bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of neutralizing antibodies to COVID-19 inactivated or subunit recombinant vaccines in hospitalized patients with liver dysfunction
Authors: Li Hu , Li Shiyin , Xu Pan , Wang Xiaohao , Deng Huan , Lei Yu , Zhong Shan
Published: January 2023

Background

The neutralizing antibodies (NAbs) response after COVID-19 vaccination after liver dysfunction is unclear. In this study, we evaluated the NAbs response after COVID-19 vaccination in hospitalized patients suffering from liver dysfunction.

Methods

In this cross-sectional study with longitudinal follow-up, we enrolled eligible patients with liver dysfunction and healthy volunteers with full-course COVID-19 vaccination. Blood samples were collected for the NAbs testing at the time of admission and after treatment. Multiple regression analysis to assess independent risk factors affecting NAbs response.

Results

A total of 137 patients and 134 healthy controls (HC) were enrolled. Both seropositivity (65.7% vs 80.6%, p<0.01) and titer (3.95 vs 4.94 log2 AU/ml, p<0.001) of NAbs in patients were significantly lower than that in HC. The decrease of antibody titer in patients was significantly faster than that in HC. After adjusting for potential confounding factors, males (odds ratio [OR]: 0.17; 95% confidence interval [CI]: 0.06, 0.46; p<0.001) and severe liver damage (OR: 0.30; 95% CI: 0.12, 0.71; p<0.01) were significantly associated with reduction of the probability of NAbs seropositivity in the multiple regression analysis. Males (β =-1.18; 95% CI: -1.73,-0.64) and chronic liver diseases (β =-1.45; 95% CI: -2.13, -0.76) were significantly associated with lower NAbs titers. In 26 patients with liver failure, both antibody seropositivity (53.8% vs 84.6%, p<0.05) and titer (3.55 vs 4.32 log2 AU/ml, p<0.001) did not decrease but increased after artificial liver plasmapheresis.

Conclusions

NAbs response to COVID-19 inactivated or subunit recombinant vaccines was waning in patients with liver dysfunction. Moreover, patients with male sex, severe liver injury and chronic liver diseases have an increased risk of poor antibody responses.
AIM2 and Psoriasis
Authors: Zhang Yuxi , Xu Xiaoqing , Cheng Hui , Zhou Fusheng
Published: January 2023

Psoriasis is a chronic inflammatory skin disease occurring worldwide, with multiple systemic complications, which seriously affect the quality of life and physical and mental health of patients. The pathogenesis of psoriasis is related to the environment, genetics, epigenetics, and dysregulation of immune cells such as T cells, dendritic cells (DCs), and nonimmune cells such as keratinocytes. Absent in melanoma 2 (AIM2), a susceptibility gene locus for psoriasis, has been strongly linked to the genetic and epigenetic aspects of psoriasis and increased in expression in psoriatic keratinocytes. AIM2 was found to be activated in an inflammasome-dependent way to release IL-1β and IL-18 to mediate inflammation, and to participate in immune regulation in psoriasis, or in an inflammasome-independent way by regulating the function of regulatory T(Treg) cells or programming cell death in keratinocytes as well as controlling the proliferative state of different cells. AIM2 may also play a role in the recurrence of psoriasis by trained immunity. In this review, we will elaborate on the characteristics of AIM2 and how AIM2 mediates the development of psoriasis.
Electroacupuncture and human iPSC-derived small extracellular vesicles regulate the gut microbiota in ischemic stroke via the brain-gut axis
Authors: Zhang Qiongqiong , Deng Peiying , Chen Suhui , Xu Hong , Zhang Yamin , Chen Hui , Zhang Jianmin , Sun Hua
Published: January 2023

Electroacupuncture (EA) and induced pluripotent stem cell (iPSC)-derived small extracellular vesicles (iPSC-EVs) have substantial beneficial effects on ischemic stroke. However, the detailed mechanisms remain unclear. Here, we explored the mechanisms underlying the regulation of EA and iPSC-EVs in the microbiome-gut-brain axis (MGBA) after ischemic stroke. Ischemic stroke mice (C57BL/6) were subjected to middle cerebral artery occlusion (MCAO) or Sham surgery. EA and iPSC-EVs treatments significantly improved neurological function and neuronal and intestinal tract injury, downregulated the levels of IL-17 expression and upregulated IL-10 levels in brain and colon tissue after cerebral ischemia−reperfusion. EA and iPSC-EVs treatments also modulated the microbiota composition and diversity as well as the differential distribution of species in the intestines of the mice after cerebral ischemia−reperfusion. Our results demonstrated that EA and iPSC-EVs treatments regulated intestinal immunity through MGBA regulation of intestinal microbes, reducing brain and colon damage following cerebral ischemia and positively impacting the outcomes of ischemic stroke. Our findings provide new insights into the application of EA combined with iPSC-EVs as a treatment for ischemic stroke.
Efficacy and safety of lenvatinib combined with PD-1/PD-L1 inhibitors plus Gemox chemotherapy in advanced biliary tract cancer
Authors: Zhu Chengpei , Xue Jingnan , Wang Yunchao , Wang Shanshan , Zhang Nan , Wang Yanyu , Zhang Longhao , Yang Xu , Long Junyu , Yang Xiaobo , Sang Xinting , Zhao Haitao
Published: January 2023

Background

Lenvatinib combined with anti-PD-1 antibodies and systemic chemotherapy has demonstrated a relatively high antitumor activity for intrahepatic cholangiocarcinoma in phase 2 clinical trials. However, its efficacy and safety in advanced biliary tract cancer (BTC) has not been reported in a real-world study.

