bluuebunny/crossref_metadata_2025 huggingface dataset:
Synaptic NMDA receptor activity at resting membrane potentials
Authors: Chiu Delia N. , Carter Brett C.
Published: July 2022

NMDA receptors (NMDARs) are crucial for glutamatergic synaptic signaling in the mammalian central nervous system. When activated by glutamate and glycine/D-serine, the NMDAR ion channel can open, but current flux is further regulated by voltage-dependent block conferred by extracellular Mg2+ ions. The unique biophysical property of ligand- and voltage-dependence positions NMDARs as synaptic coincidence detectors, controlling a major source of synaptic Ca2+ influx. We measured synaptic currents in layer 2/3 neurons after stimulation in layer 4 of somatosensory cortex and found measurable NMDAR currents at all voltages tested. This NMDAR current did not require concurrent AMPAR depolarization. In physiological ionic conditions, the NMDAR current response at negative potentials was enhanced relative to ionic conditions typically used in slice experiments. NMDAR activity was also seen in synaptic recordings from hippocampal CA1 neurons, indicating a general property of NMDAR signaling. Using a fluorescent Ca2+ indicator, we measured responses to stimulation in layer 4 at individual synaptic sites, and Ca2+ influx could be detected even with AMPARs blocked. In current clamp recordings, we found that resting membrane potential was hyperpolarized by ∼7 mV and AP firing threshold depolarized by ∼4 mV in traditional compared to physiological ionic concentrations, and that NMDARs contribute to EPSPs at resting membrane potentials. These measurements demonstrate that, even in the presence of extracellular Mg2+ and absence of postsynaptic depolarization, NMDARs contribute to synaptic currents and Ca2+ influx.
Stage-Dependent Changes of Visual Function and Electrical Response of the Retina in the rd10 Mouse Model
Authors: Cha Seongkwang , Ahn Jungryul , Jeong Yurim , Lee Yong Hee , Kim Hyong Kyu , Lee Daekee , Yoo Yongseok , Goo Yong Sook
Published: July 2022

One of the critical prerequisites for the successful development of retinal prostheses is understanding the physiological features of retinal ganglion cells (RGCs) in the different stages of retinal degeneration (RD). This study used our custom-made rd10 mice, C57BL/6-Pde6bem1(R560C)Dkl/Korl mutated on the Pde6b gene in C57BL/6J mouse with the CRISPR/Cas9-based gene-editing method. We selected the postnatal day (P) 45, P70, P140, and P238 as representative ages for RD stages. The optomotor response measured the visual acuity across degeneration stages. At P45, the rd10 mice exhibited lower visual acuity than wild-type (WT) mice. At P140 and older, no optomotor response was observed. We classified RGC responses to the flashed light into ON, OFF, and ON/OFF RGCs via in vitro multichannel recording. With degeneration, the number of RGCs responding to the light stimulation decreased in all three types of RGCs. The OFF response disappeared faster than the ON response with older postnatal ages. We elicited RGC spikes with electrical stimulation and analyzed the network-mediated RGC response in the rd10 mice. Across all postnatal ages, the spikes of rd10 RGCs were less elicited by pulse amplitude modulation than in WT RGCs. The ratio of RGCs showing multiple peaks of spike burst increased in older ages. The electrically evoked RGC spikes by the pulse amplitude modulation differ across postnatal ages. Therefore, degeneration stage-dependent stimulation strategies should be considered for developing retinal prosthesis and successful vision restoration.
Prospective CERAD Neuropsychological Assessment in Patients With Multiple System Atrophy
Authors: Maass Fabian , Hermann Peter , Varges Daniela , Nuhn Sabine , van Riesen Christoph , Jamous Ala , Focke Niels K. , Hewitt Manuel , Leha Andreas , Bähr Mathias , Zerr Inga
Published: July 2022

The objective of the study was to characterize the pattern of cognitive dysfunction in patients with multiple system atrophy (MSA) applying a standardized neuropsychological assessment. A total of 20 patients with the diagnosis of probable or possible MSA were enrolled for neuropsychological assessment applying the CERAD plus battery. All patients were tested at baseline and 14/20 patients received additional follow-up assessments (median follow-up of 24 months). Additionally, relationship between cortical thickness values/subcortical gray matter volumes and CERAD subitems was evaluated at baseline in a subgroup of 13/20 patients. Trail Making Test (TMT) was the most sensitive CERAD item at baseline with abnormal performance (z-score < −1.28) in one or both pathological TMT items (TMT-A, TMT-B) in 60% of patients with MSA. Additionally, there was a significant inverse correlation between the volume of the left and the right accumbens area and the TMT A item after adjusting for age (left side: p = 0.0009; right side p = 0.003). Comparing both subtypes, patients with MSA-C had significant lower values in phonemic verbal fluency (p = 0.04) and a trend for lower values in semantic verbal fluency (p = 0.06) compared to MSA-P. Additionally, patients with MSA-C showed significantly worse performance in the TMT-B task (p = 0.04) and a trend for worse performance in the TMT-A task (p = 0.06). Concerning longitudinal follow-up, a significant worsening in the TMT-B (p = 0.03) can be reported in MSA. In conclusion, frontal-executive dysfunction presents the hallmark of cognitive impairment in MSA.
Proteomic Profiling of Plasma Biomarkers Associated With Return to Sport Following Concussion: Findings From the NCAA and Department of Defense CARE Consortium
Authors: Vorn Rany , Mithani Sara , Devoto Christina , Meier Timothy B. , Lai Chen , Yun Sijung , Broglio Steven P. , McAllister Thomas W. , Giza Christopher C. , Kim Hyung-Suk , Huber Daniel , Harezlak Jaroslaw , Cameron Kenneth L. , McGinty Gerald , Jackson Jonathan , Guskiewicz Kevin M. , Mihalik Jason P. , Brooks Alison , Duma Stefan , Rowson Steven , Nelson Lindsay D. , Pasquina Paul , McCrea Michael A. , Gill Jessica M.
Published: July 2022

