bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigating the macular choriocapillaris in early primary open-angle glaucoma using swept-source optical coherence tomography angiography
Authors: Lun Katherine , Sim Yin Ci , Chong Rachel , Wong Damon , Tan Bingyao , Husain Rahat , Aung Tin , Sng Chelvin C. A. , Schmetterer Leopold , Chua Jacqueline
Published: September 2022

Introduction

There has been a growing interest in the role of vascular factors in glaucoma. Studies have looked at the characteristics of macular choriocapillaris in patients with glaucoma but with conflicting results. Our study aims to use swept-source optical coherence tomography angiography (SS-OCTA) to evaluate macular choriocapillaris metrics in normal participants and compare them with patients with early primary open-angle glaucoma (POAG) (mean deviation better than −6dB).

Methods

In this prospective, observational, cross-sectional study, 104 normal controls (157 eyes) and 100 patients with POAG (144 eyes) underwent 3 mm × 3mm imaging of the macula using the Plex Elite 9000 (Zeiss Meditec, Dublin, CA, USA). Choriocapillaris OCTA images were extracted from the device’s built-in review software and were subsequently evaluated for the density and size of choriocapillaris flow deficits.

Results

After adjusting for confounding factors, the density of flow deficits was independently higher in those aged 53 years and above (P ≤ 0.024) whereas the average flow deficit size was significantly larger in those aged 69 years and above (95% CI = 12.39 to 72.91; P = 0.006) in both normal and POAG patients. There were no significant differences in the density of flow deficits (P = 0.453) and average flow deficit size (P = 0.637) between normal and POAG participants.

Conclusion

Our study found that macular choriocapillaris microvasculature on SS-OCTA is unaltered by subjects with POAG. This suggests that OCTA macular choriocapillaris may not be potentially helpful in differentiating early glaucoma from healthy eyes.
Hydrological connectivity promotes coalescence of bacterial communities in a floodplain
Authors: Pan Baozhu , Liu Xinyuan , Chen Qiuwen , Sun He , Zhao Xiaohui , Huang Zhenyu
Published: September 2022

Floodplains play essential roles in the ecological functions of regional environments. The merging and coalescence of bacterial communities in aquatic environments results in periodic patterns driven by regular hydrological activities, which may, in turn, influence ecological activities. However, the degree of bacterial community coalescence in the lateral and vertical directions as well as the underlying hydrological mechanism of floodplain ecosystems is poorly understood. Therefore, we investigated the spatiotemporal patterns and coalescence processes of planktonic and sedimentary bacterial communities during normal and high-water periods in a floodplain ecosystem of the Yellow River source region. We classified bacterial operational taxonomic units (OTUs) based on 16S rRNA gene sequencing, and quantified community coalescence by calculating the proportions of overlapping OTUs, the contributions of upstream sources to downstream sinks, and positive/negative cohesion. The results revealed major differences in the composition and diversity of planktonic and sedimentary bacterial communities. Bacterial community diversity in the high-water period was higher than in the normal period. Laterally, hydrological connectivity promoted the immigration and coalescence of bacterial communities to oxbow lakes in both the mainstream and tributaries, with the coalescence degree of planktonic bacteria (2.9%) higher than that of sedimentary bacteria (1.7%). Vertically, the coalescence degree of mainstream planktonic and sedimentary bacterial communities was highest, reaching 2.9%. Co-occurrence network analysis revealed that hydrological connectivity increased the complexity of the bacterial network and enhanced the coalescence of keystone species to oxbow lakes. Furthermore, community coalescence improved the competitiveness and dispersal of bacterial communities. This study demonstrated that coalescence of bacterial communities is driven by hydrological connectivity in a floodplain ecosystem. Further studies should investigate the processes of bacterial community coalescence in floodplains in more detail, which could provide new approaches for environmental protection and ecological function preservation.
Epigenetic memory contributing to the pathogenesis of AKI-to-CKD transition
Authors: Tanemoto Fumiaki , Nangaku Masaomi , Mimura Imari
Published: September 2022

Epigenetic memory, which refers to the ability of cells to retain and transmit epigenetic marks to their daughter cells, maintains unique gene expression patterns. Establishing programmed epigenetic memory at each stage of development is required for cell differentiation. Moreover, accumulating evidence shows that epigenetic memory acquired in response to environmental stimuli may be associated with diverse diseases. In the field of kidney diseases, the “memory” of acute kidney injury (AKI) leads to progression to chronic kidney disease (CKD); epidemiological studies show that patients who recover from AKI are at high risk of developing CKD. The underlying pathological processes include nephron loss, maladaptive epithelial repair, inflammation, and endothelial injury with vascular rarefaction. Further, epigenetic alterations may contribute as well to the pathophysiology of this AKI-to-CKD transition. Epigenetic changes induced by AKI, which can be recorded in cells, exert long-term effects as epigenetic memory. Considering the latest findings on the molecular basis of epigenetic memory and the pathophysiology of AKI-to-CKD transition, we propose here that epigenetic memory contributing to AKI-to-CKD transition can be classified according to the presence or absence of persistent changes in the associated regulation of gene expression, which we designate “driving” memory and “priming” memory, respectively. “Driving” memory, which persistently alters the regulation of gene expression, may contribute to disease progression by activating fibrogenic genes or inhibiting renoprotective genes. This process may be involved in generating the proinflammatory and profibrotic phenotypes of maladaptively repaired tubular cells after kidney injury. “Priming” memory is stored in seemingly successfully repaired tubular cells in the absence of detectable persistent phenotypic changes, which may enhance a subsequent transcriptional response to the second stimulus. This type of memory may contribute to AKI-to-CKD transition through the cumulative effects of enhanced expression of profibrotic genes required for wound repair after recurrent AKI. Further understanding of epigenetic memory will identify therapeutic targets of future epigenetic intervention to prevent AKI-to-CKD transition.
2-AG and anandamide enhance hippocampal long-term potentiation via suppression of inhibition
Authors: Lemtiri-Chlieh Fouad , Levine Eric S.
Published: September 2022

