bluuebunny/crossref_metadata_2025 huggingface dataset:
Acoustic deterrence to facilitate the conservation of pantropical spotted dolphins (Stenella attenuata) in the Western Pacific Ocean
Authors: Fu Weijie , Song Zhongchang , Wang Teng , Gao Zhanyuan , Li Jie , Zhang Peng , Zhang Yu
Published: October 2022

Commercial fishing constitutes an important food source but induces undesirable bycatch on animals worldwide. This study extends bycatch research geographically to the Western Pacific Ocean, filling a knowledge gap regarding bycatch and mitigation measures in the region. Bycatch has caused many lethal consequences to the pantropical spotted dolphins (Stenella attenuata) during their interaction with fisheries in the research area. We provided a self-developed acoustic deterrent system and conducted field experiments, suggesting its effectiveness as a potential useful conservation tool to reduce bycatch. Dolphins departed the area and the number of dolphins in sight declined to zero after the deployment of the system. Additional evidence was reflected in acoustic recordings, showing the number of clicks emitted by dolphins decreased from 1,502 to 136 per minute after the ADS was activated. Meanwhile, click amplitude was reduced by 84%, indicating an increase in the distance between dolphins and the system. These combined results indicate that the system was effective in driving dolphins away to facilitate the conservation of the species by protecting them from potential bycatch.
Establishment of methods for rapid detection of Prymnesium parvum by recombinase polymerase amplification combined with a lateral flow dipstick
Authors: Luo Ningjian , Huang Hailong , Jiang Haibo
Published: October 2022

Prymnesium parvum is a toxic algal bloom (HAB)-forming species. The toxicity of this alga is a result of a collection of compounds known as prymnesins. Prymnesins exert harmful effects upon fish, shellfish, and mollusks, causing huge economic losses. In the present study, a new method was developed for the detection of P. parvum. The novel method utilizes isothermal amplification, known as recombinase polymerase amplification (RPA), in combination with lateral-flow dipstick (LFD). Herein, a set of primers and probes were designed for internal transcribed spacer (ITS) sequences, and a specific and sensitive RPA-LFD rapid detection method was established for P. parvum. Meanwhile, we verified its feasibility for the detection of environmental samples. It was demonstrated that the optimal amplification temperature and time for RPA were 39°C and 15 min. RPA/RPA-LFD was experimentally verified to be specific, demonstrating no cross-reaction with distinct control microalgae, and furthermore, the total time required for the RPA-LFD experiment was 20 min. Meanwhile, the detection limit for the genomic DNA of P. parvum was 1.5×10-1 pg/μL, and the detection limit for plasmids was 2.35 pg/μL. In addition, the results herein revealed that the RPA-LFD assay was 100 times more sensitive than PCR for detection of P. parvum. In conclusion, we developed an RPA-LFD that does not require precision instruments, and can be utilized for rapid on-site detection of P. parvum. In the future, the RPA-LFD can be considered for practical application for environmental detection of the toxic algal species.
A positive association between hunger in childhood and frailty in old age: Findings from the Chinese longitudinal healthy longevity survey
Authors: Gao Tianjing , Han Siyue , Mo Guangju , Sun Qing , Zhang Min , Liu Huaqing
Published: October 2022

Background

Childhood hunger not only directly affects the physical and mental health of children and adolescents but also has a long-term negative effect on later health outcomes. In this cross-sectional study, we used a nationally representative Chinese sample to examine the relationship between hunger in childhood and frailty in older adults.

Materials and methods

The data were obtained from the 2018 Chinese Longitudinal Healthy Longevity Survey. The frailty index with 44 health deficits was used to identify frailty. Childhood hunger was measured by the question “Did you often go to bed hungry as a child?” Insurance status was categorized as New Rural Cooperative Medical Scheme (NRCMS), Urban Basic Medical Insurance Scheme (UBMIS), others, and no insurance. Multivariate logistic regression analysis was performed to estimate the adjusted relationship between childhood hunger and frailty.

Results

A total of 7,342 older people aged 65 years and older were analyzed in this study. Older people who experienced childhood hunger were more likely to have frailty than those who did not (OR = 1.13, 95% CI: 1.02–1.26), after adjustment for sociodemographic characteristics, family/social support, socioeconomic status, insurance status, and health behaviors. The association of childhood hunger with frailty was found in the 65–79 years group (OR = 1.21, 95% CI: 1.03–1.43), women (OR = 1.25, 95% CI: 1.08–1.45), individuals with rural residence (OR = 1.16, 95% CI: 1.03–1.31), agricultural work (OR = 1.16, 95% CI: 1.00–1.34), financial dependence (OR = 1.18, 95% CI: 1.02–1.37), and those participating in NRCMS (OR = 1.35, 95% CI: 1.16–1.56). Participants with hunger in childhood who were 80 years or older (OR = 0.80, 95% CI: 0.65–0.98) had lower odds of frailty. NRCMS (OR = 1.42, 95% CI: 1.02–1.98) showed increased odds of childhood hunger-related frailty.

