bluuebunny/crossref_metadata_2025 huggingface dataset:
Harmonization of multi-scanner in vivo magnetic resonance spectroscopy: ENIGMA consortium task group considerations
Authors: Harris Ashley D. , Amiri Houshang , Bento Mariana , Cohen Ronald , Ching Christopher R. K. , Cudalbu Christina , Dennis Emily L. , Doose Arne , Ehrlich Stefan , Kirov Ivan I. , Mekle Ralf , Oeltzschner Georg , Porges Eric , Souza Roberto , Tam Friederike I. , Taylor Brian , Thompson Paul M. , Quidé Yann , Wilde Elisabeth A. , Williamson John , Lin Alexander P. , Bartnik-Olson Brenda
Published: January 2023

Magnetic resonance spectroscopy is a powerful, non-invasive, quantitative imaging technique that allows for the measurement of brain metabolites that has demonstrated utility in diagnosing and characterizing a broad range of neurological diseases. Its impact, however, has been limited due to small sample sizes and methodological variability in addition to intrinsic limitations of the method itself such as its sensitivity to motion. The lack of standardization from a data acquisition and data processing perspective makes it difficult to pool multiple studies and/or conduct multisite studies that are necessary for supporting clinically relevant findings. Based on the experience of the ENIGMA MRS work group and a review of the literature, this manuscript provides an overview of the current state of MRS data harmonization. Key factors that need to be taken into consideration when conducting both retrospective and prospective studies are described. These include (1) MRS acquisition issues such as pulse sequence, RF and B0 calibrations, echo time, and SNR; (2) data processing issues such as pre-processing steps, modeling, and quantitation; and (3) biological factors such as voxel location, age, sex, and pathology. Various approaches to MRS data harmonization are then described including meta-analysis, mega-analysis, linear modeling, ComBat and artificial intelligence approaches. The goal is to provide both novice and experienced readers with the necessary knowledge for conducting MRS data harmonization studies.
Acupuncture treatment of a pregnant patient with Bell's palsy in the third trimester: Case report
Authors: Lan Danchun , Deng Wenfei , He Kunze , Li Qian , Peng Xin , Lao Jinxiong , Li Ziyong
Published: January 2023

At present, the optimal treatment for Bell's palsy remains controversial, and the combination of corticosteroids and antiviral medication is usually recommended in the early stage. However, treatment is often delayed because the effects of these drugs on pregnant women and fetuses are still unclear. As a safe and effective complementary alternative therapy, acupuncture can alleviate Bell's palsy symptoms and improve the quality of life of the patient. Herein, we report the clinical presentation of a 27-year-old woman with Bell's palsy who was 26 weeks pregnant at the time of diagnosis. After five courses of treatment, the patient made a complete recovery.
The Active Inference Model of Coherence Therapy
Authors: Chamberlin D. Eric
Published: January 2023

Coherence Therapy is an empirically derived experiential psychotherapy based on Psychological Constructivism. Symptoms are viewed as necessary output from an implicit model of the world. The therapist curates experiences and directs attention toward discovering the model. Rendered explicit, the model is juxtaposed with contradictory knowledge driving memory re-consolidation with resolution of the symptom. The Bayesian Brain views perception and action as inferential processes. Prior beliefs are combined in a generative model to explain the hidden causes of sensations through a process of Active Inference. Prior beliefs that are poor fits to the real world are suboptimal. Suboptimal priors with optimal inference produce Bayes Optimal Pathology with behavioral symptoms. The Active Inference Model of Coherence Therapy posits that Coherence Therapy is a dyadic act of therapist guided Active Inference that renders the (probable) hidden causes of a client’s behavior conscious. The therapist’s sustained attention on the goal of inference helps to overcome memory control bias against retrieval of the affectively charged suboptimal prior. Serial experiences cue memory retrieval and re-instantiation of the physiological/affective state that necessitates production of the symptom in a particular context. As this process continues there is a break in modularity with assimilation into broader networks of experience. Typically, the symptom produced by optimal inference with the suboptimal prior is experienced as unnecessary/inappropriate when taken out of the particular context. The implicit construct has been re-represented and rendered consciously accessible, by a more complex but more accurate model in which the symptom is necessary in some contexts but not others. There is an experience of agency and control in symptom creation, accompanied by the spontaneous production of context appropriate behavior. The capacity for inference has been restored. The Active Inference Model of Coherence Therapy provides a framework for Coherence Therapy as a computational process which can serve as the basis for new therapeutic interventions and experimental designs integrating biological, cognitive, behavioral, and environmental factors.
Restoring morphology of light sheet microscopy data based on magnetic resonance histology
Authors: Tian Yuqi , Cook James J. , Johnson G. Allan
Published: January 2023