It is widely accepted that exogenous cannabinoids can impair short-term memory and cognition in humans and other animals. This is likely related to the inhibition of long-term potentiation (LTP), a form of synaptic plasticity, by the global and sustained activation of CB1 cannabinoid receptors in the presence of exogenous agonists. Conversely, the temporally and spatially restricted release of endogenous cannabinoid (eCB) ligands may enhance synaptic plasticity in a synapse-specific manner. We examined the role of eCB signaling in LTP by recording field excitatory postsynaptic potentials (fEPSPs) in the CA1 stratum radiatum in hippocampal slices from juvenile mice. LTP was induced either electrically, by theta burst stimulation (TBS), or pharmacologically, by treatment for 15 min with a solution designed to increase intracellular cAMP (chem-LTP). A stable and long-lasting potentiation in fEPSP slope following TBS was significantly reduced by blocking cannabinoid receptor activation with CB1 receptor antagonists. Chem-LTP caused a sustained 2-fold increase in fEPSP slope and was also blocked by CB1 receptor antagonists. TBS-LTP was partially reduced by inhibiting the synthesis of the endogenous ligands 2-arachidonylglycerol (2-AG) and anandamide. A similar effect was observed with chem-LTP. Blocking inhibitory synapses completely prevented the effect of CB1 receptor antagonists or inhibition of eCB synthesis on TBS-LTP and chem-LTP. These results indicate that simultaneous activation of CB1 receptors by 2-AG and anandamide enhances TBS-induced and pharmacologically-induced LTP, and this effect is mediated by the suppression of inhibition at GABAergic synapses.
Clinical effectiveness of nimodipine for the prevention of poor outcome after aneurysmal subarachnoid hemorrhage: A systematic review and meta-analysis
Authors: Hao Guangzhi , Chu Guangxin , Pan Pengyu , Han Yuwei , Ai Yunzheng , Shi Zuolin , Liang Guobiao
Published: September 2022

Objective

In clinical practice, nimodipine is used to control cerebral vasospasm (CVS), which is one of the major causes of severe disability and mortality in patients with aneurysmal subarachnoid hemorrhage (aSAH). However, the exact efficacy of nimodipine use for patients with aSAH is still controversial due to the lack of sufficient and up-to-date evidence.

Methods

In this meta-analysis, the latest databases of the Cochrane Central Register of Controlled Trials, PubMed-Medline, Web of Science, Embase, Scopus, and OVID-Medline were comprehensively searched for retrieving all randomized controlled trials (RCTs) regarding the efficacy of nimodipine in patients with aSAH. The primary outcome was a poor outcome, and the secondary outcomes were mortality and cerebral vasospasm (CVS). After detailed statistical analysis of different outcome variables, further evidence quality evaluation and recommendation grade assessment were carried out.

Results

Approximately 13 RCTs met the inclusion criteria, and a total of 1,727 patients were included. Meta-analysis showed that a poor outcome was significantly reduced in the nimodipine group [RR, 0.69 (0.60–0.78); I2 = 29%]. Moreover, nimodipine also dramatically decreased the mortality [RR, 0.50 (0.32–0.78); I2 = 62%] and the incidence of CVS [RR, 0.68 (0.46–0.99); I2 = 57%]. Remarkably, we found a poor outcome and mortality were both significantly lower among patients with aSAH, with the mean age < 50 than that mean age ≥ 50 by subgroup analysis. Furthermore, the evidence grading of a poor outcome and its age subgroup in this study was assessed as high.

Conclusion

Nimodipine can significantly reduce the incidence of a poor outcome, mortality, and CVS in patients with aSAH. Moreover, we strongly recommend that patients with aSAH, especially those younger than 50 years old, should use nimodipine as early as possible in order to achieve a better clinical outcome, whether oral medication or endovascular direct medication.

Systematic review registration

www.york.ac.uk/inst/crd, identifier: CRD42022334619.
Enhanced temporal complexity of EEG signals in older individuals with high cognitive functions
Authors: Iinuma Yuta , Nobukawa Sou , Mizukami Kimiko , Kawaguchi Megumi , Higashima Masato , Tanaka Yuji , Yamanishi Teruya , Takahashi Tetsuya
Published: September 2022

