bluuebunny/crossref_metadata_2025 huggingface dataset:
Characteristics and prognostic analysis of simultaneous bilateral sudden sensorineural hearing loss
Authors: Wang Yingjun , Xiong Wenping , Sun Xiao , Duan Fujia , Lu Kunpeng , Wang Haibo , Wang Mingming
Published: May 2023

Objective

To evaluate the clinical characteristics of simultaneous bilateral sudden sensorineural hearing loss (Si-BSSNHL) as well as its prognostic factors.

Methods

Patients with Si-BSSNHL who were admitted to the Department of Otology Medicine between December 2018 and December 2021 were enrolled in the case group. Propensity score matching (PSM) for sex and age was used to select the control group, which included people who had unilateral sudden sensorineural hearing loss (USSNHL) during the same time period. Hearing recovery, audiological examinations, vestibular function assessments, laboratory tests, and demographic and clinical manifestations were analyzed for intergroup comparisons. Binary logistic regressions were used for both univariate and multivariate analyses of Si-BSSNHL prognostic factors.

Results

Before PSM, the Si-BSSNHL and USSNHL groups differed significantly (p < 0.05) in terms of time from onset to treatment, initial pure-tone average (PTA), final PTA, hearing gain, audiogram curve type, proportion of tinnitus, high-density lipoprotein level, homocysteine level, and effective rate. After PSM, significant differences were also observed in time from onset to treatment, initial PTA, final PTA, hearing gain, total and indirect bilirubin levels, homocysteine level, and effective rate between the two groups (p < 0.05). There was a significant difference in the classification of therapeutic effects between the two groups (p < 0.001). For prognostic analysis, the audiogram curve type was significantly different between the effective group and the ineffective groups of Si-BSSNHL (p = 0.01), in which the sloping type was an independent risk factor for the prognosis of the right ear in Si-SSNHL (95% confidence interval, 0.006–0.549, p = 0.013).

Conclusion

Patients with Si-BSSNHL had mild deafness, elevated total and indirect bilirubin and homocysteine levels, and poorer prognosis than those with USSNHL. Audiogram curve type was linked to the therapeutic effect of Si-BSSNHL, and the sloping type was an independent risk factor for a poor prognosis in the right ear of Si-SSNHL.
Gut dysmotility in children with neurological impairment: the nutritional management
Authors: Corsello Antonio , Scatigno Lorenzo , Govoni Annalisa , Zuccotti Gianvincenzo , Gottrand Frédéric , Romano Claudio , Verduci Elvira
Published: May 2023

Intestinal motility disorders represent a frequent problem in children with neurological impairment. These conditions are characterized by abnormal movements of the gut, which can result in symptoms such as constipation, diarrhea, reflux, and vomiting. The underlying mechanisms leading to dysmotility are various, and the clinical manifestations are often nonspecific. Nutritional management is an important aspect of care for children with gut dysmotility, as it can help to improve their quality of life. Oral feeding, when safe and in the absence of risk of ingestion or severe dysphagia, should always be encouraged. When oral nutrition is insufficient or potentially harmful, it is necessary to switch to an enteral by tube or parenteral nutrition before the onset of malnutrition. In most cases, children with severe gut dysmotility may require feeding via a permanent gastrostomy tube to ensure adequate nutrition and hydration. Drugs may be necessary to help manage gut dysmotility, such as laxatives, anticholinergics and prokinetic agents. Nutritional management of patients with neurological impairment often requires an individualized care plan to optimize growth and nutrition and to improve overall health outcomes. This review tries to sum up most significant neurogenetic and neurometabolic disorders associated with gut dysmotility that may require a specific multidisciplinary care, identifying a proposal of nutritional and medical management.
Resting-state fMRI can detect alterations in seizure onset and spread regions in patients with non-lesional epilepsy: a pilot study
Authors: Sathe Anish V. , Matias Caio M. , Kogan Michael , Ailes Isaiah , Syed Mashaal , Kang KiChang , Miao Jingya , Talekar Kiran , Faro Scott , Mohamed Feroze B. , Tracy Joseph , Sharan Ashwini , Alizadeh Mahdi
Published: May 2023

Introduction

Epilepsy is defined as non-lesional (NLE) when a lesion cannot be localized via standard neuroimaging. NLE is known to have a poor response to surgery. Stereotactic electroencephalography (sEEG) can detect functional connectivity (FC) between zones of seizure onset (OZ) and early (ESZ) and late (LSZ) spread. We examined whether resting-state fMRI (rsfMRI) can detect FC alterations in NLE to see whether noninvasive imaging techniques can localize areas of seizure propagation to potentially target for intervention.

Methods

This is a retrospective study of 8 patients with refractory NLE who underwent sEEG electrode implantation and 10 controls. The OZ, ESZ, and LSZ were identified by generating regions around sEEG contacts that recorded seizure activity. Amplitude synchronization analysis was used to detect the correlation of the OZ to the ESZ. This was also done using the OZ and ESZ of each NLE patient for each control. Patients with NLE were compared to controls individually using Wilcoxon tests and as a group using Mann-Whitney tests. Amplitude of low-frequency fluctuations (ALFF), fractional ALFF (fALFF), regional homogeneity (ReHo), degree of centrality (DoC), and voxel-mirrored homotopic connectivity (VMHC) were calculated as the difference between NLE and controls and compared between the OZ and ESZ and to zero. A general linear model was used with age as a covariate with Bonferroni correction for multiple comparisons.

