 2023

Introduction

Anti-disialoganglioside 2 (anti-GD2) monoclonal antibodies (mAbs) are associated with Grade ≥3 (≥G3) adverse events (AEs) such as severe pain, hypotension, and bronchospasm. We developed a novel method of administering the GD2-binding mAb naxitamab, termed “Step-Up” infusion (STU), to reduce the risk of AEs of severe pain, hypotension, and bronchospasm.

Methods

Forty-two patients with GD2-positive tumors received naxitamab under “compassionate use” protocols and administered via either the standard infusion regimen (SIR) or the STU regimen. The SIR comprises a 60-min infusion of 3 mg/kg/day on Day 1 of cycle 1 and a 30- to 60-min infusion on Day 3 and Day 5, as tolerated. The STU regimen uses a 2-h infusion on Day 1, initiated at a rate of 0.06 mg/kg/h during 15 min (0.015 mg/kg) and which increases gradually to a cumulative dose of 3 mg/kg; on Days 3 and 5, the 3-mg/kg dose is initiated at 0.24 mg/kg/h (0.06 mg/kg) and delivered in 90 min according to the same gradual-increase strategy. AEs were graded according to Common Terminology Criteria for Adverse Events version 4.0.

Results

The frequency of infusions with an associated G3 AE was reduced from 8.1% (23/284 infusions) with SIR to 2.5% (5/202 infusions) with STU. The odds of an infusion being associated with a G3 AE reduced by 70.3% with STU vs. SIR (odds ratio: 0.297; p = 0.037). Mean serum naxitamab levels pre- and post-STU (11.46 µg/ml pre-infusion; 100.95 µg/ml post-infusion) were within the range reported for SIR.

Discussion

The comparable pharmacokinetics of naxitamab during SIR and STU may indicate that switching to STU reduces G3 AEs without impact on efficacy.
Current research trends, hotspots, and frontiers of medical nutrition therapy on cancer: a bibliometric analysis
Authors: Xia Hongfang , Wang Liang , Wang Haihua
Published: May 2023

Background

There is a high prevalence of malnutrition in cancer patients, which seriously affects the anti-cancer therapy effect and outcomes, causing a huge disease burden worldwide. Appropriate nutritional support is important for cancer prevention and control. The aim of this study was to explore the development trends, hotspots, and frontiers of Medical Nutrition Therapy (MNT) on Cancer from a bibliometric perspective, and provide new insights for future research and clinic practices.

Methods

The global literature of MNT on Cancer published between 1975 and 2022 were searched in the Web of Science Core Collection Database (WOSCC). After refining the data, descriptive analysis and data visualization were performed with bibliometric tools (CiteSpace, VOSviewer, and R package “bibliometrix”).

Results

A total of 10,339 documents with a timespan from 1982 to 2022 were included in this study. The number of documents had increased continuously over the past 40 years, especially with a steep rise from 2016 to 2022. The majority of scientific production outputs were from the United States, which had the most core research institutions and authors. The published documents could be clustered into three themes respectively labeled by terms “double-blind”, “cancer” and “quality-of-life”. “gastric cancer”, “outcome”, “inflammation”, “sarcopenia” and “exercise” were the most prominent keywords in recent years. “breast-cancer”, “colorectal-cancer”, “expression”, “risk”, “in-vitro”, “quality-of-life”, “cancer” and “life” might represent the newly emerged topics.

Conclusions

There were a good research foundation and reasonable disciplinary structure in the field of medical nutrition therapy for cancer at present. The core research team was mainly located in the United States, England, and other developed countries. According to the current trends in publications, more articles shall be published in the future. Nutritional metabolism, malnutrition risk, and the impact of nutritional therapy on prognosis might be research hotspots. In particular, it was important to focus on specific cancer, such as breast cancer, colorectal cancer, and gastric cancer, which might be the frontiers.
Addition of gadolinium contrast to three-dimensional SSFP MR sequences improves the visibility of coronary artery anatomy in young children
Authors: Shen Quanli , Lin Chengxiang , Yao Qiong , Wang Junbo , Zhou Jian , He Lan , Chen Gang , Hu Xihong
Published: May 2023

Objective

This study aims to compare the value of a gadolinium contrast-enhanced 1.5-T three-dimensional (3D) steady-state free precession (SSFP) sequence with that of a noncontrast 3D SSFP sequence for magnetic resonance coronary angiography in a pediatric population.

