bluuebunny/crossref_metadata_2025 huggingface dataset:
Alterations in white matter integrity and network topological properties are associated with a decrease in global motion perception in older adults
Authors: Yan Shizhen , Zhang Yuping , Yin Xiaojuan , Chen Juntao , Zhu Ziliang , Jin Hua , Li Han , Yin Jianzhong , Jiang Yunpeng
Published: March 2023

Previous studies have mainly explored the effects of structural and functional aging of cortical regions on global motion sensitivity in older adults, but none have explored the structural white matter (WM) substrates underlying the age-related decrease in global motion perception (GMP). In this study, random dot kinematogram and diffusion tensor imaging were used to investigate the effects of age-related reductions in WM fiber integrity and connectivity across various regions on GMP. We recruited 106 younger adults and 94 older adults and utilized both tract-based spatial statistics analysis and graph theoretical analysis to comprehensively investigate group differences in WM microstructural and network connections between older and younger adults at the microscopic and macroscopic levels. Moreover, partial correlation analysis was used to explore the relationship between alterations in WM and the age-related decrease in GMP. The results showed that decreased GMP in older adults was related to decreased fractional anisotropy (FA) of the inferior frontal-occipital fasciculus, inferior longitudinal fasciculus, anterior thalamic radiation, superior longitudinal fasciculus, and cingulum cingulate gyrus. Decreased global efficiency of the WM structural network and increased characteristic path length were closely associated with decreased global motion sensitivity. These results suggest that the reduced GMP in older adults may stem from reduced WM integrity in specific regions of WM fiber tracts as well as decreased efficiency of information integration and communication between distant cortical regions, supporting the “disconnection hypothesis” of cognitive aging.
Chemokines in patients with Alzheimer's disease: A meta-analysis
Authors: Wang Hecheng , Zong Yu , Zhu Lei , Wang Weiyi , Han Yanshuo
Published: March 2023

Background

Alzheimer's disease (AD) is the most common neurodegenerative disease in elderly people. Many researches have reported that neuroinflammation is related to AD. Chemokines are a class of small cytokines that play important roles in cell migration and cell communication, which involved in neuroinflammation. Up to now there is no meta-analysis to explore the difference of chemokines between AD patients and healthy elderly individuals.

Method

We searched PubMed, Web of science, Cochrane library, EMBASE and Scopus databases from inception to January 2022. Data were extracted by two independent reviewers, and the Review Manager 5.3 was used for the meta-analysis.

Result

Thirty-two articles were included and analyzed. The total number of participants in the included study was 3,331. We found that the levels of CCL5 (SMD = 2.56, 95% CI: 1.91–3.21), CCL15 (SMD = 3.30, 95% CI: 1.48–5.13) and IP-10 (SMD = 3.88, 95% CI: 1.84–5.91) in the plasma of AD patients were higher than healthy people. MCP-1 protein (SMD = 0.67, 95% CI: 0.29–1.05) in the AD patients' CSF was higher than healthy controls.

Conclusion

These results suggested that chemokines may play an important role in AD. These findings could provide evidences for the diagnosis and treatment of AD.

Systematic review registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021278736, identifier: CRD42021278736.
Utility of quantitative MRI metrics in brain ageing research
Authors: Filip Pavel , Kokošová Viktória , Valenta Zdeněk , Baláž Marek , Mangia Silvia , Michaeli Shalom , Vojtíšek Lubomír
Published: March 2023

The advent of new, advanced quantitative MRI metrics allows for in vivo evaluation of multiple biological processes highly relevant for ageing. The presented study combines several MRI parameters hypothesised to detect distinct biological characteristics as myelin density, cellularity, cellular membrane integrity and iron concentration. 116 healthy volunteers, continuously distributed over the whole adult age span, underwent a multi-modal MRI protocol acquisition. Scatterplots of individual MRI metrics revealed that certain MRI protocols offer much higher sensitivity to early adulthood changes while plateauing in higher age (e.g., global functional connectivity in cerebral cortex or orientation dispersion index in white matter), while other MRI metrics provided reverse ability—stable levels in young adulthood with sharp changes with rising age (e.g., T1ρ and T2ρ). Nonetheless, despite the previously published validations of specificity towards microstructural biology based on cytoarchitectonic maps in healthy population or alterations in certain pathologies, several metrics previously hypothesised to be selective to common measures failed to show similar scatterplot distributions, pointing to further confounding factors directly related to age. Furthermore, other metrics, previously shown to detect different biological characteristics, exhibited substantial intercorrelations, be it due to the nature of the MRI protocol itself or co-dependence of relevant biological microstructural processes. All in all, the presented study provides a unique basis for the design and choice of relevant MRI parameters depending on the age group of interest. Furthermore, it calls for caution in simplistic biological inferences in ageing based on one simple MRI metric, even though previously validated under other conditions. Complex multi-modal approaches combining several metrics to extract the shared subcomponent will be necessary to achieve the desired goal of histological MRI.
Molecular identity of the lateral lemniscus nuclei in the adult mouse brain
Authors: García-Guillén Isabel M. , Aroca Pilar , Marín Faustino
Published: March 2023