Objective

To investigate the plasma proteomic profiling in identifying biomarkers related to return to sport (RTS) following a sport-related concussion (SRC).

Methods

This multicenter, prospective, case-control study was part of a larger cohort study conducted by the NCAA-DoD Concussion Assessment, Research, and Education (CARE) Consortium, athletes (n = 140) with blood collected within 48 h of injury and reported day to asymptomatic were included in this study, divided into two groups: (1) recovery <14-days (n = 99) and (2) recovery ≥14-days (n = 41). We applied a highly multiplexed proteomic technique that uses DNA aptamers assay to target 1,305 proteins in plasma samples from concussed athletes with <14-days and ≥14-days.

Results

We identified 87 plasma proteins significantly dysregulated (32 upregulated and 55 downregulated) in concussed athletes with recovery ≥14-days relative to recovery <14-days groups. The significantly dysregulated proteins were uploaded to Ingenuity Pathway Analysis (IPA) software for analysis. Pathway analysis showed that significantly dysregulated proteins were associated with STAT3 pathway, regulation of the epithelial mesenchymal transition by growth factors pathway, and acute phase response signaling.

Conclusion

Our data showed the feasibility of large-scale plasma proteomic profiling in concussed athletes with a <14-days and ≥ 14-days recovery. These findings provide a possible understanding of the pathophysiological mechanism in neurobiological recovery. Further study is required to determine whether these proteins can aid clinicians in RTS decisions.
Characterizing the evolution of oculomotor and vestibulo-ocular function over time in children and adolescents after a mild traumatic brain injury
Authors: Crampton Adrienne , Schneider Kathryn J. , Grilli Lisa , Chevignard Mathilde , Katz-Leurer Michal , Beauchamp Miriam H. , Debert Chantel , Gagnon Isabelle J.
Published: July 2022

Background

Impairments to oculomotor (OM) and vestibulo-ocular reflex (VOR) function following pediatric mTBI have been demonstrated but are poorly understood. Such impairments can be associated with more negative prognosis, affecting physical and mental wellbeing, emphasizing the need to more fully understand how these evolve.

Objectives

to determine i) the extent to which performance on clinical and computerized tests of OM and VOR function varies over time in children and adolescents at 21 days, 3-, and 6-months post-mTBI; ii) the proportion of children and adolescents with mTBI presenting with abnormal scores on these tests at each timepoint.

Design

Prospective longitudinal design.

Setting

Tertiary care pediatric hospital.

Participants

36 participants with mTBI aged 6 to18.

Procedures

Participants were assessed on a battery of OM and VOR tests within 21 days, at 3- and 6-months post injury.

Outcome measures

Clinical measures: Vestibular/ocular motor screening tool (VOMS) (symptom provocation and performance); Computerized measures: reflexive saccade test (response latency), video head impulse test (VOR gain), and dynamic visual acuity test (LogMAR change).

Analysis

Generalized estimating equations (parameter estimates and odd ratios) estimated the effect of time. Proportions above and below normal cut-off values were determined.

Results

Our sample consisted of 52.8% females [mean age 13.98 (2.4) years, assessed on average 19.07 (8–33) days post-injury]. Older children performed better on visual motion sensitivity (OR 1.43, p = 0.03) and female participants worse on near point of convergence (OR 0.19, p = 0.03). Change over time (toward recovery) was demonstrated by VOMS overall symptom provocation (OR 9.90, p = 0.012), vertical smooth pursuit (OR 4.04, p = 0.03), voluntary saccade performance (OR 6.06, p = 0.005) and right VOR gain (0.068, p = 0.013). Version performance and VOR symptom provocation showed high abnormal proportions at initial assessment.

Discussion

Results indicate impairments to the VOR pathway may be present and driving symptom provocation. Vertical smooth pursuit and saccade findings underline the need to include these tasks in test batteries to comprehensively assess the integrity of OM and vestibular systems post-mTBI.