Conclusion

Exposure to hunger during childhood is linked to frailty among older adults, and age, financial support, and insurance status may mediate this relationship. Targeted interventions and policies to address frailty in older adults should be implemented.
Decrease of FZD4 exon 1 methylation in probands from FZD4-associated FEVR family of phenotypic heterogeneity
Authors: Liu Miaomiao , Luo Jia , Feng Huazhang , Li Jing , Zhang Xiang , Zhao Peiquan , Fei Ping
Published: October 2022

Familial exudative vitreoretinopathy (FEVR) is an important cause of childhood blindness and is clinically characterized by phenotypic heterogeneity. FEVR patients harboring the same genetic mutation vary widely in disease severity. The purpose of this study was to explore non-genetic factors that regulate FEVR phenotypic heterogeneity. We detected methylation levels of 21 CpG sites located at the FZD4 exon 1 region of 11 probands, 12 asymptomatic/paucisymptomatic carriers and 11 non-carriers from 10 unrelated FZD4-associated FEVR families using bisulfite amplicon sequencing (BSAS). Our results showed reduced methylation level of FZD4 exon 1 in probands, suggesting that FZD4 exon 1 methylation level may be negatively linked with FEVR disease severity. It provided a new research direction for follow-up research, helping us better understand the complexity of the FEVR-causing mechanism.
Gilvimarinus xylanilyticus sp. nov., a novel 1,3-xylanase-secreting bacterium isolated from a marine green alga
Authors: Zhang Yan-Jiao , Sun Hai-Ning , Xu Ting-Ting , Zhao Dian-Li , Yu Chun-Mei , Zhang Yi , Zhang Xi-Ying , Chen Xiu-Lan , Zhang Yu-Qiang , Zhao Fang
Published: October 2022

1,3-xylan, an important organic carbon in the ocean, is peculiar to marine algae. 1,3-xylanase-secreting bacteria and their extracellular 1,3-xylanases play pivotal roles in the degradation and biomass conversion of 1,3-xylan. However, only a few 1,3-xylanase-secreting bacteria and 1,3-xylanases have been reported. Here, we identified a novel marine bacterium capable of secreting 1,3-xylanases, designated as strain HB14T. Phylogenetic analysis revealed that strain HB14T clustered tightly with known species of the genus Gilvimarinus, showing the highest 16S rRNA gene sequence similarity (97.7%) with the type strain of Gilvimarinus chinensis. Based on phylogenetic, genomic, chemotaxonomic and phenotypic studies, strain HB14T was classified as a representative of a novel species in the genus Gilvimarinus, for which the name Gilvimarinus xylanilyticus sp. nov. was proposed. The type strain is HB14T (=CCTCC AB 2022109T = KCTC 92379T). Four 1,3-xylanases secreted by strain HB14T were identified based on genome and secretome analyses, and the two (Xyn65 and Xyn80) with relatively higher abundance in secretome were successfully expressed in Escherichia coli and biochemically characterized. They showed the highest activity at pH 6.0–7.0 and 40°C and released mainly 1,3-xylobiose and 1,3-xylotriose from 1,3-xylan. These data suggest that strain HB14T acts as a player in marine 1,3-xylan degradation and recycling and that its extracellular 1,3-xylanases may have a good potential in 1,3-xylooligosaccharides preparation.
Spiroplasma as facultative bacterial symbionts of stinkbugs
Authors: Kakizawa Shigeyuki , Hosokawa Takahiro , Oguchi Kohei , Miyakoshi Kaori , Fukatsu Takema
Published: October 2022

Many insects are associated with facultative symbiotic bacteria, and their infection prevalence provides an important clue to understand the biological impact of such microbial associates. Here we surveyed diverse stinkbugs representing 13 families, 69 genera, 97 species and 468 individuals for Spiroplasma infection. Diagnostic PCR detection revealed that 4 families (30.8%), 7 genera (10.1%), 11 species (11.3%) and 21 individuals (4.5%) were Spiroplasma positive. All the 21 stinkbug samples with Spiroplasma infection were subjected to PCR amplification and sequencing of Spiroplasma’s 16S rRNA gene. Molecular phylogenetic analysis uncovered that the stinkbug-associated Spiroplasma symbionts were placed in three distinct clades in the Spiroplasmataceae, highlighting multiple evolutionary origins of the stinkbug-Spiroplasma associations. The Spiroplasma phylogeny did not reflect the host stinkbug phylogeny, indicating the absence of host-symbiont co-speciation. On the other hand, the Spiroplasma symbionts associated with the same stinkbug family tended to be related to each other, suggesting the possibility of certain levels of host-symbiont specificity and/or ecological symbiont sharing. Amplicon sequencing analysis targeting bacterial 16S rRNA gene, FISH visualization of the symbiotic bacteria, and rearing experiments of the host stinkbugs uncovered that the Spiroplasma symbionts are generally much less abundant in comparison with the primary gut symbiotic bacteria, localized to various tissues and organs at relatively low densities, and vertically transmitted to the offspring. On the basis of these results, we conclude that the Spiroplasma symbionts are, in general, facultative bacterial associates of low infection prevalence that are not essential but rather commensalistic for the host stinkbugs, like the Spiroplasma symbionts of fruit flies and aphids, although their impact on the host phenotypes should be evaluated in future studies.
Study of the effect of bacterial-mediated legume plant growth using bacterial strain Serratia marcescens N1.14 X-45
Authors: Zheng Jiaxin , Liu Chao , Liu Jiayi , Zhuang Jia Yao
Published: October 2022