The dorsal (DLL), intermediate (ILL), and ventral (VLL) lateral lemniscus nuclei are relay centers in the central auditory pathway of the brainstem, commonly referred to as the lateral lemniscus nuclei (LLN). The LLN are situated in the prepontine and pontine hindbrain, from rhombomeres 1 to 4, extending from the more rostral DLL to the caudal VLL, with the ILL lying in between. These nuclei can be distinguished morphologically and by topological and connectivity criteria, and here, we set out to further characterize the molecular nature of each LLN. We searched in situ hybridization studies in the Allen Mouse Brain Atlas for genes differentially expressed along the rostrocaudal axis of the brainstem, identifying 36 genes from diverse functional families expressed in the LLN. Available information in the databases indicated that 7 of these 36 genes are either associated with or potentially related to hearing disorders. In conclusion, the LLN are characterized by specific molecular profiles that reflect their rostrocaudal organization into the three constituent nuclei. This molecular regionalization may be involved in the etiology of some hearing disorders, in accordance with previous functional studies of these genes.
Hierarchical strategy for sEMG classification of the hand/wrist gestures and forces of transradial amputees
Authors: Leone Francesca , Mereu Federico , Gentile Cosimo , Cordella Francesca , Gruppioni Emanuele , Zollo Loredana
Published: March 2023

Introduction

The myoelectric control strategy, based on surface electromyographic signals, has long been used for controlling a prosthetic system with multiple degrees of freedom. Several methods classify gestures and force levels but the simultaneous real-time control of hand/wrist gestures and force levels did not yet reach a satisfactory level of effectiveness.

Methods

In this work, the hierarchical classification approach, already validated on 31 healthy subjects, was adapted for the real-time control of a multi-DoFs prosthetic system on 15 trans-radial amputees. The effectiveness of the hierarchical classification approach was assessed by evaluating both offline and real-time performance using three algorithms: Logistic Regression (LR), Non-linear Logistic Regression (NLR), and Linear Discriminant Analysis (LDA).

Results

The results of this study showed the offline performance of amputees was promising and comparable to healthy subjects, with mean F1 scores of over 90% for the “Hand/wrist gestures classifier” and 95% for the force classifiers, implemented with the three algorithms with features extraction (FE). Another significant finding of this study was the feasibility of using the hierarchical classification strategy for real-time applications, due to its ability to provide a response time of 100 ms while maintaining an average online accuracy of above 90%.

Discussion

A possible solution for real-time control of both hand/wrist gestures and force levels is the combined use of the LR algorithm with FE for the "Hand/wrist gestures classifier", and the NLR with FE for the Spherical and Tip force classifiers.
Hypoxic culture of umbilical cord mesenchymal stem cell-derived sEVs prompts peripheral nerve injury repair
Authors: Zhu Ziying , Zhang Yujun , Huang Zhihua , Hao Haojie , Yan Muyang
Published: March 2023

Introduction

Repair and regeneration of the peripheral nerve are important for the treatment of peripheral nerve injury (PNI) caused by mechanical tears, external compression injuries and traction injuries. Pharmacological treatment can promote the proliferation of fibroblasts and Schwann cells (SCs), which longitudinally fill the endoneurial canal and form Bungner’s band, helping the repair of peripheral nerves. Therefore, the development of new drugs for the treatment of PNI has become a top priority in recent years.

Methods

Here, we report that small extracellular vesicles (sEVs) produced from umbilical cord mesenchymal stem cells (MSC-sEVs) cultured under hypoxia promote repair and regeneration of the peripheral nerve in PNI and may be a new therapeutic drug candidate.

Results

The results showed that the amount of secreted sEVs was significantly increased in UC-MSCs compared with control cells after 48 h of culture at 3% oxygen partial pressure in a serum-free culture system. The identified MSC-sEVs could be taken up by SCs in vitro, promoting the growth and migration of SCs. In a spared nerve injury (SNI) mouse model, MSC-sEVs accelerated the recruitment of SCs at the site of PNI and promoted peripheral nerve repair and regeneration. Notably, repair and regeneration in the SNI mouse model were enhanced by treatment with hypoxic cultured UC-MSC-derived sEVs.

Discussion

Therefore, we conclude that hypoxic cultured UC-MSC-derived sEVs may be a promising candidate drug for repair and regeneration in PNI.
Excitatory synchronization of rat hippocampal interneurons during network activation in vitro
Authors: Pendeliuk Viktoria S. , Melnick Igor V.
Published: March 2023

Introduction

Hippocampal interneurons (INs) are known to synchronize their electrical activity via mechanisms, which are poorly defined due to immense complexity of neural tissue but seem to depend on local cell interactions and intensity of network activity.

Methods

Here, synchronization of INs was studied using paired patch-clamp recordings in a simplified culture model with intact glutamate transmission. The level of network activity was moderately elevated by field electric stimulation, which is probably an analogue of afferent processing in situ.