Recent studies suggest that the maintenance of cognitive function in the later life of older people is an essential factor contributing to mental wellbeing and physical health. Particularly, the risk of depression, sleep disorders, and Alzheimer's disease significantly increases in patients with mild cognitive impairment. To develop early treatment and prevention strategies for cognitive decline, it is necessary to individually identify the current state of cognitive function since the progression of cognitive decline varies among individuals. Therefore, the development of biomarkers that allow easier measurement of cognitive function in older individuals is relevant for hyperaged societies. One of the methods used to estimate cognitive function focuses on the temporal complexity of electroencephalography (EEG) signals. The characteristics of temporal complexity depend on the time scale, which reflects the range of neuron functional interactions. To capture the dynamics, composed of multiple time scales, multiscale entropy (MSE) analysis is effective for comprehensively assessing the neural activity underlying cognitive function in the brain. Thus, we hypothesized that EEG complexity analysis could serve to assess a wide range of cognitive functions in older adults. To validate our hypothesis, we divided older participants into two groups based on their cognitive function test scores: a high cognitive function group and a low cognitive function group, and applied MSE analysis to the measured EEG data of all participants. The results of the repeated-measures analysis of covariance using age and sex as a covariate in the MSE profile showed a significant difference between the high and low cognitive function groups (F = 10.18, p = 0.003) and the interaction of the group × electrodes (F = 3.93, p = 0.002). Subsequently, the results of the post-hoct-test showed high complexity on a slower time scale in the frontal, parietal, and temporal lobes in the high cognitive function group. This high complexity on a slow time scale reflects the activation of long-distance neural interactions among various brain regions to achieve high cognitive functions. This finding could facilitate the development of a tool for diagnosis of cognitive decline in older individuals.
Separating neuronal activity and systemic low-frequency oscillation related BOLD responses at nodes of the default mode network during resting-state fMRI with multiband excitation echo-planar imaging
Authors: Tachibana Atsushi , Ikoma Yoko , Hirano Yoshiyuki , Kershaw Jeff , Obata Takayuki
Published: September 2022

Functional magnetic resonance imaging (fMRI) evaluates brain activity using blood oxygenation level-dependent (BOLD) contrast. Resting-state fMRI (rsfMRI) examines spontaneous brain function using BOLD in the absence of a task, and the default mode network (DMN) has been identified from that. The DMN is a set of nodes within the brain that appear to be active and in communication when the subject is in an awake resting state. In addition to signal changes related to neural activity, it is thought that the BOLD signal may be affected by systemic low-frequency oscillations (SysLFOs) that are non-neuronal in source and likely propagate throughout the brain to arrive at different regions at different times. However, it may be difficult to distinguish between the response due to neuronal activity and the arrival of a SysLFO in specific regions. Conventional single-shot EPI (Conv) acquisition requires a longish repetition time, but faster image acquisition has recently become possible with multiband excitation EPI (MB). In this study, we evaluated the time-lag between nodes of the DMN using both Conv and MB protocols to determine whether it is possible to distinguish between neuronal activity and SysLFO related responses during rsfMRI. While the Conv protocol data suggested that SysLFOs substantially influence the apparent time-lag of neuronal activity, the MB protocol data implied that the effects of SysLFOs and neuronal activity on the BOLD response may be separated. Using a higher time-resolution acquisition for rsfMRI might help to distinguish neuronal activity induced changes to the BOLD response from those induced by non-neuronal sources.
Carbohydrate and sleep: An evaluation of putative mechanisms
Authors: Benton David , Bloxham Anthony , Gaylor Chantelle , Brennan Anthony , Young Hayley A.
Published: September 2022

Sleep problems are extremely common in industrialized countries and the possibility that diet might be used to improve sleep has been considered. The topic has been reviewed many times, resulting in the frequent suggestion that carbohydrate increases the uptake of tryptophan by the brain, where it is metabolized into serotonin and melatonin, with the suggestion that this improves sleep. An alternative mechanism was proposed based on animal literature that has been largely ignored by those considering diet and sleep. The hypothesis was that, as in the hypothalamus there are glucose-sensing neurons associated with the sleep-wake cycle, we should consider the impact of carbohydrate-induced changes in the level of blood glucose. A meta-analysis found that after consuming a lower amount of carbohydrate, more time was spent in slow-wave sleep (SWS) and less in rapid-eye-movement sleep. As the credibility of alternative mechanisms has tended not to have been critically evaluated, they were considered by examining their biochemical, nutritional, and pharmacological plausibility. Although high carbohydrate consumption can increase the uptake of tryptophan by the brain, it only occurs with such low levels of protein that the mechanism is not relevant to a normal diet. After entering the brain tryptophan is converted to serotonin, a neurotransmitter known to influence so many different aspects of sleep and wakefulness, that it is not reasonable to expect a uniform improvement in sleep. Some serotonin is converted to melatonin, although the exogenous dose of melatonin needed to influence sleep cannot be credibly provided by the diet. This review was registered in the International Prospective Register of Systematic Reviews (CRD42020223560).
A pilot study of cognitive behavioural therapy integrated with activity pacing for fatigued breast cancer patients undergoing chemotherapy in Ethiopia
Authors: Getu Mikiyas Amare , Chen Changying , Addissie Adamu , Seife Edom , Wang Panpan , Kantelhardt Eva Johanna
Published: September 2022

Background

Fatigue is a common symptom in breast cancer patients, and it is one of the major factors that influence the quality of life (QoL). Cognitive behavioural therapy (CBT) has been recommended to manage cancer-related fatigue. In this study, CBT will be integrated with activity pacing (AP), which can help breast cancer patients achieve a balance between activity and rest. Therefore, this pilot study aimed to investigate the acceptability, feasibility, and efficacy of the CBT-AP intervention.

Methods

A total of 10 fatigued breast cancer patients undergoing chemotherapy were included in the study. The acceptability and feasibility of the study were measured by the patient recruitment rate, attrition rate, intervention fidelity, intervention compliance, and therapist’s and participant’s evaluations of the intervention. The outcomes were measured at baseline and at 6 weeks of intervention.