Methods

Patients with advanced BTC who received lenvatinib combined with PD-1/PD-L1 inhibitors plus oxaliplatin and gemcitabine (Gemox) chemotherapy were retrospectively screened. The overall survival, progression-free survival, objective response rate, disease control rate, clinical benefit rate, and safety were evaluated.

Results

Fifty-seven patients with advanced BTC were included in the study. The median follow-up time was 15.1 (95% CI: 13.6–19.7) months. The median overall survival and progression-free survival were 13.4 (95% CI: 10.0–NA), and 9.27 (95% CI: 7.1–11.6) months, respectively. The objective response rate, disease control rate and clinical benefit rate were 43.9% (95% CI: 31.8%–56.7%), 91.2% (95% CI: 81.1%–96.2%), and 73.7% (95% CI: 61.0%–83.4%), respectively. Subgroup analysis revealed that the first-line treatment group had a longer median progression-free survival (12.13 vs. 6.77 months, P<0.01) and median overall survival (25.0 vs. 11.6 months, P=0.029) than the non-first-line treatment group. Moreover, three patients underwent conventional surgery after treatment. All patients (100%) experienced adverse events, and 45.6% (26/57) experienced grade 3 or 4 adverse events. The most commonly observed grade 3 or 4 adverse events was myelosuppression (7/57, 12.3%). No grade 5 adverse events were reported.

Conclusion

Lenvatinib combined with PD-1/PD-L1 inhibitors and Gemox chemotherapy represents an effective and tolerable treatment option in patients with advanced BTC.
Absorption-based algorithm for satellite estimating the particulate organic carbon concentration in the global surface ocean
Authors: Li Qiang , Jiang Lingling , Chen Yanlong , Tang Junwu , Gao Siwen
Published: January 2023

Particulate organic carbon (POC) in the surface ocean contributes to understanding the global ocean carbon cycle system. The surface POC concentration can be effectively detected using satellites. In open oceans, the blue-to-green band ratio (BG) algorithm is often used to obtain global surface ocean POC concentrations. However, POC concentrations are underestimated in waters with complex optical environments. To generate a more accurate global POC mapping in the surface ocean, we developed a new ocean color algorithm using a mixed global-scale in situ POC dataset with the concentration ranging from 11.10 to 4389.28 mg/m3. The new algorithm (a-POC) was established to retrieve the POC concentration using the strong relationship between the absorption coefficient at 490 nm (a(490)) and POC, in which a(490) was from the Ocean Color Climate Change Initiative (OC-CCI) v5.0 suite. Afterward, the a-POC algorithm was applied to OC-CCI v5.0 data for special regions and the global ocean. The performances of the a-POC algorithm and the BG algorithm were compared by combining the match-ups of satellite data and in situ dataset. The results showed that the statistical parameters of the a-POC algorithm were similar to those of the BG algorithm in the Atlantic oligotrophic gyre regions, with a median absolute percentage deviation (MAPD) value of 22.04%. In the eastern coastal waters of the United States and the Chesapeake Bay, the POC concentration retrieved by the a-POC algorithm was highly consistent with the match-ups, and MAPD values were 33.06% and 26.11%. The a-POC algorithm was also applied to the Ocean and Land Color Instrument (OLCI) data pre-processed with different atmospheric correction algorithms to evaluate the universality. The result showed that the a-POC algorithm was robust and less sensitive to atmospheric correction than the BG algorithm.
Seasonal variability in spatial patterns of sea surface cold- and warm fronts over the continental shelf of the northern South China Sea
Authors: Chen Jiayuan , Hu Zifeng
Published: January 2023

Ubiquitous fronts are a key part of energy transfer from large scales to small scales and exert a great impact on material exchange and biogeochemical processes. The spatial pattern and seasonal variability of cold- and warm fronts over the wide shelf of the northern South China Sea (SCS) are investigated using a 20-year time series (2002−2021) of 1-km spatial resolution Group for High Resolution Sea Surface Temperature (GHRSST) images. Our analysis shows distinct spatial and temporal variability in the occurrence of the cold- and warm fronts. Over the inner shelf (depth <50 m), the band-shaped cold fronts are predominately observed during spring through autumn from east of Hainan Island to Taiwan Shoal, with the presence of the maximum intensity and probability in winter. The frontal formations are possibly associated with the joint effect of the Guangdong Coastal Current (GCC) and the South China Sea Warm Current. During summer, the inshore fronts have relatively low probability and gradient magnitude. The warm fronts mainly occur off the western Guangdong coast possibly due to the southwestward-flowing GCC, whereas the cold fronts dominate off the eastern Guangdong coast and the eastern Hainan Island largely because of the coastal upwelling. Over the outer shelf (depth >50 m), the finer-scale cold- and warm fronts are discretely observed, with relatively weaker intensity and lower probability. The frontal activities are very vigorous in winter but slightly quiescent in summer, apparently resulting from the influence of the rich submesoscale processes in the SCS. This study could help improve our understanding of the SCS oceanic multiscale dynamics.
The structure of MadC from Clostridium maddingley reveals new insights into class I lanthipeptide cyclases
Authors: Knospe C. Vivien , Kamel Michael , Spitz Olivia , Hoeppner Astrid , Galle Stefanie , Reiners Jens , Kedrov Alexej , Smits Sander H. J. , Schmitt Lutz
Published: January 2023