Results

Even in baseline conditions, ∼45% of spontaneous inhibitory postsynaptic currents (sIPSCs) resulting from firing of individual presynaptic INs coincided between cells within ±1 ms due to simple divergence of inhibitory axons. Brief network activation induced an appearance of ‘hypersynchronous’ (∼80%) population sIPSCs occurring in response to coherent discharges of several INs with jitter ±4 ms. Notably, population sIPSCs were preceded by transient inward currents (TICs). Those were excitatory events capable to synchronize firing of INs, in this respect being reminiscent of so-called fast prepotentials observed in studies on pyramidal neurons. TICs also had network properties consisting of heterogeneous components: glutamate currents, local axonal and dendritic spikelets, and coupling electrotonic currents likely via gap junctions; putative excitatory action of synaptic gamma-aminobutyric acid (GABA) was not involved. The appearance of population excitatory-inhibitory sequences could be initiated and reproduced by firing of a single excitatory cell reciprocally connected with one IN.

Discussion

Our data demonstrate that synchronization of INs is initiated and dominated by glutamatergic mechanisms, which recruit, in a whole-sale manner, into supporting action other excitatory means existing in a given neural system.
The controlling nutritional status score and risk factors associated with malnutrition in patients with acute ischemic stroke
Authors: Chen Yuanyuan , Yang Hongyan , Lan Meijuan , Wei Hui , Chen Yanqin
Published: March 2023

Objectives

Malnutrition is an independent risk factor for poor outcomes in patients who suffered an acute ischemic stroke (AIS). The controlling nutritional status (CONUT) score can provide information for nutritional management in AIS patients. However, the risk factors associated with the CONUT score have not been established to date. Therefore, in this study, we aimed to investigate the CONUT score of patients with AIS and explore the potential risk factors associated with it.

Methods

We conducted a retrospective review of the data from consecutive AIS patients who were recruited in the CIRCLE study. Within 2 days of admission, we gathered the CONUT score, the Nutritional Risk Screening 2002, the Modified Rankin Scale, the National Institutes of Health Neurological Deficit Score (NIHSS), and demographic data from medical records. We used chi-squared tests to examine admission, and a logistic regression analysis was performed to explore the risk factors associated with CONUT in patients with AIS.

Results

A total of 231 patients with AIS participated in the study, with a mean age of 62.32 ± 13.0 years and a mean NIHSS of 6.77 ± 3.8. Of these patients, 41(17.7%) had hyperlipidemia. In terms of nutritional assessment, 137(59.3%) patients with AIS had high CONUT scores, 86(37.2%) patients with AIS had low or high BMI, and 117(50.6%) patients with AIS had NRS-2002 scores below 3. The chi-squared tests showed that age, NIHSS, body mass index (BMI), and hyperlipidemia were associated with the CONUT score (P < 0.05). The logistic regression analysis showed that low NIHSS scores (OR = 0.055 95% CI: 0.003–0.893), younger age (OR = 0.159 95% CI: 0.054–0.469), and hyperlipidemia (OR = 0.303 95% CI: 0.141–0.648) were independently associated with lower CONUT scores (P < 0.05), whereas BMI was not found to be independently associated with the CONUT.

Conclusions

More than half of the patients with AIS were at risk of malnutrition, with age and neurological deficits being identified as risk factors for nutritional control. Hyperlipidemia was found to be a protective factor of the CONUT, while NRS-2002 and BMI did not affect the nutritional control in patients with AIS.
Cocktail-party listening and cognitive abilities show strong pleiotropy
Authors: Mathias Samuel R. , Knowles Emma E. M. , Mollon Josephine , Rodrigue Amanda L. , Woolsey Mary K. , Hernandez Alyssa M. , Garret Amy S. , Fox Peter T. , Olvera Rene L. , Peralta Juan M. , Kumar Satish , Göring Harald H. H. , Duggirala Ravi , Curran Joanne E. , Blangero John , Glahn David C.
Published: March 2023

Introduction

The cocktail-party problem refers to the difficulty listeners face when trying to attend to relevant sounds that are mixed with irrelevant ones. Previous studies have shown that solving these problems relies on perceptual as well as cognitive processes. Previously, we showed that speech-reception thresholds (SRTs) on a cocktail-party listening task were influenced by genetic factors. Here, we estimated the degree to which these genetic factors overlapped with those influencing cognitive abilities.

Methods

We measured SRTs and hearing thresholds (HTs) in 493 listeners, who ranged in age from 18 to 91 years old. The same individuals completed a cognitive test battery comprising 18 measures of various cognitive domains. Individuals belonged to large extended pedigrees, which allowed us to use variance component models to estimate the narrow-sense heritability of each trait, followed by phenotypic and genetic correlations between pairs of traits.

Results

All traits were heritable. The phenotypic and genetic correlations between SRTs and HTs were modest, and only the phenotypic correlation was significant. By contrast, all genetic SRT–cognition correlations were strong and significantly different from 0. For some of these genetic correlations, the hypothesis of complete pleiotropy could not be rejected.

