bluuebunny/crossref_metadata_2025 huggingface dataset:
Epidemiological features of traumatic spinal cord injury in China: A systematic review and meta-analysis
Authors: Hu Youpeng , Li Lianxin , Hong Binxue , Xie Yizhou , Li Tong , Feng Chaoqun , Yang Fei , Wang Yehui , Zhang Jie , Yu Yang , Fan Xiaohong
Published: March 2023

Background

Traumatic spinal cord injury (TSCI) is a highly fatal and disabling event, and its incidence rate is increasing in China. Therefore, we collated the epidemiological factors of TSCI in different regions of China to update the earlier systematic review published in 2018.

Method

We searched four English and three Chinese electronic databases from 1978 to October 1, 2022. From the included reports, information on sample characteristics, incidence, injury characteristics, prognostic factors, and economic burden was extracted. The selection of data was based on the PRISMA statement. The quality of the included studies was assessed by the Agency for Healthcare Research and Quality (AHRQ) tool. The results of the meta-analysis were presented in the form of pooled frequency and forest plots.

Results

A total of 59 reports (60 studies) from 23 provinces were included, of which 41 were in the Chinese language. The random pooled incidence of TSCI in China was estimated to be 65.15 per million (95% CI: 47.20–83.10 per million), with a range of 6.7 to 569.7 per million. The pooled male-to-female ratio was 1.95:1. The pooled mean age of the cases at the time of injury was 45.4 years. Motor vehicle accidents (MVAs) and high falls were found to be the leading causes of TSCI. Incomplete quadriplegia and AISA/Frankel grade D were the most common types of TSCI. Cervical level injury was the most prevalent. The pooled in-hospital mortality and complication rates for TSCI in China were 3% (95% CI: 2–4%) and 35% (95% CI: 23–47%). Respiratory problems were the most common complication and the leading cause of death.

Conclusion

Compared with previous studies, the epidemiological data on TSCI in China has changed significantly. A need to update the data over time is essential to implement appropriate preventive measures and formulate interventions according to the characteristics of the Chinese population.
Case report: Two clusters of Creutzfeldt–Jakob disease cases within 1 year in West Michigan
Authors: Rong Ling Ling , Lannen Nicholas J. , Tank Evan C. , Feistel Jessica L. , Therasse Christopher J. , Potluri Anvita , Khan Muhib , Min Jiangyong
Published: March 2023

Background

Creutzfeldt–Jakob disease (CJD) is a rare, rapidly progressive, and uniformly fatal neurodegenerative disease. The reported incidence of CJD is 1 to 2 per million people worldwide annually, with fewer than 1,000 cases in the United States per year. In this study, we report a unique case series on temporo-spatial clusters of CJD cases in West Michigan.

Methods

A total of five CJD cases consisting of two temporal clusters were seen from July 2021 to June 2022 at Corewell Health West hospitals. All patients had brain MRI, EEG, and CSF tests. Four patients underwent autopsies.

Results

All patients' MRIs showed characteristic CJD patterns. Four patients had positive CJD panels in CSF. One patient had typical CJD EEG findings. Four patients were confirmed as sporadic CJD by autopsy. All patients died within 3 months after CJD was suspected.

Discussion

All patients lived within a 90-mile radius of Grand Rapids, MI, and two lived in the same county. West Michigan has a population of 1.6 million people, and the four counties where five patients lived have a combined population of 395,104, indicating CJD's new case rate of 3.1 and 12.5 per million people, respectively. Corewell Health is one of the three major healthcare systems in West Michigan. The actual incidence of CJD in West Michigan is likely even higher. This dense temporal and spatial cluster of CJD cases poses a serious public health challenge and warrants urgent investigation.
Relationships between respiratory and oromotor events differ between motor phenotypes in patients with obstructive sleep apnea
Authors: Okura Mutsumi , Kato Takafumi , Mashita Midori , Muraki Hisae , Sugita Hideko , Ohi Motoharu , Taniguchi Mitsutaka
Published: March 2023

Purpose

The present study investigated the relationship between sleep bruxism (SB) and obstructive sleep apnea (OSA) in relation to the sleep architecture.

Methods

We conducted a cross-sectional study. Polysomnographic recordings were performed on 36 patients. Sleep, respiratory, and oromotor variables, such as rhythmic masticatory muscle activity (RMMA) and non-specific masticatory muscle activity (NSMA), were compared between OSA patients with or without SB. A correlation analysis of the frequency of respiratory and oromotor events in NREM and REM sleep was performed. The frequency of oromotor events following respiratory events was also assessed.

Results

The proportion of REM sleep was higher in OSA patients with SB than in those without SB (p = 0.02). The apnea-hypopnea index (AHI) did not significantly differ between the two groups; however, AHI was approximately 8-fold lower during REM sleep in OSA patients with SB (p = 0.01) and the arousal threshold was also lower (p = 0.04). Although the RMMA index was higher in OSA patients with than in those without SB (p < 0.01), the NSMA index did not significantly differ. The percentage of RMMA following respiratory events was significantly higher in OSA patients with than in those without SB, whereas that of NSMA did not significantly differ. The frequency of oromotor events throughout the whole night positively correlated with AHI. However, regardless of the sleep state, AHI did not correlate with the RMMA index, but positively correlated with the NSMA index.