Implications

Findings demonstrate 1) added value in including symptom and performance-based measures in when OM and VOR assessments; 2) the relative stability of constructs measured beyond 3 months post mTBI.
Toward improving control performance of myoelectric arm prosthesis by adding wrist position feedback
Authors: Zheng Yue , Tian Lan , Li Xiangxin , Tan Yingxiao , Yang Zijian , Li Guanglin
Published: July 2022

Wearing a myoelectric prosthesis is a basic way for limb amputees to restore their lost limb functions in the activities of daily living (ADLs). However, it is estimated that around 40% of amputees refuse the prosthesis. One of the primary reasons would be that the current prostheses lack appropriate sensory feedback. Currently, the amputees only depend on their visual feedback (Vis-FB) when using their arm prostheses. It would be difficult for them to accurately control the wrist position, which is vital for flexible manipulation in ADLs. This manuscript designed a myoelectric arm prosthesis with wrist position feedback (WP-FB). To study the effect level of position feedback on prosthetic control, two tests were performed. The vibrotactile perception range test aims to analyze the perception sensitivity of the vibration in humans and obtain the optimal perception range utilized in the sensory feedback test. The sensory feedback test analyzes the effectiveness of the position feedback by comparing three feedback methods of Vis-FB, WP-FB, and a combination of Vis-FB and WP-FB (VP-FB). These tests were conducted by asking six able-bodied subjects to perform 20 movement combinations of five target positions. The WP-FB was transiently activated with five vibrating motors embedded in an armband to stimulate the arm stump when the prosthetic wrist rotates to the target positions. Our experimental results showed that when WP-FB was added to the prosthetic control, the absolute angular error (AAE) of the prosthetic wrist declined from 4.50° to 1.08° while the success rate 3 (SR3) increased from 0.34 to 0.84, respectively. This study demonstrates the importance of WP-FB to the effective control of the arm prosthesis.
Untypical Contrast Normalization Explains the “Weak Outnumber Strong” Numerosity Illusion
Authors: Lei Quan , Reeves Adam
Published: July 2022

Less salient, lower contrast disks appear to be more numerous than more salient, higher contrast disks when intermingled in equal numbers into the same display (Lei and Reeves, 2018), but they are equal in perceived numerosity when segregated into different displays. Comparative judgements indicate that the apparent numerosity of the lower contrast disks is unaffected by being intermingled with high contrast disks, whereas the high contrast disks are reduced in numerosity by being intermingled with the low contrast ones (Lei and Reeves, 2018). Here, we report that this illusion also occurs for absolute judgements of the numerosities of displays of from 20 to 80 disks. A model based on luminance-difference contrast normalization (LDCN) explains the illusory loss of high-contrast (salient) items along with veridical perception of the low-contrast ones. The model correctly predicts that perceived numerosity is linearly related to the square-root of the number of disks, with the extent of the illusion depending on an attentionally-weighted function of contrast and assimilation.
Visible and Near-Infrared Spectroscopy Combined With Bayes Classifier Based on Wavelength Model Optimization Applied to Wine Multibrand Identification
Authors: Pan Tao , Li Jiaqi , Fu Chunli , Chang Nailiang , Chen Jiemei
Published: July 2022

The identification of high-quality wine brands can avoid adulteration and fraud and protect the rights and interests of producers and consumers. Since the main components of wine are roughly the same, the characteristic components that can distinguish wine brands are usually trace amounts and not unique. The conventional quantitative detection method for brand identification is complicated and difficult. The naive Bayes (NB) classifier is an algorithm based on probability distribution, which is simple and particularly suitable for multiclass discriminant analysis. However, the absorbance probability between spectral wavelengths is not necessarily strongly independent, which limits the application of Bayes method in spectral pattern recognition. This research proposed a Bayes classifier algorithm based on wavelength optimization. First, a large-scale wavelength screening for equidistant combination (EC) was performed, and then wavelength step-by-step phase-out (WSP) was carried out to reduce the correlation between wavelengths and improve the accuracy of Bayes discrimination. The proposed EC-WSP-Bayes method was applied to the 5-category discriminant analysis of wine brand identification based on visible and near-infrared (Vis-NIR) spectroscopy. Among them, four types of wine brands were collected from regular sales channels as identification brands. The fifth type of samples was composed of 21 other commercial brand wines and home-brewed wines from various sources, as the interference brand. The optimal EC-WSP-Bayes model was selected, the corresponding wavelength combination was 404, 600, 992, 2,070, 2,266, and 2,462 nm located in the visible light, shortwave NIR, and combination frequency regions. In modeling and independent validation, the total recognition accuracy rate (RARTotal) reached 98.1 and 97.6%, respectively. The technology is quick and easy, which is of great significance to regulate the alcohol market. The proposed model of less-wavelength and high-efficiency (N = 6) can provide a valuable reference for small special instruments. The proposed integrated chemometric method can reduce the correlation between wavelengths, improve the recognition accuracy, and improve the applicability of the Bayesian method.
Diet Quality and Cognitive Performance in Children Born Very Low Birth Weight
Authors: Sato Julie , McGee Meghan , Bando Nicole , Law Nicole , Unger Sharon , O'Connor Deborah L.
Published: July 2022

