bluuebunny/crossref_metadata_2025 huggingface dataset:
A novel repeat sequence-based PCR (rep-PCR) using specific repeat sequences of Mycobacterium intracellulare as a DNA fingerprinting
Authors: Shin Jeong-Ih , Ha Jong-Hun , Kim Kyu-Min , Choi Jeong-Gyu , Park Seo-Rin , Park Hyun-Eui , Park Jin-Sik , Byun Jung-Hyun , Jung Myunghwan , Baik Seung-Chul , Lee Woo-Kon , Kang Hyung-Lyun , Yoo Jung-Wan , Shin Min-Kyoung
Published: April 2023

Repetitive sequence-based PCR (rep-PCR) is a potential epidemiological technique that can provide high-throughput genotype fingerprints of heterogeneous Mycobacterium strains rapidly. Previously published rep-PCR primers, which are based on nucleotide sequences of Gram-negative bacteria may have low specificity for mycobacteria. Moreover, it was difficult to ensure the continuity of the study after the commercial rep-PCR kit was discontinued. Here, we designed a novel rep-PCR for Mycobacterium intracellulare, a major cause of nontuberculous mycobacterial pulmonary disease with frequent recurrence. We screened the 7,645 repeat sequences for 200 fragments from the genome of M. intracellulare ATCC 13950 in silico, finally generating five primers with more than 90% identity for a total of 226 loci in the genome. The five primers could make different band patterns depending on the genome of three different M. intracellulare strains using an in silico test. The novel rep-PCR with the five primers was conducted using 34 bacterial samples of 7 species containing 25 M. intracellulare clinical isolates, compared with previous published rep-PCRs. This shows distinguished patterns depending on species and blotting assay for 6 species implied the sequence specificity of the five primers. The Designed rep-PCR had a 95–98% of similarity value in the reproducibility test and showed 7 groups of fingerprints in M. intracellulare strains. Designed rep-PCR had a correlation value of 0.814 with VNTR, reference epidemiological method. This study provides a promising genotype fingerprinting method for tracing the recurrence of heterogeneous M. intracellulare.
Association between gray matter atrophy, cerebral hypoperfusion, and cognitive impairment in Alzheimer’s disease
Authors: Dong Haoyang , Guo Lining , Yang Hailei , Zhu Wenshuang , Liu Fang , Xie Yingying , Zhang Yu , Xue Kaizhong , Li Qiang , Liang Meng , Zhang Nan , Qin Wen
Published: April 2023

Background

Alzheimer’s disease (AD) is one of the most severe neurodegenerative diseases leading to dementia in the elderly. Cerebral atrophy and hypoperfusion are two important pathophysiological characteristics. However, it is still unknown about the area-specific causal pathways between regional gray matter atrophy, cerebral hypoperfusion, and cognitive impairment in AD patients.

Method

Forty-two qualified AD patients and 49 healthy controls (HC) were recruited in this study. First, we explored voxel-wise inter-group differences in gray matter volume (GMV) and arterial spin labeling (ASL) -derived cerebral blood flow (CBF). Then we explored the voxel-wise associations between GMV and Mini-Mental State Examination (MMSE) score, GMV and CBF, and CBF and MMSE to identify brain targets contributing to cognitive impairment in AD patients. Finally, a mediation analysis was applied to test the causal pathways among atrophied GMV, hypoperfusion, and cognitive impairment in AD.

Results

Voxel-wise permutation test identified that the left middle temporal gyrus (MTG) had both decreased GMV and CBF in the AD. Moreover, the GMV of this region was positively correlated with MMSE and its CBF, and CBF of this region was also positively correlated with MMSE in AD (p < 0.05, corrected). Finally, mediation analysis revealed that gray matter atrophy of left MTG drives cognitive impairment of AD via the mediation of CBF (proportion of mediation = 55.82%, β = 0.242, 95% confidence interval by bias-corrected and accelerated bootstrap: 0.082 to 0.530).

Conclusion

Our findings indicated suggested that left MTG is an important hub linking gray matter atrophy, hypoperfusion, and cognitive impairment for AD, and might be a potential treatment target for AD.
Normative mice retinal thickness: 16-month longitudinal characterization of wild-type mice and changes in a model of Alzheimer's disease
Authors: Batista Ana , Guimarães Pedro , Martins João , Moreira Paula I. , Ambrósio António Francisco , Castelo-Branco Miguel , Serranho Pedro , Bernardes Rui
Published: April 2023

Animal models of disease are paramount to understand retinal development, the pathophysiology of eye diseases, and to study neurodegeneration using optical coherence tomography (OCT) data. In this study, we present a comprehensive normative database of retinal thickness in C57BL6/129S mice using spectral-domain OCT data. The database covers a longitudinal period of 16 months, from 1 to 16 months of age, and provides valuable insights into retinal development and changes over time. Our findings reveal that total retinal thickness decreases with age, while the thickness of individual retinal layers and layer aggregates changes in different ways. For example, the outer plexiform layer (OPL), photoreceptor inner segments (ILS), and retinal pigment epithelium (RPE) thickened over time, whereas other retinal layers and layer aggregates became thinner. Additionally, we compare the retinal thickness of wild-type (WT) mice with an animal model of Alzheimer's disease (3 × Tg-AD) and show that the transgenic mice exhibit a decrease in total retinal thickness compared to age-matched WT mice, with statistically significant differences observed at all evaluated ages. This normative database of retinal thickness in mice will serve as a reference for future studies on retinal changes in neurodegenerative and eye diseases and will further our understanding of the pathophysiology of these conditions.
Clinical frailty scale as a predictor of outcome in elderly patients affected by moderate or severe traumatic brain injury
Authors: Zacchetti Lucia , Longhi Luca , Zangari Rosalia , Aresi Silvia , Marchesi Federica , Gritti Paolo , Biroli Francesco , Lorini Luca Ferdinando
Published: April 2023

Background

Older age is a well-known risk factor for unfavorable outcome in traumatic brain injury (TBI). However, many older people with TBI respond well to aggressive treatments, suggesting that chronological age and TBI severity alone may be inadequate prognostic markers. Frailty is an age-related homeostatic imbalance of loss of physiologic and cognitive reserve resulting in both limitation in autonomy of activities of daily living and vulnerability to adverse events. We hypothesized that frailty would be associated with 6-month adverse functional outcome in older people affected by moderate or severe TBI.