Conclusion

In consideration of the limitations of the present study, the results obtained indicate that OSA patients with SB have a unique phenotype of OSA and also emphasize the distinct relationship of respiratory events with RMMA and NSMA.
Functional magnetic resonance imaging providing the brain effect mechanism of acupuncture and moxibustion treatment for depression
Authors: Wong Kelvin K. L. , Xu Jinping , Chen Cang , Ghista Dhanjoo , Zhao Hong
Published: March 2023

The efficacy of acupuncture and moxibustion in the treatment of depression has been fully recognized internationally. However, its central mechanism is still not developed into a unified standard, and it is generally believed that the central mechanism is regulation of the cortical striatum thalamic neural pathway of the limbic system. In recent years, some scholars have applied functional magnetic resonance imaging (fMRI) to study the central mechanism and the associated brain effects of acupuncture and moxibustion treatment for depression. This study reviews the acupuncture and moxibustion treatment of depression from two aspects: (1) fMRI study of the brain function related to the acupuncture treatment of depression: different acupuncture and moxibustion methods are summarized, the fMRI technique is elaborately explained, and the results of fMRI study of the effects of acupuncture are analyzed in detail, and (2) fMRI associated “brain functional network” effects of acupuncture and moxibustion on depression, including the effects on the hippocampus, the amygdala, the cingulate gyrus, the frontal lobe, the temporal lobe, and other brain regions. The study of the effects of acupuncture on brain imaging is not adequately developed and still needs further improvement and development. The brain function networks associated with the acupuncture treatment of depression have not yet been adequately developed to provide a scientific and standardized mechanism of the effects of acupuncture. For this purpose, this study analyzes in-depth the clinical studies on the treatment of anxiety and depression by acupuncture and moxibustion, by depicting how the employment of fMRI technology provides significant imaging changes in the brain regions. Therefore, the study also provides a reference for future clinical research on the treatment of anxiety and depression.
A new biomarker combining multimodal MRI radiomics and clinical indicators for differentiating inverted papilloma from nasal polyp invaded the olfactory nerve possibly
Authors: Du Lianze , Yuan Qinghai , Han Qinghe
Published: March 2023

Background and purpose

Inverted papilloma (IP) and nasal polyp (NP), as two benign lesions, are difficult to distinguish on MRI imaging and clinically, especially in predicting whether the olfactory nerve is damaged, which is an important aspect of treatment and prognosis. We plan to establish a new biomarker to distinguish IP and NP that may invade the olfactory nerve, and to analyze its diagnostic efficacy.

Materials and methods

A total of 74 cases of IP and 55 cases of NP were collected. A total of 80% of 129 patients were used as the training set (59 IP and 44 NP); the remaining were used as the testing set. As a multimodal study (two MRI sequences and clinical indicators), preoperative MR images including T2-weighted magnetic resonance imaging (T2-WI) and contrast-enhanced T1-weighted magnetic resonance imaging (CE-T1WI) were collected. Radiomic features were extracted from MR images. Then, the least absolute shrinkage and selection operator (LASSO) regression method was used to decrease the high degree of redundancy and irrelevance. Subsequently, the radiomics model is constructed by the rad scoring formula. The area under the curve (AUC), accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the model have been calculated. Finally, the decision curve analysis (DCA) is used to evaluate the clinical practicability of the model.

Results

There were significant differences in age, nasal bleeding, and hyposmia between the two lesions (p < 0.05). In total, 1,906 radiomic features were extracted from T2-WI and CE-T1WI images. After feature selection, using 12 key features to bulid model. AUC, sensitivity, specificity, and accuracy on the testing cohort of the optimal model were, respectively, 0.9121, 0.828, 0.9091, and 0.899. AUC on the testing cohort of the optimal model was 0.9121; in addition, sensitivity, specificity, and accuracy were, respectively, 0.828, 0.9091, and 0.899.

Conclusion

A new biomarker combining multimodal MRI radiomics and clinical indicators can effectively distinguish between IP and NP that may invade the olfactory nerve, which can provide a valuable decision basis for individualized treatment.
The instant effect of embodiment via mirror visual feedback on electroencephalogram-based brain connectivity changes: A pilot study
Authors: Ding Li , Sun Qiang , Jiang Ning , He Jiayuan , Jia Jie
Published: March 2023

The therapeutic efficacy of mirror visual feedback (MVF) is attributed to the perception of embodiment. This study intends to investigate the instantaneous effect of embodiment on brain connectivity. Twelve healthy subjects were required to clench and open their non-dominant hands and keep the dominant hands still during two experimental sessions. In the first session, the dominant hand was covered and no MVF was applied, named the sham-MVF condition. Random vibrotactile stimulations were applied to the non-dominant hand with MVF in the subsequent session. Subjects were asked to pedal while having embodiment perception during motor tasks. As suggested by previous findings, trials of no vibration and continuous vibration were selected for this study, named the condition of MVF and vt-MVF. EEG signals were recorded and the alterations in brain connectivity were analyzed. The average node degrees of sham-MVF, MVF, and vt-MVF conditions were largely different in the alpha band (9.94, 11.19, and 17.37, respectively). Further analyses showed the MVF and vt-MVF had more nodes with a significantly large degree, which mainly occurred in the central and the visual stream involved regions. Results of network metrics showed a significant increment of local and global efficiency, and a reduction of characteristic path length for the vt-MVF condition in the alpha and beta bands compared to sham-MVF, and in the alpha band compared to MVF. Similar trends were found for MVF condition in the beta band compared to sham-MVF. Moreover, significant leftward asymmetry of global efficiency and rightward asymmetry of characteristic path length was reported in the vt-MVF condition in the beta band. These results indicated a positive impact of embodiment on network connectivity and neural communication efficiency, which reflected the potential mechanisms of MVF for new insight into neural modulation.
Morphological feature and mapping inflammation in classified carotid plaques in symptomatic and asymptomatic patients: A hybrid 18F-FDG PET/MR study
Authors: Zhang Yue , Cui Bixiao , Yang Hongwei , Ma Jie , Yang Yu , Yang Bin , Ma Yan , Jiao Liqun , Li Xiang , Lu Jie
Published: March 2023