Children born very low birth weight (VLBW, <1,500 g) are at high risk for cognitive and academic difficulties later in life. Although early nutrition (e.g., breastfeeding) is positively correlated with IQ in children born VLBW, the association between dietary intake in childhood and cognitive performance is unknown. Thus, our study is the first to investigate the relationship between diet quality, as measured by the Healthy Eating Index-2010 (HEI-2010) and cognitive performance in a Canadian cohort of 5-year-old children born VLBW (n = 158; 47% female). Diet quality was measured using two 24-h diet recalls obtained from parents and cognitive performance was assessed using the Wechsler Preschool and Primary Scale of Intelligence-IV (WPPSI-IV). To account for additional sociodemographic factors that could influence neurodevelopment, linear regression analyses were adjusted for sex, household income above/below the poverty line, maternal education, birth weight and breastfeeding duration. Mean ± SD HEI-2010 score was 58.2 ± 12.4, with most children (67%) having diets in “need of improvement” (scores 51–80). HEI-2010 scores were not significantly associated with IQ or any other WPPSI-IV composite score. Significant predictors of IQ in our model were birth weight, sex, and maternal education. Our findings emphasize the important role of maternal education and other sociodemographic factors on neurodevelopment in children born VLBW. Further, despite not finding any significant association between HEI-2010 scores and IQ, our results highlight the need to improve diet quality in young children born VLBW. Further research is needed to confirm the impact of diet quality on cognitive performance in this vulnerable population.
A Narrative Review of Recent Advances in Rapid Assessment of Anthocyanins in Agricultural and Food Products
Authors: Manzoor Muhammad Faisal , Hussain Abid , Naumovski Nenad , Ranjha Muhammad Modassar Ali Nawaz , Ahmad Nazir , Karrar Emad , Xu Bin , Ibrahim Salam A.
Published: July 2022

Anthocyanins (ACNs) are plant polyphenols that have received increased attention recently mainly due to their potential health benefits and applications as functional food ingredients. This has also created an interest in the development and validation of several non-destructive techniques of ACN assessments in several food samples. Non-destructive and conventional techniques play an important role in the assessment of ACNs in agricultural and food products. Although conventional methods appear to be more accurate and specific in their analysis, they are also associated with higher costs, the destruction of samples, time-consuming, and require specialized laboratory equipment. In this review article, we present the latest findings relating to the use of several spectroscopic techniques (fluorescence, Raman, Nuclear magnetic resonance spectroscopy, Fourier-transform infrared spectroscopy, and near-infrared spectroscopy), hyperspectral imaging, chemometric-based machine learning, and artificial intelligence applications for assessing the ACN content in agricultural and food products. Furthermore, we also propose technical and future advancements of the established techniques with the need for further developments and technique amalgamations.
Microbial and Transcriptomic Profiling Reveals Diet-Related Alterations of Metabolism in Metabolic Disordered Mice
Authors: Zhu Weize , Hong Ying , Li Yue , Li Yan , Zhong Jing , He Xiaofang , Zheng Ningning , Sheng Lili , Li Houkai
Published: July 2022

Metabolic disorders are the prelude of metabolic diseases, which are mainly due to the high-energy intake and genetic contribution. High-fat diet (HFD) or high-sucrose diet is widely used for inducing metabolic disorders characterized by increased body weight, insulin resistance, hepatic steatosis, and alteration of gut microbiome. However, the triangle relationship among diets, gut microbiome, and host metabolism is poorly understood. In our study, we investigated the dynamic changes in gut microbiota, and host metabolism in mice that were fed with either chow diet, HFD, or chow diet with 30% sucrose in drinking water (HSD) for continued 12 weeks. The gut microbiota was analyzed with 16S rDNA sequencing on feces. Hepatic gene expression profile was tested with transcriptomics analysis on liver tissue. The host metabolism was evaluated by measuring body weight, insulin sensitivity, serum lipids, and expression of proteins involved in lipid metabolism of liver. The results showed that HFD feeding affected body weight, insulin resistance, and hepatic steatosis more significantly than HSD feeding. 16S rRNA gene sequencing showed that HFD rapidly and steadily suppressed species richness, altered microbiota structure and function, and increased the abundance of bacteria responsible for fatty acid metabolism and inflammatory signaling. In contrast, HSD had minor impact on the overall bacteria structure or function but activated microbial bile acid biosynthesis. Fecal microbiota transplantation suggested that some metabolic changes induced by HFD or HSD feeding were transferrable, especially in the weight of white adipose tissue and hepatic triglyceride level that were consistent with the phenotypes in donor mice. Moreover, transcriptomic results showed that HFD feeding significantly inhibited fatty acid degradation and increase inflammation, while HSD increased hepatic de novo lipogenesis and inhibited primary bile acid synthesis alternative pathway. In general, our study revealed the dynamic and diversified impacts of HFD and HSD on gut microbiota and host metabolism.
Adherence to a Paleolithic Diet in Combination With Lifestyle Factors Reduces the Risk for the Presence of Non-Alcoholic Fatty Liver Disease: A Case-Control Study
Authors: Sohouli Mohammad Hassan , Fatahi Somaye , Izze da Silva Magalhães Elma , Rodrigues de Oliveira Bianca , Rohani Pejman , Ezoddin Neda , Roshan Mehdi Mehdinezhad , Hekmatdoost Azita
Published: July 2022

Background

Evidence suggests the role of changing traditional lifestyle patterns, such as Paleolithic, to the modern lifestyle in the incidence and epidemic of chronic diseases. The purpose of this study was to investigate the associations between the Paleolithic diet (PD) and the Paleolithic-like lifestyle and the risk of non-alcoholic fatty liver disease (NAFLD) among an adult population.

Materials and Methods

This case-control study was carried out among 206 patients with NAFLD and 306 healthy subjects aged >18 years. PD score was evaluated using a validated 168-item quantitative food frequency questionnaire. In addition, to calculate the Paleolithic-like lifestyle score, the components of physical activity, body mass index (BMI), and smoking status of the participants were combined with the score of the PD.