Methods

This was a single-center prospective observational study. We enrolled consecutive patients aged ≥65 years after TBI with Glasgow Coma Scale ≤13 and admitted to our Neurosurgical Intensive Care Unit. Frailty was evaluated by Clinical Frailty Scale (CFS). Relationships between TBI severity, frailty and extended Glasgow Outcome Scale (GOSE) at 6-month were evaluated.

Results

Sixty patients were studied, 65% were males, their age was 76 years (IQR 70–80) and their admission GCS was 8 (IQR 6–11) with a GCS motor score of 5 (IQR 4–5). Twenty eight were vulnerable-frail (defined as CFS ≥ 4). Vulnerable-frail patients showed greater 6-month mortality and unfavorable outcome compared to non-frail [87% vs. 30% OR and 95% CI: 15.7 (3.9–55.2), p < 0.0001 and 92% vs. 51% OR and 95% CI: 9.9 (2.1–46.3), p = 0.002]. In univariate analysis patients with unfavorable outcome were more frequently male and vulnerable-frail, had a higher prevalence of pre-existing neurodegenerative disease, abnormal pupil, lower GCS and had worst CT scan characteristics. At multivariate analysis, only CFS ≥ 4 and traumatic subarachnoid hemorrhage remained associated to 6-month outcome.

Conclusion

Frailty was associated with 6 month-outcome, suggesting that the pre-injury functional status could represent an additional indicator to stratify patient’s severity and to predict outcome.
CAR T-cell-associated neurotoxicity in central nervous system hematologic disease: Is it still a concern?
Authors: Velasco Roser , Mussetti Alberto , Villagrán-García Macarena , Sureda Anna
Published: April 2023

Chimeric antigen receptor (CAR) T-cell systemic immunotherapy has revolutionized how clinicians treat several refractory and relapsed hematologic malignancies. Due to its peculiar mechanism of action, CAR T-cell-based therapy has enlarged the spectrum of neurological toxicities. CAR T-cell-associated neurotoxicity—initially defined as CAR T-cell-related encephalopathy syndrome (CRES) and currently coined within the acronym ICANS (immune effector cell-associated neurotoxicity syndrome)—is perhaps the most concerning toxicity of CAR T-cell therapy. Importantly, hematologic malignancies (especially lymphoid malignancies) may originate in or spread to the central nervous system (CNS) in the form of parenchymal and/or meningeal disease. Due to the emergence of deadly and neurological adverse events, such as fatal brain edema in some patients included in early CAR T-cell trials, safety concerns for those with CNS primary or secondary infiltration arose and contributed to the routine exclusion of individuals with pre-existing or active CNS involvement from pivotal trials. However, based primarily on the lack of evidence, it remains unknown whether CNS involvement increases the risk and/or severity of CAR T-cell-related neurotoxicity. Given the limited treatment options available for patients once they relapse with CNS involvement, it is of high interest to explore the role of novel clinical strategies including CAR T cells to treat leukemias/lymphomas and myeloma with CNS involvement. The purpose of this review was to summarize currently available neurological safety data of CAR T-cell-based immunotherapy from the clinical trials and real-world experiences in adult patients with CNS disease due to lymphoma, leukemia, or myeloma. Increasing evidence supports that CNS involvement in hematologic disease should no longer be considered per se as an absolute contraindication to CAR T-cell-based therapy. While the incidence may be high, severity does not appear to be impacted significantly by pre-existing CNS status. Close monitoring by trained neurologists is recommended.
Prognostic significance of TMEM131L in glioma and establishment of oxidative stress prognostic model
Authors: Shan Li , Zhu Xiaoli , Qiu Hui-Zhu , Zuo Er-Dong , Cheng Xu
Published: April 2023

Gliomas are the most aggressive of all brain tumors. In this study, it was found that there is a significant expression of transmembrane-like 131 (TMEM131L) in glioma tissues. The relevance of TMEM131L in the diagnosis and clinical prognosis of GBM and LGG was verified by additional clinical correlation and survival analysis. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve reflected the diagnostic effect of TMEM131L on the clinicopathologic features of glioma. As a unique molecular marker for the poor prognosis of overall survival (OS), PFI, and DSS in patients with GCB and LGG, TMEM131L might be employed, according to time-dependent ROC curves and Kaplan–Meier survival analysis at 1, 3, and 5 years. The potential methylation sites of TMEM131L were selected by correlation analysis between TMEM131L and DNA methylation sites. Meanwhile, TMEM131L was significantly correlated with matrix, immunity, and estimated scores of GBM and LGG. The CIBERSORT analysis revealed a significant correlation between immune checkpoint and infiltration of 22 different kinds of immune cells. Coexpression genes of TMEM131L associated with oxidative stress phenotype were screened by the LASSO logistic regression analysis. Nomogram and calibration curves further confirmed that the prognostic model composed of SYT1, CREB3L3, ITPR1, RASGRF2, PDX1, and RASGRF1 has good stability and potential application value for poor prognosis in patients with glioma.
Accelerated MRI using intelligent protocolling and subject-specific denoising applied to Alzheimer's disease imaging
Authors: Ravi Keerthi Sravan , Nandakumar Gautham , Thomas Nikita , Lim Mason , Qian Enlin , Jimeno Marina Manso , Poojar Pavan , Jin Zhezhen , Quarterman Patrick , Srinivasan Girish , Fung Maggie , Vaughan John Thomas , Geethanath Sairam
Published: April 2023