The combination of cellular-resolution whole brain light sheet microscopy (LSM) images with an annotated atlas enables quantitation of cellular features in specific brain regions. However, most existing methods register LSM data with existing canonical atlases, e.g., The Allen Brain Atlas (ABA), which have been generated from tissue that has been distorted by removal from the skull, fixation and physical handling. This limits the accuracy of the regional morphologic measurement. Here, we present a method to combine LSM data with magnetic resonance histology (MRH) of the same specimen to restore the morphology of the LSM images to the in-skull geometry. Our registration pipeline which maps 3D LSM big data (terabyte per dataset) to MRH of the same mouse brain provides registration with low displacement error in ∼10 h with limited manual input. The registration pipeline is optimized using multiple stages of transformation at multiple resolution scales. A three-step procedure including pointset initialization, automated ANTs registration with multiple optimized transformation stages, and finalized application of the transforms on high-resolution LSM data has been integrated into a simple, structured, and robust workflow. Excellent agreement has been seen between registered LSM data and reference MRH data both locally and globally. This workflow has been applied to a collection of datasets with varied combinations of MRH contrasts from diffusion tensor images and LSM with varied immunohistochemistry, providing a routine method for streamlined registration of LSM images to MRH. Lastly, the method maps a reduced set of the common coordinate framework (CCFv3) labels from the Allen Brain Atlas onto the geometrically corrected full resolution LSM data. The pipeline maintains the individual brain morphology and allows more accurate regional annotations and measurements of volumes and cell density.
Blockade of D-serine signaling and adult hippocampal neurogenesis attenuates remote contextual fear memory following multiple memory retrievals in male mice
Authors: Inoue Ran , Ni Xiance , Mori Hisashi
Published: January 2023

The retrieval of fear memories induces two opposing processes, reconsolidation, and extinction. The memory reconsolidation is an active process that involves gene expression and updates an existing memory. It is hypothesized that blockade of reconsolidation by manipulating the neurobiological factors, which are mechanistically involved in the process, could weaken or disrupt the original fear memory. The N-methyl-D-aspartate (NMDA) receptor and hippocampal neurogenesis play crucial roles in hippocampus-dependent memory processes, including reconsolidation. Using contextual fear conditioning paradigm with multiple retrievals, we attempted to weaken the original contextual fear memory by repeatedly disrupting retrieval-induced reconsolidation via downregulation of NMDA receptor signaling and inhibition of neurogenesis. In the first experiment, prior to fear conditioning, NMDA receptor signaling was downregulated by the genetic reduction of its co-agonist, D-serine, and the neurogenesis was dampened by focal X-ray irradiation on the hippocampus. We found that simultaneous D-serine reduction and neurogenesis dampening resulted in a progressive decrease in freezing following each retrieval, leading to an attenuation of remote contextual fear memory on day 28. In the second experiment using the same behavioral protocols, after conditioning, pharmacological approaches were conducted to simultaneously block D-serine signaling and neurogenesis, resulting in a similar suppressive effect on the remote fear memory. The present findings provide insights for understanding the role of D-serine-mediated NMDA receptor signaling and neurogenesis in memory retrieval and the maintenance of remote fear memory, and improving the efficacy of exposure-based therapy for the treatment of post-traumatic stress disorder (PTSD).
Does context matter in misophonia? A multi-method experimental investigation
Authors: Siepsiak Marta , Vrana Scott R. , Rynkiewicz Andrzej , Rosenthal M. Zachary , Dragan Wojciech Łukasz
Published: January 2023

Introduction

Misophonia is a recently defined disorder in which certain aversive repetitive sounds and associated stimuli elicit distressing and impairing affective, behavioral, and physiological responses. The responses in misophonia may be stronger when the sound is produced by close friends and family, suggesting that the context in which a triggering cue occurs may have an important role in misophonia. As such, the goal of this study was to test experimentally whether the context of the sound source influences affective and psychophysiological responses to triggering stimuli in misophonia.

Methods

Sixty one adults with misophonia and 45 controls listened to audio recordings (8 s) of human eating, animals eating, and human mouth smacking sounds (without eating). After a break, the same audio recordings were presented embedded within videos of human eating (congruent stimuli), animals eating (congruent stimuli), and, in the mouth smacking condition, with visually incongruent stimuli (hands playing in mud or in a bowl with a watery dough). Psychophysiological responses—skin conductance response (SCR) and heart rate (HR), and self-reported affective responses (valence, arousal, dominance) were gathered during the experiment in a laboratory.

Results

Participants with misophonia assessed all the stimuli as more negative and arousing than the controls, and reported feeling less dominant with respect to the sounds. Animal and mouth smacking sounds were assessed by all the participants as less negative and arousing than human eating sounds, but only in the audio-video conditions. SCR data partially confirmed increased psychophysiological arousal in misophonia participants during an exposure to mouth sounds, but did not reflect the self-report changes in response to different contexts. Misophonia participants had deeper deceleration of HR than controls during human eating sound with congruent video stimuli, while there was no group difference during human mouth smacking with incongruent video stimuli.

Conclusion

Results suggest that the context of mouth sounds influences affective experiences in adults with misophonia, but also in participants without misophonia. Presentation of animal eating sounds with congruent visual stimuli, or human mouth smacking sounds with incongruent stimuli, decreased self-report reaction to common misophonic triggers.
Guanylyl cyclase/natriuretic peptide receptor-A: Identification, molecular characterization, and physiological genomics
Authors: Pandey Kailash N.
Published: January 2023