Discussion

Overall, the results suggest that there was substantial genetic overlap between SRTs and a wide range of cognitive abilities, including abilities without a major auditory or verbal component. The findings highlight the important, yet sometimes overlooked, contribution of higher-order processes to solving the cocktail-party problem, raising an important caveat for future studies aiming to identify specific genetic factors that influence cocktail-party listening.
Habituation deficit of visual evoked potentials in migraine patients with hypermobile Ehlers-Danlos syndrome
Authors: Maestrini Ilaria , Rocchi Lorenzo , Puledda Francesca , Viganò Alessandro , Giuliani Giada , Jannini Tommaso Benedetto , Celletti Claudia , Altieri Marta , Camerota Filippo , Toscano Massimiliano , Di Piero Vittorio
Published: March 2023

Objectives

Migraine is one of the most frequent clinical manifestations of hypermobile Ehlers-Danlos syndrome (hEDS). The comorbidity between these two diseases has been only partially investigated. We aimed to observe whether neurophysiological alterations described in migraineurs in visual evoked potentials (VEPs) were present in hEDS patients with migraine.

Methods

We enrolled 22 hEDS patients with migraine (hEDS) and 22 non-hEDS patients with migraine (MIG), with and without aura (according to ICHD-3), as well as 22 healthy controls (HC). Repetitive pattern reversal (PR)-VEPs were recorded in basal conditions in all participants. During uninterrupted stimulation, 250 cortical responses were recorded (4,000 Hz sample rate) and divided into epochs of 300 ms after the stimulus. Cerebral responses were divided into five blocks. The habituation was calculated as the slope interpolating the amplitudes in each block, for both the N75-P100 and P100-N145 components of PR-VEP.

Results

We observed a significant habituation deficit of the P100-N145 component of PR-VEP in hEDS compared to HC (p = 0.002), unexpectedly more pronounced than in MIG. We observed only a slight habituation deficit of N75-P100 in hEDS, with a slope degree that was intermediate between MIG and HC.

Discussion

hEDS patients with migraine presented an interictal habituation deficit of both VEPs components like MIG. Pathophysiological aspects underlying the pathology could account for the peculiar pattern of habituation in hEDS patients with migraine characterized by a pronounced habituation deficit in the P100-N145 component and a less clear-cut habituation deficit in the N75-P100 component with respect to MIG.
Gene network reveals LASP1, TUBA1C, and S100A6 are likely playing regulatory roles in multiple sclerosis
Authors: Karimi Nafiseh , Motovali-Bashi Majid , Ghaderi-Zefrehei Mostafa
Published: March 2023

Introduction

Multiple sclerosis (MS), a non-contagious and chronic disease of the central nervous system, is an unpredictable and indirectly inherited disease affecting different people in different ways. Using Omics platforms genomics, transcriptomics, proteomics, epigenomics, interactomics, and metabolomics database, it is now possible to construct sound systems biology models to extract full knowledge of the MS and recognize the pathway to uncover the personalized therapeutic tools.

Methods

In this study, we used several Bayesian Networks in order to find the transcriptional gene regulation networks that drive MS disease. We used a set of BN algorithms using the R add-on package bnlearn. The BN results underwent further downstream analysis and were validated using a wide range of Cytoscape algorithms, web based computational tools and qPCR amplification of blood samples from 56 MS patients and 44 healthy controls. The results were semantically integrated to improve understanding of the complex molecular architecture underlying MS, distinguishing distinct metabolic pathways and providing a valuable foundation for the discovery of involved genes and possibly new treatments.

Results

Results show that the LASP1, TUBA1C, and S100A6 genes were most likely playing a biological role in MS development. Results from qPCR showed a significant increase (P < 0.05) in LASP1 and S100A6 gene expression levels in MS patients compared to that in controls. However, a significant down regulation of TUBA1C gene was observed in the same comparison.

Conclusion

This study provides potential diagnostic and therapeutic biomarkers for enhanced understanding of gene regulation underlying MS.
Serum neurofilament light chain levels are associated with early neurological deterioration in minor ischemic stroke
Authors: Li Jie , Zhang Ping , Zhu Yalan , Duan Yong , Liu Shan , Fan Jie , Chen Hong , Wang Chun , Yi Xingyang
Published: March 2023

Objectives

Patients with minor ischemic stroke (MIS) frequently suffer from early neurological deterioration (END) and become disabled. Our study aimed to explore the association between serum neurofilament light chain (sNfL) levels and END in patients with MIS.

Methods

We conducted a prospective observational study in patients with MIS [defined as a National Institutes of Health Stroke Scale (NIHSS) score 0–3] admitted within 24 h from the onset of symptoms. sNfL levels were measured at admission. The primary outcome was END, defined as an increase in the NIHSS score by ≥2 points within 5 days after admission. Univariate and multivariate analyses were performed to explore the risk factors associated with END. Stratified analyses and interaction tests were conducted to identify variables that might modify the association between sNfL levels and END.

Results

A total of 152 patients with MIS were enrolled, of which 24 (15.8%) developed END. The median sNfL level was 63.1 [interquartile range (IQR), 51.2–83.4] pg/ml on admission, which was significantly higher than that of 40 age- and sex-matched healthy controls (median 47.6, IQR 40.8–56.1 pg/ml; p < 0.001). Patients with MIS with END had a higher level of sNfL (with ND: median 74.1, IQR 59.5–89.8 pg/ml; without END: median 61.2, IQR 50.5–82.2 pg/ml; p = 0.026). After adjusting for age, baseline NIHSS score, and potential confounding factors in multivariate analyses, an elevated sNfL level (per 10 pg/mL) was associated with an increased risk of END [odds ratio (OR) 1.35, 95% confidence interval (CI) 1.04–1.77; p = 0.027). Stratified analyses and interaction tests demonstrated that the association between sNfL and END did not change by age group, sex, baseline NIHSS score, Fazekas' rating scale, hypertension, diabetes mellitus, intravenous thrombolysis, and dual antiplatelet therapy in patients with MIS (all p for interaction > 0.05). END was associated with an increased risk of unfavorable outcomes (modified Rankin scale score ranging from 3 to 6) at 3 months.