Results

The pre–post study suggested that CBT-AP was found to be acceptable and feasible for fatigued breast cancer patients undergoing chemotherapy. Among 27 eligible participants, 10 (37.03%) participants accepted our invitation to participate in the study. One participant dropped out from the intervention because of serious illness, and the dropout rate was 10%.

Both the intervention fidelity and intervention compliance were found to be satisfactory.

Fatigue severity [Brief Fatigue Inventory (BFI)] was reduced in 77.77% of participants from baseline to 6 weeks of intervention. The global health status/QoL scale and physical, emotional, and social functioning scales were improved from baseline to 6 weeks of intervention. All symptom scales, except constipation, diarrhea, and financial difficulties, were decreased after the intervention. Depression [Public Health Questionnaire (PHQ)-9] was reduced in 55.55% of participants.

Conclusion

This study suggested that CBT-AP is an acceptable, feasible, and potentially efficacious intervention to reduce fatigue and improve the QoL of breast cancer patients. The efficacy of a CBT-AP programme is going to be investigated in subsequent larger randomized clinical trials.
Case report: Plasma cell leukemia secondary to multiple myeloma successfully treated with anti-BCMA CAR-T cell therapy
Authors: Deng Jingjing , Lin Yuehui , Zhao Defeng , Tong Chunrong , Chang Alex H. , Chen Wenming , Gao Wen
Published: September 2022

Chimeric antigen receptor (CAR)-T cell therapy provides an effective salvage treatment for relapsed/refractory multiple myeloma (RRMM) patients. End-stage RRMM with plasma cell leukemia (PCL) transformation is highly aggressive and resistant to conventional therapy. There is an urgent need for new therapeutics and CAR-T therapy may play an important role. We report a case of PCL secondary to RRMM successfully treated with CAR-T cell therapy targeting B-cell maturation antigen (BCMA). A woman was diagnosed as having MM 4 years ago and progressed to secondary PCL (sPCL) of five prior lines of treatment including proteasome inhibitors, an immunomodulatory agent, cytotoxic drugs, and an anti-CD38 monoclonal antibody. After receiving a BCMA CAR-T therapy, she achieved a stringent complete response that lasted 9 months. Then, the patient irregularly took venetoclax 10 mg per day due to a slightly higher λ FLC concentration, which did not meet the criteria for progression. She maintained a complete response for the following 7 months. In conclusion, BCMA CAR-T therapy may be a promising therapeutic approach in PCL patients. More studies are needed to evaluate the benefit of anti-BCMA CAR-T therapy in PCL patients.

Clinical Trial Registration:www.chictr.org.cn, ChiCTR1900024388, Registered 9 July 2019.
Neoadjuvant immunotherapy and neoadjuvant chemotherapy in resectable non-small cell lung cancer: A systematic review and single-arm meta-analysis
Authors: Wang He , Liu Tingting , Chen Jun , Dang Jun
Published: September 2022

Background

It remains uncertain whether neoadjuvant immune checkpoint inhibitor (nICI) is superior to neoadjuvant chemotherapy (nCT) in resectable non-small cell lung cancer. In addition, there are outstanding questions for nICI such as the ideal treatment mode and predictors.

Methods

PubMed, Embase, Cochrane Library, Web of Science, and scientific meetings were searched for eligible single-arm or multi-arm trials until 31 December 2021. The primary outcomes of interest were major pathological response (MPR) and pathological complete response (pCR). The random-effect model was used for statistical analysis.

Results

Twenty-four trials of nICI (n = 1,043) and 29 trials of nCT (n = 2,337) were identified. nICI combination therapy was associated with higher MPR (63.2%, 95% CI: 54.2%–72.1%) and pCR (35.3%, 95% CI: 27.4%–43.3%) rates compared to nCT (16.2%, 95% CI: 7.5%–25.0%, P < 0.001 and 5.5%, 95% CI: 3.5%–7.5%, P < 0.001) and nICI monotherapy (23.3%, 95% CI: 12.7%–33.8%, P < 0.001, and 6.5%, 95% CI: 1.7%–11.2%, P < 0.001). As for safety, nICI monotherapy had the best tolerability; nICI combination showed a similar surgical resection rate and higher R0 resection rate compared to nCT. PD-1 inhibitor and high PD-L1 expression (≥1% or ≥50%) were correlated with higher MPR and pCR rates compared to PD-L1 inhibitor and PD-L1 expression <1%.

Conclusions

nICI combination therapy is associated with higher MPR and pCR rates compared to nCT and nICI monotherapy. PD-1 inhibitor seems to be superior to PD-L1 inhibitor. PD-L1 status appears to be predictive of MPR and pCR for patients receiving nICI.

Systematic Review Registration

https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=278661, CRD42021278661.
The core genes of cuproptosis assists in discerning prognostic and immunological traits of clear cell renal cell carcinoma
Authors: Chu Binxiang , Hong Zhenghua , Zheng Xiaohe
Published: September 2022

Objective

Cuproptosis, a nascent and unique pattern of cell death, is poised to spark a new rush of biological research. Yet, the subsumed mechanism of cuproptosis in carcinoma is not wholly clarified. The exclusive aim of this work is to define a novel classification algorithm and risk-prognosis scoring framework based on the expression modalities of cuproptosis genes to monitor clear cell renal cell carcinoma (ccRCC) patients’ prognosis and immunotherapeutic response.