The rapid emergence of microbial multi-resistance against antibiotics has led to intense search for alternatives. One of these alternatives are ribosomally synthesized and post-translationally modified peptides (RiPPs), especially lantibiotics. They are active in a low nanomolar range and their high stability is due to the presence of characteristic (methyl-) lanthionine rings, which makes them promising candidates as bacteriocides. However, innate resistance against lantibiotics exists in nature, emphasizing the need for artificial or tailor-made lantibiotics. Obviously, such an approach requires an in-depth mechanistic understanding of the modification enzymes, which catalyze the formation of (methyl-)lanthionine rings. Here, we determined the structure of a class I cyclase (MadC), involved in the modification of maddinglicin (MadA) via X-ray crystallography at a resolution of 1.7 Å, revealing new insights about the structural composition of the catalytical site. These structural features and substrate binding were analyzed by mutational analyses of the leader peptide as well as of the cyclase, shedding light into the mode of action of MadC.
Epidemiological and genomic characteristics of global mcr-positive Escherichia coli isolates
Authors: Shi Jiping , Zhu Hong , Liu Chang , Xie Hui , Li Chuchu , Cao Xiaoli , Shen Han
Published: January 2023

Objective

The worldwide dissemination of colistin-resistant Escherichia coli (E. coli) endangers public health. This study aimed to better understand the global genomic epidemiology of E. coli isolates carrying mobilized colistin resistance (mcr) genes, providing information to assist in infection and prevention.

Methods

Escherichia coli genomes were downloaded from NCBI, and mcr was detected using BLASTP. Per software was used to extract information on hosts, resources, collection data, and countries of origin from GenBank. Sequence types (STs), prevalence of plasmids, antimicrobial resistance genes (ARG), and virulence factors (VF) in these genomes were analyzed. Statistical analyses were performed to assess the relationships between mcr, ARGs, plasmids, and STs.

Results

In total, 778 mcr-positive isolates were identified. Four mcr variants were detected, with mcr-1 (86.1%) being the most widespread, followed by mcr-9 (5.7%), mcr-5 (4.4%), and mcr-3 (3.0%). Multiple ARGs were identified, with blaCTX–M (53.3%), fosA (28.8%), qnr (26.1%), blaNDM (19.8%), and aac (6’)-Ib-cr (14.5%) being the most common. Overall, 239 distinct STs were identified, of which ST10 (13.8%) was the most prevalent. A total of 113 different VFs were found, terC (99.9%) and gad (83.0%) were most frequently detected. Twenty types of plasmids were identified; IncFIB (64.1%), IncX (42.3%), and IncX (42.3%) were the most common replicons. IncI2 and IncX4 were frequently detected in mcr-1-positive isolates, whereas IncFII, IncI1-I, and IncHI2 were dominant plasmids in mcr-3, mcr-5, and mcr-9-positive isolates, respectively. A higher frequency of ARGs and VFs was observed among ST156 and ST131 isolates.

Conclusion

Our data indicated that more than half of the mcr-positive E. coli strains carried endemic ARGs and VFs. ST10 and ST156 isolates deserved further attention, given the rapid transmission of ST10 and the convergence of ARGs and VFs in ST156.
PSC-derived intestinal organoids with apical-out orientation as a tool to study nutrient uptake, drug absorption and metabolism
Authors: Kakni Panagiota , López-Iglesias Carmen , Truckenmüller Roman , Habibović Pamela , Giselbrecht Stefan
Published: January 2023

Intestinal organoids recapitulate many features of the in vivo gastrointestinal tract and have revolutionized in vitro studies of intestinal function and disease. However, the restricted accessibility of the apical surface of the organoids facing the central lumen (apical-in) limits studies related to nutrient uptake and drug absorption and metabolism. Here, we demonstrate that pluripotent stem cell (PSC)-derived intestinal organoids with reversed epithelial polarity (apical-out) can successfully recapitulate tissue-specific functions. In particular, these apical-out organoids show strong epithelial barrier formation with all the major junctional complexes, nutrient transport and active lipid metabolism. Furthermore, the organoids express drug-metabolizing enzymes and relevant apical and basolateral transporters. The scalable and robust generation of functional, apical-out intestinal organoids lays the foundation for a completely new range of organoid-based high-throughput/high-content in vitro applications in the fields of nutrition, metabolism and drug discovery.
Frailty as a dynamic process in a diverse cohort of older persons with dialysis-dependent CKD
Authors: Kutner Nancy G. , Zhang Rebecca
Published: January 2023