Conclusion

Early neurological deterioration is common in minor ischemic stroke and is associated with poor prognosis. The elevated sNfL level was associated with an increased risk of early neurological deterioration in patients with minor ischemic stroke. sNfL might be a promising biomarker candidate that can help to identify patients with minor ischemic stroke at high risk of neurological deterioration, for reaching individual therapeutic decisions in clinical practice.
Understanding the employment impact of neuromyelitis optica spectrum disorder in the USA: Mixed methods
Authors: Mateen Farrah J. , Trápaga Hacker Cristina M.
Published: March 2023

Neuromyelitis optica spectrum disorder (NMOSD) is a rare and disabling neurological disorder, marked by recurrent attacks of the central nervous system. NMO has a high female predominance and disproportionately affects racial and ethnic groups who are under- and unemployed in the USA. Three focus groups, involving 20 working age adults with NMOSD in the USA, were convened via Zoom online, to discuss the topic of employment in NMOSD. Consolidated Criteria for Reporting Qualitative research (COREQ) were followed. Discussions were coded for major themes using an inductive approach. The following themes emerged: (1) Barriers due to NMOSD on employment including (i) visible and invisible symptoms, (ii) the burden of treatment, and (iii) time to diagnosis; (2) Mitigating factors when NMOSD affects employment; (3) Impact of COVID-19; (4) Impact on income; (5) Impact on new and future employment and higher education opportunities; and (6) Unmet needs that are pragmatically addressable, outside of major policy or scientific changes.
Individual response to transcranial direct current stimulation as a function of working memory capacity and electrode montage
Authors: Menze Inga , Mueller Notger G. , Zaehle Tino , Schmicker Marlen
Published: March 2023

Introduction

Attempts to improve cognitive abilities via transcranial direct current stimulation (tDCS) have led to ambiguous results, likely due to the method’s susceptibility to methodological and inter-individual factors. Conventional tDCS, i.e., using an active electrode over brain areas associated with the targeted cognitive function and a supposedly passive reference, neglects stimulation effects on entire neural networks.

Methods

We investigated the advantage of frontoparietal network stimulation (right prefrontal anode, left posterior parietal cathode) against conventional and sham tDCS in modulating working memory (WM) capacity dependent transfer effects of a single-session distractor inhibition (DIIN) training. Since previous results did not clarify whether electrode montage drives this individual transfer, we here compared conventional to frontoparietal and sham tDCS and reanalyzed data of 124 young, healthy participants in a more robust way using linear mixed effect modeling.

Results

The interaction of electrode montage and WM capacity resulted in systematic differences in transfer effects. While higher performance gains were observed with increasing WM capacity in the frontoparietal stimulation group, low WM capacity individuals benefited more in the sham condition. The conventional stimulation group showed subtle performance gains independent of WM capacity.

Discussion

Our results confirm our previous findings of WM capacity dependent transfer effects on WM by a single-session DIIN training combined with tDCS and additionally highlight the pivotal role of the specific electrode montage. WM capacity dependent differences in frontoparietal network recruitment, especially regarding the parietal involvement, are assumed to underlie this observation.
A review of neuroendocrine immune system abnormalities in IBS based on the brain–gut axis and research progress of acupuncture intervention
Authors: Sun Zhangyin , Wang Xuejiao , Feng Shangsheng , Xie Chaoju , Xing Yu , Guo Liang , Zhao Jingyu , Ji Changchun
Published: March 2023

Irritable bowel syndrome (IBS) is a common digestive disorder observed in clinics. Current studies suggest that the pathogenesis of the disease is closely related to abnormal brain–gut interactions, hypokinesia, visceral sensory hypersensitivity in the gastrointestinal tract, and alterations in the intestinal microenvironment. However, it is difficult for a single factor to explain the heterogeneity of symptoms. The Rome IV criteria emphasized the holistic biologic-psycho-social model of IBS, suggesting that symptoms of the disease are closely related to neurogastroenterology and various abnormalities in brain–gut interaction. This study comprehensively reviewed the relationship between the brain–gut axis and IBS, the structure of the brain–gut axis, and the relationship between the brain–gut axis and intestinal microenvironment, and discussed the relationship between the abnormal regulation of the nervous system, endocrine system, and immune system and the incidence of IBS on the basis of brain–gut axis. In terms of treatment, acupuncture therapy can regulate the neuroendocrine-immune system of the body and improve the intestinal microenvironment, and it has the advantages of safety, economy, and effectiveness. We study the pathogenesis of IBS from local to global and micro to macro, and review the use of acupuncture to treat the disease as a whole so as to provide new ideas for the treatment of the disease.
Extramural vascular invasion nomogram before radical resection of rectal cancer based on magnetic resonance imaging
Authors: Tian Lianfen , Li Ningqin , Xie Dong , Li Qiang , Zhou Chuanji , Zhang Shilai , Liu Lijuan , Huang Caiyun , Liu Lu , Lai Shaolu , Wang Zheng
Published: March 2023

Purpose

This study verified the value of magnetic resonance imaging (MRI) to construct a nomogram to preoperatively predict extramural vascular invasion (EMVI) in rectal cancer using MRI characteristics.