Magnetic Resonance Imaging (MR Imaging) is routinely employed in diagnosing Alzheimer's Disease (AD), which accounts for up to 60–80% of dementia cases. However, it is time-consuming, and protocol optimization to accelerate MR Imaging requires local expertise since each pulse sequence involves multiple configurable parameters that need optimization for contrast, acquisition time, and signal-to-noise ratio (SNR). The lack of this expertise contributes to the highly inefficient utilization of MRI services diminishing their clinical value. In this work, we extend our previous effort and demonstrate accelerated MRI via intelligent protocolling of the modified brain screen protocol, referred to as the Gold Standard (GS) protocol. We leverage deep learning-based contrast-specific image-denoising to improve the image quality of data acquired using the accelerated protocol. Since the SNR of MR acquisitions depends on the volume of the object being imaged, we demonstrate subject-specific (SS) image-denoising. The accelerated protocol resulted in a 1.94 × gain in imaging throughput. This translated to a 72.51% increase in MR Value—defined in this work as the ratio of the sum of median object-masked local SNR values across all contrasts to the protocol's acquisition duration. We also computed PSNR, local SNR, MS-SSIM, and variance of the Laplacian values for image quality evaluation on 25 retrospective datasets. The minimum/maximum PSNR gains (measured in dB) were 1.18/11.68 and 1.04/13.15, from the baseline and SS image-denoising models, respectively. MS-SSIM gains were: 0.003/0.065 and 0.01/0.066; variance of the Laplacian (lower is better): 0.104/−0.135 and 0.13/−0.143. The GS protocol constitutes 44.44% of the comprehensive AD imaging protocol defined by the European Prevention of Alzheimer's Disease project. Therefore, we also demonstrate the potential for AD-imaging via automated volumetry of relevant brain anatomies. We performed statistical analysis on these volumetric measurements of the hippocampus and amygdala from the GS and accelerated protocols, and found that 27 locations were in excellent agreement. In conclusion, accelerated brain imaging with the potential for AD imaging was demonstrated, and image quality was recovered post-acquisition using DL-based image denoising models.
Respiratory muscle ultrasonography evaluation and its clinical application in stroke patients: A review
Authors: Liu Xiaoman , Yang Ying , Jia Jie
Published: April 2023

Background

Respiratory muscle ultrasound is a widely available, highly feasible technique that can be used to study the contribution of the individual respiratory muscles related to respiratory dysfunction. Stroke disrupts multiple functions, and the respiratory function is often significantly decreased in stroke patients.

Method

A search of the MEDLINE, Web of Science, and PubMed databases was conducted. We identified studies measuring respiratory muscles in healthy and patients by ultrasonography. Two reviewers independently extracted and documented data regarding to the criteria. Data were extracted including participant demographics, ultrasonography evaluation protocol, subject population, reference values, etc.

Result

A total of 1954 participants from 39 studies were included. Among them, there were 1,135 participants from 19 studies on diaphragm, 259 participants from 6 studies on extra-diaphragmatic inspiratory muscles, and 560 participants from 14 studies on abdominal expiratory muscles. The ultrasonic evaluation of diaphragm and abdominal expiratory muscle thickness had a relatively typically approach, while, extra-diaphragmatic inspiratory muscles were mainly used in ICU that lack of a consistent paradigm.

Conclusion

Diaphragm and expiratory muscle ultrasound has been widely used in the assessment of respiratory muscle function. On the contrary, there is not enough evidence to assess extra-diaphragmatic inspiratory muscles by ultrasound. In addition, the thickness of the diaphragm on the hemiplegic side was lower than that on the non-hemiplegic side in stroke patients. For internal oblique muscle (IO), rectus abdominis muscle (RA), transversus abdominis muscle (TrA), and external oblique muscle (EO), most studies showed that the thickness on the hemiplegic side was lower than that on the non-hemiplegic side.

Clinical Trial Registration: The protocol of this review was registered in the PROSPERO database (CRD42022352901).
DeepDixon synthetic CT for [18F]FET PET/MRI attenuation correction of post-surgery glioma patients with metal implants
Authors: Ladefoged Claes Nøhr , Andersen Flemming Littrup , Andersen Thomas Lund , Anderberg Lasse , Engkebølle Christian , Madsen Karine , Højgaard Liselotte , Henriksen Otto Mølby , Law Ian
Published: April 2023

Purpose

Conventional magnetic resonance imaging (MRI) can for glioma assessment be supplemented by positron emission tomography (PET) imaging with radiolabeled amino acids such as O-(2-[18F]fluoroethyl)-L-tyrosine ([18F]FET), which provides additional information on metabolic properties. In neuro-oncology, patients often undergo brain and skull altering treatment, which is known to challenge MRI-based attenuation correction (MR-AC) methods and thereby impact the simplified semi-quantitative measures such as tumor-to-brain ratio (TBR) used in clinical routine. The aim of the present study was to examine the applicability of our deep learning method, DeepDixon, for MR-AC in [18F]FET PET/MRI scans of a post-surgery glioma cohort with metal implants.

Methods

The MR-AC maps were assessed for all 194 included post-surgery glioma patients (318 studies). The subgroup of 147 patients (222 studies, 200 MBq [18F]FET PET/MRI) with tracer uptake above 1 ml were subsequently reconstructed with DeepDixon, vendor-default atlas-based method, and a low-dose computed tomography (CT) used as reference. The biological tumor volume (BTV) was delineated on each patient by isocontouring tracer uptake above a TBR threshold of 1.6. We evaluated the MR-AC methods using the recommended clinical metrics BTV and mean and maximum TBR on a patient-by-patient basis against the reference with CT-AC.