Purpose

To investigate morphological and inflamed-metabolism features of carotid atherosclerotic plaques between symptomatic and asymptomatic patients with hybrid 18F-FDG PET/MR imaging.

Methods

A total of 20 symptomatic and 20 asymptomatic patients with carotid plaques underwent hybrid 18F-FDG PET/MR scans. American heart association (AHA) lesion types were classified, and plaque compositions were further determined on consecutive MRI axial sections in both carotid arteries. 18F-FDG uptake in carotid arteries was quantified using region of interest (ROI) methods based on maximum standardized uptake values (SUVmax) and target-to-background ratio (TBR) on corresponding positron emission tomography (PET) images.

Results

A total of seventy-one carotid plaques were quantified. AHA type VI was the most common (23, 32.4%), and the region of carotid bifurcation was the most common place presenting lesions (32, 45.1%). Compared with the asymptomatic group, the prevalence of high-risk features including plaque burden, lumen stenosis, maximum necrotic core area, and maximum intra-plaque hemorrhage area increased in the symptomatic group. Carotid TBR values of plaque in symptomatic group (TBR = 2.56 ± 0.34) was significantly higher than that in asymptomatic group (TBR = 1.57 ± 0.14) (P < 0.05). hs-CRP is an independent risk factor for the stability of carotid plaque. The correlation between normalized wall index (NWI) and TBR values was significantly positive in both the symptomatic and the asymptomatic groups (P < 0.01), and both NWI and TBR were significantly correlated with the level of hs-CRP (P < 0.01).

Conclusion

Integrated 18F-FDG PET/MR scans presented distinct risk features between symptomatic and asymptomatic patients. Hybrid 18F-FDG PET/MR systems combined with clinical serum hs-CRP may help distinguish vulnerable carotid plaques.
Cerebral blood flow characteristics of drug-naïve attention-deficit/hyperactivity disorder with social impairment: Evidence for region–symptom specificity
Authors: Zhang Kangfuxi , Yuan Jing , Pei Xuyao , Fu Zhao , Zhao Yilu , Hu Na , Wang Yufeng , Yang Li , Cao Qingjiu
Published: March 2023

Background

Social deficits are among the most important functional impairments in attention-deficit/hyperactivity disorder (ADHD). However, the relationship between social impairment and ADHD core symptoms as well as the underlying cerebral blood flow (CBF) characteristics remain unclear.

Methods

A total of 62 ADHD subjects with social deficits (ADHD + SD), 100 ADHD subjects without social deficits (ADHD-SD) and 81 age-matched typically developing controls (TDC) were enrolled. We first examined the correlation between the Social Responsiveness Scale (SRS-1) and ADHD core symptoms (inattention, hyperactivity, and impulsion) and then explored categorical and dimensional ADHD-related regional CBF by arterial spin labeling (ASL). For the categorical analysis, a voxel-based comparison of CBF maps between the ADHD + SD, ADHD-SD, and TDC groups was performed. For the dimensional analysis, the whole-brain voxel-wise correlation between CBF and ADHD symptoms (inattention, hyperactivity/impulsivity, and total scores) was evaluated in three groups. Finally, correlations between the SRS-1 and ADHD-related regional CBF were investigated. We applied Gaussian random field (GRF) for the correction of multiple comparisons in imaging results (voxel-level P < 0.01, and cluster-level P < 0.05).

Results

The clinical characteristics analysis showed that social deficits positively correlated with ADHD core symptoms, especially in social communication and autistic mannerisms domains. In the categorical analysis, we found that CBF in the left middle/inferior temporal gyrus in ADHD groups was higher than TDCs and was negatively correlated with the social motivation scores. Moreover, in dimensional analysis, we found that CBF in the left middle frontal gyrus was negatively correlated with the inattention scores, SRS total scores and autistic mannerisms scores in ADHD + SD subjects.

Conclusion

The present study shows that inattention, hyperactivity, and impulsivity may be responsible for the occurrence of social deficits in ADHD, with autistic traits being another significant contributing factor. Additionally, CBF in the left middle/inferior temporal gyrus and the left middle frontal gyrus might represent the corresponding physiological mechanisms underlying social deficits in ADHD.
S100B chaperone multimers suppress the formation of oligomers during Aβ42 aggregation
Authors: Figueira António J. , Saavedra Joana , Cardoso Isabel , Gomes Cláudio M.
Published: March 2023