Soil microorganisms play an indispensable role in plant growth and are widely used to promote plant growth. However, poor microbial strains are homogeneous. The heavy application of chemical fertilizers and pesticides to agricultural soil has adversely affected the soil flora, necessitating the regulation of the soil flora to maintain soil health. In this study, X-45, a highly efficient and phosphorus-dissolving strain of the lysogenic bacterium Serratia marcescens N1.14 was isolated from bare rock slope soil samples from Yueyang Avenue, Hunan Province, China. We observed that microbial strain X-45 could release P from the rocks into solution when the sample rocks were used as the only phosphorus source. Furthermore, we observed that the P content in media increased by 3.08 X compared to the control. After applying X-45 as a bacterial fertilizer, the growth of potted Indigofera pseudotinctoria plants significantly increased, the soil physicochemical properties were significantly improved, and the relative abundance of Bradyrhizobium in the soil increased significantly from 1 to 42%. Besides, Bradyrhizobium became the most dominant genus in the soil. The indirect promotion of another beneficial microorganism by X-45 further revealed the intrinsic mechanism by which X-45 exerted its effect on plant promotion and soil improvement. Using this bacteria, the hypothesis of the superposition effect of legume plant promotion was also confirmed.
Risk factors and predictive models of poor prognosis and delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage complicated with hydrocephalus
Authors: Wang Lintao , Zhang Qingqing , Zhang Gaoqi , Zhang Wanwan , Chen Wenwu , Hou Fandi , Zheng Zhanqiang , Guo Yong , Chen Zhongcan , Wang Yanxia , Hernesniemi Juha , Andrade-Barazarte Hugo , Li Xiaohui , Li Tianxiao , Feng Guang , Gu Jianjun
Published: October 2022

Objective

To evaluate the correlation of serum biological markers and related scales to the occurrence of delayed cerebral ischemia and clinical prognosis in patients with aneurysmal subarachnoid hemorrhage (aSAH) complicated with acute hydrocephalus before admission.

Methods

The clinical data of 227 patients with pre-admission aSAH complicated with acute hydrocephalus admitted to Henan Provincial People's Hospital from April 2017 to December 2020 were retrospectively analyzed. Patients were grouped according to the presence or absence of delayed cerebral ischemia (DCI) after surgery and the prognosis at 6 months after discharge. Univariate and multivariable logistic regression analysis were performed to analyze the relationship between serum biological indicators combined with aneurysm related clinical score scale and the occurrence and prognosis of delayed cerebral ischemia. ROC curves and nomogram were drawn.

Results

Multivariable Logistic regression analysis showed that high Hunt-Hess grade and surgical clipping were independent risk factors for postoperative DCI (P < 0.05). Older age, higher Hunt-Hess grade, higher CRP and neutrophil levels were independent risk factors for poor prognosis at 6 months after surgery (P < 0.05). ROC curve analysis showed that the area under the curve (AUC) of Hunt-Hess grade and surgical method for predicting DCI in patients with aSAH combined with hydrocephalus after surgery were 0.665 and 0.593. The combined AUC of Hunt-Hess grade and surgical method was 0.685, the sensitivity was 64.9%, and the specificity was 64.7%. The AUC of CRP, neutrophil, age and Hunt-Hess grade for predicting poor prognosis in patients with aSAH combined with hydrocephalus at 6 months after surgery were 0.804, 0.735, 0.596, 0.757, respectively. The combined AUC of CRP, neutrophil, age, Hunt-Hess grade was 0.879, the sensitivity was 79%, and the specificity was 84.5%. According to the correction curve, the predicted probability of the nomogram is basically consistent with the actual probability.

Conclusion

Hunt-Hess grade and surgical method are independent predictors of postoperative DCI in patients with aSAH complicated with hydrocephalus. “CRP,” “neutrophil,” “age” and “Hunt-Hess grade” at admission are independent predictors of clinical prognosis in patients with aSAH complicated with hydrocephalus. The combination of the above indicators has high predictive value.
Episodic ataxias in children and adolescents: Clinical findings and suggested diagnostic criteria
Authors: Filippopulos Filipp Maximilian , Schnabel Lutz , Dunker Konstanze , Strobl Ralf , Huppert Doreen
Published: October 2022

Background

The main clinical presentation of episodic ataxias (EAs) consists of vertigo and dizziness attacks lasting for minutes to hours with widely varying accompanying symptoms. The differentiation of EA and episodic vertigo/dizziness syndromes in childhood and adolescence such as vestibular migraine (VM) and recurrent vertigo of childhood (RVC) can be challenging. Furthermore, only few prospective studies of children/adolescents with EA are available.

Objective

This study aims to characterize clinical and instrument-based findings in EA patients under 18 years of age, to delineate the clinical and therapeutic course in EA, and to present potentially new genetic mutations. Furthermore, the study aims to differentiate distinct characteristics between EA, VM, and RVC patients.

Methods

We prospectively collected clinical and instrument-based data of patients younger than 18 years, who presented at the German Center for Vertigo and Balance Disorders (DSGZ) at the LMU University Hospital in Munich with EA, VM, or RVC between January 2016 and December 2021. All patients underwent a comprehensive evaluation of neurological, ocular-motor, vestibular and cochlear function, including video-oculography with caloric testing, video head impulse test, vestibular evoked myogenic potentials, posturography, and gait analysis.

Results

Ten patients with EA, 15 with VM, and 15 with RVC were included. In EA the main symptoms were vertigo/dizziness attacks lasting between 5 min and 12 h. Common accompanying symptoms included walking difficulties, paleness, and speech difficulties. Six EA patients had a previously unknown gene mutation. In the interictal interval all EA patients showed distinct ocular-motor deficits. Significant differences between EA, VM, and RVC were found for accompanying symptoms such as speech disturbances and paleness, and for the trigger factor “physical activity”. Furthermore, in the interictal interval significant group differences were observed for different pathological nystagmus types, a saccadic smooth pursuit, and disturbed fixation suppression.