Results

Five out of 8 patients with NLE showed decreased correlations from the OZ to the ESZ. Group analysis showed patients with NLE had lower connectivity with the ESZ. Patients with NLE showed higher fALFF and ReHo in the OZ but not the ESZ, and higher DoC in the OZ and ESZ. Our results indicate that patients with NLE show high levels of activity but dysfunctional connections in seizure-related areas.

Discussion

rsfMRI analysis showed decreased connectivity directly between seizure-related areas, while FC metric analysis revealed increases in local and global connectivity in seizure-related areas. FC analysis of rsfMRI can detect functional disruption that may expose the pathophysiology underlying NLE.
Subthalamic nucleus stimulation attenuates motor seizures via modulating the nigral orexin pathway
Authors: Xue Tao , Wang Shu , Chen Shujun , Wang Huizhi , Liu Chong , Shi Lin , Bai Yutong , Zhang Chunkui , Han Chunlei , Zhang Jianguo
Published: May 2023

Background

Focal motor seizures that originate in the motor region are a considerable challenge because of the high risk of permanent motor deficits after resection. Deep brain stimulation of the subthalamic nucleus (STN-DBS) is a potential treatment for motor epilepsy that may enhance the antiepileptic actions of the substantia nigra pars reticulata (SNr). Orexin and its receptors have a relationship with both STN-DBS and epilepsy. We aimed to investigate whether and how STN inputs to the SNr regulate seizures and the role of the orexin pathway in this process.

Methods

A penicillin-induced motor epileptic model in adult male C57BL/6 J mice was established to evaluate the efficacy of STN-DBS in modulating seizure activities. Optogenetic and chemogenetic approaches were employed to regulate STN-SNr circuits. Selective orexin receptor type 1 and 2 antagonists were used to inhibit the orexin pathway.

Results

First, we found that high-frequency ipsilateral or bilateral STN-DBS was effective in reducing seizure activity in the penicillin-induced motor epilepsy model. Second, inhibition of STN excitatory neurons and STN-SNr projections alleviates seizure activities, whereas their activation amplifies seizure activities. In addition, activation of the STN-SNr circuits also reversed the protective effect of STN-DBS on motor epilepsy. Finally, we observed that STN-DBS reduced the elevated expression of orexin and its receptors in the SNr during seizures and that using a combination of selective orexin receptor antagonists also reduced seizure activity.

Conclusion

STN-DBS helps reduce motor seizure activity by inhibiting the STN-SNr circuit. Additionally, orexin receptor antagonists show potential in suppressing motor seizure activity and may be a promising therapeutic option in the future.
The analysis of brain functional connectivity of post-stroke cognitive impairment patients: an fNIRS study
Authors: Zou Jiahuan , Yin Yongyan , Lin Zhenfang , Gong Yulai
Published: May 2023

Background

Post-stroke cognitive impairment (PSCI) is a considerable risk factor for developing dementia and reoccurrence of stroke. Understanding the neural mechanisms of cognitive impairment after stroke can facilitate early identification and intervention.

Objectives

Using functional near-infrared spectroscopy (fNRIS), the present study aimed to examine whether resting-state functional connectivity (FC) of brain networks differs in patients with PSCI, patients with Non-PSCI (NPSCI), and healthy controls (HCs), and whether these features could be used for clinical diagnosis of PSCI.

Methods

The present study recruited 16 HCs and 32 post-stroke patients. Based on the diagnostic criteria of PSCI, post-stroke patients were divided to the PSCI or NPSCI group. All participants underwent a 6-min resting-state fNRIS test to measure the hemodynamic responses from regions of interests (ROIs) that were primarily distributed in the prefrontal, somatosensory, and motor cortices.

Results

The results showed that, when compared to the HC group, the PSCI group exhibited significantly decreased interhemispheric FC and intra-right hemispheric FC. ROI analyses showed significantly decreased FC among the regions of somatosensory cortex, dorsolateral prefrontal cortex, and medial prefrontal cortex for the PSCI group than for the HC group. However, no significant difference was found in the FC between the PSCI and the NPSCI groups.

Conclusion

Our findings provide evidence for compromised interhemispheric and intra-right hemispheric functional connectivity in patients with PSCI, suggesting that fNIRS is a promising approach to investigate the effects of stroke on functional connectivity of brain networks.
Temporal transcriptional control of neural induction in human induced pluripotent stem cells
Authors: Gupta Shakti , Polit Lucia Dutan , Fitzgerald Michael , Rowland Helen A. , Murali Divya , Buckley Noel J. , Subramaniam Shankar
Published: May 2023

Introduction

Neural induction of human induced pluripotent stem cells represents a critical switch in cell state during which pluripotency is lost and commitment to a neural lineage is initiated. Although many of the key transcription factors involved in neural induction are known, we know little of the temporal and causal relationships that are required for this state transition.

Methods

Here, we have carried out a longitudinal analysis of the transcriptome of human iPSCs undergoing neural induction. Using the temporal relationships between the changing profile of key transcription factors and subsequent changes in their target gene expression profiles, we have identified distinct functional modules operative throughout neural induction.