Materials and methods

There were 55 rectal cancer patients with EMVI and 49 without EMVI in the internal training group. The external validation group consisted of 54 rectal cancer patients with EMVI and 55 without EMVI. High-resolution rectal T2WI, pelvic diffusion-weighted imaging (DWI) sequences, and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) were used. We collected the following data: distance between the lower tumor margin and the anal margin, distance between the lower tumor margin and the anorectal ring, tumor proportion of intestinal wall, mrT stage, maximum tumor diameter, circumferential resection margin, superior rectal vein width, apparent diffusion coefficient (ADC), T2WI EMVI score, DWI and DCE-MRI EMVI scores, demographic information, and preoperative serum tumor marker data. Logistic regression analyses were used to identify independent risk factors of EMVI. A nomogram prediction model was constructed. Receiver operating characteristic curve analysis verified the predictive ability of the nomogram. P < 0.05 was considered significant.

Result

Tumor proportion of intestinal wall, superior rectal vein width, T2WI EMVI score, and carbohydrate antigen 19-9 were significant independent predictors of EMVI in rectal cancer and were used to create the model. The areas under the receiver operating characteristic curve, sensitivities, and specificities of the nomogram were 0.746, 65.45%, and 83.67% for the internal training group, respectively, and 0.780, 77.1%, and 71.3% for the external validation group, respectively.

Data conclusion

A nomogram including MRI characteristics can predict EMVI in rectal cancer preoperatively and provides a valuable reference to formulate individualized treatment plans and predict prognosis.
Squamous cell carcinoma of ascending colon with pMMR/MSS showed a partial response to PD-1 blockade combined with chemotherapy: A case report
Authors: Liu Yan , Du Junliang , Zhang Pan , Meng Wenjuan , Xiao Haifeng
Published: March 2023

Primary colon squamous cell carcinoma (SCC) is extremely rare and associated with a poor prognosis. Moreover, there is no treatment guideline for this disease. Proficient mismatch repair/microsatellite-stable (pMMR/MSS) colorectal adenocarcinoma is refractory to immune monotherapy. Although the combination of immunotherapy with chemotherapy in pMMR/MSS colorectal cancer (CRC) is currently under investigation, the clinical activity of this approach in colorectal SCC remains unknown. In this article, we report the case of a pMMR/MSS CRC patient with ascending colon SCC who had high programmed cell death–ligand 1 (PD-L1) expression and the a missense mutation in codon 600 of the B-Raf proto-oncogene (BRAF V600E) mutation. The patient exhibited a significant response to the combination of immunotherapy and chemotherapy. After eight cycles of treatment with the combination of sintilimab and mFOLFOX6 (oxaliplatin, fluorouracil, and leucovorin), computed tomography–guided microwave ablation of the liver metastasis was performed. The patient achieved excellent durable response and continues to experience a good quality of life. The present case indicates that programmed cell death 1 blockade combined with chemotherapy may be an effective therapy for patients with pMMR/MSS colon SCC and high PD-L1 expression. Furthermore, PD-L1 expression may be a biomarker for immunotherapy in patients with colorectal SCC.
Detection of missed deaths in cancer registry data to reduce bias in long-term survival estimation
Authors: Dahm Stefan , Barnes Benjamin , Kraywinkel Klaus
Published: March 2023

Background

Population-based cancer survival estimates can provide insight into the real-world impacts of healthcare interventions and preventive services. However, estimation of survival rates obtained from population-based cancer registries can be biased due to missed incidence or incomplete vital status data. Long-term survival estimates in particular are prone to overestimation, since the proportion of deaths that are missed, for example through unregistered emigration, increases with follow-up time. This also applies to registry-based long-term prevalence estimates. The aim of this report is to introduce a method to detect missed deaths within cancer registry data such that long-term survival of cancer patients does not exceed survival in the general population.

Methods

We analyzed data from 15 German epidemiologic cancer registries covering the years 1970-2016 and from Surveillance, Epidemiology, and End Results (SEER)-18 registries covering 1975-2015. The method is based on comparing survival times until exit (death or follow-up end) and ages at exit between deceased patients and surviving patients, stratified by diagnosis group, sex, age group and stage. Deceased patients with both follow-up time and age at exit in the highest percentile were regarded as outliers and used to fit a logistic regression. The regression was then used to classify each surviving patient as a survivor or a missed death. The procedure was repeated for lower percentile thresholds regarding deceased persons until long-term survival rates no longer exceeded the survival rates in the general population.

Results

For the German cancer registry data, 0.9% of total deaths were classified as having been missed. Excluding these missed deaths reduced 20-year relative survival estimates for all cancers combined from 140% to 51%. For the whites in SEER data, classified missed deaths amounted to 0.02% of total deaths, resulting in 0.4 percent points lower 20-year relative survival rate for all cancers combined.