The natriuretic peptides (NPs) hormone family, which consists mainly of atrial, brain, and C-type NPs (ANP, BNP, and CNP), play diverse roles in mammalian species, ranging from renal, cardiac, endocrine, neural, and vascular hemodynamics to metabolic regulations, immune responsiveness, and energy distributions. Over the last four decades, new data has transpired regarding the biochemical and molecular compositions, signaling mechanisms, and physiological and pathophysiological functions of NPs and their receptors. NPs are incremented mainly in eliciting natriuretic, diuretic, endocrine, vasodilatory, and neurological activities, along with antiproliferative, antimitogenic, antiinflammatory, and antifibrotic responses. The main locus responsible in the biological and physiological regulatory actions of NPs (ANP and BNP) is the plasma membrane guanylyl cyclase/natriuretic peptide receptor-A (GC-A/NPRA), a member of the growing multi-limbed GC family of receptors. Advances in this field have provided tremendous insights into the critical role of Npr1 (encoding GC-A/NPRA) in the reduction of fluid volume and blood pressure homeostasis, protection against renal and cardiac remodeling, and moderation and mediation of neurological disorders. The generation and use of genetically engineered animals, including gene-targeted (gene-knockout and gene-duplication) and transgenic mutant mouse models has revealed and clarified the varied roles and pleiotropic functions of GC-A/NPRA in vivo in intact animals. This review provides a chronological development of the biochemical, molecular, physiological, and pathophysiological functions of GC-A/NPRA, including signaling pathways, genomics, and gene regulation in both normal and disease states.
The calcineurin regulator Sarah enables distinct forms of homeostatic plasticity at the Drosophila neuromuscular junction
Authors: Armstrong Noah S. , Frank C. Andrew
Published: January 2023

Introduction: The ability of synapses to maintain physiological levels of evoked neurotransmission is essential for neuronal stability. A variety of perturbations can disrupt neurotransmission, but synapses often compensate for disruptions and work to stabilize activity levels, using forms of homeostatic synaptic plasticity. Presynaptic homeostatic potentiation (PHP) is one such mechanism. PHP is expressed at the Drosophila melanogaster larval neuromuscular junction (NMJ) synapse, as well as other NMJs. In PHP, presynaptic neurotransmitter release increases to offset the effects of impairing muscle transmitter receptors. Prior Drosophila work has studied PHP using different ways to perturb muscle receptor function—either acutely (using pharmacology) or chronically (using genetics). Some of our prior data suggested that cytoplasmic calcium signaling was important for expression of PHP after genetic impairment of glutamate receptors. Here we followed up on that observation.

Methods: We used a combination of transgenic Drosophila RNA interference and overexpression lines, along with NMJ electrophysiology, synapse imaging, and pharmacology to test if regulators of the calcium/calmodulin-dependent protein phosphatase calcineurin are necessary for the normal expression of PHP.

Results: We found that either pre- or postsynaptic dysregulation of a Drosophila gene regulating calcineurin, sarah (sra), blocks PHP. Tissue-specific manipulations showed that either increases or decreases in sra expression are detrimental to PHP. Additionally, pharmacologically and genetically induced forms of expression of PHP are functionally separable depending entirely upon which sra genetic manipulation is used. Surprisingly, dual-tissue pre- and postsynaptic sra knockdown or overexpression can ameliorate PHP blocks revealed in single-tissue experiments. Pharmacological and genetic inhibition of calcineurin corroborated this latter finding.

Discussion: Our results suggest tight calcineurin regulation is needed across multiple tissue types to stabilize peripheral synaptic outputs.
Postprandial lipemic response in dairy-avoiding females following an equal volume of sheep milk relative to cow milk: A randomized controlled trial
Authors: Teng Fei , Samuelsson Linda M. , Milan Amber Marie , Subbaraj Arvind , Agnew Michael , Shrestha Aahana , Cameron-Smith David , Day Li
Published: January 2023

Background

Sheep milk (SM) is an alternate dairy source, which despite many similarities, has both compositional and structural differences in lipids compared to cow milk (CM). Studies are yet to examine the apparent digestibility of SM lipids, relative to CM, and the potential impact on the plasma lipidome.

Objective

To determine the response of the circulatory lipidome to equal volume servings of SM and CM, in females who avoid dairy products.

Method

In a double-blinded, randomized, cross-over trial, self-described dairy avoiding females (n = 30; 24.4 ± 1.1 years) drank SM or CM (650 mL; 33.4 vs. 21.3 g total lipid content; reconstituted from spray dried milk powders) following an overnight fast. Blood samples were collected at fasting and at regular intervals over 4 h after milk consumption. The plasma lipidome was analyzed by LC-MS and fatty acids were quantified by GC-FID.

Results

The overall postprandial triglyceride (TG) response was similar between SM and CM. TG concentrations were comparable at fasting for both groups, however they were higher after CM consumption at 30 min (interaction milk × time p = 0.003), well before any postprandial lipemic response. This was despite greater quantities provided by SM. However, there were notable differences in the postprandial fatty acid response, with SM leading to an increase in short- and medium-chain fatty acids (MCFAs) (C6:0, C8:0, and C10:0) and several long-chain fatty acids (LCFAs) (C18:1 t11, c9, t11-CLA, and C20:0; interaction time × milk p < 0.05). This corresponded to a greater postprandial response for medium chain triglycerides (MCTs) C10:0, including TG(10:0/14:0/18:1), TG(16:0/10:0/12:0), and TG(16:0/10:0/14:0) (interaction time × milk p < 0.05).

Conclusions

Despite a higher fat content, SM ingestion resulted in a greater circulating abundance of MCTs, without increasing total postprandial triglyceride response, when compared to CM. The greater abundance and postprandial appearance of MCTs may provide advantageous metabolic responses in children and adults.