Conclusion

By combining clinical and ocular-motor characteristics we propose diagnostic criteria that can help to diagnose EA among children/adolescents and identify patients with EA even without distinct genetic findings. Nevertheless, broad genetic testing (e.g., next generation sequencing) in patients fulfilling the diagnostic criteria should be conducted to identify even rare or unknown genetic mutations for EA.
New insight into neurological degeneration: Inflammatory cytokines and blood–brain barrier
Authors: Yang Jie , Ran Mingzi , Li Hongyu , Lin Ye , Ma Kui , Yang Yuguang , Fu Xiaobing , Yang Siming
Published: October 2022

Neurological degeneration after neuroinflammation, such as that resulting from Alzheimer’s disease (AD), stroke, multiple sclerosis (MS), and post-traumatic brain injury (TBI), is typically associated with high mortality and morbidity and with permanent cognitive dysfunction, which places a heavy economic burden on families and society. Diagnosing and curing these diseases in their early stages remains a challenge for clinical investigation and treatment. Recent insight into the onset and progression of these diseases highlights the permeability of the blood–brain barrier (BBB). The primary factor that influences BBB structure and function is inflammation, especially the main cytokines including IL-1β, TNFα, and IL-6, the mechanism on the disruption of which are critical component of the aforementioned diseases. Surprisingly, the main cytokines from systematic inflammation can also induce as much worse as from neurological diseases or injuries do. In this review, we will therefore discuss the physiological structure of BBB, the main cytokines including IL-1β, TNFα, IL-6, and their mechanism on the disruption of BBB and recent research about the main cytokines from systematic inflammation inducing the disruption of BBB and cognitive impairment, and we will eventually discuss the need to prevent the disruption of BBB.
A protein- and fiber-rich diet with astaxanthin alleviates high-fat diet-induced obesity in beagles
Authors: Xue Jinhua , Lu Yuanyuan , Zou Toujun , Shi Wei , Wang Shuang , Cheng Xu , Wan Juan , Chen Yun , Wang Min , Wang Qingzheng , Yang Xia , Ding Mingxing , Qi Zhili , Ding Yi , Hu Manli , Zhang Xin , Li Hongliang , Hu Yufeng
Published: October 2022

Background and aims

Overweight or obesity is one of the most prevalent health burdens in companion pets and predisposes subjects to multiple comorbidities and reduced longevity. Dietary management and sufficient exercise are effective options for weight loss but challenged by modern lifestyle and calorie control-triggered malnutrition. Therefore, this study aimed to develop a formulated obesity control diet characterized by protein- and fiber-rich diet and supplemented with astaxanthin. We systemically evaluated global influences of the designed weight-loss diet on metabolic homeostasis in an obese beagle model.

Materials and methods

Beagles were induced for obesity by a 24-week HFD treatment and then included into weight-loss programs. Briefly, obese beagles were randomly assigned to two groups that were fed with a formulated weight-loss diet or control diet, respectively. Body weight and body condition scoring (BCS) were analyzed biweekly. Computed tomography (CT), nuclear magnetic resonance imaging (MRI) measurements, and blood and adipose tissue biopsies were collected at 0 and 8 weeks. Plasma lipids and adipocyte size were also measured after 8 weeks of weight-loss diet feeding. The global influence of the formulated diet on the whole spectrum of gene panels were examined by adipose RNA assays.

Results

Twenty-four weeks of continuous HFD feeding significantly induced obesity in beagles, as evidenced by increased body weight, BCS, abdominal fat mass, and serum lipid levels. The obese and metabolic condition of the modeled canine were effectively improved by an 8-week weight-loss diet administration. Importantly, we did not observe any side effects during the weight loss duration. Transcriptional analysis of adipose tissues further supported that a weight-loss diet significantly increased energy metabolism-related pathways and decreased lipid synthesis-related pathways.

Conclusion

The prescribed weight-loss diet exhibited profound benefits in canine weight management with well safety and palatability. These findings support effective strategies of nutritional management and supplementation approaches for weight control in companion animals.
Association between systemic inflammation and water composition and survival in colorectal cancer
Authors: Lin Shi-Qi , Xie Hai-Lun , Ge Yi-Zhong , Ruan Guo-Tian , Zhang Qi , Song Meng-Meng , Zhang He-Yang , Zhang Xi , Li Xiang-Rui , Tang Meng , Shen Xian , Song Chun-Hua , Li Wei , Shi Han-Ping
Published: October 2022

Background

Systemic inflammation and water composition are important factors affecting cancer prognosis. This study aimed to explore the association between the neutrophil-to-lymphocyte ratio (NLR) and intracellular water/total body water (ICW/TBW) ratio and overall survival (OS) in colorectal cancer (CRC).

Methods

This multicenter, prospective cohort included 628 patients with CRC between June 2012 and December 2019. The association between the covariates and OS was assessed using a Cox proportional hazards model and restricted cubic spline models. Concordance index (C-index), which integrated discriminant improvement (IDI) index and continuous net reclassification index, (cNRI) was used to compare the predictive ability of the markers.

Results

The optimal cutoff values for the NLR and ICW/TBW ratio were 2.42 and 0.61, respectively. The NLR was negatively associated with OS, while the ICW/TBW ratio was positively correlated with OS. NLR ≥2.42 and ICW/TBW ratio <0.61 were both independent poor prognostic factors (hazard ratio [HR]: 2.04, 95% confidence interval [CI]: 1.44–2.88 and HR: 1.45, 95% CI: 1.04–2.02, respectively). Subsequently, we combined the two factors to construct an inflammation-water score (IWS). Patients with IWS (2, ≥1) had worse OS (HR: 2.86 and 95% CI: 1.77–4.63; HR: 1.74 and 95% CI 1.17–2.57, respectively) than those without one. Compared to its component factors, IWS score showed better predictive ability for C-index, IDI index, and cNRI.