Results

In addition to modules that govern loss of pluripotency and gain of neural ectoderm identity, we discover other modules governing cell cycle and metabolism. Strikingly, some of these functional modules are retained throughout neural induction, even though the gene membership of the module changes. Systems analysis identifies other modules associated with cell fate commitment, genome integrity, stress response and lineage specification. We then focussed on OTX2, one of the most precociously activated transcription factors during neural induction. Our temporal analysis of OTX2 target gene expression identified several OTX2 regulated gene modules representing protein remodelling, RNA splicing and RNA processing. Further CRISPRi inhibition of OTX2 prior to neural induction promotes an accelerated loss of pluripotency and a precocious and aberrant neural induction disrupting some of the previously identified modules.

Discussion

We infer that OTX2 has a diverse role during neural induction and regulates many of the biological processes that are required for loss of pluripotency and gain of neural identity. This dynamical analysis of transcriptional changes provides a unique perspective of the widespread remodelling of the cell machinery that occurs during neural induction of human iPSCs.
Deletion of p75NTR rescues the synaptic but not the inflammatory status in the brain of a mouse model for Alzheimer’s disease
Authors: Demuth Hendrik , Hosseini Shirin , Düsedeau Henning Peter , Dunay Ildiko Rita , Korte Martin , Zagrebelsky Marta
Published: May 2023

Introduction

Alzheimer’s disease (AD), is characterized by a gradual cognitive decline associated with the accumulation of Amyloid beta (Aβ)-oligomers, progressive neuronal degeneration and chronic neuroinflammation. Among the receptors shown to bind and possibly transduce the toxic effects of Aβ-oligomers is the p75 neurotrophin receptor (p75NTR). Interestingly, p75NTR mediates several crucial processes in the nervous system, including neuronal survival and apoptosis, maintenance of the neuronal architecture, and plasticity. Furthermore, p75NTR is also expressed in microglia, the resident immune cells of the brain, where it is markedly increased under pathological conditions. These observations indicate p75NTR as a potential candidate for mediating Aβ-induced toxic effects at the interface between the nervous and the immune system, thereby potentially participating in the crosstalk between these two systems.

Methods

Here we used APP/PS1 transgenic mice (APP/PS1tg) and compared the Aβ-induced alterations in neuronal function, chronic inflammation as well as their cognitive consequences between 10 months old APP/PS1tg and APP/PS1tg x p75NTRexonIV knockout mice.

Results

Electrophysiological recordings show that a loss of p75NTR rescues the impairment in long-term potentiation at the Schaffer collaterals in the hippocampus of APP/PS1tg mice. Interestingly, however loss of p75NTR does not influence the severity of neuroinflammation, microglia activation or the decline in spatial learning and memory processes observed in APP/PS1tg mice.

Conclusion

Together these results indicate that while a deletion of p75NTR rescues the synaptic defect and the impairment in synaptic plasticity, it does not affect the progression of the neuroinflammation and the cognitive decline in a mouse model for AD.
Feasibility study on the use of “Qi-tonifying medicine compound” as an anti-fatigue functional food ingredient based on network pharmacology and molecular docking
Authors: Wu Yi , Ma Yixuan , Cao Jinguo , Xie Rui , Chen Feng , Hu Wen , Huang Yushan
Published: May 2023

Introduction

Fatigue has attracted broad attention in recent years due to its high morbidity rates. The use of functional foods to relieve fatigue-associated symptoms is becoming increasingly popular and has achieved relatively good results. In this study, network pharmacology and molecular docking strategies were used to establish the material basis and mechanisms of Chinese herbal compounds in fatigue treatment. According to traditional medicine theories and relevant guidance documents published by the Chinese Ministry of Health, four herbal medicines, including Eucommia ulmoides Oliver bark, Eucommia ulmoides Oliver male flower, Panax notoginseng, and Syzygium aromaticum (EEPS), were selected to constitute the anti-fatigue herbal compound that may be suitable as functional food ingredients.

Methods

The major active ingredients in EEPS were identified via comprehensive literature search and Traditional Chinese Medicine Systems Pharmacology database search. Corresponding targets for these ingredients were predicted using SwissTargetPrediction. The network was constructed using Cytoscape 3.9.1 to obtain key ingredients. Prediction of absorption, distribution, metabolism, excretion and toxicity properties was performed using the ADMETIab 2.0 database. The anti-fatigue targets were retrieved from GeneCards v5.13, OMIM, TTD and DisGeNET 7.0 databases. Then, the potential targets of EEPS in fatigue treatment were screened through a Venn diagram. A protein–protein interaction (PPI) network of these overlapping targets was constructed, and the hub targets in the network selected through topological screening. Gene Ontology and KEGG pathway enrichment analyses were performed using the DAVID database and the bioinformatics online platform. Finally, AutoDock tools were used to verify the binding capacity between the key active ingredients and the core targets.

Results and Discussion

This study identified the active ingredients and potential molecular mechanisms of EEPS in fatigue treatment, which will provide a foundation for future research on applications of herbal medicines in the functional food industry.
Differential effects of high dose omega-3 fatty acids on metabolism and inflammation in patients with obesity: eicosapentaenoic and docosahexaenoic acid supplementation
Authors: Borja-Magno Angélica , Guevara-Cruz Martha , Flores-López Adriana , Carrillo-Domínguez Silvia , Granados Julio , Arias Clorinda , Perry Mary , Sears Barry , Bourges Hector , Gómez F. Enrique
Published: May 2023

Background

Obesity is complicated by low-grade chronic inflammation characterised by increases in inflammatory proteins and cells in peripheral blood. It has been known that omega-3 fatty acids (FA) like eicosapentaenoic (EPA) and docosahexaenoic (DHA) could modulate the inflammatory process and improve metabolic markers.