Extracellular aggregation of the amyloid-β 1–42 (Aβ42) peptide is a major hallmark of Alzheimer’s disease (AD), with recent data suggesting that Aβ intermediate oligomers (AβO) are more cytotoxic than mature amyloid fibrils. Understanding how chaperones harness such amyloid oligomers is critical toward establishing the mechanisms underlying regulation of proteostasis in the diseased brain. This includes S100B, an extracellular signaling Ca2+-binding protein which is increased in AD as a response to neuronal damage and whose holdase-type chaperone activity was recently unveiled. Driven by this evidence, we here investigate how different S100B chaperone multimers influence the formation of oligomers during Aβ42 fibrillation. Resorting to kinetic analysis coupled with simulation of AβO influx distributions, we establish that supra-stoichiometric ratios of dimeric S100B-Ca2+ drastically decrease Aβ42 oligomerization rate by 95% and AβO levels by 70% due to preferential inhibition of surface-catalyzed secondary nucleation, with a concomitant redirection of aggregation toward elongation. We also determined that sub-molar ratios of tetrameric apo-S100B decrease Aβ42 oligomerization influx down to 10%, while precluding both secondary nucleation and, more discreetly, fibril elongation. Coincidently, the mechanistic predictions comply with the independent screening of AβO using a combination of the thioflavin-T and X-34 fluorophores. Altogether, our findings illustrate that different S100B multimers act as complementary suppressors of Aβ42 oligomerization and aggregation, further underpinning their potential neuroprotective role in AD.
Development and validation of a short nutrition literacy scale for young adults
Authors: Vrinten Jules , Van Royen Kathleen , Pabian Sara , De Backer Charlotte , Matthys Christophe
Published: March 2023

Background

Due to their high media use, young adults are frequently exposed to contradictory or even erroneous nutrition information. To properly handle and critically assess nutrition information, young adults (both general population and patient populations) need adequate levels of nutrition literacy. Currently there is a lack of suitable instruments to measure nutrition literacy in young adults (18–25 years). Therefore the aim of this study was to develop and validate a Short Nutrition Literacy (S-NutLit) scale for use in this age group.

Methods

Development and validation of the S-NutLit consisted of six phases: (1) item generation based on literature, (2) expert assessments to evaluate content validity, (3) cognitive interviews with the target population to assess face validity and readability, (4) pre-test to reduce the number of items, (5) validation survey to assess dimensionality with exploratory factor analyses, internal reliability with Cronbach alpha, construct and criterion validity by examining associations with age, gender, education level, health literacy, general literacy, dietary behaviors and physical activity with correlations, ANOVAs, and t-tests, (6) two-week follow-up survey to assess test–retest reliability with intra-class correlations.

Results

Starting from an initial pool of 53 items, expert assessments and cognitive interviews led to the reformulation, removal, and construction of items. Young adults aged 18–25 years participated in cognitive interviews (n = 12), pre-test (n = 101), validation survey (n = 300), and reliability survey (n = 92). The final S-NutLit consisted of 11 items rated on a 5-point scale distributed across two subscales (i.e., information skills and expert skills). Cronbach alpha values ranged from 0.79 to 0.83 and intraclass correlations from 0.61–0.79 (p < 0.001). Significant associations were observed with health literacy (r = 0.27, p < 0.001), general literacy and numeracy (rs = 0.12, p = 0.046), and education level (rs = 0.13, p = 0.025).

Conclusion

Findings indicate that the S-NutLit is a valid and reliable tool to assess nutrition literacy among young adults. The S-NutLit fills a gap in the field by offering a short measure of nutrition literacy and may be incorporated in digital technology to support the nutrition care process.
Docosahexaenoic acid supplementation in gestational diabetes mellitus and neonatal metabolic health biomarkers
Authors: Xu Ya-Jie , Wang Wen-Juan , Zhang Qiu-Yi , Yang Meng-Nan , Zhang Lin , He Hua , Dong Yu , Ouyang Fengxiu , Gao Ying , Zhang Jun , Zheng Tao , Luo Zhong-Cheng
Published: March 2023

Background and objective

Gestational diabetes mellitus (GDM) “programs” an elevated risk of metabolic dysfunctional disorders in the offspring, and has been associated with elevated leptin and decreased adiponectin levels in cord blood. We sought to assess whether docosahexaenoic acid (DHA) supplementation in GDM affects neonatal metabolic health biomarkers especially leptin and adiponectin.

Methods

In a randomized controlled trial, singleton pregnant women with de novo diagnosis of GDM at 24–28  weeks of gestation were randomized to dietary supplementation of 500 mg DHA per day (intervention, n = 30) until delivery or standard care (control, n = 38). The primary outcomes were cord blood leptin and total adiponectin concentrations. Secondary outcomes included high-molecular-weight (HMW) adiponectin and insulin-like growth factor-1 (IGF-1) concentrations in cord blood, maternal glycemic control post-intervention and birth weight (z score). In parallel, 38 euglycemic pregnant women were recruited for comparisons of cord blood biomarkers.

Results

There were no significant differences in cord serum leptin, total and HMW adiponectin and IGF-1 concentrations between DHA supplementation and control groups (all p > 0.05). Maternal fasting and 2-h postprandial blood glucose levels at 12–16 weeks post-intervention were similar between the two groups. The newborns in the DHA group had higher birth weight z scores (p = 0.02). Cord blood total and HMW adiponectin concentrations were significantly lower in GDM vs. euglycemic pregnancies.

Conclusion

Docosahexaenoic acid supplementation at 500  mg/day in GDM women did not affect neonatal metabolic biomarkers including leptin, adiponectin and IGF-1. The results are reassuring in light of the absence of influence on neonatal adipokines (leptin and adiponectin), and potential benefits to fetal growth and development.