Results

The mean PD and Paleolithic-like lifestyle scores were 38.11 ± 5.63 and 48.92 ± 6.45, respectively. After adjustment for potential confounders, higher scores of adherence to the PD diet conferred a protection for the presence of NAFLD [odds ratio (OR): 0.53; 95% confidence interval (CI): 0.28–0.98; P for trend = 0.021]. Furthermore, PD and healthy lifestyle habits were negatively associated with NAFLD (OR = 0.42, 95% CI 0.23–0.78; P for trend = 0.007).

Conclusion

Our data suggest that the PD alone and in combination with lifestyle factors was associated with decreased risk of NAFLD in a significant manner in the overall population. However, prospective studies are needed to further investigate this association.
Information disorder and organic food purchasing behavior: A moderated mediation model
Authors: Zheng Yan , Cao Dayu
Published: July 2022

On the one hand, fast social media and internet evolution has brought opportunities to the development of the organic food industry. On the other hand, the excessive utilization of social media and internet has also exerted some negative effects on consumers in terms of information disorder and hindered the industrial progression of organic foods. This study aimed to probe into the relationships between organic food information uncertainty, information search anxiety, information overload and purchase behavior under the mediating role of attitude and the moderating role of involvement, introducing the concept of information disorder in the context of this issue. The data (cross-sectional) of 620 organic food consumers in Jiangxi Province, China were subjected to SEM (structural equation modeling). The results showed that organic food information uncertainty and information search anxiety significantly affected attitude, and attitude had a positive impact on purchase behavior. In addition, attitude significantly mediated the effects of organic food information uncertainty and information search anxiety on purchase behavior. Moreover, the indirect relationship between organic food information uncertainty and purchase behavior was moderated by involvement.
Integrative analysis of the metabolome and transcriptome reveals the molecular mechanism of chlorogenic acid synthesis in peach fruit
Authors: Su Ziwen , Jia Haoran , Sun Meng , Cai Zhixiang , Shen Zhijun , Zhao Bintao , Li Jiyao , Ma Ruijuan , Yu Mingliang , Yan Juan
Published: July 2022

As the most abundant phenolic acid in peach fruit, chlorogenic acid (CGA) is an important entry point for the development of natural dietary supplements and functional foods. However, the metabolic and regulation mechanisms underlying its accumulation in peach fruits remain unclear. In this study, we evaluated the composition and content of CGAs in mature fruits of 205 peach cultivars. In peach fruits, three forms of CGA (52.57%), neochlorogenic acid (NCGA, 47.13%), and cryptochlorogenic acid (CCGA, 0.30%) were identified. During the growth and development of peach fruits, the content of CGAs generally showed a trend of rising first and then decreasing. Notably, the contents of quinic acid, shikimic acid, p-coumaroyl quinic acid, and caffeoyl shikimic acid all showed similar dynamic patterns to that of CGA, which might provide the precursor material basis for the accumulation of CGA in the later stage. Moreover, CGA, lignin, and anthocyanins might have a certain correlation and these compounds work together to maintain a dynamic balance. By the comparative transcriptome analysis, 8 structural genes (Pp4CL, PpCYP98A, and PpHCT) and 15 regulatory genes (PpMYB, PpWRKY, PpERF, PpbHLH, and PpWD40) were initially screened as candidate genes of CGA biosynthesis. Our findings preliminarily analyzed the metabolic and molecular regulation mechanisms of CGA biosynthesis in peach fruit, which provided a theoretical basis for developing high-CGA content peaches in future breeding programs.
GNG12 as A Novel Molecular Marker for the Diagnosis and Treatment of Glioma
Authors: Liu Runze , Liu Zhendong , Zhao Yaoye , Cheng Xingbo , Liu Binfeng , Wang Yanbiao , Wang Jialin , Lian Xiaoyu , Zhu Yongjie , Gao Yanzheng
Published: July 2022

Purpose

GNG12 influences a variety of tumors; however, its relationship with glioma remains unclear. The aim of this study was to comprehensively investigate the relationship between GNG12 and the clinical characteristics and prognosis of glioma patients and reveal the mechanisms causing the malignant process of GNG12.

Materials and Methods

We obtained information on clinical samples from multiple databases. The expression level of GNG12 was validated using a RT-qPCR and IHC. KM curves were used to assess the correlation between the GNG12 expression and OS of glioma patients. An ROC curve was drawn to assess the predictive performance of GNG12. Univariate and multivariate Cox analyses were performed to analyze the factors affecting the prognosis of patients with glioma. GSEA and TIMER databases were used to estimate the relationship between GNG12 expression, possible molecular mechanisms, and immune cell infiltration. CMap analysis was used to screen candidate drugs for glioma. Subsequent in vitro experiments were used to validate the proliferation and migration of glioma cells and to explore the potential mechanisms by which GNG12 causes poor prognosis in gliomas.