Results

Ninety-seven percent of the studies (310/318) did not have any major artifacts using DeepDixon, which resulted in a Dice coefficient of 0.89/0.83 for tissue/bone, respectively, compared to 0.84/0.57 when using atlas. The average difference between DeepDixon and CT-AC was within 0.2% across all clinical metrics, and no statistically significant difference was found. When using DeepDixon, only 3 out of 222 studies (1%) exceeded our acceptance criteria compared to 72 of the 222 studies (32%) with the atlas method.

Conclusion

We evaluated the performance of a state-of-the-art MR-AC method on the largest post-surgical glioma patient cohort to date. We found that DeepDixon could overcome most of the issues arising from irregular anatomy and metal artifacts present in the cohort resulting in clinical metrics within acceptable limits of the reference CT-AC in almost all cases. This is a significant improvement over the vendor-provided atlas method and of particular importance in response assessment.
Prenatal ethanol exposure leads to persistent anxiety-like behavior during adulthood indicated by reduced horizontal and vertical exploratory behaviors
Authors: Wang An-Li , Micov Veronika B. , Kwarteng Francis , Wang Ruixiang , Hausknecht Kathryn A. , Oubraim Saida , Haj-Dahmane Samir , Shen Roh-Yu
Published: April 2023

Background

Fetal alcohol spectrum disorders (FASD) caused by prenatal ethanol exposure (PE) consist of many cognitive/behavioral deficits. Studies have reported that PE leads to impairments of learning and memory, attention, executive function, and anxiety. Open field (OF) is a common behavioral model which offers comprehensive ethological information. Here, we analyzed multiple parameters of OF to examine anxiety behavior and habituation after PE.

Material and Methods

Pregnant Sprague Dawley rats were gavaged twice/day with 0 or 3 g/kg/treatment ethanol (15% w/v) during gestational day (GD) 8–20, mimicking second-trimester heavy PE in humans. The control and PE adult offspring were subjected to OF task in different ambient light levels with or without acute stress.

Results

Prenatal ethanol exposure did not influence the overall locomotor activities or habituation in the OF. In lower ambient light, no PE effects could be detected. In higher ambient light, female PE rats showed less activities in the center zone, indicative of increased anxiety. Males show lower activities in the center zone only after acute stress. Rats spent <2% of the time in the center zone compared to >75% of the time in the corner zone where they engaged in frequent rearing activities (vertical exploration; exploratory rearing). Prenatal ethanol exposure led to lower rearing activities in the corner in both males and females. Acute stress masks the PE effects in males but not in females.

Discussion

The results support that heavy PE leads to persistent anxiety-like behavior during adulthood in both sexes. This conclusion is supported by using multiple parameters of exploratory behavior in the OF, including the rearing activities in the corner to reach reliable quantification of anxiety-like behavior.
Effects of exercise therapy on patients with poststroke cognitive impairment: A systematic review and meta-analysis
Authors: Zhang Yuanxing , Qiu Xichenhui , Chen Jinghao , Ji Cuiling , Wang Fang , Song Dan , Liu Caiyan , Chen Lu , Yuan Ping
Published: April 2023

Objective

To evaluate the effects of exercise therapy on patients with poststroke cognitive impairment and compare the differences in the effect of this method when compared with conventional measures, providing evidence for a more standardized and effective clinical application of exercise therapy.

Methods

A search was conducted using 7 electronic databases, including PubMed, CINAHL, Web of Science, CENTRAL, CNKI, Wanfang, SinoMed, and clinical trials registry platforms for randomized controlled trials concerning exercise therapy on patients with poststroke cognitive impairment. Two researchers independently screened the literature, evaluated the quality, and extracted information. Meta-analysis was carried out using Review Manager 5.4 software.

Results

There were 11 studies with 1,382 patients. Meta-analysis showed that exercise therapy could improve cognitive function [SMD = 0.67, 95% CI (0.31, 1.04), P = 0.0003], motor function [SMD = 1.81, 95% CI (0.41, 3.20), P = 0.01], and the activities of daily living [MD = 8.11, 95% CI (3.07, 13.16), P = 0.002] in patients with poststroke cognitive impairment.

Conclusion

Exercise therapy can not only improve cognitive function in patients with poststroke cognitive impairment but also improve motor function and the activities of daily living. Medical staff should prioritize the management of patients with poststroke cognitive impairment and carry out exercise therapy actively to improve the cognitive function of patients with stroke.

Systematic review registration

https://www.crd.york.ac.uk/prospero/, identifier: CRD42023397553.
Cryo-EM tomography and automatic segmentation delineate modular structures in the postsynaptic density
Authors: Jung Jae Hoon , Chen Xiaobing , Reese Thomas S.
Published: April 2023