Unique identifier and registry

U1111-1209-7768; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=375324.
Associations between negative gender attitudes and eating behaviors in Chinese children and adolescents
Authors: Cao Ruiyao , Chen Jiaoyan , Wang Yuanyuan , Peng Xingwang , Han Mei , Liu Keke , Zhang Juan , Yao Rongying , Han Hui , Fu Lianguo
Published: January 2023

Background

Negative gender cognitive attitudes (disliking one’s own gender or wanting to be the opposite gender) and unhealthy eating behaviors have become common in Chinese children and adolescents. The aim of this study was to analyze the associations between negative gender attitudes and eating behaviors among Chinese children and adolescents.

Methods

Primary and secondary school students aged 8–15 years were selected as participants using a stratified cluster random sampling method. The self-designed questionnaire was used to investigate the participants’ negative gender cognitive attitudes. Eating frequency questionnaire was used to investigate participants’ eating behaviors. Under the leading reading of standardized training investigators, the questionnaire for children aged 8–15 years was completed by themselves in the form of centralized filling.

Results

A total of 6.5% [43/657, boys: 6.1% (21/347), girls: 7.1% (22/310)] of children disliked their own gender, 8.8% [58/657, boys: 5.5% (19/347), girls: 12.6% (39/310)] of children wanted to be of the opposite gender, and the proportion of girls with negative gender attitudes was higher than that of boys (P < 0.05). Boys who disliked their own gender or wanted to be the opposite gender had higher frequencies of unhealthy eating behaviors and lower frequencies of healthy eating behaviors than boys who liked their own gender or did not want to be the opposite gender (P < 0.05). Girls who disliked their own gender or wanted to be the opposite gender had higher frequencies of protein eating behaviors than girls who liked their own gender or did not want to be the opposite gender (P < 0.05). There was a significant interaction between disliking one’s own gender and wanting to be the opposite gender in midnight snack eating among boys (P < 0.05) and in carbonated drink and high protein eating behaviors among girls (P < 0.05).

Conclusion

Boys with negative gender cognitive attitudes express more unhealthy eating behaviors and fewer healthy eating behaviors; girls with negative gender cognitive attitudes exhibit more protein eating behaviors.
Structural elucidation of a novel arabinogalactan LFP-80-W1 from Lycii fructus with potential immunostimulatory activity
Authors: Liang Xiaofei , Liu Mengqiu , Guo Sheng , Zhang Fang , Cui Wanchen , Zeng Fei , Xu Mingming , Qian Dawei , Duan Jinao
Published: January 2023

Polysaccharides are the most important effective components of Lycii fructus, which has a variety of biological activities and broad application prospects in the fields of medicine and food. In this study, we reported a novel arabinogalactan LFP-80-W1 with potential immunostimulatory activity. LFP-80-W1 was a continuous symmetrical single-peak with an average molecular weight of 4.58 × 104 Da and was mainly composed of arabinose and galactose. Oligosaccharide sequencing analyses and NMR data showed that the LFP-80-W1 domain consists of a repeated 1,6-linked β-Galp main chain with branches arabinoglycan and arabinogalactan at position C-3. Importantly, we found that LFP-80-W1 could activate the MAPK pathway and promote the release of NO, IL-6, and TNF-α cytokines in vitro. Therefore, our findings suggest that the homogeneous arabinogalactan from Lycii fructus, can be used as a natural immunomodulator.
12-week curcumin supplementation may relieve postexercise muscle fatigue in adolescent athletes
Authors: Bai Kai-Yuan , Liu Gin-Hua , Fan Chun-Hao , Kuo Liang-Tseng , Hsu Wei-Hsiu , Yu Pei-An , Chen Chi-Lung
Published: January 2023

Introduction

High-intensity exercise causes oxidative stress, muscle soreness, and muscle fatigue, leading to reduced exercise performance. Curcumin possesses antioxidative and anti-inflammatory properties and thus alleviates postexercise damage. Therefore, this study evaluated the effect of curcumin on athletes’ postexercise recovery.

Methods

A non-randomized prospective cohort investigation was done. We recruited middle and high school athletes engaged in wrestling, soccer, and soft tennis. During the 12-week daily exercise training, the participants were assigned to receive curcumin supplementation (curcumin group) or not (control group). Body composition, exercise performance, inflammatory factors, muscle fatigue, and muscle soreness were recorded at the baseline and end of the study. We used the Mann–Whitney U test to compare the participants’ demographics, such as age, height, weight, and training years. The Wilcoxon test was used to compare the differences between the groups before and after curcumin supplementation.

Results

Of 28 participants (21 men and 7 women, with a mean age of 17 years), 13 were in the curcumin group and 15 in the control group. A significant decrease in muscle fatigue and muscle soreness scores was observed in the curcumin group after 12 weeks. Moreover, a significant decrease in the 8-hydroxy-2 deoxyguanosine level and a significant increase in basic metabolic rate and fat-free mass were observed in the curcumin group.

Conclusion

Curcumin can reduce muscle fatigue and soreness after exercise, indicating its potential to alleviate postexercise damage. It could be considered to cooperate with nutritional supplements in regular training in adolescent athletes.
Prognostic value of tumor mutation burden in patients with advanced gastric cancer receiving first-line chemotherapy
Authors: Duan Xiao-Peng , Liu Ke , Jiao Xiao-Dong , Qin Bao-Dong , Li Bing , He Xi , Ling Yan , Wu Ying , Chen Shi-Qi , Zang Yuan-Sheng
Published: January 2023

Background

Tumor mutation burden (TMB) is a promising biomarker positively associated with the benefit of immunotherapy and that might predict the outcome of chemotherapy. We described the prognostic value of TMB in advanced gastric cancer and explored the underlying mechanism.