Objective

This study aimed to determine the effect of high-dose omega-3 FA on metabolic and inflammatory markers among patients with obesity and healthy volunteers.

Methods

This prospective study included 12 women with obesity (body mass index [BMI] ≥ 35.0 kg/m2) and 12 healthy women (BMI < 24.0 kg/m2) who were supplemented with a dose of 4.8 g/day (3.2 g EPA plus 1.6 g DHA) for 3 months followed by no treatment for 1 month. Plasma metabolic and inflammatory markers and levels of mRNA transcripts of CD4+ T lymphocyte subsets were determined monthly.

Results

None of the participants exhibited changes in weight or body composition after study completion. EPA and DHA supplementation improved metabolic (insulin, Homeostatic Model Assessment of Insulin Resistance [HOMA-IR], triglyceride [TG]/ high-density lipoprotein [HDL] ratio, TG, and arachidonic acid [AA]/EPA ratio) and tumor necrosis factor-alpha (TNF-α). Moreover, the levels of mRNA transcripts of T CD4+ lymphocyte subsets (TBX21, IFNG, GATA-3, interleukin [IL]-4, FOXP3, IL-10 IL-6, and TNF-α), were down-regulated during the intervention phase. After 1 month without supplementation, only insulin, HOMA-IR and the mRNA transcripts remained low, whereas all other markers returned to their levels before supplementation.

Conclusion

Supplementation with high-dose omega-3 FAs could modulate metabolism and inflammation in patients with obesity without weight loss or changes in body composition. However, these modulatory effects were ephemeral and with clear differential effects: short-duration on metabolism and long-lasting on inflammation.
Characterization of manganized soluble dietary fiber complexes from tigernut meal and study of the suppressive activity of digestive enzymes in vitro
Authors: Wang Yifei , Wang Weihao , Wu Yunjiao , JiLiu Junlan , Hu Xin , Wei Mingzhi , Cao LongKui
Published: May 2023

In this study, manganized soluble dietary fiber (SDF–Mn(II)) was prepared from tigernut meal using a microwave solid-phase synthesis method with SDF. Microscopic morphological and structural analyses of SDF–Mn(II) were carried out using scanning electron microscopy, Fourier infrared spectroscopy, UV full-band scanning, X-ray diffraction, a thermal analyzer, gel permeation chromatography, and nuclear magnetic resonance, and its in vitro hypoglycemic activity was initially investigated. The results of these analyses revealed that the reaction of Mn(II) with SDF mainly involved hydroxyl and carbonyl groups, with the Nuclear magnetic resonance (NMR) analysis showing that specific covalent binding was produced and substitution was mainly carried out at the C6 position. Moreover, compared with SDF, the SDF–Mn(II) complex exhibited a porous structure, red-shifted, and color-enhancing effects on the UV characteristic peaks, significantly increased crystallinity and decreased molecular weight, and improved thermal stability; in addition, SDF–Mn(II) afforded significantly enhanced inhibition of α-amylase and α-glucosidase and possesses good in vitro digestive enzyme inhibition activity.
Case Report: Early detection and intervention of congenital portosystemic shunts in children
Authors: Zhang Ying , Yu Tianzhuo , Mi Yanhong , Zhang Wenzhi , Yang Gaoyi
Published: May 2023

Congenital portosystemic shunts (CPSS) are rare vascular anomalies that cause abnormal communications between the portal and systemic venous systems and may be incidentally detected on imaging or via abnormal laboratory parameters due to the lack of specificity in the condition’s clinical presentation. Ultrasound (US) is a common tool for examining abdominal solid organs and vessels and is the initial imaging modality for diagnosing CPSS. Here we report the case of an 8-year-old Chinese boy with CPSS diagnosed using color Doppler US. Doppler US first found intrahepatic tumor, then revealed that the left portal vein was directly communicating with the inferior vena cava, and the boy was finally diagnosed with intrahepatic portosystemic shunts. Interventional therapy was employed to occlude the shunt. During the follow-up, the intrahepatic tumor disappeared and no complications. Hence, to be able to differentiate such vascular anomalies, clinicians should be fairly acquainted with the normal ultrasonographic anatomical features in daily clinical work. Furthermore, increased disease awareness and advances in imaging equipment and technology are essential for CPSS diagnosis.
Risk factors for pulmonary cement embolism after percutaneous vertebroplasty and radiofrequency ablation for spinal metastases
Authors: Wang Luqiang , Lu Ming , Zhang Xinxin , Zhao Zhenguo , Li Xiaoyang , Liu Ting , Xu Libin , Yu Shengji
Published: May 2023

Objective

Pulmonary cement embolism is a rare but underestimated complication of vertebroplasty due to the relative lack of study and examination. This study aims to investigate the incidence of pulmonary cement embolism in patients with spinal metastasis who undergo PVP with RFA and to analyze the relative risk factors.

Methods

A total of 47 patients were retrospectively included and classified into pulmonary cement embolism (PCE) group and non-pulmonary cement embolism (NPCE) group by comparing pre- and postoperative pulmonary CT scan images. The demographic and clinical information of the patients was obtained. Demographic data in the two groups were compared using the chi-square test for qualitative data and the unpaired t test for quantitative data. Multiple logistic regression analysis was used to identify risk factors related to pulmonary cement embolism.