Clinical Trial Registration:

Clinicaltrials.gov, NCT03569501.
Astaxanthin supplementation counters exercise-induced decreases in immune-related plasma proteins
Authors: Nieman David C. , Woo Jongmin , Sakaguchi Camila A. , Omar Ashraf M. , Tang Yang , Davis Kierstin , Pecorelli Alessandra , Valacchi Giuseppe , Zhang Qibin
Published: March 2023

Objectives

Astaxanthin is a dark red keto-carotenoid found in aquatic animals such as salmon and shrimp, and algae (Haematococcus pluvialis). Astaxanthin has a unique molecular structure that may facilitate anti-oxidative, immunomodulatory, and anti-inflammatory effects during physiological stress. The primary objective of this study was to examine the efficacy of 4-week ingestion of astaxanthin in moderating exercise-induced inflammation and immune dysfunction using a multi-omics approach.

Methods

This study employed a randomized, double blind, placebo controlled, crossover design with two 4-week supplementation periods and a 2-week washout period. Study participants were randomized to astaxanthin and placebo trials, with supplements ingested daily for 4 weeks prior to running 2.25 h at close to 70%VO2max (including 30 min of 10% downhill running). After the washout period, participants repeated all procedures using the counterbalanced supplement. The astaxanthin capsule contained 8 mg of algae astaxanthin. Six blood samples were collected before and after supplementation (overnight fasted state), immediately post-exercise, and at 1.5, 3, and 24 h-post-exercise. Plasma aliquots were assayed using untargeted proteomics, and targeted oxylipin and cytokine panels.

Results

The 2.25 h running bout induced significant muscle soreness, muscle damage, and inflammation. Astaxanthin supplementation had no effect on exercise-induced muscle soreness, muscle damage, and increases in six plasma cytokines and 42 oxylipins. Notably, astaxanthin supplementation countered exercise-induced decreases in 82 plasma proteins (during 24 h recovery). Biological process analysis revealed that most of these proteins were involved in immune-related functions such as defense responses, complement activation, and humoral immune system responses. Twenty plasma immunoglobulins were identified that differed significantly between the astaxanthin and placebo trials. Plasma levels of IgM decreased significantly post-exercise but recovered after the 24 h post-exercise recovery period in the astaxanthin but not the placebo trial.

Discussion

These data support that 4-week astaxanthin versus placebo supplementation did not counter exercise-induced increases in plasma cytokines and oxylipins but was linked to normalization of post-exercise plasma levels of numerous immune-related proteins including immunoglobulins within 24 h. Short-term astaxanthin supplementation (8 mg/day during a 4-week period) provided immune support for runners engaging in a vigorous 2.25 h running bout and uniquely countered decreases in plasma immunoglobulin levels.
New prognostic system specific for epidermal growth factor receptor-mutated lung cancer brain metastasis
Authors: Zhu Li-Hua , Fan Xing-Wen , Sun Lu , Ni Ting-ting , Li Ya-qi , Wu Chao-Yang , Wu Kai-Liang
Published: March 2023

Introduction

Brain metastases (BM) from lung cancer are heterogeneous, and accurate prognosis is required for effective treatment strategies. This study aimed to identify prognostic factors and develop a prognostic system exclusively for epidermal growth factor receptor (EGFR)-mutated lung cancer BM.

Methods

In total, 173 patients with EGFR-mutated lung cancer from two hospitals who developed BM and received tyrosine kinase inhibitor (TKI) and brain radiation therapy (RT) were included. Univariate and multivariate analyses were performed to identify significant EGFR-mutated BM prognostic factors to construct a new EGFR recursive partitioning analysis (RPA) prognostic index. The predictive discrimination of five prognostic scoring systems including RPA, diagnosis-specific prognostic factors indexes (DS-GPA), basic score for brain metastases (BS-BM), lung cancer using molecular markers (lung-mol GPA) and EGFR-RPA were analyzed using log-rank test, concordance index (C-index), and receiver operating characteristic curve (ROC). The potential predictive factors in the multivariable analysis to construct a prognostic index included Karnofsky performance status, BM at initial lung cancer diagnosis, BM progression after TKI, EGFR mutation type, uncontrolled primary tumors, and number of BM.

Results and discussion

In the log-rank test, indices of RPA, DS-GPA, lung-mol GPA, BS-BM, and EGFR-RPA were all significant predictors of overall survival (OS) (p ≤ 0.05). The C-indices of each prognostic score were 0.603, 0.569, 0.613, 0.595, and 0.671, respectively; The area under the curve (AUC) values predicting 1-year OS were 0.565 (p=0.215), 0.572 (p=0.174), 0.641 (p=0.007), 0.585 (p=0.106), and 0.781 (p=0.000), respectively. Furthermore, EGFR-RPA performed better in terms of calibration than other prognostic indices.BM progression after TKI and EGFR mutation type were specific prognostic factors for EGFR-mutated lung cancer BM. EGFR-RPA was more precise than other models, and useful for personal treatment.
Venetoclax resistance induced by activated T cells can be counteracted by sphingosine kinase inhibitors in chronic lymphocytic leukemia
Authors: Sarapura Martinez Valeria J. , Buonincontro Brenda , Cassarino Chiara , Bernatowiez Juliana , Colado Ana , Cordini Gregorio , Custidiano Maria del Rosario , Mahuad Carolina , Pavlovsky Miguel A. , Bezares Raimundo F. , Favale Nicolás O. , Vermeulen Mónica , Borge Mercedes , Giordano Mirta , Gamberale Romina
Published: March 2023