Results

GNG12 was overexpressed in glioma patients and GNG12 expression level correlated closely with clinical features, including age and histological type, etc. Subsequently, the K-M survival analysis indicated that the expression level of GNG12 was relevant to the prognosis of glioma, and the ROC curve implied that GNG12 can predict glioma stability. Univariate and multivariate analyses showed that GNG12 represents a risk factor for glioma occurrence. GNG12 expression is closely associated with some immune cells. Additionally, several in vitro experiments demonstrated that down-regulation of GNG12 expression can inhibits the proliferation and migration capacity of glioma cells. Ultimately, the results for the GSEA and WB experiments revealed that GNG12 may promote the malignant progression of gliomas by regulating the cell adhesion molecule cell signaling pathway.

Conclusion

In this study, we identified GNG12 as a novel oncogene elevated in gliomas. Reducing GNG12 expression inhibits the proliferation and migration of glioma cells. In summary, GNG12 can be used as a novel biomarker for the early diagnosis of human gliomas and as a potential therapeutic target.
Case Report: Invasive Fungal Infection and Daratumumab: A Case Series and Review of Literature
Authors: Farina Francesca , Ferla V. , Marktel S. , Clerici D. , Mastaglio S. , Perini T. , Oltolini C. , Greco R. , Aletti F. , Assanelli A. , Lupo-Stanghellini M. T. , Bernardi M. , Corti C. , Ciceri F. , Marcatti M.
Published: July 2022

Life expectancy of multiple myeloma (MM) patients has improved in last years due to the advent of anti-CD38 monoclonal antibodies in combination with immunomodulators and proteasome inhibitors. However, morbidity and mortality related to infections remain high and represent a major concern. This paper describes the “real life” risk of invasive fungal infections (IFI) in patients treated with daratumumab-based therapy and reviews the relevant literature. In a series of 75 patients we only observed three cases of fungal pneumonia. Unfortunately, the early signs and symptoms were not specific for fungal infection. Diagnostic imaging, microbiology and patient history, especially previous therapies, are critical in the decision to start antifungal treatment. Recognising the subgroup of MM patients with high risk of IFI can increase the rate of diagnosis, adequate treatment and MM-treatment recovery.
Immune Characteristics and Prognosis Analysis of the Proteasome 20S Subunit Beta 9 in Lower-Grade Gliomas
Authors: Liu Junzhe , Yang Xinyu , Ji Qiankun , Yang Lufei , Li Jingying , Long Xiaoyan , Ye Minhua , Huang Kai , Zhu Xingen
Published: July 2022

Glioma is a common intracranial malignancy in adults and has a high mortality due to its poor prognosis and high recurrence rate. Dysregulation of protein degradation is one of the main promoting factors in glioma development. As an indispensable unit of the proteasome, Proteasome 20S Subunit Beta 9 (PSMB9) is one of the major enzymes in ubiquitin-dependent protein degradation in cells. In addition, proteasomes also participate in a series of cellular processing, like immune regulation, nerve signal transduction, material transport through channels, cell adhesion, and various signaling pathways. However, the relationship between the PSMB9 expression and the occurrence of lower-grade glioma (LGG) is still unknown. First, we collected the RNA-seq and clinical information about LGG clinical samples from The Cancer Genome Atlas (TCGA) cohort, Chinese Glioma Genome Atlas (CGGA; including CGGAseq1 and CGGAseq2) cohort, and Gene Expression Omnibus (GEO; GSE16011, GSE61374, and Rembrandt) cohort. Then, these data were used for differential analysis, survival analysis, enrichment analysis, clinical model construction, etc. In addition, we combine immune-related data for immune-related analysis, including immune infiltration and immunotherapy. Through the above research, we have provided a new biomarker for LGG prognosis prediction and more comprehensively explained the role of PSMB9 in the development of LGG. This study determined that PSMB9 can be used as an immunotherapy target through the analysis of immune data, providing new ideas for the clinical treatment of LGG.
Clear Improvement in Real-World Chronic Myeloid Leukemia Survival: A Comparison With Randomized Controlled Trials
Authors: Vener Claudia , Rossi Silvia , Minicozzi Pamela , Marcos-Gragera Rafael , Poirel Hélène A. , Maynadié Marc , Troussard Xavier , Pravettoni Gabriella , De Angelis Roberta , Sant Milena ,   the EUROCARE-6 Working Group
Published: July 2022

Tyrosine kinase inhibitors (TKIs) have been improving the prognosis of patients with chronic myeloid leukemia (CML), but there are still large differences in survival among European countries. This raises questions on the added value of results from population-based studies, which use real-world data, compared to results of randomized controlled trials (RCTs) involving patients with CML. There are also questions about the extent of the findings on RCTs effectiveness for patients in the general population. We compare survival data extracted from our previous systematic review and meta-analysis of CML RCTs with the latest updated population-based survival data of EUROCARE-6, the widest collaborative study on cancer survival in Europe. The EUROCARE-6 CML survival estimated in patients (15–64 years) diagnosed in 2000–2006 vs. 2007–2013 revealed that the prognostic improvement highlighted by RCTs was confirmed in real-world settings, too. The study shows, evaluating for the first time all European regions, that the optimal outcome figures obtained in controlled settings for CML are also achievable (and indeed achieved) in real-world settings with prompt introduction of TKIs in daily clinical practice. However, some differences still persist, particularly in Eastern European countries, where overall survival values are lower than elsewhere, probably due to a delayed introduction of TKIs. Our results suggest an insufficient adoption of adequate protocols in daily clinical practice in those countries where CML survival values remain lower in real life than the values obtained in RCTs. New high-resolution population-based studies may help to identify failures in the clinical pathways followed there.
Progressing Towards a Human-Centric Approach in Cancer Research
Authors: Parekh Aditya , Das Subhayan , Das Chandan K. , Mandal Mahitosh
Published: July 2022