Results

Pulmonary cement embolism was detected in 11 patients (23.4%), and all patients were asymptomatic and followed up regularly. Risk analysis showed that multiple segments (≥3, p=0.022), thoracic vertebrae (p=0.0008), and unipedicular puncture approach (p=0.0059) were risk factors for pulmonary cement embolism. There was a high incidence of pulmonary cement embolism if bone cement leaked into the para vertebral venous plexus in the thoracic vertebra (p<0.0001). Vein leakage of cement was related to the integrity of the vertebral cortex.

Conclusion

The number of involved vertebrae, lesion location, and puncture approach are independent risk factors for pulmonary cement embolism. There was a high incidence of pulmonary cement embolism if bone cement leaked into the para vertebral venous plexus in the thoracic vertebra. Surgeons should consider these factors when formulating therapeutic strategies.
Peptides for diagnosis and treatment of ovarian cancer
Authors: Guo Ling , Wang Jing , Li Nana , Cui Jialin , Su Yajuan
Published: May 2023

Ovarian cancer is the most deadly gynecologic malignancy, and its incidence is gradually increasing. Despite improvements after treatment, the results are unsatisfactory and survival rates are relatively low. Therefore, early diagnosis and effective treatment remain two major challenges. Peptides have received significant attention in the search for new diagnostic and therapeutic approaches. Radiolabeled peptides specifically bind to cancer cell surface receptors for diagnostic purposes, while differential peptides in bodily fluids can also be used as new diagnostic markers. In terms of treatment, peptides can exert cytotoxic effects directly or act as ligands for targeted drug delivery. Peptide-based vaccines are an effective approach for tumor immunotherapy and have achieved clinical benefit. In addition, several advantages of peptides, such as specific targeting, low immunogenicity, ease of synthesis and high biosafety, make peptides attractive alternative tools for the diagnosis and treatment of cancer, particularly ovarian cancer. In this review, we focus on the recent research progress regarding peptides in the diagnosis and treatment of ovarian cancer, and their potential applications in the clinical setting.
Mitochondrial metabolic reprogramming-mediated immunogenic cell death reveals immune and prognostic features of clear cell renal cell carcinoma
Authors: Yang Lin , Xiong Jing , Li Sheng , Liu Xiaoqiang , Deng Wen , Liu Weipeng , Fu Bin
Published: May 2023

Background

Mitochondrial metabolic reprogramming (MMR)-mediated immunogenic cell death (ICD) is closely related to the tumor microenvironment (TME). Our purpose was to reveal the TME characteristics of clear cell renal cell carcinoma (ccRCC) by using them.

Methods

Target genes were obtained by intersecting ccRCC differentially expressed genes (DEGs, tumor VS normal) with MMR and ICD-related genes. For the risk model, univariate COX regression and K-M survival analysis were used to identify genes most associated with overall survival (OS). Differences in the TME, function, tumor mutational load (TMB), and microsatellite instability (MSI) between high and low-risk groups were subsequently compared. Using risk scores and clinical variables, a nomogram was constructed. Predictive performance was evaluated by calibration plots and receiver operating characteristics (ROC).

Results

We screened 140 DEGs, including 12 prognostic genes for the construction of risk models. We found that the immune score, immune cell infiltration abundance, and TMB and MSI scores were higher in the high-risk group. Thus, high-risk populations would benefit more from immunotherapy. We also identified the three genes (CENPA, TIMP1, and MYCN) as potential therapeutic targets, of which MYCN is a novel biomarker. Additionally, the nomogram performed well in both TCGA (1-year AUC=0.862) and E-MTAB-1980 cohorts (1-year AUC=0.909).

Conclusions

Our model and nomogram allow accurate prediction of patients’ prognoses and immunotherapy responses.
Epidemiology and survival outcomes of patients with orbital region non-cutaneous squamous cell carcinoma: a population-based analysis
Authors: He Lin-feng , Mou Pei , Wei Rui-li
Published: May 2023

Background

Non-cutaneous squamous cell carcinoma (ncSCC) of the orbital region is very rare. Thus, its epidemiological characteristics and prognosis are poorly understood. The aim of the study was to assess the epidemiological characteristics and survival outcomes of ncSCC of the orbital region.

Methods

Incidence and demographic data on ncSCC of the orbital region were extracted from the Surveillance, Epidemiology, and End Results (SEER) database and analyzed. The chi-square test was used to calculate the differences between groups. Univariate and multivariate Cox regression analyses were performed to determine the independent prognostic factors for disease-specific survival (DSS) and overall survival (OS).

Results

The overall incidence of ncSCC in the orbital region from 1975 to 2019 was 0.68/1,000,000, and the incidence showed an increasing trend during this period. A total of 1,265 patients with ncSCC of the orbital region (mean age, 65.3 years) were identified in the SEER database. Of these, 65.1% were aged ≥60 years, 87.4% were White, and 73.5% were male. The conjunctiva (74.5%) was the most common primary site, followed by the orbit (12.1%), lacrimal apparatus (10.8%), and overlapping lesion of the eye and adnexa (2.7%). Multivariate Cox regression analysis revealed that age, primary site, SEER summary stage, and surgery were independent prognostic factors for DSS, whereas age, sex, marital status, primary site, SEER summary stage, and surgery were independent prognostic factors for OS.