Methods

We enrolled 155 TMB-evaluated advanced gastric cancer patients and analyzed the relationship between clinicopathological characteristics and both overall survival (OS) and progression-free survival (PFS) among 40 patients treated with first-line chemotherapy. We further verified the distribution of TMB and analyzed the potential mechanism underlying the prognosis based on The Cancer Genome Atlas (TCGA) database.

Results

Among the 155 patients, 29 (18.7%) were TMB-high (TMB ≥ 10), roughly the same as the proportion in the TCGA data. Of the 40 patients receiving first-line chemotherapy, the median OS (7.9 vs. 12.1 months; HR 3.18; p = 0.0056) and PFS (4.4 vs. 6.2 months; HR 2.94; p = 0.0099) of the tissue-tested TMB (tTMB)-high patients were inferior to those of the tTMB-low patients. Similarly, unfavorable median OS (9.9 vs. 12.1 months; HR 2.11; p = 0.028) and PFS (5.3 vs. 6.5 months; HR 2.49; p = 0.0054) were shown in the blood-tested TMB (bTMB)-high than in the bTMB-low patients. The Cox analysis demonstrated that both tTMB-high and bTMB-high were significant independent predictors of dreadful OS and PFS. The differentially expressed genes (DEGs) according to TMB status were most significantly enriched in the downregulated metabolic pathway among the TMB-high patients.

Conclusions

TMB-high advanced gastric cancer patients accounted for around one-sixth and had a poorer prognosis than TMB-low patients when treated with first-line chemotherapy. The potential mechanism might be the downregulated metabolic activity in TMB-high patients.
Prognostic value of lymph node micrometastasis in esophageal cancer: A systematic review and meta-analysis
Authors: Yang Jing , Liu Qianqian , Bai Yuping , Zhao Haitong , He Tingting , Zhao Ziru , Huang Min , Jiang Mengyuan , Zhang Rui , Zhang Min
Published: January 2023

Objective

Whether lymph node micrometastasis (LNM) increases the risk in esophageal cancer patients remains controversial. We conducted a systematic review and meta-analysis to explore the prognosis value of LNM in esophageal cancer patients.

Methods

Two reviewers independently searched electronic databases, including PubMed, Embase, and the Cochrane Library, for eligible citations until February 2022. We calculated pooled estimates of the hazards ratio with a random-effects model. The certainty of evidence was determined by the Grade of Recommendations Assessment, Development, and Evaluation (GRADE) method. A sensitivity analysis was performed to assess the stability. Publication bias was assessed using funnel plots and Egger’s test. We also performed subgroup analysis to explore the source of heterogeneity.

Results

A total of 16 studies, with 1,652 patients, were included. The overall survival (OS) was significantly increased with LNM negativity compared with LNM positivity (HR 1.95; 95% CI, 1.53–2.49; P < 0.001; I2 = 0.0%, P = 0.930; certainty of evidence: low). Relapse-free survival (RFS) was significantly increased with LNM negativity compared with LNM positivity (HR 3.39; 95% CI, 1.87–6.16; P < 0.001; I2 = 50.18%, P = 0.060; certainty of evidence: moderate). No significant difference was observed in recurrence between the two groups (certainty of evidence: low). Sensitivity analysis revealed a stable trend. In addition, the funnel plot and Egger’s test did not show significant publication bias.

Conclusion

LNM positivity worsens the prognosis in esophageal cancer, and the evidence for RFS is moderate. Future relevant high-quality studies are warranted to validate our results further and provide a reference for guidelines.

Systematic review registration

https://www.crd.york.ac.uk/prospero, identifier (CRD42022321768).
Treatment dependent impact of plasma-derived exosomes from head and neck cancer patients on the epithelial-to-mesenchymal transition
Authors: Hofmann Linda , Waizenegger Marie , Röth Ralph , Schmitteckert Stefanie , Engelhardt Daphne , Schuler Patrick J. , Laban Simon , Hoffmann Thomas K. , Brunner Cornelia , Theodoraki Marie-Nicole
Published: January 2023

Background

Epithelial to mesenchymal transition (EMT) is a key process in carcinogenesis of head and neck squamous cell carcinoma (HNSCC), contributing to tumor invasiveness, distant metastasis, and recurrence. Exosomes are known mediators and regulators of EMT. Here, we analyze the impact of exosomes that were primed by conventional therapy on EMT modulation.

Methods

Plasmas of n = 22 HNSCC patients were collected before and after standard of care surgery and adjuvant or primary (chemo)radiotherapy. Exosomes were isolated by size exclusion chromatography. Upon co-incubation of exosomes with HNSCC cells, the cellular EMT profile was analyzed by flow cytometry and RT-qPCR. Wound healing assays were performed to evaluate migratory potential of exosome-treated cells.

Results

Reduction of total exosome protein after therapy and in vitro exosome induced EMT profiles were dependent on the type of treatment. Exosomal TFG-β and miRNA cargo were partly responsible for observed exosome induced EMT changes. Exosomes from recurrent patients induced higher tumor cell migration after therapy than exosomes from disease-free patients.