Despite the advancement in research methodologies and technologies for cancer research, there is a high rate of anti-cancer drug attrition. In this review, we discuss different conventional and modern approaches in cancer research and how human-centric models can improve on the voids conferred by more traditional animal-centric models, thereby offering a more reliable platform for drug discovery. Advanced three-dimensional cell culture methodologies, along with in silico computational analysis form the core of human-centric cancer research. This can provide a holistic understanding of the research problems and help design specific and accurate experiments that could lead to the development of better cancer therapeutics. Here, we propose a new human-centric research roadmap that promises to provide a better platform for cancer research and drug discovery.
Transmembrane Protein 100 Inhibits the Progression of Colorectal Cancer by Promoting the Ubiquitin/Proteasome Degradation of HIF-1α
Authors: Zheng Ying , Zhao Yitong , Jiang Jiong , Zou Baicang , Dong Lei
Published: July 2022

Transmembrane protein 100 (TMEM100) is involved in embryonic cardiovascular system development. However, the biological role of TMEM100 in human cancers, particularly colorectal cancer (CRC), is unclear. In this study, tissue microarrays were stained using immunohistochemistry methods to evaluate the association between TMEM100 levels and clinic-pathological features for CRC. Kaplan–Meier and log-rank tests revealed that decreased levels of TMEM100 correlated with shorter overall survival. Cox regression revealed that reduced levels of TMEM100 was an independent prognostic factor for detrimental survival in CRC. A lentiviral vector was used to overexpress TMEM100 in HCT116 cells, and small interfering RNA was used to knockdown TMEM100 in SW480 cells. The CCK-8 assay, colony formation analysis, cell cycle analysis, cell migration assay, mouse xenograft model and mouse lung metastasis model showed that TMEM100 suppressed CRC cell proliferation and migration in vitro and in vivo. IHC scores of TMEM100 and HIF-1α were significantly negatively correlated. A half-time determination analysis in which cells were treated with cycloheximide revealed that TMEM100 shortened the HIF-1α half-life. Further immunoprecipitation experimental results showed that TMEM100 promoted the ubiquitination of HIF-1α, which caused HIF-1α degradation via the 26S proteasome pathway. Angiogenesis assay and migration assay results revealed that TMEM100 suppressed the migration and angiogenesis induction capacities of HCT116 cells, but this inhibitory effect was abolished when HIF-1α degradation was blocked by MG132 treatment. These results indicated that TMEM100 inhibited the migration and the angiogenesis induction capacities of CRC cells by enhancing HIF-1α degradation via ubiquitination/proteasome pathway.
Emerging Applications of Deep Learning in Bone Tumors: Current Advances and Challenges
Authors: Zhou Xiaowen , Wang Hua , Feng Chengyao , Xu Ruilin , He Yu , Li Lan , Tu Chao
Published: July 2022

Deep learning is a subfield of state-of-the-art artificial intelligence (AI) technology, and multiple deep learning-based AI models have been applied to musculoskeletal diseases. Deep learning has shown the capability to assist clinical diagnosis and prognosis prediction in a spectrum of musculoskeletal disorders, including fracture detection, cartilage and spinal lesions identification, and osteoarthritis severity assessment. Meanwhile, deep learning has also been extensively explored in diverse tumors such as prostate, breast, and lung cancers. Recently, the application of deep learning emerges in bone tumors. A growing number of deep learning models have demonstrated good performance in detection, segmentation, classification, volume calculation, grading, and assessment of tumor necrosis rate in primary and metastatic bone tumors based on both radiological (such as X-ray, CT, MRI, SPECT) and pathological images, implicating a potential for diagnosis assistance and prognosis prediction of deep learning in bone tumors. In this review, we first summarized the workflows of deep learning methods in medical images and the current applications of deep learning-based AI for diagnosis and prognosis prediction in bone tumors. Moreover, the current challenges in the implementation of the deep learning method and future perspectives in this field were extensively discussed.
The Role of Clonal Evolution on Progression, Blood Parameters, and Response to Therapy in Multiple Myeloma
Authors: Sandmann Sarah , Karsch Katharina , Bartel Peter , Exeler Rita , Brix Tobias J. , Mai Elias K. , Varghese Julian , Lenz Georg , Khandanpour Cyrus
Published: July 2022

Introduction

A variety of biomarkers are considered for diagnosis (e.g., β2-microgobulin, albumin, or LDH) and prognosis [e.g., cytogenetic aberrations detected by fluorescence in situ hybridization (FISH)] of multiple myeloma (MM). More recently, clonal evolution has been established as key. Little is known on the clinical implications of clonal evolution.

Methods

We performed in-depth analyses of 25 patients with newly diagnosed MM with respect to detailed clinical information analyzing blood samples collected at several time points during follow-up (median follow-up: 3.26 years since first diagnosis). We split our cohort into two subgroups: with and without new FISH clones developing in the course of disease.