Conclusions

The incidence of ncSCC in the orbital region has increased over the past 40 years. It usually affects White people, men, and people aged ≥60 years, and its most common site is the conjunctiva. Orbital SCC has worse survival outcomes than SCC of other sites in the orbital region. Surgery is the independent protective treatment for ncSCC of the orbital region.
Should personalised dosing have a role in cancer treatment?
Authors: Villette Claire C. , Orrell David , Millen Jim , Chassagnole Christophe
Published: May 2023

Almost all pharmaceutical products are approved on the basis of their effect in patients representing the “average” of the population studied in registrational trials, with most drug labels allowing, at most, for empirical dose reduction in the case of toxicity. In this perspective article we explore some of the evidence that supports the use of personalised dosing in cancer treatment and show how we have been able to build on existing models linking dose, exposure and toxicity to demonstrate how dose optimisation, including increasing the dose, has the potential to significantly improve efficacy outcomes. We also explore, through the lens of our own experience of developing a personalised dosing platform, some of the hurdles that stand in the way of implementing a personalised approach to dosing in real world settings. In particular, our experience is illustrated by the application of a dosing platform for docetaxel treatment in prostate cancer.
Liquid biopsies and minimal residual disease in myeloid malignancies
Authors: Allam Sabine , Nasr Kristina , Khalid Farhan , Shah Zunairah , Khan Suheb Mahammed Ziauddin , Mulla Sana , Vikash Sindhu , Bou Zerdan Maroun , Anwer Faiz , Chaulagain Chakra P.
Published: May 2023

Minimal residual disease (MRD) assessment through blood component sampling by liquid biopsies (LBs) is increasingly being investigated in myeloid malignancies. Blood components then undergo molecular analysis by flow cytometry or sequencing techniques and can be used as a powerful tool for prognostic and predictive purposes in myeloid malignancies. There is evidence and more is evolving about the quantification and identification of cell-based and gene-based biomarkers in myeloid malignancies to monitor treatment response. MRD based acute myeloid leukemia protocol and clinical trials are currently incorporating LB testing and preliminary results are encouraging for potential widespread use in clinic in the near future. MRD monitoring using LBs are not standard in myelodysplastic syndrome (MDS) but this is an area of active investigation. In the future, LBs can replace more invasive techniques such as bone marrow biopsies. However, the routine clinical application of these markers continues to be an issue due to lack of standardization and limited number of studies investigating their specificities. Integrating artificial intelligence (AI) could help simplify the complex interpretation of molecular testing and reduce errors related to operator dependency. Though the field is rapidly evolving, the applicability of MRD testing using LB is mostly limited to research setting at this time due to the need for validation, regulatory approval, payer coverage, and cost issues. This review focuses on the types of biomarkers, most recent research exploring MRD and LB in myeloid malignancies, ongoing clinical trials, and the future of LB in the setting of AI.
Are radiomic spleen features useful for assessing the differentiation status of advanced gastric cancer?
Authors: Lyu Dongbo , Liang Pan , Huang Chencui , Chen Xingzhi , Cheng Ming , Zhu Bingbing , Liu Mengru , Yue Songwei , Gao Jianbo
Published: May 2023

Background

The differentiation status of gastric cancer is related to clinical stage, treatment and prognosis. It is expected to establish a radiomic model based on the combination of gastric cancer and spleen to predict the differentiation degree of gastric cancer. Thus, we aim to determine whether radiomic spleen features can be used to distinguish advanced gastric cancer with varying states of differentiation.

Materials and methods

January 2019 to January 2021, we retrospectively analyzed 147 patients with advanced gastric cancer confirmed by pathology. The clinical data were reviewed and analyzed. Three radiomics predictive models were built from radiomics features based on gastric cancer (GC), spleen (SP) and combination of two organ position (GC+SP) images. Then, three Radscores (GC, SP and GC+SP) were obtained. A nomogram was developed to predict differentiation statue by incorporating GC+SP Radscore and clinical risk factors. The area under the curve (AUC) of operating characteristics (ROC) and calibration curves were assessed to evaluate the differential performance of radiomic models based on gastric cancer and spleen for advanced gastric cancer with different states of differentiation (poorly differentiated group and non- poorly differentiated group).

Results

There were 147 patients evaluated (mean age, 60 years ± 11SD, 111 men). Univariate and multivariate logistic analysis identified three clinical features (age, cTNM stage and CT attenuation of spleen arterial phase) were independent risk factors for the degree of differentiation of GC (p =0.004,0.000,0.020, respectively). The clinical radiomics (namely, GC+SP+Clin) model showed powerful prognostic ability in the training and test cohorts with AUCs of 0.97 and 0.91, respectively. The established model has the best clinical benefit in diagnosing GC differentiation.

Conclusion

By combining radiomic features (GC and spleen) with clinical risk factors, we develop a radiomic nomogram to predict differentiation status in patients with AGC, which can be used to guide treatment decisions.
High-frequency irreversible electroporation improves survival and immune cell infiltration in rodents with malignant gliomas
Authors: Campelo Sabrina N. , Lorenzo Melvin F. , Partridge Brittanie , Alinezhadbalalami Nastaran , Kani Yukitaka , Garcia Josefa , Saunier Sofie , Thomas Sean C. , Hinckley Jonathan , Verbridge Scott S. , Davalos Rafael V. , Rossmeisl John H.
Published: May 2023

Background

Irreversible electroporation (IRE) has been previously investigated in preclinical trials as a treatment for intracranial malignancies. Here, we investigate next generation high-frequency irreversible electroporation (H-FIRE), as both a monotherapy and a combinatorial therapy, for the treatment of malignant gliomas.