Conclusion

A high NLR and a low ICW/TBW ratio were independent risk factors for poor prognosis in patients with CRC. The combination of the two factors can provide a better prognostic prediction effect.
Prognostic value of PET/CT and MR-based baseline radiomics among patients with non-metastatic nasopharyngeal carcinoma
Authors: Kulanthaivelu Roshini , Kohan Andres , Hinzpeter Ricarda , Liu Zhihui Amy , Hope Andrew , Huang Shao Hui , Waldron John , O’Sullivan Brian , Ortega Claudia , Metser Ur , Veit-Haibach Patrick
Published: October 2022

Purpose

Radiomics is an emerging imaging assessment technique that has shown promise in predicting survival among nasopharyngeal carcinoma (NPC) patients. Studies so far have focused on PET or MR-based radiomics independently. The aim of our study was to evaluate the prognostic value of clinical and radiomic parameters derived from both PET/CT and MR.

Methods

Retrospective evaluation of 124 NPC patients with PET/CT and radiotherapy planning MR (RP-MR). Primary tumors were segmented using dedicated software (LIFEx version 6.1) from PET, CT, contrast-enhanced T1-weighted (T1-w), and T2-weighted (T2-w) MR sequences with 376 radiomic features extracted. Summary statistics describe patient, disease, and treatment characteristics. The Kaplan–Meier (KM) method estimates overall survival (OS) and progression-free survival (PFS). Clinical factors selected based on univariable analysis and the multivariable Cox model were subsequently constructed with radiomic features added.

Results

The final models comparing clinical, clinical + RP-MR, clinical + PET/CT and clinical + RP-MR + PET/CT for OS and PFS demonstrated that combined radiomic signatures were significantly associated with improved survival prognostication (AUC 0.62 vs 0.81 vs 0.75 vs 0.86 at 21 months for PFS and 0.56 vs 0.85 vs 0.79 vs 0.96 at 24 months for OS). Clinical + RP-MR features initially outperform clinical + PET/CT for both OS and PFS (<18 months), and later in the clinical course for PFS (>42 months).

Conclusion

Our study demonstrated that PET/CT-based radiomic features may improve survival prognostication among NPC patients when combined with baseline clinical and MR-based radiomic features.
Vaginal microbiota and HPV clearance: A longitudinal study
Authors: Shi Wenpei , Zhu Haiyan , Yuan Lei , Chen Xiaoyue , Huang Xiaojie , Wang Kai , Li Zhen
Published: October 2022

Although vaginal microbiota (VM) may interact with human papillomavirus (HPV) infection and clearance, longitudinal data remain very limited. We aimed to investigate the association between VM at baseline and the clearance of high-risk HPV (HR-HPV) infection within 12 months. Cervical swabs were collected at diagnosis from 85 patients with HR-HPV infection and histologically confirmed cervical lesions, including cervicitis, low-grade squamous intraepithelial lesion and high-grade squamous intraepithelial lesion. Microbiome analysis was performed using 16S rRNA gene sequencing. Among the 73 women included in the analyses, HPV clearance was observed in 58.9% of the patients within 12 months. No significant difference was observed between the HPV-cleared and HPV-uncleared groups regarding age, disease stage, HPV subtype, VM community state types, and VM diversity (α and β). Women with the depletion of enterococcus ASV_62 and enrichment in Lactobacillus iners at baseline were less likely to have HPV clearance at month 12. Further analysis revealed a significant negative association between high abundance of L. iners and HPV clearance in patients who received non-operative treatment (OR = 3.94, p = 0.041), but not in those who received operative treatment (OR = 1.86, p = 0.660). Our findings provide new evidence for the potential role of VM in the persistent HR-HPV infections.
Early monocyte response following local ablation in hepatocellular carcinoma
Authors: Kimm Melanie A. , Kästle Sophia , Stechele Matthias M. R. , Öcal Elif , Richter Lisa , Ümütlü Muzaffer R. , Schinner Regina , Öcal Osman , Salvermoser Lukas , Alunni-Fabbroni Marianna , Seidensticker Max , Goldberg S. Nahum , Ricke Jens , Wildgruber Moritz
Published: October 2022

Local ablative therapies are established treatment modalities in the treatment of early- and intermediate-stage hepatocellular carcinoma (HCC). Systemic effects of local ablation on circulating immune cells may contribute to patients’ response. Depending on their activation, myeloid cells are able to trigger HCC progression as well as to support anti-tumor immunity. Certain priming of monocytes may already occur while still in the circulation. By using flow cytometry, we analyzed peripheral blood monocyte cell populations from a prospective clinical trial cohort of 21 HCC patients following interstitial brachytherapy (IBT) or radiofrequency ablation (RFA) and investigated alterations in the composition of monocyte subpopulations and monocytic myeloid-derived suppressor cells (mMDSCs) as well as receptors involved in orchestrating monocyte function. We discovered that mMDSC levels increased following both IBT and RFA in virtually all patients. Furthermore, we identified varying alterations in the level of monocyte subpopulations following radiation compared to RFA. (A) Liquid biopsy liquid biopsy of circulating monocytes in the future may provide information on the inflammatory response towards local ablation as part of an orchestrated immune response.
Dynamic parameters for fluid responsiveness in mechanically ventilated children: A systematic review
Authors: Yenjabog Patcha , Kanchongkittiphon Wacharoot , Chutipongtanate Somchai , Lertbunrian Rojjanee , Ungprasert Patompong
Published: October 2022

Objective

Fluid administration is the initial step of treatment of unstable pediatric patients. Evaluation of fluid responsiveness is crucial in mechanically ventilated children to avoid fluid overload, which increases mortality. We aim to review and compare the diagnostic performance of dynamically hemodynamic parameters for predicting fluid responsiveness in mechanically ventilated children.