This study examines frailty status evolution observed in a two-year follow-up of a cohort of older persons (age ≥65) with chronic kidney disease (CKD) undergoing maintenance hemodialysis (HD) treatment. Frailty, a geriatric syndrome that connotes a state of low physiologic reserve and vulnerability to stressors, is associated with increased risk for multiple adverse health outcomes in studies of persons with CKD as well as older persons in the general population. The Fried frailty index defines frailty as the presence of 3 or more of 5 indicators—recent unintentional weight loss, slowed gait speed, decreased muscle strength, self-reported exhaustion, and low physical activity. In the seminal work by Fried and colleagues, persons who were characterized by 1-2 of the Fried index criteria were termed “pre-frail” and considered at risk for subsequently becoming frail, potentially providing insight regarding intervention targets that might slow or prevent individuals’ transition from pre-frail to frail status. Other less frequently studied types of transitions may also be informative, including “recovery or reversion” (improvement) by people whose longitudinal assessments indicate movement from frailty to prefrailty or robust, or from prefrailty to robust. These status changes are also a potential source of insights relevant for prevention or remediation of frailty, but research focusing on the various ways that individuals may transition between frailty states over time remains limited, and no previous research has examined varying patterns of frailty status evolution in an older cohort of persons with dialysis-dependent CKD. In a study cohort of dialysis-dependent older persons, we characterized patterns of frailty status evolution by age, sex, race/ethnicity, and treatment vintage; by longitudinal profiles of non-sedentary behavior; and by self-report indicators relevant for dimensions emphasized in the Age-Friendly 4Ms Health System (What Matters, Mobility, Mentation). Our study suggests that strategies to promote resiliency among older persons with dialysis-dependent CKD can be informed not only by frailty status transition that indicates improvement over time but also by older adults’ maintenance of (stable) robust status over time, and we concur that inclusion of both frailty and resilience measures is needed in future longitudinal studies and clinical trials.
Pre- and in-hospital delays in the use of thrombolytic therapy for patients with acute ischemic stroke in rural and urban Egypt
Authors: Nasreldein Ahmed , Walter Silke , Mohamed Khaled O. , Shehata Ghaydaa Ahmed , Ghali Azza A. , Dahshan Ahmed , Faßbender Klaus , Abd-Allah Foad
Published: January 2023

Background

Reducing pre- and in-hospital delays plays an important role in increasing the rate of intravenous thrombolysis (IVT) in patients with acute ischemic stroke. In Egypt, the IVT rate has increased steadily but is still far away from an ideal rate.

Aim

The study aimed to investigate the factors associated with pre- and in-hospital delays of IVT among patients with acute ischemic stroke coming from urban and rural communities.

Methods

This prospective, multicenter, observational cohort study was conducted from January 2018 to January 2019. Patients with acute ischemic stroke, who did not receive IVT, were included in the study. Patients were recruited from three large university stroke centers in Egypt, Assiut (south of Egypt), Tanta (north of Egypt), both serving urban and rural patients, and the University Hospital in Cairo (capital city), only serving an urban community. All participants underwent the National Institutes of Health Stroke Scale and full neurological assessment, urgent laboratory investigations, and computed tomography or magnetic resonance imaging to confirm the stroke diagnosis. The patients were subjected to a structured questionnaire that was designed to determine the parameters and time metrics for the pre- and in-hospital delays among patients from rural and urban regions.

Results

A total of 618 patients were included in the study, of which 364 patients (58.9%) lived in rural regions and 254 (41.1%) in urban regions. General demographic characteristics were similar between both groups. Approximately 73.3% of patients who arrived within the therapeutic time window were urban patients. The time from symptom onset till hospital arrival (onset to door time, ODT) was significantly longer among rural patients (738 ± 690 min) than urban patients (360 ± 342 min). Delayed onset to alarm time (OAT), initial misdiagnosis, and presentation to non-stroke-ready hospitals were the most common causes of pre-hospital delay and were significantly higher in rural patients. For patients arriving within the time window, the most common causes of in-hospital delays were prolonged laboratory investigations and imaging duration.

Conclusion

The limited availability of stroke-ready hospitals in rural Egypt leads to delays in stroke management, with subsequent treatment inequality of rural patients with acute stroke.
Modulatory effects of mesenchymal stem cells on microglia in ischemic stroke
Authors: Hao Lei , Yang Yongtao , Xu Xiaoli , Guo Xiuming , Zhan Qunling
Published: January 2023

Ischemic stroke accounts for 70–80% of all stroke cases. Immunity plays an important role in the pathophysiology of ischemic stroke. Microglia are the first line of defense in the central nervous system. Microglial functions are largely dependent on their pro-inflammatory (M1-like) or anti-inflammatory (M2-like) phenotype. Modulating neuroinflammation via targeting microglia polarization toward anti-inflammatory phenotype might be a novel treatment for ischemic stroke. Mesenchymal stem cells (MSC) and MSC-derived extracellular vesicles (MSC-EVs) have been demonstrated to modulate microglia activation and phenotype polarization. In this review, we summarize the physiological characteristics and functions of microglia in the healthy brain, the activation and polarization of microglia in stroke brain, the effects of MSC/MSC-EVs on the activation of MSC in vitro and in vivo, and possible underlying mechanisms, providing evidence for a possible novel therapeutics for the treatment of ischemic stroke.
Application of TBSS-based machine learning models in the diagnosis of pediatric autism
Authors: He Xiongpeng , Zhao Xin , Sun Yongbing , Geng Pengfei , Zhang Xiaoan
Published: January 2023

Objective

To explore the microstructural changes of white matter in children with pediatric autism by using diffusion kurtosis imaging (DKI), and evaluate whether the combination of tract-based spatial statistics (TBSS) and back-propagation neural network (BPNN)/support vector machine (SVM)/logistic regression (LR) was feasible for the classification of pediatric autism.