Methods

Hydrogel tissue scaffolds and numerical modeling were used to inform in-vivo H-FIRE pulsing parameters for our orthotopic tumor-bearing glioma model. Fischer rats were separated into five treatment cohorts including high-dose H-FIRE (1750V/cm), low-dose H-FIRE (600V/cm), combinatorial high-dose H-FIRE + liposomal doxorubicin, low-dose H-FIRE + liposomal doxorubicin, and standalone liposomal doxorubicin groups. Cohorts were compared against a standalone tumor-bearing sham group which received no therapeutic intervention. To further enhance the translational value of our work, we characterize the local and systemic immune responses to intracranial H-FIRE at the study timepoint.

Results

The median survival for each cohort are as follows: 31 days (high-dose H-FIRE), 38 days (low-dose H-FIRE), 37.5 days (high-dose H-FIRE + liposomal doxorubicin), 27 days (low-dose H-FIRE + liposomal doxorubicin), 20 days (liposomal doxorubicin), and 26 days (sham). A statistically greater overall survival fraction was noted in the high-dose H-FIRE + liposomal doxorubicin (50%, p = 0.044), high-dose H-FIRE (28.6%, p = 0.034), and the low-dose H-FIRE (20%, p = 0.0214) compared to the sham control (0%). Compared to sham controls, brain sections of rats treated with H-FIRE demonstrated significant increases in IHC scores for CD3+ T-cells (p = 0.0014), CD79a+ B-cells (p = 0.01), IBA-1+ dendritic cells/microglia (p = 0.04), CD8+ cytotoxic T-cells (p = 0.0004), and CD86+ M1 macrophages (p = 0.01).

Conclusions

H-FIRE may be used as both a monotherapy and a combinatorial therapy to improve survival in the treatment of malignant gliomas while also promoting the presence of infiltrative immune cells.
Aneuploid subtypes of circulating tumor cells and circulating tumor-derived endothelial cells predict the overall survival of advanced lung cancer
Authors: Zhang Jie , Hong Yang , Wang Liang , Hu Weiheng , Tian Guangming , Wu Di , Wang Yang , Dai Ling , Zhang Ziran , Yang Yue , Fang Jian
Published: May 2023

Objective

This study aimed to detect circulating tumor cells (CTCs) and circulating tumor-derived endothelial cells (CTECs) in patients with advanced lung cancer, for describing the distribution characteristics of CTC and CTEC subtypes, exploring the correlation between CTC/CTEC subtypes and novel prognostic biomarkers.

Methods

A total of 52 patients with advanced lung cancer were enrolled in this study. Using the subtraction enrichment-immunofluorescence in situ hybridization (SE-iFISH) system, CTCs and CTECs derived from these patients were identified.

Results

Based on cell size, there were 49.3% small and 50.7% large CTCs, and 23.0% small and 77.0% large CTECs. Triploidy, tetraploidy, and multiploidy varied in the small and large CTCs/CTECs. Besides these three aneuploid subtypes, monoploidy was found in the small and large CTECs. Triploid and multiploid small CTCs and tetraploid large CTCs were associated with shorter overall survival (OS) in patients with advanced lung cancer. However, none of the CTECs subtypes showed a significant correlation with patient prognosis. In addition, we found strong positive correlations (P<0.0001) in the four groups including triploid small cell size CTCs and multiploid small cell size CTECs, and multiploid small cell size CTCs and monoploid small cell size CTECs. Furthermore, combined detection of the specific subtypes, including triploid small CTC and monoploid small CTEC, triploid small CTC and triploid small CTEC, and multiploid small CTC and monoploid small CTEC, were associated with poor prognosis in advanced lung cancer.

Conclusions

Aneuploid small CTCs are associated with the outcome of patients with advanced lung cancer. In particular, the combined detection of triploid small CTCs and monoploid small CTECs, triploid small CTCs and triploid small CTECs, and multiploid small CTCs and monoploid small CTECs has clinical significance for predicting prognosis in patients with advanced lung cancer.
Transcranial magnetic stimulation for the treatment of chronic low back pain: a narrative review
Authors: Olechowski Camille , Gener Maricar , Aiyer Rohit , Mischel Nicholas
Published: May 2023

Background

Chronic low back pain is a debilitating condition that impacts millions of individuals around the world, and also has an enormous economic impact. The impact of chronic pain does not only involve physical health, but can also play a detrimental role in a patient's mental health. Consequently, it is critical to approach these patients with multimodal management. Initially, a treatment plan which includes medications, psychotherapy, physical therapy, and invasive interventions can be utilized for chronic back pain. However, many patients experience refractory low back pain to these initial treatments, which can result in non-resolving chronic pain. As a result, many new interventions have been developed in recent years to treat refractory low back pain, including non-invasive transcranial magnetic stimulation. In recent years, there has been some limited and preliminary evidence for the treatment of chronic low back pain with transcranial magnetic stimulation, as further investigation on this intervention is warranted. After reviewing analytically high impact studies, our objective is to provide a narrative review of the treatment of chronic low back pain with repetitive transcranial magnetic stimulation (rTMS).

Methods

We performed a comprehensive database search on PubMed, Embase, PsychInfo, Web of Science, and CINAHL for literature that pertains to the treatment of chronic low back pain with transcranial magnetic stimulation using these terms: “Chronic Low Back Pain and Transcranial Magnetic Stimulation”, “Low Back Pain and Transcranial Magnetic Stimulation”, “Chronic Back Pain and Transcranial Magnetic Stimulation”, “Chronic Low Back Pain and TMS”, “Low Back Pain and TMS”, and “Chronic Back Pain and TMS”. We aim to provide a narrative review of the role of rTMS in CLBP.