Conclusion

The method described here classified a relatively small proportion of missed deaths yet reduced long-term survival estimates to more plausible levels. The effects of missed deaths should be considered when calculating long-term survival or prevalence estimates.
Basal cell carcinoma of the prostate with squamous metaplasia: A case report and literature review
Authors: Wang Junwei , Zhang Cunming , Chen Baijun , Wu Qingqing
Published: March 2023

Basal cell carcinoma of the prostate (BCCP) is a rare tumor with a total incidence of 140 cases to date. However, BCCP with squamous metaplasia has not been reported as of date. In this paper, we report the first case of BCCP with squamous metaplasia. The patient was hospitalized for progressive dyspareunia and had been treated for recurrent urinary retention four times in 5 years. Rectal examination showed that the prostate was medium in texture with no palpable nodules. The levels of total prostate specific antigen (tPSA), free prostate specific antigen (fPSA), and fPSA/tPSA (f/t) ratio were 1.29 ng/mL, 0.4 ng/mL, and 0.31, respectively. Ultrasound of the urinary tract showed that the prostate gland was 51 mm*40 mm*38 mm in size. We performed transurethral resection of the prostate. Histopathology confirmed the diagnosis of basal cell carcinoma with focal squamous differentiation, and immunohistochemical staining was positive for P63 and 34βE12. A laparoscopic radical prostatectomy was performed 45 days after the first surgery and the postoperative pathology showed a small amount of residual tumor with negative margins and no involvement of the seminal vesicles and vas deferens. The patient was followed up for 50 months and was doing well by the end of our study. We describe the clinical symptoms, pathological features, treatment, and prognosis of patients with BCCP with squamous metaplasia. The relevant published literature is also briefly reviewed.
Application and progress of palliative therapy in advanced gastric carcinomas
Authors: Luo Xiao-fan , Luo Ye-hao , Zhao Xin-yi , Lin Xue-ting , Li Wen-ling , Jie Jie , Wu Di , Fang Gang , Pang Yu-zhou , Huang An
Published: March 2023

Gastric carcinomas have high morbidity and mortality. It produces no noticeable symptoms in the early stage while causing complex complications in its advanced stage, making treatment difficult. Palliative therapy aims to relieve the symptoms of cancer patients and focuses on improving their quality of life. At present, five palliative therapies for advanced gastric carcinomas are offered: resection, gastrojejunostomy, stenting, chemotherapy, and radiotherapy. In recent years, palliative therapy has been used in the clinical treatment of advanced gastric carcinomas and related complications because of its efficacy in gastric outlet obstruction and gastric bleeding. In the future, multimodal and interdisciplinary palliative therapies can be applied to control general symptoms to improve patients’ condition, prolong their lifespan and improve their quality of life.
Survival outcomes and prognostic factors of lung cancer patients with the MET exon 14 skipping mutation: A single-center real-world study
Authors: Gow Chien-Hung , Hsieh Min-Shu , Chen Yi-Lin , Liu Yi-Nan , Wu Shang-Gin , Shih Jin-Yuan
Published: March 2023

Introduction

The MET exon 14 skipping (METex14) mutation is an important oncogenic driver in lung cancer. We performed a retrospective analysis of clinical data from lung cancer patients with the METex14 mutation to analyze their survival outcomes and associated prognostic factors.

Methods

A one-step reverse transcription-polymerase chain reaction to examine the presence of the METex14 mutation was performed using RNA samples from 1374 lung cancer patients with no detected EGFR and ALK mutations. Pathological features and immunohistochemistry (IHC) results for c-MET were analyzed in patients with METex14-positive tumors.

Results

METex14 was identified in 69 patients with lung cancer, including 53 adenocarcinoma (ADC) and 16 non-ADC patients. In comparison with patients without the METex14 mutation, lung cancer patients harboring the METex14 mutation were generally elderly individuals, never-smokers, and had poor performance scores. A higher frequency of METex14 mutations was detected in pulmonary sarcomatoid carcinoma (PSC) patients (24.3%, n = 9/37). However, stage IV PSC patients with or without the METex14 mutations showed similarly poor overall survival (OS) (p = 0.429). For all 36 METex14-positive lung ADCs, multivariate analysis showed several poor prognostic factors, including strong c-MET IHC staining (p = 0.006), initial brain metastasis (p = 0.005), and administration of only supportive care (p < 0.001). After excluding seven patients who received only supportive care, we further analyzed 29 stage IV lung ADC patients with METex14 mutations who received anti-cancer treatment. Multivariate analysis showed that pemetrexed treatment (p = 0.003), lung radiotherapy (p = 0.020), initial brain metastasis (p = 0.005), and strong c-MET IHC staining (p = 0.012) were independent prognostic factors for OS in these patients.