Design

A systematic review was performed using four electronic databases, including PubMed, EMBASE, Scopus, and Central, for published articles from 1 January 2010 to 31 December 2020. Studies were included if they described diagnostic performance of dynamic parameters after fluid challenge was performed in mechanically ventilated children.

Settings

Pediatric intensive and cardiac intensive care unit, and operative room.

Patients

Children aged 1 month to 18 years old who were under mechanical ventilation and required an intravenous fluid challenge.

Measurements and Main Results

Twenty-seven studies were included in the systematic review, which included 1,005 participants and 1,138 fluid challenges. Respiratory variation in aortic peak velocity was reliable among dynamic parameters for predicting fluid responsiveness in mechanically ventilated children. All studies of respiratory variation in aortic peak velocity showed that the area under the receiver operating characteristic curve ranged from 0.71 to 1.00, and the cutoff value for determining fluid responsiveness ranged from 7% to 20%. Dynamic parameters based on arterial blood pressure (pulse pressure variation and stroke volume variation) were also used in children undergoing congenital heart surgery. The plethysmography variability index was used in children undergoing neurological and general surgery, including the pediatric intensive care patients.

Conclusions

The respiratory variation in aortic peak velocity exhibited a promising diagnostic performance across all populations in predicting fluid responsiveness in mechanically ventilated children. High sensitivity is advantageous in non-cardiac surgical patients and the pediatric intensive care unit because early fluid resuscitation improves survival in these patients. Furthermore, high specificity is beneficial in congenital heart surgery because fluid overload is particularly detrimental in this group of patients.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=206400
Blinatumomab for treating pediatric B-lineage acute lymphoblastic leukemia: A retrospective real-world study
Authors: Wu Ying , Li Yanming , Fan Jia , Qi Peijing , Lin Wei , Yang Jie , Liu Huiqing , Wang Xiaoling , Zheng Huyong , Wang Tianyou , Zhang Ruidong
Published: October 2022

Objectives

Blinatumomab was shown to be safe and effective for consolidation therapy in B-cell acute lymphoblastic leukemia (B-ALL). This study aimed to investigate the effectiveness and safety of blinatumomab in pediatric B-ALL patients in a real-world setting.

Methods

This was a retrospective, observational study that included patients who initiated blinatumomab treatment between October 1, 2020 and June 20, 2022. Patients with B-ALL diagnosis, age below 18 years, and at least one blinatumomab treatment cycle were included. Treatment-related toxicities were assessed.

Result

Totally 23 pediatric patients were included in this study, with a median age of 6 years (range, 2 to 11 years). Blinatumomab therapy was applied for MRD-positive (disease ≥0.01%, n = 3) or chemotherapy-ineligible (n = 20) B-ALL cases. The median follow-up time was 9 months, and all evaluable patients achieved complete molecular remission with undetectable MRD. Four relapsed B-ALL cases proceeded to hematopoietic stem cell transplantation (HSCT) without further bridging therapy, while the others underwent maintenance chemotherapy after blinatumomab treatment. Grade ≥3 febrile neutropenia, white blood cell decrease and seizure were observed in 57%, 48% and 4.3% of patients, respectively. One case discontinued therapy due to neurologic toxicities. Elevated cytokine levels were observed in 4 patients. In all 23 patients, increased T-cell and low B-cell counts (<10/μl) were detected during blinatumomab therapy.

Conclusion

These encouraging results suggest blinatumomab in pediatric B-ALL patients with MRD+ or chemotherapy-related toxicities is effective and safe in the short run, although long-term follow-up is still needed.
Effectiveness of a peer group-based online intervention program in empowering families of children with disabilities at home
Authors: Wakimizu Rie , Matsuzawa Akemi , Fujioka Hiroshi , Nishigaki Kaori , Sato Iori , Suzuki Seigo , Iwata Naoko
Published: October 2022

Background

The empowerment of families raising children with disabilities (CWD) is crucial in maintaining their health. We developed an evidence-based, family empowerment intervention program focusing on social resource utilization and reducing care burden.

Objective

This study aimed to determine the program's effectiveness in promoting family empowerment.

Methods

We compared an intervention group that started the online intervention program a week after initial evaluation and a group that received delayed intervention (waitlist-controlled group) at three time points: initial (T1), post-course (T2), and follow-up (T3). The required sample size was 52.

Results

There were 60 participants who applied to the program. One participant dropped out due to scheduling issues, and the others were assigned to either the intervention group (n = 29) or the waitlist-controlled group (n = 30). Those who responded to the baseline questionnaire (T1: 26 from the intervention group; 29 from the waitlist-controlled group) comprised the final sample. Among them, 20 members of the intervention group and 20 of the waitlist-controlled group attended all four sessions (completion rates of 77% and 69%, respectively). The attendance rate for sessions 1–4 was 94%, 89%, 81%, and 83%, respectively. The participant numbers in each session ranged from 5 to 18 per month. The baseline outcome score did not differ between the groups. The primary outcome, family empowerment, measured using the family empowerment scale (FES), was significantly higher at T2 for the intervention group than in the waitlist-controlled group and was sustained in the sensitivity analysis. The intervention group's FES, in the family relationships (FA) and relationships with service systems (SS) subdomains, increased significantly, unlike involvement with the community (SP). The intervention group experienced lower care burden and higher self-compassion, especially in the isolation and over-identification items of the self-compassion scale-short form (SCS-SF). The intervention group's FES (total, FA, SS) and SCS-SF (total, common humanity, isolation) changed significantly between T1 and T2, and all, except common humanity, were sustained up to T3; this group's FES (SP) and SCS (negative score, over-identification) changed significantly between T1 and T3. The waitlist-controlled group's FES (total, FA) and SCS (total) changed significantly and were sustained between T2 and T3.