Results

Initial search results from September to November 2021 using the above-mentioned search criteria included 458 articles, of which 164 duplicates were removed and 280 were further excluded by a three-person (CO, NM and RA) screening process. Articles were further filtered based on various exclusion and inclusion criteria. The resulting 6 studies are discussed.

Discussion

The studies reviewed suggest the potential benefit in chronic lower back pain symptoms after various rTMS protocols and sites of stimulation. However, the included studies are not without issues in design for example: not randomized, not blinded, or have small sample size. This review highlights the need for scaled, better controlled research studies and standardization of treatment protocols to determine if rTMS for chronic lower back pain will be accepted as a standard treatment option for patients with chronic lower back pain symptoms.
Correlation analysis of CD8+ cell overexpression and prognosis of hemorrhagic fever with renal syndrome—a case-control study
Authors: Wang Min , Zhou Yong , Wang Ying , Du Yanqiang , Guo Zhangyan , Ma Le , Zhang Hua , Wang Yi
Published: May 2023

Background

Hemorrhagic fever with Renal Syndrome (HFRS) is an infectious disease caused by Hantavirus with fever, hemorrhage and acute kidney injury (AKI) as clinical characteristics. The research on the etiology and pathogenesis of diseases has become a focus of attention. However, there are few related medical studies in children with HFRS. The prognosis of the children with HFRS remains to be explored.

Objectives

We explored risk factors in children with HFRS and summarize sensitive indicators that are conducive to the prognosis of the disease.

Methods

We designed a case-control study and recruited 182 HFRS pediatric patients (2014.01–2022.08). They were divided into two groups according to the severity of disease, including the control group(158 cases with mild and moderate subgroup)and the observation group (24 cases with severe and critical subgroup). Risk factors influencing prognosis were analyzed by binary logistic regression. The cutoff value, sensitivity and specificity of the risk factors prediction were calculated by receiver operating characteristic (ROC) and Yoden index.

Results

Lymphocyte subsets characteristics analysis showed that in observation group the indexes were decreased in lymphocyte, T lymphocytes (CD3)+, helper/inducible T lymphocytes (CD4+)/inhibition/cytotoxic T cells (CD8+), B lymphocytes (CD19+); and the elevated index was CD8+, the difference were all significant between two groups. (P < 0.05). With death as the primary outcome, it was found that the serum CD8+ (odds ratio [OR] 2.91, 95% confidence interval [CI] 1.65, 4.00; P < 0.01) was risk factor and significantly associated with mortality. The cutoff value of the serum CD8+ was 845 × 106/L, the sensitivity and specificity were 78.5%, 85.4%. With complications as the secondary outcomes, the serum CD8+ (OR 2.69, 95% CI 1.15, 4.88; P < 0.01) was found to be risk factors. The cutoff of the serum CD8+ was 690 × 106/L, the sensitivity and specificity were 69.3%, 75.1% respectively.

Conclusion

CD8+ may be significantly correlated with the severity and prognosis of HFRS in children.
Case report: cerebral venous sinus thrombosis and pulmonary embolism as the initial presentation in a child with asymptomatic primary nephrotic syndrome
Authors: Wang Qinhui , Cui Yaru , Liang Ping , Wang Chuan , Zhou Kaiyu , Ma Fan , Duan Hongyu
Published: May 2023

Background

Cerebral venous sinus thrombosis (CVST) is rare, but potentially life-threatening. The clinical course definitely become more unpredictable and fatal in patients complicated by pulmonary embolism (PE). Nephrotic syndrome (NS) is an uncommon etiology of CVST. Concurrence of CVST and PE at the initial onset of NS is extremely unusual and rarely reported. Considering that edema might be absent in NS individuals, thromboembolic events probably become unrecognized, thereby causing a missed or delayed diagnosis and poor outcome. Herein, we described an extraordinary case of an adolescent boy presenting with both CVST and PE initially just within 5 days of disease onset, who was ultimately diagnosed with asymptomatic NS, aiming to emphasize a high index of suspicion of these diseases in patients with conditions of hypercoagulability.

Case presentation

A 13-year-old male child presented acutely with dizziness, fever and dyspnea, with signs of shock but undetected edema. Initial laboratory investigations revealed hypoalbuminemia, typical images of pneumonia, and normal radiographic findings on non-enhanced computed tomography of head. Despite evidence of hypoalbuminemia and neurological symptoms, the child was still misdiagnosed as pneumonia. His dyspnea and period of headache deteriorated even if hemodynamic stability and undetected fever after initial therapy. The delayed urinalysis and 24-h urine examination both showed massive proteinuria. A computed tomography angiography of chest along with cranial magnetic resonance imaging/magnetic resonance venography were subsequently performed, consistent with the imaging features of PE and CVST, respectively. The diagnosis of asymptomatic primary NS complicated by PE and CVST was ultimately confirmed. The patient received corticosteroids and antithrombotic therapy with satisfactory results.

Conclusion

A persistent clinical suspicion of CVST should be borne in mind in patients with a sudden, new or worsening headache, specifically among those with prothrombotic conditions. NS should always be considered in the differential diagnosis of risk factors for CVST, even in absence of edema. Since CVST and PE can be present simultaneously at extraordinary early-onset of NS, early radiological diagnosis is clinically substantial to proper management and satisfactory long-term outcomes.