Postsynaptic densities (PSDs) are large protein complexes associated with the postsynaptic membrane of excitatory synapses important for synaptic function including plasticity. Conventional electron microscopy (EM) typically depicts PSDs as compact disk-like structures of hundreds of nanometers in size. Biochemically isolated PSDs were also similar in dimension revealing a predominance of proteins with the ability to polymerize into an extensive scaffold; several EM studies noted their irregular contours with often small granular structures (<30 nm) and holes. Super-resolution light microscopy studies observed clusters of PSD elements and their activity-induced lateral movement. Furthermore, our recent EM study on PSD fractions after sonication observed PSD fragments (40–90 nm in size) separate from intact PSDs; however, such structures within PSDs remained unidentified. Here we examined isolated PSDs by cryo-EM tomography with our new approach of automatic segmentation that enables delineation of substructures and their quantitative analysis. The delineated substructures broadly varied in size, falling behind 30 nm or exceeding 100 nm and showed that a considerable portion of the substructures (>38%) in isolated PSDs was in the same size range as those fragments. Furthermore, substructures spanning the entire thickness of the PSD were found, large enough to contain both membrane-associated and cytoplasmic proteins of the PSD; interestingly, they were similar to nanodomains in frequency. The structures detected here appear to constitute the isolated PSD as modules of various compositions, and this modular nature may facilitate remodeling of the PSD for proper synaptic function and plasticity.
Evaluating the association between dietary salt intake and the risk of atrial fibrillation using Mendelian randomization
Authors: Wang Sicen , Cheng Ye , Zheng Qi , Su Xin , Deng Yingjian
Published: April 2023

Background

Previous studies have suggested that dietary salt intake affects atrial fibrillation (AF); however, the causal association between them still remains unclear. Thus, we conducted this Mendelian randomization (MR) study to explore the correlation between them.

Methods

Genetic instruments for dietary salt intake were from a genome-wide association study (GWAS), which included 462,630 European individuals. Summary-level data for AF were obtained from another published GWAS (22,068 cases and 116,926 controls). The inverse-variance weighting (IVW) method was performed as the primary MR analysis. Multiple MR methods, including Robust Adjusted Profile Score (MR-RAPS), maximum likelihood estimation, and Mendelian randomization pleiotropy residual sum and outlier test (MR-PRESSO) were conducted as complementary analyses. The MR-Egger regression intercept and MR-PRESSO global test were conducted to test potential horizontal pleiotropy. The IVW (Q) method and MR-Egger were performed to detect heterogeneity.

Results

Our results suggested that high dietary salt intake was significantly correlated with increased risk of AF [IVW: odds ratio (OR), 1.36; 95% confidence interval (CI), 1.04–1.77; p = 2.25E-02]. The maximum likelihood estimation (OR, 1.37; 95% CI, 1.05–1.78; p = 2.09E-02), MR-RAPS (OR, 1.37; 95% CI, 1.03–1.81; p = 2.79E-02), and MR-PRESSO method (OR, 1.36; 95% CI, 1.05–1.76; p = 2.37E-02) also showed that dietary salt intake was significantly correlated with the risk of AF.

Conclusion

The findings of this study provide robust evidence supporting the correlation between dietary salt intake and the risk of AF. Future studies are required to further clarify this relationship and translate the findings into clinical and public health practice.
Ultrasound treatment enhanced the functional properties of phycocyanin with phlorotannin from Ascophyllum nodosum
Authors: Bai Ying , Li Xueting , Xie Yuqianqian , Wang Yingzhen , Dong Xiuping , Qi Hang
Published: April 2023

Introduction

Phycocyanin offers advantageous biological effects, including immune-regulatory, anticancer, antioxidant, and anti-inflammation capabilities. While PC, as a natural pigment molecule, is different from synthetic pigment, it can be easily degradable under high temperature and light conditions.

Methods

In this work, the impact of ultrasound treatment on the complex of PC and phlorotannin structural and functional characteristics was carefully investigated. The interaction between PC and phlorotannin after ultrasound treatment was studied by UV–Vis, fluorescence spectroscopy, circular dichroism (CD) spectroscopy, fourier transform infrared (FTIR) spectroscopy. Additionally, the antioxidant potential and in vitro digestibility of the complexes were assessed.

Results

The result was manifested as the UV–Vis spectrum reduction effect, fluorescence quenching effect and weak conformational change of the CD spectrum of PC. PC was identified as amorphous based on the X-ray diffraction (XRD) data and that phlorotannin was embedded into the PC matrix. The differential scanning calorimetry (DSC) results showed that ultrasound treatment and the addition of phlorotannin could improve the denaturation peak temperatures (Td) of PC to 78.7°C. In vitro digestion and free radical scavenging experiments showed that appropriate ultrasound treatment and the addition of phlorotannin were more resistant to simulated gastrointestinal conditions and could improve DPPH and ABTS+ free radical scavenging performance.

Discussion

Ultrasound treatment and the addition of phlorotannin changed the structural and functional properties of PC. These results demonstrated the feasibility of ultrasound-assisted phlorotannin from A. nodosum in improving the functional properties of PC and provided a possibility for the application of PC-polyphenol complexes as functional food ingredients or as bioactive materials.
Impact of the adjuvant management and risk factors on survival in FIGO stage 3 endometrial cancer patients
Authors: Tong Nora , Kumar Aalok , Gelowitz Gerald , Tinker Anna , Holloway Caroline , Ko Jenny
Published: April 2023

Objective

Patients with FIGO stage III endometrial cancer routinely receive adjuvant therapy. The purpose of this study was to evaluate overall survival (OS) and disease-free survival (DFS) in patients with stage IIIA to IIIC2 patients by treatment modality received and risk factors.

Materials/methods

Patients with stage III endometrial cancer treated from 2000-2010 were identified in the provincial cancer registry. Clinicopathologic characteristics, adjuvant treatments and outcomes were compared using descriptive and multivariable analyses.