Methods

DKI data were retrospectively collected from 32 children with autism and 27 healthy controls (HCs). Kurtosis fractional anisotropy (FAK), mean kurtosis (MK), axial kurtosis (KA), radial kurtosis (RK), fractional anisotropy (FA), axial diffusivity (DA), mean diffusivity (MD) and Radial diffusivity (DR) were generated by iQuant workstation. TBSS was used to detect the regions of parameters values abnormalities and for the comparison between these two groups. In addition, we also introduced the lateralization indices (LI) to study brain lateralization in children with pediatric autism, using TBSS for additional analysis. The parameters values of the differentiated regions from TBSS were then calculated for each participant and used as the features in SVM/BPNN/LR. All models were trained and tested with leave-one-out cross validation (LOOCV).

Results

Compared to the HCs group, the FAK, DA, and KA values of multi-fibers [such as the bilateral superior longitudinal fasciculus (SLF), corticospinal tract (CST) and anterior thalamic radiation (ATR)] were lower in pediatric autism group (p < 0.05, TFCE corrected). And we also found DA lateralization abnormality in Superior longitudinal fasciculus (SLF) (the LI in HCs group was higher than that in pediatric autism group). However, there were no significant differences in FA, MD, MK, DR, and KR values between HCs and pediatric autism group (P > 0.05, TFCE corrected). After performing LOOCV to train and test three model (SVM/BPNN/LR), we found the accuracy of BPNN (accuracy = 86.44%) was higher than that of LR (accuracy = 76.27%), but no different from SVM (RBF, accuracy = 81.36%; linear, accuracy = 84.75%).

Conclusion

Our proposed method combining TBSS findings with machine learning (LR/SVM/BPNN), was applicable in the classification of pediatric autism with high accuracy. Furthermore, the FAK, DA, and KA values and Lateralization index (LI) value could be used as neuroimaging biomarkers to discriminate the children with pediatric autism or not.
Neural basis of dysphagia in stroke: A systematic review and meta-analysis
Authors: Qin Yin , Tang Yuting , Liu Xiaoying , Qiu Shuting
Published: January 2023

Objectives

Dysphagia is a major cause of stroke infection and death, and identification of structural and functional brain area changes associated with post-stroke dysphagia (PSD) can help in early screening and clinical intervention. Studies on PSD have reported numerous structural lesions and functional abnormalities in brain regions, and a systematic review is lacking. We aimed to integrate several neuroimaging studies to summarize the empirical evidence of neurological changes leading to PSD.

Methods

We conducted a systematic review of studies that used structural neuroimaging and functional neuroimaging approaches to explore structural and functional brain regions associated with swallowing after stroke, with additional evidence using a live activation likelihood estimation (ALE) approach.

Results

A total of 35 studies were included, including 20 studies with structural neuroimaging analysis, 14 studies with functional neuroimaging analysis and one study reporting results for both. The overall results suggest that structural lesions and functional abnormalities in the sensorimotor cortex, insula, cerebellum, cingulate gyrus, thalamus, basal ganglia, and associated white matter connections in individuals with stroke may contribute to dysphagia, and the ALE analysis provides additional evidence for structural lesions in the right lentiform nucleus and right thalamus and functional abnormalities in the left thalamus.

Conclusion

Our findings suggest that PSD is associated with neurological changes in brain regions such as sensorimotor cortex, insula, cerebellum, cingulate gyrus, thalamus, basal ganglia, and associated white matter connections. Adequate understanding of the mechanisms of neural changes in the post-stroke swallowing network may assist in clinical diagnosis and provide ideas for the development of new interventions in clinical practice.
2.5D and 3D segmentation of brain metastases with deep learning on multinational MRI data
Authors: Ottesen Jon André , Yi Darvin , Tong Elizabeth , Iv Michael , Latysheva Anna , Saxhaug Cathrine , Jacobsen Kari Dolven , Helland Åslaug , Emblem Kyrre Eeg , Rubin Daniel L. , Bjørnerud Atle , Zaharchuk Greg , Grøvik Endre
Published: January 2023

Introduction

Management of patients with brain metastases is often based on manual lesion detection and segmentation by an expert reader. This is a time- and labor-intensive process, and to that end, this work proposes an end-to-end deep learning segmentation network for a varying number of available MRI available sequences.

Methods

We adapt and evaluate a 2.5D and a 3D convolution neural network trained and tested on a retrospective multinational study from two independent centers, in addition, nnU-Net was adapted as a comparative benchmark. Segmentation and detection performance was evaluated by: (1) the dice similarity coefficient, (2) a per-metastases and the average detection sensitivity, and (3) the number of false positives.

Results

The 2.5D and 3D models achieved similar results, albeit the 2.5D model had better detection rate, whereas the 3D model had fewer false positive predictions, and nnU-Net had fewest false positives, but with the lowest detection rate. On MRI data from center 1, the 2.5D, 3D, and nnU-Net detected 79%, 71%, and 65% of all metastases; had an average per patient sensitivity of 0.88, 0.84, and 0.76; and had on average 6.2, 3.2, and 1.7 false positive predictions per patient, respectively. For center 2, the 2.5D, 3D, and nnU-Net detected 88%, 86%, and 78% of all metastases; had an average per patient sensitivity of 0.92, 0.91, and 0.85; and had on average 1.0, 0.4, and 0.1 false positive predictions per patient, respectively.