The treatment of chronic lymphocytic leukemia (CLL) patients with venetoclax-based regimens has demonstrated efficacy and a safety profile, but the emergence of resistant cells and disease progression is a current complication. Therapeutic target of sphingosine kinases (SPHK) 1 and 2 has opened new opportunities in the treatment combinations of cancer patients. We previously reported that the dual SPHK1/2 inhibitor, SKI-II enhanced the in vitro cell death triggered by fludarabine, bendamustine or ibrutinib and reduced the activation and proliferation of chronic lymphocytic leukemia (CLL) cells. Since we previously showed that autologous activated T cells from CLL patients favor the activation of CLL cells and the generation of venetoclax resistance due to the upregulation of BCL-XL and MCL-1, we here aim to determine whether SPHK inhibitors affect this process. To this aim we employed the dual SPHK1/2 inhibitor SKI-II and opaganib, a SPHK2 inhibitor that is being studied in clinical trials. We found that SPHK inhibitors reduce the activation of CLL cells and the generation of venetoclax resistance induced by activated T cells mainly due to a reduced upregulation of BCL-XL. We also found that SPHK2 expression was enhanced in CLL cells by activated T cells of the same patient and the presence of venetoclax selects resistant cells with high levels of SPHK2. Of note, SPHK inhibitors were able to re-sensitize already resistant CLL cells to a second venetoclax treatment. Our results highlight the therapeutic potential of SPHK inhibitors in combination with venetoclax as a promising treatment option for the patients.
Long term outcomes of occipital nerve stimulation
Authors: Montenegro Monique M. , Kissoon Narayan R.
Published: March 2023

Background

Occipital nerve stimulation (ONS) has been investigated as a potential treatment for disabling headaches and has shown promise for disorders such as chronic migraine and cluster headache. Long term outcomes stratified by headache subtype have had limited exploration, and literature on outcomes of this neuromodulatory intervention spanning 2 or more years is scarce.

Measures

We performed a narrative review on long term outcomes with ONS for treatment of headache disorders. We surveyed the available literature for studies that have outcomes for 24 months or greater to see if there is a habituation in response over time. Review of the literature revealed evidence in treatment of occipital neuralgia, chronic migraine, cluster headache, cervicogenic headache, short lasting unilateral neuralgiform headache attacks (SUNHA) and paroxysmal hemicrania. While the term “response” varied per individual study, a total of 17 studies showed outcomes in ONS with long term sustained responses (as defined per this review) in the majority of patients with specific headache types 177/311 (56%). Only 7 studies in total (3 cluster, 1 occipital neuralgia, 1 cervicogenic headache, 1 SUNHA, 1 paroxysmal hemicrania) provided both short-term and long-term responses up to 24 months to ONS. In cluster headache, the majority of patients (64%) were long term responders (as defined per this review) and only a minority of patients 12/62 (19%) had loss of efficacy (e.g., habituation). There was a high number 313/439 (71%) of adverse events per total number of patients in the studies including lead migration, requirements of revision surgery, allergy to surgical materials, infection and intolerable paresthesias.

Conclusions

With the evidence available, the response to ONS was sustained in the majority of patients with cluster headache with low rates of loss of efficacy in this patient population. There was a high percent of adverse events per number of patients in long term follow-up and likely related to the off-label use of leads typically used for spinal cord stimulation. Further longitudinal assessments of outcomes in occipital nerve stimulation with devices labelled for use in peripheral nerve stimulation are needed to evaluate the extent of habituation to treatment in headache.
Mitochondria-associated gene expression perturbation predicts clinical outcomes and shows potential for targeted therapy in neuroblastoma
Authors: Chai Chengwei , Chen Yan , Luo Yuanyuan , Zhang Hong , Ye Zhihua , He Xiaobing , Zou Yan , Xu Yingyi , Li Le , Tang Jue , Wu Qiang
Published: March 2023

Background

Mitochondria have long been considered a potential target in cancer therapy because malignant cells are known for their altered energy production. However, there is a lack of comprehensive research on the involvement of mitochondria-associated proteins (MAPs) in neuroblastoma (NB), and their potential as therapeutic targets is yet to be fully explored.

Methods

MAP genes were defined based on the protein-coding genes with mitochondrial localization. The mRNA expression patterns and dynamics of MAP genes associated with NB were investigated by integrating publicly available transcriptional profiles at the cellular and tissue levels. Multivariate Cox regression analysis was conducted to reveal the association of MAP genes with the overall survival (OS) and clinical subgroups of NB patients. The single-cell RNA-seq dataset and gene dependency screening datasets were analyzed to reveal the therapeutic potential of targeting MAP genes.

Results

We compiled a total of 1,712 MAP genes. We found the global and cell type-specific mRNA expression changes of the MAP genes associated with NB status and survival. Our analyses revealed a group of MAP gene signatures independent of MYCN-amplification status associated with NB outcome. We provided computational evidence with selected MAP genes showing good performance in predicting long-term prognosis. By analyzing gene dependency of the MAP genes in NB cell lines and ex vivo human primary T cells, we demonstrated the therapeutic potential of targeting several MAP genes in NB tumors.