Methods

We pooled ccRCC data from three large-scale databases as the training subset and gathered a panel of clinical queues, termed the Taizhou cohort, which served as the validation setup. Wilcox test was conducted for comparison of expression variation, while the cox analysis and KM curves were utilized to visualize prognosis. Unsupervised clustering analysis was used to identify cuproptosis phenotypes in ccRCC. Concurrently, LASSO regression-based computational scoring model. A step further, gene set enrichment analysis (GSEA) was performed to check potential biological processes and the “CIBERSORT” R package was used to estimate the proportion of immune cells. To last, immunohistochemistry and qRT-PCR were carried out for the assay of critical genes for cuproptosis.

Results

Here, we glimpse the prognostic power of cuproptosis genes in pan-cancer by investigating 33 cancers with multi-omics data to map their genetic heterogeneity landscape. In parallel, we devoted extra attention to their strategic potential role in ccRCC, identifying two phenotypes of cuproptosis with different immune microenvironmental characteristics by pooling ccRCC data from three large-scale databases. Additionally, we compiled a cuproptosis scoring system for clinicians to determine the prognosis, immunotherapy response, and chemosensitivity of ccRCC patients. Notably, we assembled a clinical cohort sample to validate the pivotal gene for cuproptosis, FDX1, to supply more clues to translate the biological significance of cuproptosis in ccRCC.

Conclusion

In all, our investigations highlight that cuproptosis is involved in various components of ccRCC and assists in the formation of the tumor immune microenvironment. These results provide partial insights to further comprehend the molecular mechanisms of cuproptosis in ccRCC and could be helpful for the development of personalized therapeutic strategies targeting copper or cuproptosis.
Lung microbiome in children with hematological malignancies and lower respiratory tract infections
Authors: Zhang Yun , Ning Haonan , Zheng Wenyu , Liu Jing , Li Fuhai , Chen Junfei
Published: September 2022

Background

Respiratory infectious complications remain a major cause of morbidity and mortality in children with hematological malignancies. Knowledge regarding the lung microbiome in aforementioned children is limited.

Methods

A prospective cohort was conducted, enrolling 16 children with hematological malignancies complicated with moderate-to-severe lower respiratory tract infections (LRTIs) versus 21 LRTI children with age, gender, weight, and infection severity matched, with no underlying malignancies, to evaluate the lung microbiome from bronchoalveolar lavage fluid samples in different groups.

Results

The lung microbiome from children with hematological malignancies and LRTIs showed obviously decreased α and β diversity; increased microbial function in infectious disease:bacteria/parasite; drug resistance:antimicrobial and human pathogenesis than the control group; a significantly reduced proportion of Firmicutes, Bacteroidota, Actinobacteriota; increased Proteobacteria at the phylum level; and distinctly elevated Parabacteroides, Klebsiella, Grimontia, Escherichia_Shigella, unclassified_Enterobacteriaceae at the genus level than the control group. Furthermore, it was revealed that α diversity (Shannon), β diversity (Bray–Curtis dissimilarity), Proteobacteria at the phylum level, and unclassified_Enterobacteriaceae and Escherichia_Shigella at the genus level were significantly negatively associated with hospitalization course whereas Firmicutes at the phylum level was established positively correlated with the hospitalization course.

Conclusions

Children with hematological malignancies and LRTIs showed obviously decreased α and β diversity, significantly increased function in infectious disease pathogenesis, antimicrobial drug resistance, and unfavorable environment tolerance. Moreover, α diversity (Shannon), β diversity (Bray–Curtis dissimilarity), and Proteobacteria may be used as negative correlated predictors for hospitalization course in these children whereas Firmicutes may be utilized as a positive correlated predictor.
Indication and eligibility of glioma patients for awake surgery: A scoping review by a multidisciplinary perspective
Authors: Fiore Giorgio , Abete-Fornara Giorgia , Forgione Arianna , Tariciotti Leonardo , Pluderi Mauro , Borsa Stefano , Bana Cristina , Cogiamanian Filippo , Vergari Maurizio , Conte Valeria , Caroli Manuela , Locatelli Marco , Bertani Giulio Andrea
Published: September 2022

Background

Awake surgery (AS) permits intraoperative mapping of cognitive and motor functions, allowing neurosurgeons to tailor the resection according to patient functional boundaries thus preserving long-term patient integrity and maximizing extent of resection. Given the increased risks of the awake scenario, the growing importance of AS in surgical practice favored the debate about patient selection concerning both indication and eligibility criteria. Nonetheless, a systematic investigation is lacking in the literature.

Objective

To provide a scoping review of the literature concerning indication and eligibility criteria for AS in patients with gliomas to answer the questions:1) "What are the functions mostly tested during AS protocols?" and 2) "When and why should a patient be excluded from AS?".

Materials and methods

Pertinent studies were retrieved from PubMed, PsycArticles and Cochrane Central Register of Controlled Trials (CENTRAL), published until April 2021 according to the PRISMA Statement Extension for Scoping Reviews. The retrieved abstracts were checked for the following features being clearly stated: 1) the population described as being composed of glioma(LGG or HGG) patients; 2) the paper had to declare which cognitive or sensorimotor function was tested, or 2bis)the decisional process of inclusion/exclusion for AS had to be described from at least one of the following perspectives: neurosurgical, neurophysiological, anesthesiologic and psychological/neuropsychological.