Results

Each subgroup showed a characteristic chromosomal profile. Forty-three percent of patients had evidence of appearing new clones. The patients with new clones showed an increased number of translocations affecting chromosomes 14 (78% vs. 33%; p = 0.0805) and 11, and alterations in chromosome 4 (amplifications and translocations). New clones, on the contrary, were characterized by alterations affecting chromosome 17. Subsequent to the development of the new clone, 6 out of 9 patients experienced disease progression compared to 3 out of 12 for patients without new clones. Duration of the therapy applied for the longest time was significantly shorter within the group of patients developing new clones (median: 273 vs. 406.5 days; p = 0.0465).

Discussion

We demonstrated that the development of new clones, carrying large-scale alterations, was associated with inferior disease course and shorter response to therapy, possibly affecting progression-free survival and overall survival as well. Further studies evaluating larger cohorts are necessary for the validation of our results.
Novel Agents For Relapsed and Refractory Classical Hodgkin Lymphoma: A Review
Authors: Zhang Yujie , Xing Zhichao , Mi Li , Li Zhihui , Zhu Jingqiang , Wei Tao , Wu Wenshuang
Published: July 2022

Classical Hodgkin lymphoma (cHL) is the most common type of HL that occurs mainly in people aged between 15–30 and over 55 years. Although its general prognosis is favorable, 10%–30% of patients with cHL will ultimately develop relapsed or refractory disease (r/r cHL). Improving the cure rate of r/r cHL has proven to be challenging. Some novel agents, such as brentuximab vedotin and immune checkpoint inhibitors, which have been used in conventional regimens for patients with r/r cHL in the past decade, have been shown to have good curative effects. This paper reviews the conventional regimens for patients with r/r cHL and focuses on the newest clinical trials and treatment measures to prolong prognosis and reduce adverse events. The evaluation of prognosis plays a vital role in analyzing the risk of relapse or disease progression; thus, finding new predictive strategies may help treat patients with r/r cHL more efficaciously.
Resident Immune Cells of the Liver in the Tumor Microenvironment
Authors: Lu Yunjie , Ma Shiying , Ding Wei , Sun Pengcheng , Zhou Qi , Duan Yunfei , Sartorius Kurt
Published: July 2022

The liver is a central immunomodulator that ensures a homeostatic balance between protection and immunotolerance. A hallmark of hepatocellular carcinoma (HCC) is the deregulation of this tightly controlled immunological network. Immune response in the liver involves a complex interplay between resident innate, innate, and adaptive immune cells. The immune response in the liver is modulated by its continuous exposure to toxic molecules and microorganisms that requires a degree of immune tolerance to protect normal tissue from damage. In HCC pathogenesis, immune cells must balance a dual role that includes the elimination of malignant cells, as well as the repair of damaged liver tissue to maintain homeostasis. Immune response in the innate and adaptive immune systems extends to the cross-talk and interaction involving immune-regulating non-hematopoietic cells, myeloid immune cells, and lymphoid immune cells. In this review, we discuss the different immune responses of resident immune cells in the tumor microenvironment. Current FDA-approved targeted therapies, including immunotherapy options, have produced modest results to date for the treatment of advanced HCC. Although immunotherapy therapy to date has demonstrated its potential efficacy, immune cell pathways need to be better understood. In this review article, we summarize the roles of specific resident immune cell subsets and their cross-talk subversion in HCC pathogenesis, with a view to identifying potential new biomarkers and therapy options.
Interplay Between Immune and Cancer-Associated Fibroblasts: A Path to Target Metalloproteinases in Penile Cancer
Authors: Cury Sarah Santiloni , Kuasne Hellen , Souza Jeferson dos Santos , Muñoz Juan Jose Moyano , da Silva Jeyson Pereira , Lopes Ademar , Scapulatempo-Neto Cristovam , Faria Eliney Ferreira , Delaissé Jean-Marie , Marchi Fabio Albuquerque , Rogatto Silvia Regina
Published: July 2022

Extracellular matrix (ECM) remodeling and inflammation have been reported in penile carcinomas (PeCa). However, the cell types and cellular crosstalk involved in PeCa are unexplored. We aimed to characterize the complexity of cells and pathways involved in the tumor microenvironment (TME) in PeCa and propose target molecules associated with the TME. We first investigated the prognostic impact of cell types with a secretory profile to identify drug targets that modulate TME-enriched cells. The secretome analysis using the PeCa transcriptome revealed the enrichment of inflammation and extracellular matrix pathways. Twenty-three secreted factors were upregulated, mainly collagens and matrix metalloproteinases (MMPs). The deregulation of collagens and MMPs was confirmed by Quantitative reverse transcription - polymerase chain reaction (RT-qPCR). Further, the deconvolution method (digital cytometry) of the bulk samples revealed a high proportion of macrophages and dendritic cells (DCs) and B cells. Increased DCs and B cells were associated with better survival. A high proportion of cancer-associated fibroblasts (CAFs) was observed in low-survival patients. Patients with increased CAFs had decreased immune cell proportions. The treatment with the MMP inhibitor GM6001 in CAF cells derived from PeCa resulted in altered cell viability. We reported a crosstalk between immune cells and CAFs, and the proportion of these cell populations was associated with prognosis. We demonstrate that a drug targeting MMPs modulates CAFs, expanding the therapeutic options of PeCa.