Conclusions

HNSCC patients’ exosomes from timepoints before and after therapy were able to confer therapy induced EMT modulation in vitro and have the potential to monitor the EMT process. Exosome induced changes in migratory potential emerged as discriminants of therapy outcome.
A pan-cancer landscape of IGF2BPs and their association with prognosis, stemness and tumor immune microenvironment
Authors: Shao Wei , Zhao Hui , Zhang Shoudu , Ding Qian , Guo Yugang , Hou Kaiqi , Kan Yunchao , Deng Fan , Xu Qian
Published: January 2023

Background

The human insulin-like growth factor 2 mRNA binding proteins 1–3 (IGF2BP1–3, also called IMP1–3) play essential roles in mRNA regulation, including its splicing, translocation, stability, and translation. However, knowledge regarding the involvement of IGF2BPs in tumor immunity and stemness across cancer types is still lacking.

Methods

In this study, we comprehensively analyzed pan-cancer multi-omic data to determine the correlation of IGF2BPs mRNA and protein expression with various cancer parameters such as mutation frequency, prognostic value, the tumor microenvironment (TME), checkpoint blockade, tumor immune infiltration, stemness and drug sensitivity. Validation of the expression of IGF2BPs in cancer samples and glioma cells were performed by quantitative real-time (qRT)-PCR, and immunofluorescence staining. Investigation of the functional role of IGF2BP3 in glioma stem cells(GSCs) were performed by sphere formation, cytotoxicity, transwell, and wound healing assays.

Results

We found that IGF2BP1 and 3 are either absent or expressed at very low levels in most normal tissues. However, IGF2BP1-3 can be re-expressed in a broad range of cancer types and diverse cancer cell lines, where their expression often correlates with poor prognosis. Immunofluorescence staining and qRT-PCR analyses also showed that the expression of IGF2BP2 and IGF2BP3 were higher in cancer tissues than that in adjacent normal tissues. Moreover, IGF2BPs are associated with TME and stemness in human pan-cancer. Remarkably, IGF2BP3 participated in the maintenance and self-renewal of glioma stem cell (GSCs). Knockdown of IGF2BP3 attenuated GSC and glioma cell proliferation, invasion, and migration.

Conclusions

Our systematic pan-cancer study confirmed the identification of IGF2BPs as therapeutic targets and highlighted the need to study their association with stemness, and the TME, which contribute to the cancer drug-discovery research. Especially, preliminary studies demonstrate the IGF2BP3 as a potential negative regulator of glioma tumorigenesis by modulating stemness.
Endoplasmic reticulum stress related IncRNA signature predicts the prognosis and immune response evaluation of uterine corpus endometrial carcinoma
Authors: Chen Jun , Shen Licong , Yang Yongwen
Published: January 2023

Background

Endoplasmic reticulum (ER) stress is closely related to the occurrence, development and treatment of tumors. Recent studies suggest ER stress as a therapeutic strategy of choice for cancer. However, ER stress-related long non-coding RNA (lncRNA) predictive value in endometrial carcinoma (UCEC) remains to be further evaluated. The purpose of this study was to establish relies on the signature of ER stress-related lncRNA forecast to predict the prognosis of patients with UCEC.

Methods

We downloaded the RNA expression profile dataset and matched clinical data from the Cancer Genome Atlas (TCGA) database, and applied univariate and multivariate Cox regression analysis to build predictive signature. Kaplan-meier method was used to evaluate overall survival (OS) and disease-free survival (DFS). Gene set enrichment analysis (GSEA) was used to study the functional characteristics. Single sample Gene set enrichment analysis (ssGSEA) was used to analyze the relationship between immune status and predicted signature. Correlations between the potential usefulness of treatment for UCEC patients and predictive signature were also analyzed.

Results

We established a signature composed of eight ER stress-related lncRNAs (MIR34AHG, AC073842.2, PINK1AS, AC024909.2, MIR31HG, AC007422.2, AC061992.1, AC003102.1). The signature of ER stress-related lncRNA provided better diagnostic value compared with age and tumor grade, and the area under the receiver operating curve was 0.788. The overall and disease-free survival probability of patients in the high-risk group is lower than that in the low-risk group. GSEA indicated that the pathways were mainly enriched for cancer, immunity and reproduction related pathways. ss-GSEA shows that prediction signature and activation of dendritic cells, immature dendritic cells, T helper cells and immune status of the Treg are significantly related. High-risk groups may against PD - 1/L1 immunotherapy and JNK inhibitors VIII, Z.LLNle.CHO, DMOG and JNK. 9 l more sensitive.

Conclusion

The ER stress signature can independently predict the prognosis of UCEC patients, and provide guidance for conventional chemotherapy and immunotherapy of UCEC patients.
Closure strategy for endoscopic pituitary surgery: Experience from 3015 patients
Authors: Baussart Bertrand , Venier Alice , Jouinot Anne , Reuter Gilles , Gaillard Stephan
Published: January 2023

Introduction

Effective strategies are required to ensure optimal management of the crucial closure step in endoscopic pituitary surgery. Many surgical techniques have been reported but no significant consensus has been defined.

Methods

Between January 2006 and March 2022, 3015 adult patients with pituitary adenomas were operated on by a single expert neurosurgical team, using a mononostril endoscopic endonasal approach. Based of preoperative risk factors of and operative findings, a detailed closure strategy was used. Body mass index >40, sellar floor lysis, number of surgeries>2, large skull base destruction, prior radiotherapy were considered as preoperative risk factors for closure failure. All patients treated with an expanded endonasal approach were excluded.