Results

One hundred and seventy-eight studies stated the functions being tested on 8004 patients. Language is the main indication for AS, even if tasks and stimulation techniques changed over the years. It is followed by monitoring of sensorimotor and visuospatial pathways. This review demonstrated an increasing interest in addressing other superior cognitive functions, such as executive functions and emotions. Forty-five studies on 2645 glioma patients stated the inclusion/exclusion criteria for AS eligibility. Inability to cooperate due to psychological disorder(i.e. anxiety),severe language deficits and other medical conditions(i.e.cardiovascular diseases, obesity, etc.)are widely reported as exclusion criteria for AS. However, a very few papers gave scale exact cut-off. Likewise, age and tumor histology are not standardized parameters for patient selection.

Conclusion

Given the broad spectrum of functions that might be safely and effectively monitored via AS, neurosurgeons and their teams should tailor intraoperative testing on patient needs and background as well as on tumor location and features. Whenever the aforementioned exclusion criteria are not fulfilled, AS should be strongly considered for glioma patients.
Pathological diagnostic nomograms for predicting malignant histology and unfavorable pathology in patients with endophytic renal tumor
Authors: Deng Xinxi , Liu Xiaoqiang , Hu Bing , Jiang Ming , Zhu Ke , Nie Jianqiang , Liu Taobin , Chen Luyao , Deng Wen , Fu Bin , Xiong Situ
Published: September 2022

Purpose

To develop and validate nomograms for pre-treatment prediction of malignant histology (MH) and unfavorable pathology (UP) in patients with endophytic renal tumors (ERTs).

Methods

We retrospectively reviewed the clinical information of 3245 patients with ERTs accepted surgical treatment in our center. Eventually, 333 eligible patients were included and randomly enrolled into training and testing sets in a ratio of 7:3. We performed univariable and multivariable logistic regression analyses to determine the independent risk factors of MH and UP in the training set and developed the pathological diagnostic models of MH and UP. The optimal model was used to construct a nomogram for MH and UP. The area under the receiver operating characteristics (ROC) curves (AUC), calibration curves and decision curve analyses (DCA) were used to evaluate the predictive performance of models.

Results

Overall, 172 patients with MH and 50 patients with UP were enrolled in the training set; and 74 patients with MH and 21 patients with UP were enrolled in the validation set. Sex, neutrophil-to-lymphocyte ratio (NLR), R score, N score and R.E.N.A.L. score were the independent predictors of MH; and BMI, NLR, tumor size and R score were the independent predictors of UP. Single-variable and multiple-variable models were constructed based on these independent predictors. Among these predictive models, the malignant histology-risk nomogram consisted of sex, NLR, R score and N score and the unfavorable pathology-risk nomogram consisted of BMI, NLR and R score performed an optimal predictive performance, which reflected in the highest AUC (0.842 and 0.808, respectively), the favorable calibration curves and the best clinical net benefit. In addition, if demographic characteristics and laboratory tests were excluded from the nomograms, only the components of the R.E.N.A.L. Nephrometry Score system were included to predict MH and UP, the AUC decreased to 0.781 and 0.660, respectively (P=0.001 and 0.013, respectively).

Conclusion

In our study, the pathological diagnostic models for predicting malignant and aggressive histological features for patients with ERTs showed outstanding predictive performance and convenience. The use of the models can greatly assist urologists in individualizing the management of their patients.
Drug resistance in multiple myeloma: Soldiers and weapons in the bone marrow niche
Authors: Solimando Antonio Giovanni , Malerba Eleonora , Leone Patrizia , Prete Marcella , Terragna Carolina , Cavo Michele , Racanelli Vito
Published: September 2022

Multiple myeloma (MM) is still an incurable disease, despite considerable improvements in treatment strategies, as resistance to most currently available agents is not uncommon. In this study, data on drug resistance in MM were analyzed and led to the following conclusions: resistance occurs via intrinsic and extrinsic mechanisms, including intraclonal heterogeneity, drug efflux pumps, alterations of drug targets, the inhibition of apoptosis, increased DNA repair and interactions with the bone marrow (BM) microenvironment, cell adhesion, and the release of soluble factors. Since MM involves the BM, interactions in the MM-BM microenvironment were examined as well, with a focus on the cross-talk between BM stromal cells (BMSCs), adipocytes, osteoclasts, osteoblasts, endothelial cells, and immune cells. Given the complex mechanisms that drive MM, next-generation treatment strategies that avoid drug resistance must target both the neoplastic clone and its non-malignant environment. Possible approaches based on recent evidence include: (i) proteasome and histone deacetylases inhibitors that not only target MM but also act on BMSCs and osteoclasts; (ii) novel peptide drug conjugates that target both the MM malignant clone and angiogenesis to unleash an effective anti-MM immune response. Finally, the role of cancer stem cells in MM is unknown but given their roles in the development of solid and hematological malignancies, cancer relapse, and drug resistance, their identification and description are of paramount importance for MM management.
Elevated plasma EDA fibronectin in primary myelofibrosis is determined by high allele burden of JAK2V617F mutation and strongly predicts splenomegaly progression
Authors: Malara Alessandro , Gruppi Cristian , Massa Margherita , Tira Maria Enrica , Rosti Vittorio , Balduini Alessandra , Barosi Giovanni
Published: September 2022