Materials and methods

Seventy-nine patients from 1 month to 18 years old participated in this study. A 3D SSFP coronary MRA at 1.5-T was applied before and after gadolinium-diethylenetriaminepentaaceticacid (DTPA) injection. The detection rates of coronary arteries and side branches were assessed by McNemar's χ2 test. The image quality, vessel length, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) of the coronary arteries were analyzed by the Wilcoxon signed-rank test. The intra- and interobserver agreements were evaluated with a weighted kappa test or an intraclass correlation efficient test.

Results

A contrast-enhanced scan detected more coronary arteries than a noncontrast-enhanced scan in patients under 2 years old (P < 0.05). The SSFP sequence with contrast media detected more coronary artery side branches in patients younger than 5 years (P < 0.05). The image quality of all the coronary arteries was better after the injection of gadolinium-DTPA in children younger than 2 years (P < 0.05) but not significantly improved in children older than 2 years (P > 0.05). The contrast-enhanced 3D SSFP protocol detected longer lengths for the left anterior descending coronary artery in children younger than 2 years and the left circumflex coronary artery (LCX) in children younger than 5 years (P < 0.05). SNR and CNR of all the coronary arteries in children younger than 5 years and the LCX and right coronary artery in children older than 5 years enhanced after the injection of gadolinium-DTPA (P < 0.05). The intra- and interobserver agreements were high (0.803–0.998) for image quality, length, SNR, and CNR of the coronary arteries in both pre- and postcontrast groups.

Conclusion

The use of gadolinium contrast in combination with the 3D SSFP sequence is necessary for coronary imaging in children under 2 years of age and may be helpful in children between 2 and 5 years. Coronary artery visualization is not significantly improved in children older than 5 years.
Application of vertical transposition flap in closure for large facial soft tissue defects in children
Authors: Feng Rui , Chen Jigang , Wang Yining
Published: May 2023

Background

While transposition flap is widely used for the repairs of facial defects, few studies has reported its application among children with large defects. In this study, we aimed to investigate the surgical techniques and principles in different locations on face of vertical transposition flap in children.

Methods

We retrospectively reviewed our hospital database and identified children who were treated with vertical transposition flap for large facial defects between January 2014 and December 2021. Information was collected including patients' demographics, location and dimension of the lesion, surgical procedure, additional surgeries, complications, and outcomes.

Results

A total of 122 patients (77 boys, 63.1%) were included in this study. The average age for participants was 3.3 years (3 months to 9 years). One hundred and four (85.3%) patients had melanin nevus and 18 (14.8%) had sebaceous nevus. The average size of defects was 5.8 cm2 (ranging from 0.8–16.5 cm2). Ten patients (8.2%) suffered from dermal layer or full-thickness necrosis in the distal part of their flaps, They all recovered after conservative treatment and there were noticeable scars at discharge. Five patients (4.1%) had slight traction of the mouth and eyelid, all recovered about 2 week after surgery. An acceptable cosmetic outcome was achieved for all the patients at last time follow-up.

Conclusions

Repairing large facial defects with vertical transposition flap is effective in Children, especially on forehead, cheek and mandible. However, this technique is far from perfect. Careful selection of appropriate patients and flap design might be needed.
The efficacy and mechanism of vonoprazan-containing triple therapy in the eradication of Helicobacter pylori
Authors: Zhang Zinan , Liu Fen , Ai Feiyan , Chen Xiong , Liu Rui , Zhang Chao , Fang Ning , Fu Tian , Wang Xiaoyan , Tang Anliu
Published: May 2023

Purpose: Vonoprazan (VPZ) produces a strong acid-inhibitory effect, which can potentially eradicate Helicobacter Pylori (H. pylori). We aimed to assess whether a 14-day VPZ-containing triple therapy was safe and effective in the Chinese population and the potential mechanism.