Discussion/Conclusion

Our results show that deep learning can yield highly accurate segmentations of brain metastases with few false positives in multinational data, but the accuracy degrades for metastases with an area smaller than 0.4 cm2.
The possible therapeutic role of curcumin and quercetin in the early-stage of COVID-19—Results from a pragmatic randomized clinical trial
Authors: Ujjan Ikram Din , Khan Saeed , Nigar Roohi , Ahmed Hammad , Ahmad Sagheer , Khan Amjad
Published: January 2023

Background

Curcumin (CUR) and quercetin (QUE), two natural polyphenols, possess diverse biological activities including broad-spectrum antiviral, antioxidant, and immunomodulatory effects. Both CUR and QUE have shown inhibition of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in in vitro assays.

Objective

In the present study we aimed to assess the possible treatment benefits of a combined curcumin and quercetin (CUR-QUE) oral supplement, alongside standard of care (SOC), in the early-stage COVID-19 infection.

Methods

This was an exploratory, pragmatic, open-label, randomized controlled clinical trial, conducted at the Department of Pathology, Liaquat University of Medical and Health Sciences, Jamshoro, PK. The study compared the treatment effect of an oral CUR-QUE supplement plus SOC vs. SOC alone, in the early-stage/mild to moderately symptomatic COVID-19 outpatients. Patients were randomized in a 1:1 ratio to CUR-QUE (n = 25) and control (n = 25) treatment groups. The CUR-QUE supplementation consisted of a daily intake of 168 mg curcumin and 260 mg quercetin, as two soft capsules, to be taken twice a day at home for 14 days.

Results

After one-week of treatment, most of the patients in the CUR-QUE group showed an expedited clearance of the viral infection i.e., 18 (72.0%) vs. 6 (24.0%) patients in the control group tested negative for SARS-CoV-2 in the nasal-oropharyngeal swab reverse transcription-polymerase chain reaction (RT-PCR) analysis (p = 0.0002). In addition, COVID-19-associated acute symptoms were also speedily resolved in the CUR-QUE treated patients, i.e., 10 (40.0%) vs. 4 (16.0%) patients in the control group (p = 0.061). The CUR-QUE supplementation therapy was well-tolerated by all 25 patients and no treatment-emergent effects or serious adverse events were reported.

Conclusion

The results revealed in this exploratory study suggest a possible therapeutic role of curcumin and quercetin in the early-stage of COVID-19. It is proposed that the two agents possibly acting in synergy, interfere the SARS-CoV-2 replication, and thus help a speedy recovery in the early-stage of COVID-19. Further research is highly encouraged.

Clinical trial registration

Clinicaltrials.gov, Identifier NCT04603690.
Association between healthy eating index-2015 and abdominal aortic calcification among US Adults
Authors: Jia Jundi , Zhang Jie , Ma Dan , Zhang Zihao , Zhao Lin , Wang Tongxin , Xu Hao
Published: January 2023

Aims

To evaluate the relationship of the healthy eating index-2015 (HEI-2015) with abdominal aortic calcification (AAC) in US adults.

Methods

We conducted a cross-sectional study with data extracted from the National Health and Nutrition Examination Survey (NHANES). AAC score was measured using the scoring system of Kauppila (AAC-24) and Schousboe (AAC-8). HEI-2015, which was used for evaluating compliance with Dietary Guidelines for Americans (DGA), was calculated through two rounds of 24-h recall interviews. HEI-2015 was categorized as inadequate (<50), average (50~70), and optimal (≥70) groups for analysis, while the AAC-24 score was grouped by whether the score was >0. Weighted multiple regression analyses were conducted to estimate the association of HEI-2015 with AAC score and the presence of AAC. Moreover, smooth curve fittings, based on a generalized additive model (GAM), were applied to evaluate a possible non-linear relationship. Sensitivity analysis and subgroup analysis were performed to provide more supporting information.

Results

A total of 2,704 participants were included in the study (mean age, 57.61 ± 11.40 years; 51.78% were women). The mean score of HEI-2015 was 56.09 ± 13.40 (41.33 ± 6.28, 59.44 ± 5.54, and 76.90 ± 5.37 for inadequate, average, and optimal groups, respectively). After adjusting for covariates, higher HEI-2015 was associated with decreased AAC score (AAC-24: β = −0.121, 95% CI: −0.214, −0.028, P = 0.010; AAC-8: β= −0.054, 95% CI: −0.088, −0.019, P = 0.003) and lower risk of AAC (OR = 0.921, 95% CI: 0.855, 0.993, P = 0.031). Among the components of HEI-2015, a higher intake of fruits, greens, and beans was associated with a lower AAC score. Subgroup analysis showed that an inverse association of HEI-2015 with AAC score existed among different groups.

Conclusion

The study presented that higher HEI-2015 was related to a lower AAC score and decreased risk of having AAC, indicating that greater compliance with 2015–2020 DGA, assessed by HEI-2015, might be beneficial for preventing vascular calcification and CVD among US adults.
The influence of the China GLIM standards on the diagnosis of malnutrition in patients with hematopoietic stem cell transplant
Authors: Guo Feng , Min Liu , Chengyuan Li , Hong Liu , Meng Wang , Chenyi Tang , Jinru Wu , Wei Wu , Hua Liu
Published: January 2023

Background

The muscle-related indicator is removed from Global Leadership Initiative on Malnutrition (GLIM) criteria implemented in China for many reasons. Patients with hematopoietic stem cell transplants are at nutrition risk and can enter into the second step of GLIM; thus, they are suitable for learning the diagnosing malnutrition significance between primary GLIM and GLIM-China criteria. This article aims to explore the role of muscle mass in the diagnostic criteria of malnutrition and the effects of GLIM-China for diagnosing malnutrition.