Results

Patients were mostly women (F/M ratio: 1.4) with a median age of 50 (range: 18 –89). Intraoperative CSF leak requiring specific surgical management was observed in 319/3015 (10.6%) of patients. If intraoperative leak occurred, patients with predictive risk factors were managed using a Foley balloon catheter in case of sellar floor lysis or BMI>40 and a multilayer repair strategy with a vascularized nasoseptal flap in other cases. Postoperative CSF leak occurred in 29/3015 (1%) of patients, while meningitis occurred in 24/3015 (0.8%) of patients. In patients with intraoperative leak, closure management failed in 11/319 (3.4%) of cases.

Conclusion

Based on our significant 16-year experience, our surgical management is reliable and easy to follow. With a planned and stepwise strategy, the closure step can be optimized and tailored to each patient with a very low failure rate.
Quantitative analysis of superb microvascular imaging for monitoring tumor response to chemoradiotherapy in locally advanced cervical cancer
Authors: Zhu Yi , Tang Yixin , Zhang Guonan , Zhang Jie , Li Yanjie , Jiang Zhuolin
Published: January 2023

Objectives

As an ultrasound (US) image processing method, superb microvascular imaging (SMI) extracts and visualizes flow signals from vessels through advanced clutter suppression technology. We investigated the feasibility of SMI in monitoring treatment response in patients with locally advanced cervical cancer (LACC) undergoing chemoradiotherapy (CRT).

Methods

Forty-nine patients underwent CRT and received SMI examination at 3 time points: before therapy (baseline), 3 weeks during, and 1 month after CRT. The maximum tumor diameter (Dmax), vascularity index (VI), and their percentage changes (ΔDmax and ΔVI) were calculated. ΔDmax was compared with MRI results as the reference standard.

Results

Based on the MRI findings, 44 were classified as complete response (CR) group and 5 as partial response (PR) group. The Dmax and ΔDmax showed decrease in CR and PR groups at 3 weeks during CRT (P< 0.05), but no significant difference between the two groups (P > 0.05). Compared to the baseline, significant decrease in VI and ΔVI were observed at during and after treatment in the two groups (P< 0.05). Moreover, there were significant differences in VI and ΔVI at 3 weeks during CRT between the CR and PR groups (P< 0.05). ΔVI at 3 weeks during CRT showed a better predictive performance for responder prognosis than VI (AUC = 0.964, AUC = 0.950, respectively, P = 0.001), with a cut-off value of 41.6% yielding 100% sensitivity and 86.4% specificity.

Conclusions

The SMI parameters (VI and ΔVI) have potential for monitoring treatment response in LACC.
MRI-based multiregional radiomics for predicting lymph nodes status and prognosis in patients with resectable rectal cancer
Authors: Li Hang , Chen Xiao-li , Liu Huan , Lu Tao , Li Zhen-lin
Published: January 2023

Purpose

To establish and evaluate multiregional T2-weighted imaging (T2WI)-based clinical-radiomics model for predicting lymph node metastasis (LNM) and prognosis in patients with resectable rectal cancer.

Methods

A total of 346 patients with pathologically confirmed rectal cancer from two hospitals between January 2019 and December 2021 were prospectively enrolled. Intra- and peritumoral features were extracted separately, and least absolute shrinkage and selection operator regression was applied for feature selection. Radiomics signatures were built using the selected features from different regions. The clinical-radiomic nomogram was developed by combining the intratumoral and peritumoral radiomics signatures score (radscore) and the most predictive clinical parameters. The diagnostic performances of the nomogram and clinical model were evaluated using the area under the receiver operating characteristic curve (AUC). The prognostic model for 3-year recurrence-free survival (RFS) was constructed using univariate and multivariate Cox analysis.

Results

The intratumoral radscore (radscore 1) included four features, the peritumoral radscore (radscore 2) included five features, and the combined intratumoral and peritumoural radscore (radscore 3) included ten features. The AUCs for radscore 3 were higher than that of radscore 1 in training cohort (0.77 vs. 0.71, P=0.182) and internal validation cohort (0.76 vs. 0.64, P=0.041). The AUCs for radscore 3 were higher than that of radscore 2 in training cohort (0.77 vs. 0.74, P=0.215) and internal validation cohort (0.76 vs. 0.68, P=0.083). A clinical-radiomic nomogram showed a higher AUC compared with the clinical model in training cohort (0.84 vs. 0.67, P<0.001) and internal validation cohort (0.78 vs. 0.64, P=0.038) but not in external validation (0.72 vs. 0.76, P=0.164). Multivariate Cox analysis showed MRI-reported extramural vascular invasion (EMVI) (HR=1.099, 95%CI: 0.462-2.616; P=0.031) and clinical-radiomic nomogram-based LNM (HR=2.232, 95%CI:1.238-7.439; P=0.017) were independent risk factors for assessing 3-year RFS. Combined clinical-radiomic nomogram based LNM and MRI-reported EMVI showed good performance in training cohort (AUC=0.748), internal validation cohort (AUC=0.706) and external validation (AUC=0.688) for predicting 3-year RFS.