Conclusions

A higher frequency of METex14 mutations was detected in PSC patients. Stage IV PSC patients with or without the METex14 mutations had similarly poor overall survival. Pemetrexed-based chemotherapy, strong c-MET ICH staining, initial brain metastasis, and lung radiotherapy, may help predict survival outcomes in patients with advanced lung ADCs harboring the METex14 mutation.
Primary Langerhans cell sarcoma in the urinary bladder: Case report and literature review
Authors: Wei Yongbao , Hong Huaishan , Huang Haijian
Published: March 2023

Langerhans cell sarcoma (LCS) is a rare malignancy of dendritic cells and usually results in a poor oncological outcome. Thus, LCS is usually given a positive administration. Herein, we presented the first case of primary LCS in the urinary bladder staged T1N0M0 and treated by TURBT and short-term local chemotherapy. Our experience in this unique case may suggest that LCS in the urinary bladder with a non-muscle-invasive stage may be managed according to the treatment model of non-muscle-invasive urothelial carcinoma of the urinary bladder.
Expression and prognostic value of PRDX family in colon adenocarcinoma by integrating comprehensive analysis and in vitro and in vivo validation
Authors: Zhou He , Li Lifa , Chen Jia , Hou Songlin , Zhou Tong , Xiong Yongfu
Published: March 2023

Background

The peroxiredoxin family, a crucial regulator of redox reactions, is strongly associated with various tumorigenesis. However, the role of peroxiredoxin4 (PRDX4) in colon adenocarcinoma (COAD) remains poorly understood.

Methods

Multicenter databases, including GEPIA, HPA, UALCAN, cBioPortal, cancerSEA, STRING, CCLE, and LinkedOmics, comprehensively analyzed transcriptional expression, prognostic value, genetic alterations, signaling pathways, and associated genes of the PRDXs in COAD patients. Colony formation, transwell, flow cytometry, sphere formation, and xenograft assays were performed to validate further in vitro and in vivo.

Results

Members of the PRDX family were differentially expressed in COAD, with each member showing varying degrees of genetic alterations. Intriguingly, only PRDX4 significantly correlated with COAD prognosis and stage. The single-cell sequencing suggested that PRDX4 is positively correlated with proliferation, apoptosis, and invasion, whereas negatively correlated with stemness. Moreover, PRDX4 involved in a series of critical biological processes, such as cell growth. Furthermore, in vivo and in vitro analyses indicated that knocking down PRDX4 inhibits the proliferation and invasion of HCT116 cells while promoting apoptosis and stemness.

Conclusions

We identified PRDX4 expression as a novel potential prognostic marker in COAD.
A novel conditioning regimen of chidamide, cladribine, gemcitabine, and busulfan in the autologous stem cell transplantation of aggressive T-cell lymphoma
Authors: Zeng Qiang , Zhang Hang , Kuang Pu , Li Jian , Chen Xinchuan , Dong Tian , Wu Qiuhui , Zhang Chuanli , Chen Chunping , Niu Ting , Liu Ting , Liu Zhigang , Ji Jie
Published: March 2023

Background

The prognosis of patients with peripheral T-cell (PTCL) or lymphoblastic T-cell lymphoma (T-LBL) remains poor under current conditioning regimens before receiving autologous stem cell transplantation (ASCT).

Methods

Patients with PTCL or T-LBL were enrolled to receive ASCT using the conditioning regimen of chidamide, cladribine, gemcitabine, and busulfan (ChiCGB). Positron emission tomography-computed tomography (PET/CT) was used to evaluate the response to ASCT. Overall survival (OS) and progression-free survival (PFS) were employed to assess the patient outcome, and adverse events were used to assess the regimen’s safety. The survival curve was estimated via the Kaplan-Meier method.

Results

Twenty-five PTCL and 11 T-LBL patients were recruited. The median time to neutrophile and platelet engraftments was 10 days (8–13 days) and 13 days (9–31 days), respectively. The 3-year PFS and OS were 81.3 ± 7.2% and 88.5 ± 5.4% for all patients; 92.0 ± 5.4% and 81.2 ± 8.8% for PTCL patients; and both 81.8 ± 11.6% for T-LBL patients, respectively. The 3-year PFS and OS were both 92.9 ± 4.9% for patients with complete response (CR) but 50.0 ± 17.7% and 75.0 ± 15.3% for patients with non-CR, respectively. Infection was the most common non-hematological toxicity, and all toxicities were mild and controllable.

Conclusions

ChiCGB was a potentially effective and well-tolerated conditioning regimen to improve the prognosis of patients with aggressive T-cell lymphoma. Future randomized controlled trials are needed to assess ChiCGB as a conditioning regimen for ASCT.
Immune cells and immune cell-targeted therapy in chronic pancreatitis
Authors: Zhang Yu , Zhang Wen-Qing , Liu Xin-Yuan , Zhang Qi , Mao Tao , Li Xiao-Yu
Published: March 2023

In recent years, studies have attempted to understand the immune cells and mechanisms underlying the pathogenesis of chronic pancreatitis (CP) by constructing a model of CP. Based on these studies, the innate immune response is a key factor in disease pathogenesis and inflammation severity. Novel mechanisms of crosstalk between immune and non-immune pancreatic cells, such as pancreatic stellate cells (PSC), have also been explored. Immune cells, immune responses, and signaling pathways in CP are important factors in the development and progression of pancreatitis. Based on these mechanisms, targeted therapy may provide a feasible scheme to stop or reverse the progression of the disease in the future and provide a new direction for the treatment of CP. This review summarizes the recent advances in research on immune mechanisms in CP and the new advances in treatment based on these mechanisms.