Conclusions

The developed intervention program promotes family empowerment in families of CWD.

Clinical Trial Registration

This study is registered as a clinical trial in the UMIN Clinical Trials Registry (https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000050422, UMIN000044172).
Pharmacological interventions on smoking cessation: A systematic review and network meta-analysis
Authors: Shang Xue , Guo Kangle , E. Fenfen , Deng Xinxin , Wang Yongsheng , Wang Ziyi , Wu Yanan , Xu Meng , Yang Chaoqun , Li Xiuxia , Yang Kehu
Published: October 2022

Objective: A network meta-analysis based on randomized controlled trials was conducted to investigate the effects of pharmacological interventions on smoking cessation.

Methods: English databases were searched to obtain randomized controlled trials reporting the effect of pharmacological interventions on smoking cessation. The risk of bias for the included trials was assessed using Cochrane Handbook tool. Stata 15.1 software was used to perform network meta-analysis, and GRADE approach was used to assess the evidence credibility on the effects of different interventions on smoking cessation.

Results: A total of 159 studies involving 60,285 smokers were included in the network meta-analysis. The analysis involved 15 interventions and which yielded 105 pairs of comparisons. Network meta-analysis showed that varenicline was more helpful for smoking cessation than other monotherapies, such as nicotine replacement therapy [Odds Ratio (OR) = 1.42, 95% confidence interval (CI) (1.16, 1.73)] and bupropion [OR = 1.52, 95% CI (1.22, 1.89)]. Furthermore, combined interventions were superior to monotherapy in achieving smoking cessation, such as varenicline plus bupropion over bupropion [OR = 2.00, 95% CI (1.11, 3.61)], varenicline plus nicotine replacement therapy over nicotine replacement therapy [OR = 1.84, 95% CI (1.07, 3.18)], and nicotine replacement therapy plus mecamylamine over naltrexone [OR = 6.29, 95% CI (1.59, 24.90)]. Finally, the surface under the cumulative ranking curve value indicated that nicotine replacement therapy plus mecamylamine had the greatest probability of becoming the best intervention.

Conclusion: Most pharmacological interventions demonstrated a benefit in smoking cessation compared with placebo, whether monotherapy or combination therapy. Moreover, confirmed evidence suggested that some combination treatments, such as varenicline plus bupropion and nicotine replacement therapy plus mecamylamine have a higher probability of being the best smoking cessation in
Protective effects and mechanism of puerarin targeting PI3K/Akt signal pathway on neurological diseases
Authors: Wang Qian , Shen Zi-Nuo , Zhang Shu-Jing , Sun Yan , Zheng Feng-Jie , Li Yu-Hang
Published: October 2022

Neurological diseases impose a tremendous and increasing burden on global health, and there is currently no curative agent. Puerarin, a natural isoflavone extracted from the dried root of Pueraria montana var. Lobata (Willd.) Sanjappa and Predeep, is an active ingredient with anti-inflammatory, antioxidant, anti-apoptotic, and autophagy-regulating effects. It has great potential in the treatment of neurological and other diseases. Phosphatidylinositol 3-kinases/protein kinase B (PI3K/Akt) signal pathway is a crucial signal transduction mechanism that regulates biological processes such as cell regeneration, apoptosis, and cognitive memory in the central nervous system, and is closely related to the pathogenesis of nervous system diseases. Accumulating evidence suggests that the excellent neuroprotective effect of puerarin may be related to the regulation of the PI3K/Akt signal pathway. Here, we summarized the main biological functions and neuroprotective effects of puerarin via activating PI3K/Akt signal pathway in neurological diseases. This paper illustrates that puerarin, as a neuroprotective agent, can protect nerve cells and delay the progression of neurological diseases through the PI3K/Akt signal pathway.
Physiologically based pharmacokinetic (PBPK) modeling of the role of CYP2D6 polymorphism for metabolic phenotyping with dextromethorphan
Authors: Grzegorzewski Jan , Brandhorst Janosch , König Matthias
Published: October 2022

The cytochrome P450 2D6 (CYP2D6) is a key xenobiotic-metabolizing enzyme involved in the clearance of many drugs. Genetic polymorphisms in CYP2D6 contribute to the large inter-individual variability in drug metabolism and could affect metabolic phenotyping of CYP2D6 probe substances such as dextromethorphan (DXM). To study this question, we (i) established an extensive pharmacokinetics dataset for DXM; and (ii) developed and validated a physiologically based pharmacokinetic (PBPK) model of DXM and its metabolites dextrorphan (DXO) and dextrorphan O-glucuronide (DXO-Glu) based on the data. Drug-gene interactions (DGI) were introduced by accounting for changes in CYP2D6 enzyme kinetics depending on activity score (AS), which in combination with AS for individual polymorphisms allowed us to model CYP2D6 gene variants. Variability in CYP3A4 and CYP2D6 activity was modeled based on in vitro data from human liver microsomes. Model predictions are in very good agreement with pharmacokinetics data for CYP2D6 polymorphisms, CYP2D6 activity as described by the AS system, and CYP2D6 metabolic phenotypes (UM, EM, IM, PM). The model was applied to investigate the genotype-phenotype association and the role of CYP2D6 polymorphisms for metabolic phenotyping using the urinary cumulative metabolic ratio (UCMR), DXM/(DXO + DXO-Glu). The effect of parameters on UCMR was studied via sensitivity analysis. Model predictions indicate very good robustness against the intervention protocol (i.e. application form, dosing amount, dissolution rate, and sampling time) and good robustness against physiological variation. The model is capable of estimating the UCMR dispersion within and across populations depending on activity scores. Moreover, the distribution of UCMR and the risk of genotype-phenotype mismatch could be estimated for populations with known CYP2D6 genotype frequencies. The model can be applied for individual prediction of UCMR and metabolic phenotype based on CYP2D6 genotype. Both, model and database are freely available for reuse.
Effects of sacubitril-valsartan on heart failure patients with mid-range ejection fractions: A systematic review and meta-analysis
Authors: Qin Jianbin , Wang Weijian , Wei Ping , Huang Ping , Lin Ruizhen , Yue Jinming
Published: October 2022