In primary myelofibrosis, extra-domain A fibronectin (EDA-FN), the result of alternative splicing of FN gene, sustains megakaryocyte proliferation and confers a pro-inflammatory phenotype to bone marrow cell niches. In this work we assessed the levels of circulating EDA-FN in plasma samples of 122 patients with primary myelofibrosis. Patients with a homozygous JAK2V617F genotype displayed the higher level of plasma EDA-FN. Increased EDA-FN levels were associated with anemia, elevated high-sensitivity C-reactive protein, bone marrow fibrosis and splanchnic vein thrombosis at diagnosis. While no correlation was observed with CD34+ hematopoietic stem cell mobilization, elevated blood level of EDA-FN at diagnosis was a predictor of large splenomegaly (over 10 cm from the left costal margin) outcome. Thus, EDA-FN expression in primary myelofibrosis may represent the first marker of disease progression, and a novel target to treat splenomegaly.
Exploring glioblastoma stem cell heterogeneity: Immune microenvironment modulation and therapeutic opportunities
Authors: Johnson Amanda L. , Laterra John , Lopez-Bertoni Hernando
Published: September 2022

Despite its growing use in cancer treatment, immunotherapy has been virtually ineffective in clinical trials for gliomas. The inherently cold tumor immune microenvironment (TIME) in gliomas, characterized by a high ratio of pro-tumor to anti-tumor immune cell infiltrates, acts as a seemingly insurmountable barrier to immunotherapy. Glioma stem cells (GSCs) within these tumors are key contributors to this cold TIME, often functioning indirectly through activation and recruitment of pro-tumor immune cell types. Furthermore, drivers of GSC plasticity and heterogeneity (e.g., reprogramming transcription factors, epigenetic modifications) are associated with induction of immunosuppressive cell states. Recent studies have identified GSC-intrinsic mechanisms, including functional mimicry of immune suppressive cell types, as key determinants of anti-tumor immune escape. In this review, we cover recent advancements in our understanding of GSC-intrinsic mechanisms that modulate GSC-TIME interactions and discuss cutting-edge techniques and bioinformatics platforms available to study immune modulation at high cellular resolution with exploration of both malignant (i.e., GSC) and non-malignant (i.e., immune) cell fractions. Finally, we provide insight into the therapeutic opportunities for targeting immunomodulatory GSC-intrinsic mechanisms to potentiate immunotherapy response in gliomas.
Strategies for selecting perforator vessels for transverse and oblique DIEP flap in male pediatric patients: Anatomical study and clinical applications
Authors: He Jiqiang , Cui Huairui , Qing Liming , Wu Panfeng , Guliyeva Gunel , Yu Fang , Tang Maolin , Tang Juyu
Published: September 2022

Background

Transverse and oblique deep inferior epigastric artery perforator (DIEP) flaps are widely used in breast, lower extremity, urogenital, head and neck reconstruction. In this report, we present our experience with selecting perforator vessels for transverse and oblique DIEP flaps based on an anatomical study and clinical cases.

Materials and methods

A detailed anatomical study of the DIEP flap was carried out using a standardized injection of lead oxide in 10 fresh cadavers. Additionally, 35 male pediatric patients (age 5–12 years) underwent lower extremity reconstruction with a DIEP flap. A transverse DIEP flap was used when the defect template did not exceed zone IV, while an oblique DIEP flap was used when the defect template exceeded zone IV.

Results

Perforators located below the umbilicus in zones I and II were rich in transverse anastomoses across the midline of the abdominal wall, which is the basis for the transverse DIEP flap. Perforators lateral to the umbilicus in zone I had true anastomoses with the musculophrenic artery, the morphological basis for the oblique DIEP flap. The DIEP flap design was transverse in 20 patients and oblique in 15. Flap sizes ranged from 8 × 4.5 cm2 to 24 × 9 cm2. One oblique DIEP flap was necrosed totally, and it was repaired by a latissimus dorsi musculocutaneous flap.

Conclusion

The transverse DIEP flap design based on the perforator located below the umbilicus in zone I is recommended for small skin and soft tissue defects. We recommend the use of the oblique DIEP flap design based on the perforator lateral to the umbilicus in zone I as an extended flap to reconstruct large tissue defects.
Traditional chinese medicine to prevent and treat diabetic erectile dysfunction
Authors: Feng Yanfei , Shi Tianhao , Fu Yuli , Lv Bodong
Published: September 2022

Diabetic erectile dysfunction (DED) is one of the most common complications of diabetes mellitus. However, current therapeutics have no satisfactory effect on DED. In recent years, traditional Chinese medicine (TCM) has shown good effects against DED. By now, several clinical trials have been conducted to study the effect of TCM in treating DED; yet, the underlying mechanism is not fully investigated. Therefore, in this review, we briefly summarized the pathophysiological mechanism of DED and reviewed the published clinical trials on the treatment of DED by TCM. Then, the therapeutic potential of TCM and the underlying mechanisms whereby TCM exerts protective effects were summarized. We concluded that TCM is more effective than chemical drugs in treating DED by targeting multiple signaling pathways, including those involved in oxidation, apoptosis, atherosclerosis, and endothelial function. However, the major limitation in the application of TCM against DED is the lack of a large-scale, multicenter, randomized, and controlled clinical trial on the therapeutic effect, and the underlying pharmaceutical mechanisms also need further investigation. Despite these limitations, clinical trials and further experimental studies will enhance our understanding of the mechanisms modulated by TCM and promote the widespread application of TCM to treat DED.
A spatially non-overlapping dual-wavelength 2D FBG for the measurement of temperature and strain
Authors: Che Zonglun , Wang Jun , Xu Pan , Gu Xijia , Ma Lina , Zhu Jing , Cao Chunyan
Published: September 2022