Results

261 patients had stage 3 endometrial cancer, 132 with stage IIIA, 9 with IIIB, 85 with IIIC1 and 35 with IIIC2. 39 had FIGO grade 1 disease; 73, grade 2; 147, grade 3. 160 had endometrioid and 35 had serous carcinoma. 161 patients received sequential adjuvant chemotherapy (CT) and radiotherapy (RT); 33 received RT only; 32 received CT only; 35 received neither. 5-year (5Y) DFS and OS were similar among stage IIIA (DFS 46.7%, OS 58.5%), IIIB (DFS 50.8%, OS 58.5%), IIIC1 (DFS 44%, OS 49.9%) and IIIC2 (DFS 42%, OS 41.6%). Use of adjuvant RT was associated with improved median DFS (53.7 vs 14.7m, p<0.00001) and OS (61.9 vs 25.7m, p<0.00001) compared to no RT. Likewise, use of adjuvant CT was also associated with improved DFS (54.8 vs 16.5m, p<0.00001) and OS (62.9 vs 26.5m, p<0.00001) compared to no CT. Those who received both chemotherapy and radiotherapy had better outcomes with 5-year DFS (58.3%) and OS (65.2%), compared with those who received monotherapy. On multivariate analysis, grade 3 disease, deep myometrial invasion >50%, and no adjuvant RT or CT were identified as adversely impacting DFS and OS.

Conclusion

In stage III endometrial cancer patients, use of both chemotherapy and radiation therapy was associated with improved DFS and OS and therefore should be recommended in all eligible patients after resection.
Long-term survival with anlotinib as a front-line treatment in an elderly NSCLC patient: A case report
Authors: Wang Jingyi , Li Xiaoqing , Zhou Juan , Qiu Dan , Zhang Mengyao , Sun Lan , Li Shengwen Calvin
Published: April 2023

Background

Half of the population of non-small cell lung cancer (NSCLC) patients are older than 70 years and have limited therapeutic options due to poor tolerance and being excluded in most clinical trials. Anlotinib hydrochloride, a novel oral multi-target tyrosine kinase inhibitor, has been approved for the standard third-line treatment for NSCLC in China. Herein we report an elderly NSCLC patient without any driver gene mutations who was undergoing anlotinib as a front-line treatment and who achieved long-term survival.

Case summary

The 77-year-old male patient was admitted to the hospital for chest tightness after engaging in physical activity for a week. The patient has been diagnosed with stage IIIB driver gene-negative squamous cell lung carcinoma. After that, he was treated with anlotinib for 2 years and 10 months from the first diagnosis until the last disease progression. Briefly, anlotinib combined with platinum-based chemotherapy was performed as the first-line therapy over six cycles. After 6 more cycles of anlotinib monotherapy maintenance, disease progression occurred. Then, anlotinib combined with tegafur was administered as a salvage treatment, and the disease was controlled again. After 29 cycles of anlotinib combined with tegafur regimens, the disease progressed finally. The patient achieved a total of 34 months of progression-free survival after anlotinib was used as the front-line treatment. He is still alive with a good performance status now (performance status score: 1).

Conclusion

This patient achieved long-term survival using anlotinib as a front-line regimen combined with chemotherapy.
The application of radiomics in esophageal cancer: Predicting the response after neoadjuvant therapy
Authors: Guo Hai , Tang Hong-Tao , Hu Wen-Long , Wang Jun-Jie , Liu Pei-Zhi , Yang Jun-Jie , Hou Sen-Lin , Zuo Yu-Jie , Deng Zhi-Qiang , Zheng Xiang-Yun , Yan Hao-Ji , Jiang Kai-Yuan , Huang Heng , Zhou Hai-Ning , Tian Dong
Published: April 2023

Esophageal cancer (EC) is one of the fatal malignant neoplasms worldwide. Neoadjuvant therapy (NAT) combined with surgery has become the standard treatment for locally advanced EC. However, the treatment efficacy for patients with EC who received NAT varies from patient to patient. Currently, the evaluation of efficacy after NAT for EC lacks accurate and uniform criteria. Radiomics is a multi-parameter quantitative approach for developing medical imaging in the era of precision medicine and has provided a novel view of medical images. As a non-invasive image analysis method, radiomics is an inevitable trend in NAT efficacy prediction and prognosis classification of EC by analyzing the high-throughput imaging features of lesions extracted from medical images. In this literature review, we discuss the definition and workflow of radiomics, the advances in efficacy prediction after NAT, and the current application of radiomics for predicting efficacy after NAT.
An updated perspective on immunoglobulin replacement in chronic lymphocytic leukaemia in the era of targeted therapies
Authors: Khan Sujoy , Allsup David , Molica Stefano
Published: April 2023

Chronic lymphocytic leukaemia (CLL) is a malignancy of clonally expanded antigen-switched, neoplastic, mature B cells. CLL is characterised by a variable degree of immunosuppression and secondary hypogammaglobulinemia. B-cell depleting therapies have historically been deployed with a proportion of patients becoming resistant to multiple lines of treatment with an associated worsening of immunosuppression and heightened infection risk. Advances in molecular diagnostics and the development of new therapies targeting Bruton’s tyrosine kinase and B-cell lymphoma-2 have resulted in novel insights into the cellular mechanisms associated with an increased infection risk and T-cell escape from the complex tumour environment found in CLL. Generally, immunoglobulin replacement therapy with polyvalent human immunoglobulin G (IgG) is indicated in patients with recurrent severe bacterial infections and low IgG levels, but there is no consensus on the threshold IgG level for initiation of such therapy. A proportion of CLL patients have residual IgG production, with preserved quality of the immunoglobulin molecules, and therefore a definition of ‘IgG quality’ may allow for lower dosing or less frequent treatment with immunoglobulin therapy in such patients. Immunoglobulin therapy can restore innate immunity and in conjunction with CLL targeted therapies may allow T-cell antigen priming, restore T-cell function thereby providing an escape from tumour-associated autoimmunity and the development of an immune-mediated anti-tumour effect. This review aims to discuss the mechanisms by which CLL-targeted therapy may exert a synergistic therapeutic effect with immunoglobulin replacement therapy both in terms of reducing tumour bulk and restoration of immune function.
SP70 is a novel biomarker of hepatocellular carcinoma
Authors: Wang Lin , Shi Hui , Wei Jia , Chen Wen-Xiu , Jin Yue-Xinzi , Gu Chun-Rong , Mu Yuan , Xu Jian , Pan Shi-Yang
Published: April 2023

Background

Tumor-specific protein 70 (SP70) was identified as a new biomarker associated with the proliferation and invasion of cancer cells. This study aimed to investigate the expression of SP70 in hepatocellular carcinoma (HCC) and assess its clinical value in the diagnosis and prediction of early HCC recurrence.