Aim: The effect of sacubitril-valsartan (ARNI) in heart failure (HF) patients with mid-range ejection fractions (HFmrEF) remains unclear. This study aimed to investigate the effects of ARNI in HFmrEF patients.

Methods: From inception to 15 February 2022, articles were searched via PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Whip, and Wanfang databases. Left ventricular functions, indicators related to HF, quality of life score, 6-Minute Walk Test, total effective rate, mortality, readmission rate, and adverse events were the outcomes. Relative risk (RR), weighted mean difference (WMD), and 95% confidence interval (CI) were used to evaluate the outcomes. The heterogeneity test was conducted for each indicator and measured by I2 statistics. Subgroup analysis was performed regarding the type of study and duration of treatment.

Results: Sixteen studies involving 1,937 patients were included in this study. Our results showed ARNI was likely to improve left ventricular function by increasing the left ventricular ejection fraction (LVEF) (WMD: 2.36, 95%CI: 1.09–3.62), stroke volume (WMD: 16.800, 95%CI: 11.385–22.215), and left ventricular short-axis shortening rate (WMD: 2.05, 95%CI: 0.25–3.86), decreasing left ventricular end-diastolic dimension (WMD: −2.48, 95%CI: −3.83 to −1.13), left atrial diameter (WMD: −2.23, 95%CI: −2.83 to −1.63), C-reactive protein level (WMD: −1.40, 95%CI: −2.62 to −0.18), and N-terminal-pro B-type natriuretic peptide level (WMD: −494.92, 95%CI: −641.34 to −348.50). ARNI has a higher total effective rate (RR: 1.15, 95%CI: 1.08–1.21), Kansas City cardiomyopathy questionnaire (WMD: 4.13, 95%CI: 3.46–4.81), and 6-Minute Walk Test (WMD: 51.35, 95%CI: 26.99–75.71) compared with angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB). In addition, ARNI decreased the readmission rate (RR: 0.54, 95%CI: 0.43–0.68) (all p < 0.05). Nevertheless, there were no significant differences in the adverse outcomes.

Conclusion: This meta-analysis suggests ARNI may be an effective strategy with which to improve the left ventricular function, and quality of life, and reduce the readmission rate in HFmrEF patients. However, long-term clinical studies with large samples are still needed to further explore the efficacy and safety of ARNI compared with ACEI or ARB in the HFmrEF population.
A VTI anisotropic media inversion method based on the exact reflection coefficient equation
Authors: Wu Fan , Li Jingye , Geng Weiheng , Tang Wei
Published: October 2022

Anisotropy is widespread in the Earth’s crust, and VTI (vertical axis symmetry transverse isotropy) anisotropy is common due to stratigraphic pressure. Disregarding anisotropy leads to inaccurate inversion results in VTI media. To estimate accurate elastic parameters, the exact reflection coefficient equation of VTI media should be used. This equation is nonlinear and more accurate than the commonly used linear reflection coefficient equation. Although the inversion based on the VTI anisotropy exact reflection coefficient equation is a complex nonlinear inversion problem, it is still computable. Therefore, for VTI media, we derive the objective function combining Bayesian theory and use the iterative reweighted least squares method for a fast and stable solution. Adding Bayesian theory can improve the robustness of the algorithm. The accuracy and noise immunity of the method is tested with synthetic data. Finally, the method is applied on field data and obtains accurate elastic parameters. The results can provide an understanding of subsurface formations and serve as the base data for calculating fluid and fracture distribution.
Novel automated spinal ultrasound segmentation approach for scoliosis visualization
Authors: Jiang Weiwei , Mei Fang , Xie Qiaolin
Published: October 2022

Scoliosis is a 3D deformity of the spine in which one or more segments of the spine curve laterally, usually with rotation of the vertebral body. Generally, having a Cobb angle (Cobb) greater than 10° can be considered scoliosis. In spine imaging, reliable and accurate identification and segmentation of bony features are crucial for scoliosis assessment, disease diagnosis, and treatment planning. Compared with commonly used X-ray detection methods, ultrasound has received extensive attention from researchers in the past years because of its lack of radiation, high real-time performance, and low price. On the basis of our previous research on spinal ultrasound imaging, this work combines artificial intelligence methods to create a new spine ultrasound image segmentation model called ultrasound global guidance block network (UGBNet), which provides a completely automatic and reliable spine segmentation and scoliosis visualization approach. Our network incorporates a global guidance block module that integrates spatial and channel attention, through which long-range feature dependencies and contextual scale information are learned. We evaluate the performance of the proposed model in semantic segmentation on spinal ultrasound datasets through extensive experiments with several classical learning segmentation methods, such as UNet. Results show that our method performs better than other approaches. Our UGBNet significantly improves segmentation precision, which can reach 74.2% on the evaluation metric of the Dice score.