Conclusions

Collectively, our study provides evidence for the MAP genes as extended candidates in NB tumor stratification and staging, prognostic prediction, and targeted drug development.
An empirical comparison of the harmful effects for randomized controlled trials and non-randomized studies of interventions
Authors: Dai Minhan , Furuya-Kanamori Luis , Syed Asma , Lin Lifeng , Wang Qiang
Published: March 2023

Introduction: Randomized controlled trials (RCTs) are the gold standard to evaluate the efficacy of interventions (e.g., drugs and vaccines), yet the sample size of RCTs is often limited for safety assessment. Non-randomized studies of interventions (NRSIs) had been proposed as an important alternative source for safety assessment. In this study, we aimed to investigate whether there is any difference between RCTs and NRSIs in the evaluation of adverse events.

Methods: We used the dataset of systematic reviews with at least one meta-analysis including both RCTs and NRSIs and collected the 2 × 2 table information (i.e., numbers of cases and sample sizes in intervention and control groups) of each study in the meta-analysis. We matched RCTs and NRSIs by their sample sizes (ratio: 0.85/1 to 1/0.85) within a meta-analysis. We estimated the ratio of the odds ratios (RORs) of an NRSI against an RCT in each pair and used the inverse variance as the weight to combine the natural logarithm of ROR (lnROR).

Results: We included systematic reviews with 178 meta analyses, from which we confirmed 119 pairs of RCTs and NRSIs. The pooled ROR of NRSIs compared to that of RCTs was estimated to be 0.96 (95% confidence interval: 0.87 and 1.07). Similar results were obtained with different sample size subgroups and treatment subgroups. With the increase in sample size, the difference in ROR between RCTs and NRSIs decreased, although not significantly.

Discussion: There was no substantial difference in the effects between RCTs and NRSIs in safety assessment when they have similar sample sizes. Evidence from NRSIs might be considered a supplement to RCTs for safety assessment.
Immunotherapies for advanced hepatocellular carcinoma
Authors: Sun Li-Yang , Zhang Kang-Jun , Xie Ya-Ming , Liu Jun-Wei , Xiao Zun-Qiang
Published: March 2023

Primary liver cancer is the second leading cause of tumor-related deaths in China, with hepatocellular carcinoma (HCC) accounting for 80%–90% of these. Since there is a lack of symptoms in the early stages of HCC, a large proportion of patients were identified with unresectable HCC when diagnosed. Due to the severe resistance to chemotherapy, patients with advanced HCC were traditionally treated with systematic therapy in the past decades, and the tyrosine kinase inhibitor (TKI) sorafenib has remained the only treatment option for advanced HCC since 2008. Immunotherapies, particularly immune checkpoint inhibitors (ICIs), have shown a strong anti-tumor effect and have been supported by several guidelines recently. ICIs, for example programmed cell death-1 (PD-1) inhibitors such as nivolumab and pembrolizumab, programmed cell death ligand 1 (PD-L1) inhibitors such as atezolizumab, and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors such as ipilimumab, the ICI-based combination with TKIs, and VEGF-neutralizing antibody or systematic or local anti-tumor therapies, are being further studied in clinical trials. However, immune-related adverse events (irAEs) including cutaneous toxicity, gastrointestinal toxicity, and hepatotoxicity may lead to the termination of ICI treatment or even threaten patients’ lives. This review aims to summarize currently available immunotherapies and introduce the irAEs and their managements in order to provide references for clinical application and further research.
A review on analytical studies in gravitational lensing
Authors: Chowdhuri Abhishek , Ghosh Saptaswa , Bhattacharyya Arpan
Published: March 2023

In this study, we review some current studies on gravitational lensing for black holes, mainly in the context of general relativity. We mainly focus on the analytical studies related to lensing with references to observational results. We start with reviewing lensing in spherically symmetric Schwarzschild spacetime, showing how to calculate deflection angles before moving to the rotating counterpart, the Kerr metric. Furthermore, we extend our studies for a particular class of newly proposed solutions called black-bounce spacetimes and discuss throughout the review how to explore lensing in these spacetimes and how the various parameters can be constrained using available astrophysical and cosmological data.
Interplay between stress and cancer—A focus on inflammation
Authors: Vignjević Petrinović Sanja , Milošević Maja S. , Marković Dragana , Momčilović Sanja
Published: March 2023

Stress is an integral part of life. While acute responses to stress are generally regarded as beneficial in dealing with immediate threats, chronic exposure to threatening stimuli exerts deleterious effects and can be either a contributing or an aggravating factor for many chronic diseases including cancer. Chronic psychological stress has been identified as a significant factor contributing to the development and progression of cancer, but the mechanisms that link chronic stress to cancer remain incompletely understood. Psychological stressors initiate multiple physiological responses that result in the activation of the hypothalamic-pituitary-adrenal (HPA) axis, sympathetic nervous system, and the subsequent changes in immune function. Chronic stress exposure disrupts the homeostatic communication between the neuroendocrine and immune systems, shifting immune signaling toward a proinflammatory state. Stress-induced chronic low-grade inflammation and a decline in immune surveillance are both implicated in cancer development and progression. Conversely, tumor-induced inflammatory cytokines, apart from driving a tumor-supportive inflammatory microenvironment, can also exert their biological actions distantly via circulation and therefore adversely affect the stress response. In this minireview, we summarize the current findings on the relationship between stress and cancer, focusing on the role of inflammation in stress-induced neuroendocrine-immune crosstalk. We also discuss the underlying mechanisms and their potential for cancer treatment and prevention.
Deep learning-based image segmentation model using an MRI-based convolutional neural network for physiological evaluation of the heart
Authors: Xu Wanni , Shi Jianshe , Lin Yunling , Liu Chao , Xie Weifang , Liu Huifang , Huang Siyu , Zhu Daxin , Su Lianta , Huang Yifeng , Ye Yuguang , Huang Jianlong
Published: March 2023