Methods

A total of 98 inpatients with hematopoietic stem cell transplants (HSCT) were recruited. Nutrition risk was assessed by using the Nutritional Risk Screening 2002 (NRS-2002). Appendicular skeletal muscle mass (ASMI) and fat-free mass index (FFMI) were determined using the bioelectrical impedance analysis (BIA) method. Malnutrition is defined by GLIM-China, GLIM, and PG-SGA. We use erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) to assess inflammation in GLIM and GLIM-China. The correlation or consistency among ASMI, FFMI, ESR, CRP, GLIM-China, GLIM, and PG-SGA was evaluated, respectively.

Results

One hundred percent instead of the patients had nutritional risk. The magnitude of malnutrition using PG-SGA, GLIM, and GLIM-China was 75.5, 80.6, and 64.3%, respectively. GLIM-China and PG-SGA showed the same performance (p = 0.052 vs. 1.00) and agreement (kappa = 0.404 vs. 0.433, p < 0.0001) with the FFMI. Consistency was noted between ASMI and PG-SGA in the assessment of malnutrition (p = 0.664) with a good agreement (kappa = 0.562, p = 0.084). ASMI and FFMI could determine muscle mass reduction, which could not be determined by BMI, albumin (ALB), and pre-albumin (pre-ALB); 34% of GLIM-China (–) patients were with low ASMI, and 40% with low FFMI; 30.0% of patients with PG-SGA (<4) still have low ASMI, and 38.2% have low FFMI.

Conclusion

If only the PG-SGA scale is used as a diagnostic criterion for evaluating malnutrition, a large proportion of patients with reduced muscle mass will be missed, but more patients with muscle loss will be missed via GLIM-China. Muscle-related indicators will help diagnose malnutrition.
Postoperative ctDNA detection predicts relapse but has limited effects in guiding adjuvant therapy in resectable stage I NSCLC
Authors: Wang Bolin , Zou Bing , Xu Shengnan , Zhao Chao , Pei Jinli , Wang Shijie , Zhao Kunlong , Yu Jinming , Liu Jie
Published: January 2023

Background

To date, identifying resectable stage I non-small cell lung cancer (NSCLC) patients likely to benefit from adjuvant therapy (ADT) remains a major challenge. Previous studies suggest that circulating tumor DNA (ctDNA) is emerging as a promising biomarker for NSCLC. However, the effectiveness of ctDNA detection in guiding ADT for resectable stage I NSCLC patients remains elusive. This study aimed to elucidate the role of ctDNA detection in estimating prognosis and guiding ADT for resectable stage I NSCLC patients.

Methods

Individual patient data and ctDNA results data were collected from 270 patients across four independent cohorts. The detection of ctDNA was conducted at 3 days to 1 month after surgery. The endpoint for this study was relapse-free survival (RFS) and overall survival (OS).

Results

Of the 270 resectable stage I NSCLC patients, 9 patients with ctDNA-positive and 261 patients with ctDNA-negative. We found that the risk of recurrence was significantly lower in the ctDNA-negative group compared to the ctDNA-positive group(HR=0.11, p<0.0001). However, there is no difference in the risk of death between the two groups (p =0.39). In the ctDNA-positive group, there were no significant differences in RFS between patients who received ADT and patients who did not receive ADT (p =0.58). In the ctDNA-negative group, those who received ADT had a worse RFS in comparison with those who did not receive ADT (HR=2.36, p =0.029). No difference in OS was seen between patients who received ADT and patients who did not receive ADT in both the ctDNA-positive group and the ctDNA-negative group (All p values>0.05). Furthermore, there was no difference in RFS and OS between patients who received chemotherapy-based or tyrosine kinase inhibitor-based ADT and patients who did not receive ADT in both the ctDNA-positive group and the ctDNA-negative group (All p values>0.05).

Conclusions

Postoperative ctDNA detection can be a prognostic marker to predict recurrence but has limited effects in guiding ADT for resectable stage I NSCLC. Future prospective investigations are needed to verify these results.
The specific signs of lung ultrasound to diagnose pulmonary hemorrhage of the newborns: Evidence from a multicenter retrospective case-control study
Authors: Liu Jing , Chi Jing-Han , Lu Zu-Lin , Fu Wei
Published: January 2023

Objectives

Pulmonary hemorrhage (PH) is one kind of critical lung diseases in newborn infants, which is the most difficult one to be diagnosed by ultrasound. This study was to investigate the specific ultrasonic signs of PH in order to better diagnose neonatal PH by using lung ultrasound (LUS).

Methods

A total 168 newborn infants were enrolled in this study, which included PH, pneumonia, meconium aspiration syndrome, and newborns without lung diseases, there were 42 cases in each group. In a quiet state, infants were placed in the supine, lateral or prone position for the examination. Each lung was divided into the anterior, lateral and posterior regions, then each region of both lungs was scanned with the probe perpendicular to the ribs or parallel to the Intercostal spaces.

Results

The major results showed that: (1) the common LUS manifestation of PH includes lung consolidation, air bronchograms, fluid bronchograms, pleural effusion, shred signs, pleural line abnormality and B-lines, while fibrin deposition sign is a rare sign of PH. (2) Co-existing of lung consolidation with fluid bronchograms and pleural effusion is the specific sign of PH with a sensitivity of 81.0%, specificity of 98.4% and the positive predictive value (PPV) was 94.4%. (3) Fibrin deposition sign is an uncommon specific LUS sign of PH with a sensitivity 28.6%, specificity of 100% and the PPV was 100%. (4) Nine patients (21.4%) were diagnosed with PH based on ultrasound findings before oronasal bleeding. (5) The survival rate of infants with PH was 100% in this study.