Methods: Enrolled patients confirmed to be infected with H. pylori were randomly divided into four groups: VPZ + doxycycline + furazolidone, VPZ + doxycycline + amoxicillin, esomeprazole (EPZ) + bismuth + doxycycline + furazolidone, and EPZ + colloidal bismuth + doxycycline + amoxicillin for 14 days. The eradication rate, medication adherence, and incidence of adverse events (AEs) were evaluated. Inhibition of H. pylori by VPZ and EPZ in vitro was assessed. H. pylori treated with appropriate concentrations of VPZ and EPZ were sequenced by transcriptome analysis to explore the antibacterial mechanism.

Results: A higher eradication rate were observed in VPZ-containing triple therapy. No obvious differences were observed in medication adherence or the incidence of AEs. VPZ had no direct inhibitory effect on H. pylori, whereas EPZ directly inhibited H. pylori may through downregulated genes related to the ribosome.

Conclusion: In the Chinese population, 14-day VPZ-containing triple therapy was safe and more effective and can be used clinically as first-line H. pylori treatment.

Clinical Trial Registration:ClinicalTrials.gov, identifier NCT05097846
Function and prognostic value of basement membrane -related genes in lung adenocarcinoma
Authors: Zhang Yurong , Li Tingting , Liu Huanqing , Wang Li
Published: May 2023

Background: Lung adenocarcinoma (LUAD) has become a common cause of cancer-related death. Many studies have shown that the basement membrane (BM) is associated with the development of cancer. However, BM-related gene expression and its relationship to LUAD prognosis remains unclear.

Methods: BM-related genes from previous studies were used. Clinical and mRNA expression information were obtained from TCGA database. Cox, minimum absolute contraction, and selection operator regression were applied to analyze the selected genes affecting LUAD prognosis. A prognostic-risk model was then established. Furthermore, this study applied Kaplan-Meier analysis to assess the outcomes of high- and low-risk groups, then explored their differences in drug sensitivity. The DSigDB database was used to screen for therapeutic small-molecule drugs.

Results: Fourteen prognostic models based on BM-related genes were successfully constructed and validated in patients with LUAD. We also found that independence was a prognostic factor in all 14 BM-based models. Functional analysis showed that the enrichment of BM-related genes mainly originated from signaling pathways related to cancer. The BM-based model also suggested that immune cell infiltration is associated with checkpoints. The low-risk patients may benefit from cyclopamine and docetaxel treatments.

Conclusion: This study identified a reliable biomarker to predict survival in patients with LUAD and offered new insights into the function of BM-related genes in LUAD.
Research on underwater wireless dynamic optical communication system based on PPM modulation
Authors: Dong Bing , Tong Shoufeng , Zhang Peng , Wang Jiaxing
Published: May 2023

In order to achieve underwater wireless dynamic optical communication, a laser communication system is proposed based on Pulse Position Modulation (PPM). In order to achieve underwater laser communication accurately, the mathematical model of underwater laser communication was constructed with small angle analysis. The pulse position modulation demodulation algorithm is designed, and the workflow of modulation and demodulation is given in the transmit module and the receive module. In the experiment, Lumileds-470 nm light source was selected for data communication for testing at a communication rate of 15 Mbp/s. In the servo control process, the square wave signal used for stepping motor drive had a stable amplitude output and a stable time width. It can well simulate the testing process of underwater dynamic scanning. In the experiment, laser light spots were obtained under different attenuation states, and the characteristics of the light spot distribution were analyzed. The numerical reconstruction of the light spot energy was completed in MATLAB. Three types of light attenuators, 1.0%, 0.1%, and 0.01%, were used to simulate different light attenuations underwater. The test results show that the system error rate is better than 10−6 when attenuation chip is 1.0%. When attenuation chip is 0.1%, the error rate of the system is reduced to 10−4. When attenuation chip is 0.01%, a valid signal cannot be obtained by the system. The feasibility of the system is verified.