Methods

A total of 1049 subjects from the First Affiliated Hospital of Nanjing Medical University were recruited in this study. Serum SP70, alpha-fetoprotein (AFP) and prothrombin induced by vitamin K absence II (PIVKA-II) were measured. The diagnostic performance for HCC was obtained using the receiver operating characteristic (ROC) curve, and recurrence-free survival (RFS) was calculated using the Kaplan–Meier method. Univariate and multivariate analyses were performed to identify predictive factors of RFS.

Results

SP70 was highly expressed in HCC cells and HCC tissue. Serum SP70 levels in the HCC group were significantly higher than in the benign liver diseases group and healthy control group (P<0.001). SP70 combined with AFP showed the best diagnostic performance (AUC=0.909, 95%CI [confidence interval]=0.890–0.929). Kaplan–Meier analysis revealed that patients with high SP70 levels had shorter median RFS than those with low SP70 levels (P=0.003). In addition, high SP70 levels were significantly associated with shorter RFS (P=0.037) in the AFP-negative subgroup. Univariate and multivariate analyses confirmed that preoperative serum SP70 level, serum AFP, tumor diameter and microvascular invasion were independent prognostic factors of RFS.

Conclusion

SP70 is a promising biomarker in diagnosing HCC. High preoperative serum SP70 level is associated with an increased risk of early relapse and could be used as a valuable marker to predict early recurrence of HCC after resection.
Advanced pancreatic cancer with KRAS wild-type and EGFR-sensitive mutation respond favorably to furmonertinib: A case report
Authors: Ma Xiaoting , Liu Xiu , Ou Kai , Zhang Manman , Gao Lizhen , Yang Lin
Published: April 2023

Pancreatic cancer is the leading cause of cancer death, and treatment options are limited and mostly ineffective. The patient we report had an EGFR exon 19 deletion and had disease progression in the short term after receiving three front-line treatment regimens. We administered furmonertinib and observed tumor shrinkage, decreased CA19-9. The progression-free survival (PFS) of furmonertinib was 4.7 months, and no adverse effects were observed. However, the patient did not benefit from subsequent nimotuzumab-based therapy. Targeted therapy driven by the detection of genetic signatures in this patient shows potential clinical benefit in refractory advanced pancreatic cancer.
The prognostic value of postoperative radiotherapy in right tumor for lung related death: based on SEER database and real-world data
Authors: Mo You , Chen Minxin , Wang Minglei , Wu Meng , Yu Jinming
Published: April 2023

Background

Postoperative radiotherapy (PORT) is a therapeutic strategy for patients with non-small cell lung cancer (NSCLC). Nevertheless, some studies suggesting PORT does not improve overall survival (OS) including Lung ART phase III trial. The role of PORT and high-risk groups need to be confirmed.

Methods

Patients from the Surveillance, Epidemiology, and End Results program (SEER) from 2004 to 2015 were eligible. Aged ≥18 years with stage IIIA-N2 NSCLC, accepted PORT or not were considered for the study. Cox regression analyses and multivariate competing risk model were performed. Propensity score matching (PSM) was conducted. Data from a single-center study in China were used for validation.

Results

In all patients with IIIA-N2 NSCLC, death from respiratory illness increased year by year, with right lung-related deaths accounting for the main proportion. In SEER database, PORT was detrimental for OS after PSM (hazard ratio [HR], 1.088; 95% CI, 1.088–1.174; P = 0.031), with a same trend for death from the lungs (HR, 1.13; 95% CI, 1.04–1.22; P = 0.005). Right tumor receiving PORT were prone to death from lung disease(HR, 1.14; 95% CI, 1.02–1.27; P = 0.018). In China single-center cohort, PORT was significantly correlated with deteriorated OS (HR 1.356; 95% CI 1.127–1.632; P <0.01), especially in the right laterality (HR 1.365; 95% CI 1.062–1.755; P = 0.015).

Conclusions

PORT was a risk factor for stage IIIA-N2 NSCLC patients, particularly with characters of right laterality, male sex, age ≥65 years, and advanced tumor stage. These patients are more likely to death from lung disease after PORT.
Super-resolution STED imaging in the inner and outer whole-mount mouse retina
Authors: Kremers Leon , Sarieva Kseniia , Hoffmann Felix , Zhao Zhijian , Ueffing Marius , Euler Thomas , Nikić-Spiegel Ivana , Schubert Timm
Published: April 2023