Background and Objective: Cardiovascular disease is a high-fatality health issue. Accurate measurement of cardiovascular function depends on precise segmentation of physiological structure and accurate evaluation of functional parameters. Structural segmentation of heart images and calculation of the volume of different ventricular activity cycles form the basis for quantitative analysis of physiological function and can provide the necessary support for clinical physiological diagnosis, as well as the analysis of various cardiac diseases. Therefore, it is important to develop an efficient heart segmentation algorithm.

Methods: A total of 275 nuclear magnetic resonance imaging (MRI) heart scans were collected, analyzed, and preprocessed from Huaqiao University Affiliated Strait Hospital, and the data were used in our improved deep learning model, which was designed based on the U-net network. The training set included 80% of the images, and the remaining 20% was the test set. Based on five time phases from end-diastole (ED) to end-systole (ES), the segmentation findings showed that it is possible to achieve improved segmentation accuracy and computational complexity by segmenting the left ventricle (LV), right ventricle (RV), and myocardium (myo).

Results: We improved the Dice index of the LV to 0.965 and 0.921, and the Hausdorff index decreased to 5.4 and 6.9 in the ED and ES phases, respectively; RV Dice increased to 0.938 and 0.860, and the Hausdorff index decreased to 11.7 and 12.6 in the ED and ES, respectively; myo Dice increased to 0.889 and 0.901, and the Hausdorff index decreased to 8.3 and 9.2 in the ED and ES, respectively.

Conclusion: The model obtained in the final experiment provided more accurate segmentation of the left and right ventricles, as well as the myocardium, from cardiac MRI. The data from this model facilitate the prediction of cardiovascular disease in real-time, thereby providing potential clinical utility.
Differences in gut bacterial community composition between modern and slower-growing broiler breeder lines: Implications of growth selection on microbiome composition
Authors: Shterzer Naama , Sbehat Yara , Poudel Binita , Rothschild Nir , Oloko Olanrewaju Eunice , Headrick Joseph , Petersen Erik , Druyan Shelly , Mills Erez
Published: March 2023

In the last century broiler chicken lines have undergone an extensive breeding regime aimed primarily at growth and high meat yield. It is not known if breeding has also resulted in a change to the broiler breeder’s associated gut microbiota. Here we compared the gut microbiota of 37-week-old commercial Cobb breeding dams with dams from a broiler Legacy line which has not undergone selection since 1986. The dams from both lines were kept together in the same shed under the same management protocol from day of hatch to avoid additional confounders. We chose this age to allow significant bacterial exchange, thus avoiding exposure dependent artifacts and so that we could compare dams at the same developmental state of adulthood and peak laying performance. Significant differences in the composition of the cecum bacterial communities were found. Bacteria of the genus Akkermansia, implicated in mucin degradation and associated with host metabolic health, accounted for 4.98% ± 5.04% of the Cobb cecum community, but were mostly absent from the ceca of the Legacy line dams. Inversely, Legacy dams had higher levels of Clostridiales, Lactobacillales and Aeromonadales. These results show that breeding has resulted in a change in the gut microbiota composition, likely by changing the physiological conditions in the mucosa. It remains unclear if changes in gut microbiota composition are a part of the mechanism affecting growth or are a secondary result of other physiological changes accelerating growth. Therefore, the identification of these changes opens the door to further targeted research.
Correction of UAV LiDAR-derived grassland canopy height based on scan angle
Authors: Xu Cong , Zhao Dan , Zheng Zhaoju , Zhao Ping , Chen Junhua , Li Xiuwen , Zhao Xueming , Zhao Yujin , Liu Wenjun , Wu Bingfang , Zeng Yuan
Published: March 2023

Grassland canopy height is a crucial trait for indicating functional diversity or monitoring species diversity. Compared with traditional field sampling, light detection and ranging (LiDAR) provides new technology for mapping the regional grassland canopy height in a time-saving and cost-effective way. However, the grassland canopy height based on unmanned aerial vehicle (UAV) LiDAR is usually underestimated with height information loss due to the complex structure of grassland and the relatively small size of individual plants. We developed canopy height correction methods based on scan angle to improve the accuracy of height estimation by compensating the loss of grassland height. Our method established the relationships between scan angle and two height loss indicators (height loss and height loss ratio) using the ground-measured canopy height of sample plots with 1×1m and LiDAR-derived heigh. We found that the height loss ratio considering the plant own height had a better performance (R2 = 0.71). We further compared the relationships between scan angle and height loss ratio according to holistic (25–65cm) and segmented (25–40cm, 40–50cm and 50–65cm) height ranges, and applied to correct the estimated grassland canopy height, respectively. Our results showed that the accuracy of grassland height estimation based on UAV LiDAR was significantly improved with R2 from 0.23 to 0.68 for holistic correction and from 0.23 to 0.82 for segmented correction. We highlight the importance of considering the effects of scan angle in LiDAR data preprocessing for estimating grassland canopy height with high accuracy, which also help for monitoring height-related grassland structural and functional parameters by remote sensing.