Conclusion

LUS is helpful for the early diagnosis of neonatal PH and may therefore improve the prognosis. The lung consolidation with fluid bronchograms and pleural effusion as well as fibrin deposition sign are specific to diagnose PH by using LUS.
Regional risk of tuberculosis and viral hepatitis with tumor necrosis factor-alpha inhibitor treatment: A systematic review
Authors: Jahnich Nina , Arkwright Peter D.
Published: January 2023

Background: TNFα inhibitors are regularly used to treat autoimmune diseases. Tuberculosis (TB) and viral hepatitis B are considered potential infectious complications, and screening and surveillance are therefore recommended. Current guidelines do not take into account regional differences in endemicity of these infections.

Methods: A systematic literature review of TB and viral hepatitis in patients receiving TNFα-inhibitors was performed, searching in PubMed, Embase, MEDLINE and Web of Science databases. Studies were selected against predefined eligibility criteria and assessed using the Newcastle-Ottawa scale. The number of TB and viral hepatitis cases/1,000 TNFα-inhibitor patients were evaluated, and regional variation compared.

Results: 105 observational studies involving over 140,000 patients were included. Overall, 1% of patients developed TB or viral hepatitis B. TB cases/1,000 TNFα-inhibitor patients were 4-fold higher in Asia, Africa, and South America than in Europe, North America, and Australasia where only 0%–0.4% of patients developed TB. Hepatitis B cases/1,000 patients were over 15-fold higher in countries with high prevalence (China, Taiwan, South Korea, Thailand) compared with low prevalence (p < 0.00001) where only 0.4% of patients developed hepatitis B. Only three of 143 patients developed viral hepatitis C, and there was insufficient data to allow regional sub-analysis.

Conclusion: TB and viral hepatitis B infections in patients treated with TNFα inhibitors are largely confined to countries with high prevalence of these infections. As only 1/2,500 patients in low prevalence countries treated with TNFα inhibitors develop TB or viral hepatitis B, we suggest an individualized, risk-based approach, rather than universal screening for all patients.
Downregulation of nuclear STAT2 protein in the spinal dorsal horn is involved in neuropathic pain following chronic constriction injury of the rat sciatic nerve
Authors: Huang Zhifeng , Ding Zijing , Xu Yangting , Xi Caiyun , He Liqiong , Luo Hui , Guo Qulian , Huang Changsheng
Published: January 2023

Regulation of gene transcription in the spinal dorsal horn (SDH) plays a critical role in the pathophysiology of neuropathic pain. In this study, we investigated whether the transcription factor STAT2 affects neuropathic pain and evaluated its possible mechanisms. A proteomic analysis showed that the nuclear fraction of STAT2 protein in the SDH was downregulated after chronic constriction injury of the rat sciatic nerve, which was associated with the development of neuropathic pain. Similarly, siRNA-induced downregulation of STAT2 in the SDH of naïve rats also resulted in pain hypersensitivity. Using RNA-sequencing analysis, we showed that reduction of nuclear STAT2 after chronic constriction injury was associated with increased expression of microglial activation markers, including the class II transactivator and major histocompatibility complex class II proteins. In addition, siRNA-induced downregulation of STAT2 promoted microglial activation and pro-inflammatory cytokine expression in the SDH. Taken together, these results showed that chronic constriction injury caused downregulation of nuclear STAT2 in the SDH, which may result in microglial activation and development of neuropathic pain. Our findings indicate that restoration of nuclear expression of STAT2 could be a potential pathway for the treatment of neuropathic pain.
Cascaded information enhancement and cross-modal attention feature fusion for multispectral pedestrian detection
Authors: Yang Yang , Xu Kaixiong , Wang Kaizheng
Published: January 2023

Multispectral pedestrian detection is a technology designed to detect and locate pedestrians in Color and Thermal images, which has been widely used in automatic driving, video surveillance, etc. So far most available multispectral pedestrian detection algorithms only achieved limited success in pedestrian detection because of the lacking take into account the confusion of pedestrian information and background noise in Color and Thermal images. Here we propose a multispectral pedestrian detection algorithm, which mainly consists of a cascaded information enhancement module and a cross-modal attention feature fusion module. On the one hand, the cascaded information enhancement module adopts the channel and spatial attention mechanism to perform attention weighting on the features fused by the cascaded feature fusion block. Moreover, it multiplies the single-modal features with the attention weight element by element to enhance the pedestrian features in the single-modal and thus suppress the interference from the background. On the other hand, the cross-modal attention feature fusion module mines the features of both Color and Thermal modalities to complement each other, then the global features are constructed by adding the cross-modal complemented features element by element, which are attentionally weighted to achieve the effective fusion of the two modal features. Finally, the fused features are input into the detection head to detect and locate pedestrians. Extensive experiments have been performed on two improved versions of annotations (sanitized annotations and paired annotations) of the public dataset KAIST. The experimental results show that our method demonstrates a lower pedestrian miss rate and more accurate pedestrian detection boxes compared to the comparison method. Additionally, the ablation experiment also proved the effectiveness of each module designed in this paper.