Since its invention, super-resolution microscopy has become a popular tool for advanced imaging of biological structures, allowing visualisation of subcellular structures at a spatial scale below the diffraction limit. Thus, it is not surprising that recently, different super-resolution techniques are being applied in neuroscience, e.g. to resolve the clustering of neurotransmitter receptors and protein complex composition in presynaptic terminals. Still, the vast majority of these experiments were carried out either in cell cultures or very thin tissue sections, while there are only a few examples of super-resolution imaging in deeper layers (30 - 50 µm) of biological samples. In that context, the mammalian whole-mount retina has rarely been studied with super-resolution microscopy. Here, we aimed at establishing a stimulated-emission-depletion (STED) microscopy protocol for imaging whole-mount retina. To this end, we developed sample preparation including horizontal slicing of retinal tissue, an immunolabeling protocol with STED-compatible fluorophores and optimised the image acquisition settings. We labelled subcellular structures in somata, dendrites, and axons of retinal ganglion cells in the inner mouse retina. By measuring the full width at half maximum of the thinnest filamentous structures in our preparation, we achieved a resolution enhancement of two or higher compared to conventional confocal images. When combined with horizontal slicing of the retina, these settings allowed visualisation of putative GABAergic horizontal cell synapses in the outer retina. Taken together, we successfully established a STED protocol for reliable super-resolution imaging in the whole-mount mouse retina at depths between 30 and 50 µm, which enables investigating, for instance, protein complex composition and cytoskeletal ultrastructure at retinal synapses in health and disease.
Risk factors and early markers for echovirus type 11 associated haemorrhage-hepatitis syndrome in neonates, a retrospective cohort study
Authors: Wang Ping , Xu Yi , Liu Ming , Li Huixian , Wang Hui , Liu Yumei , Wang Bin , Xia Shiwen , Su Heng , Wei Mou , Tao Li , Chen Xiaowen , Lu Bingtai , Gu Xiaoqiong , Lyu Hui , Zhou Wei , Zhang Huayan , Gong Sitang
Published: April 2023

Background

Echovirus type 11(E-11) can cause fatal haemorrhage-hepatitis syndrome in neonates. This study aims to investigate clinical risk factors and early markers of E-11 associated neonatal haemorrhage-hepatitis syndrome.

Methods

This is a multicentre retrospective cohort study of 105 neonates with E-11 infection in China. Patients with haemorrhage-hepatitis syndrome (the severe group) were compared with those with mild disease. Clinical risk factors and early markers of haemorrhage-hepatitis syndrome were analysed. In addition, cytokine analysis were performed in selective patients to explore the immune responses.

Results

In addition to prematurity, low birth weight, premature rupture of fetal membrane, total parenteral nutrition (PN) (OR, 28.7; 95% CI, 2.8–295.1) and partial PN (OR, 12.9; 95% CI, 2.2–77.5) prior to the onset of disease were identified as risk factors of developing haemorrhage-hepatitis syndrome. Progressive decrease in haemoglobin levels (per 10 g/L; OR, 1.5; 95% CI, 1.1–2.0) and platelet (PLT) < 140 × 10⁹/L at early stage of illness (OR, 17.7; 95% CI, 1.4–221.5) were associated with the development of haemorrhage-hepatitis syndrome. Immunological workup revealed significantly increased interferon-inducible protein-10(IP-10) (P < 0.0005) but decreased IFN-α (P < 0.05) in peripheral blood in severe patients compared with the mild cases.

Conclusions

PN may potentiate the development of E-11 associated haemorrhage-hepatitis syndrome. Early onset of thrombocytopenia and decreased haemoglobin could be helpful in early identification of neonates with the disease. The low level of IFN-α and elevated expression of IP-10 may promote the progression of haemorrhage-hepatitis syndrome.
Association of interleukin-4, interleukin-13 gene polymorphisms, HLA-DQ and DR genotypes with genetic susceptibility of type-1 Diabetes Mellitus in Kuwaiti children
Authors: Haider Mohammad Z. , Al Rushood Maysoun , Alsharhan Hind , Rasoul Majedah A. , Al-Mahdi Maria , Al-Kandari Hessa
Published: April 2023

Background

Type-1 diabetes mellitus (T1DM) is a complex multifactorial disease with an autoimmune etiology and is thought to result from an interaction between genetic and non-genetic factors. Cytokines play a crucial role in the pathogenesis of autoimmune diseases due to their effector and regulatory functions in immune responses. Interleukin-4 (IL4) and Interleukin-13 (IL13) are anti-inflammatory cytokines and are considered as important mediators in pathology of the autoimmune diseases.

Methods

We have determined the genotype frequency of IL4 gene promoter polymorphism (−590C/T, rs2243250), IL13 gene polymorphism p.(Arg130Glu, rs20541) and human leukocyte antigen, HLA-DQ and DR genotypes in Kuwaiti children with T1DM to investigate their role in genetic susceptibility. This study included 261 Kuwaiti children with T1DM and 214 healthy controls. The genotypes for IL4 (−590C/T) and IL13 p.(Arg130Glu) gene polymorphisms were detected by PCR-RFLP methods. HLA-DQ and DR genotypes were determined by sequence-specific PCR methods.

Results

The CC genotype of IL4 gene polymorphism (−590C/T) was significantly related to the risk for T1DM in Kuwaiti patients (OR 1.64). The homozygous AA (QQ) and heterozygous AG (RQ) genotypes of IL13 gene polymorphism p.(Arg130Glu), also manifested a statistically significant association with T1DM (OR 2.92 and 4.79). In 55% T1DM patients, the HLA genotype was either DQ2/DQ2 or in combination with a DQ8 allele. Collectively, 91% Kuwaiti T1DM patients had either DQ2 or DQ8 alleles in different combinations highlighting them as the high risk-genotypes in comparison to the controls. In the case of HLA-DR, the genotypes DR3/DRB5, DR3/DR4, DR3/DR7 and DR4/DR4 showed highest frequency amongst the Kuwaiti T1DM patients and thus can be considered as high-risk genotypes when compared to the controls. A high degree of co-inheritance (>80%) was detected between IL4 and IL13 gene polymorphism genotypes (CC and QQ) and the high-risk HLA-DQ and DR genotypes amongst the Kuwaiti T1DM patients.

Conclusions

We have identified the association of IL4 and IL13 gene polymorphisms with susceptibility to T1DM in Kuwaiti children and the co-inheritance of these polymorphisms with high-risk HLA genotypes. The findings may contribute to early identification of childhood diabetes.