Conclusion

A clinical-radiomics nomogram exhibits good performance for predicting preoperative LNM. Combined clinical-radiomic nomogram based LNM and MRI-reported EMVI showed clinical potential for assessing 3-year RFS.
Advances in research on the relationship between thymoquinone and pancreatic cancer
Authors: Zhao Zhanxue , Liu Linxun , Li Shuai , Hou Xiaofan , Yang Jinyu
Published: January 2023

Pancreatic cancer has one of the worst prognoses among the most common cancers in the world. Its characteristics include a high rate of metastasis and chemotherapeutic resistance, which present major challenges to the medical community. The potential anticancer effects of thymoquinone (TQ), which is the main bioactive compound of the black seeds of the Nigella sativa plant, have recently received widespread attention for their potential use in treating pancreatic cancer. TQ can inhibit cell proliferation, promote cancer cell apoptosis, inhibit cell invasion and metastasis, enhance chemotherapeutic sensitivity, inhibit angiogenesis, and exert anti-inflammatory effects. These anticancer effects predominantly involve the nuclear factor (NF)-κB, phosphoinositide 3 kinase (PI3K)/Akt, Notch, transforming growth factor (TGF)-β, c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (MAPK) signaling pathways as well as the regulation of the cell cycle, matrix metallopeptidase (MMP)-9 expression, and pyruvate kinase isozyme type M2 (PKM2) activity. TQ regulates the occurrence and development of pancreatic cancer at multiple levels and through multiple targets that communicate with each other. In this review, we summarize and discuss the analogs and carriers of TQ that have been developed in recent years. Given its multilevel anticancer effects, TQ may become a new therapeutic drug for treating pancreatic cancer in the future. This review presents a brief introduction to the research that has been conducted on TQ in relation to pancreatic cancer to provide a theoretical basis for future studies on the topic.
The role of radiotherapy in HER2+ early-stage breast cancer patients after breast-conserving surgery
Authors: Yang Huanzuo , Qiu Mengxue , Feng Yu , Wen Nan , Zhou Jiao , Qin Xiangquan , Li Juan , Liu Xinran , Wang Xiaodong , Du Zhenggui
Published: January 2023

Background

Due to radioresistance, some HER2+ patients may gain limited benefit from radiotherapy (RT) after breast-conserving surgery (BCS). This study aimed to develop an individualized nomogram to identify early-stage HER2+ patients who could omit RT after BCS.

Methods

The data of HER2+ patients with T0-2N0M0 breast cancer after BCS between 2010 and 2015 were extracted from Surveillance, Epidemiology, and End Results (SEER). Based on the independent prognostic factors determined by the Cox analysis in patients without RT after propensity score matching (PSM), the nomogram and risk stratification model were constructed, and then the prognosis of patients with and without RT was compared in each stratified group.

Results

A total of 10799 early-stage HER2+ patients after BCS were included. Baseline characteristics were similar between groups after PSM. Multivariate Cox analysis indicated that RT could improve overall survival (OS) (HR: 0.45, P<0.001) and breast cancer-specific survival (BCSS) (HR: 0.53, P<0.001). Age, marital status, tumor location, tumor size, and chemotherapy were identified by multivariate Cox analysis in patients without RT and were incorporated into a well-validated nomogram. The risk stratification model based on the nomogram indicated that RT was associated with improved OS (HR 0.40, P< 0.001) and BCSS (HR 0.39, P< 0.001) in the high-risk group but not in the low-risk group [OS: HR 1.04, P = 0.94; BCSS: HR 1.06, P = 0.93].

Conclusion

RT could significantly improve the OS and BCSS of HER2+ early-stage breast cancer patients after BCS on the whole. For high-risk patients, RT is an essential component of cancer therapy. However, the omission of radiotherapy may be considered for low-risk HER2+ early-stage patients. Further validation and improvement of the nomogram by prospective study or randomized controlled trials are warranted.
Case Report: Successful treatment of severe pneumocystis carinii pneumonia in a case series of primary nephrotic syndrome after receiving anti-CD20 monoclonal antibody therapy
Authors: Liu Lili , Zheng Weihua , Wang Ping , Wu Ying , Zhu Guanghua , Yang Rong , Gu Li , Huang Wenyan , Kang Yulin
Published: January 2023

Rituximab is emerging as a new steroid sparing agent in children with difficult-to-treat nephrotic syndrome due to its ability of depleting CD20-positive B cells. Life-threatening adverse events such as pneumocystis carinii pneumonia may occur even though it seems to be well tolerated. Since rituximab is wildly used in immune-mediated diseases, it is important to manage its severe adverse events. To explore the importance of early diagnosis and treatment of pneumocystis carinii pneumonia in children with primary nephrotic syndrome (PNS) after receiving rituximab therapy, we retrospectively analyzed the clinical data of PNS patients younger than 18 years old with pneumocystis carinii pneumonia who were hospitalized in our center. Clinical features and laboratory test results were retrieved from the electronic medical records. Severe pneumocystis carinii pneumonia occurred in one child with steroid resistant nephrotic syndrome and two with steroid dependent nephrotic syndrome patients after rituximab treatment. These patients were diagnosed in time by metagenomic next-generation sequencing (mNGS) for pathogen detection. Fortunately, all three patients survived after antifungal treatment and achieved complete remission eventually. In conclusion, early diagnosis by using mNGS and timely antifungal treatment is the key to successful management of pneumocystis carinii pneumonia in children with difficult-to-treat PNS.
Clinical review of humic acid as an antiviral: Leadup to translational applications in clinical humeomics
Authors: Socol David C.
Published: January 2023

This clinical review presents what is known about the antiviral features of humic substances (HS) to the benefit of the clinical healthcare provider using available data in humeomics, the study of the soil humeome. It provides the reader with a working framework of historical studies and includes clinically relevant data with the goal of providing a broad appreciation of the antiviral potential of humic substances while also preparing for a translational leap into the clinical application of humic acid.