This work designed a dual-wavelength 2D fiber Bragg grating (FBG) engraved on the single-mode fiber to measure the temperature and strain. The FBG is composed of two sub-gratings that are not overlapped spatially at the same location of the fiber core. Experiments showed that the temperature and strain sensitivities of this grating were separately measured to be 10.64 p.m./°C and 0.882,731 p.m./μɛ at the central wavelength of 1,548 nm, and 10.74 p.m./°C and 0.916,080 p.m./μɛ at the central wavelength of 1,550 nm. These coefficients constitute a coefficient matrix that can solve the problem of cross sensitivity between temperature and strain, which has been verified by varying central wavelengths caused by the synchronous change of temperature and strain.
Features of intercity bus passenger group mobility behaviors in the context of smart tourism
Authors: Han Shao-Yong , Zhan Jing-Chun , Xie Cui-Hua , Wang Zhen
Published: September 2022

The features of intercity bus passenger group mobility behaviors have important guiding significance for the transportation department. Based on passengers’ intercity bus ticket reservation records (roundtrips from Shanghai or Chongqing city) from a smart tourism app, the travel behaviors of these two groups of bus passengers are analyzed and compared. In each group, the passengers’ travelling interval time presents a power-law with a cutoff index, and the passengers’ travelling behaviors have negative memory and low burstiness. Also, travel distance displays a scale-free property, and it is more likely to have an exponential distribution. Furthermore, the difference in cyclotron radius between these two groups’ travelling distances is quite significant; roundtrips from Shanghai are frequent. Last, holidays have a significant influence on passengers’ travel behaviors, which leads to more trips. The research conclusions are helpful to deeply understand the features of human mobility behaviors in theory, and can assist the transportation department in traffic planning in the application.
Functional quantification of oral motor cortex at rest and during tasks using activity phase ratio: A zero-setting vector functional near-infrared spectroscopy study
Authors: Arai Masaaki , Kato Hikaru , Kato Toshinori
Published: September 2022

Oral frailty associated with oral hypokinesia may cause dementia. Functional near-infrared spectroscopy (fNIRS) can be used while the participants are in seating position with few restrictions. Thus, it is useful for assessing brain function, particularly oral motor activity. However, methods for identifying oral motor cortex (OMC) activation via the scalp have not been established. The current study aimed to detect OMC activation, an indicator of activity phase ratio (APR), which reflects increased oxygen consumption (0 < [deoxyhemoglobin (ΔDeoxyHb) or 0 < {[ΔDeoxyHb- oxyhemoglobin (ΔOxyHb)/√2]}, via fNIRS to accurately identify local brain activity. The APR, calculated via zero-set vector analysis, is a novel index for quantifying brain function both temporally and spatially at rest and during tasks. In total, 14 healthy participants performed bite tasks for 3 s per side for 10 times while in the sitting position. Then, time-series data on concentration changes in ΔOxyHb and ΔDeoxyHb were obtained via fNIRS. The anatomical location of the OMC was determined using a pooled data set of three-dimensional magnetic resonance images collected in advance from 40 healthy adults. In the zero-set vector analysis, the average change in ΔOxyHb and ΔDeoxyHb concentrations was utilized to calculate the APR percentage in 140 trials. The significant regions (z-score of ≥2.0) of the APR and ΔOxyHb in the task were compared. During the bite task, the APR significantly increased within the estimated OMC region (56–84 mm lateral to Cz and 4–20 mm anterior to Cz) in both the right and left hemispheres. By contrast, the ΔOxyHb concentrations increased on the bite side alone beyond the OMC region. The mean APR at rest for 2 s before the task showed 59.5%–62.2% in the left and right OMCs. The average APR for 3 s during the task showed 75.3% for the left OMC and 75.7% for the right OMC during the left bite task, and 65.9% for the left OMC and 80.9% for the right OMC during the right bite task. Interestingly, the average increase in APR for the left and right OMCs for the left bite task and the right bite task was 13.9% and 13.7%, respectively, showing almost a close match. The time course of the APR was more limited to the bite task segment than that of ΔOxyHb or ΔDexyHb concentration, and it increased in the OMC. Hence, the APR can quantitatively monitor both the resting and active states of the OMC in the left and right hemispheres. Using the zero-set vector-based fNIRS, the APR can be a valid indicator of oral motor function and bite force.
Natural deep eutectic solvents in phytonutrient extraction and other applications
Authors: Li Dan
Published: September 2022

Natural deep eutectic solvents (NaDESs) are considered a new type of green solvent with attractive application prospects in many fields because of their simple preparation, low cost, environmental friendliness, low volatility, high solvency capacity, designable structure, and easy biodegradability. Due to their biocompatibility, they are safe to use and are particularly suitable for natural product applications. In recent years, NaDESs have been used to extract phytonutrients (e.g., flavonoids, saponins, polysaccharides, alkaloids, quinones, phenolic acids, volatile oils, etc.) to improve their solubility, stability, and bioavailability. This review is intended to summarize and discuss recent progress in the field of natural products related to materials and preparation methods, physicochemical properties, enhancing extraction and separation, increasing solubility, improving stability and bioavailability, facilitating oral absorption of phytonutrients, and finally, highlighting the challenge for future work.