bluuebunny/crossref_metadata_2025 huggingface dataset:
Voxel-based Dosimetry Predicting Treatment Response and Related Toxicity in HCC Patients Treated with Resin-based Y90 Radioembolization: A prospective, single-arm study
Authors: Kokabi Nima , Arndt-Webster Linzi , Chen Bernard , Brandon David , Sethi Ila , Davarpanahfakhr Amir , Galt James , Elsayed Mohammad , Bercu Zachary , Cristescu Mircea , Kappadath S Cheenu , Schuster David M
Published: November 2022

Background:
There is an increasing body of evidence indicating Y90 dose thresholds for tumor response and treatment related toxicity. These thresholds are poorly studied in resin Y90 particularly in hepatocellular carcinoma (HCC).
Purpose:
To evaluate the efficacy of prospective voxel-based dosimetry for predicting treatment response and adverse events (AE’s) in patients with HCC undergoing resin-based Y90 radioembolization.
Materials and Methods:
This correlative study was based on a prospective single-arm clinical trial (NCT04172714) which evaluated the efficacy of low/scout (15 mCi) activity of resin-based Y90 for treatment planning. Partition model was used with the goal of tumor dose (TD) > 200 Gy and non-tumoral liver dose (NTLD) < 70 Gy for non-segmental therapies. Single compartment dose of 200 Gy was used for segmentectomies. Prescribed Y90 activity minus scout activity was administered for therapeutic Y90 followed by Y90-PET/CT. Sureplan® (MIM Software, Cleveland, OH) was used for dosimetry analysis. Treatment response was evaluated at 3 and 6 months. Receiver operating characteristic curve determined TD response threshold for objective (OR) and complete response (CR) as well as non-tumor liver dose (NTLD) threshold that predicted AE’s.
Results:
N = 30 patients were treated with 33 tumors (19 segmental and 14 non-segmental). One patient died before the first imaging and clinical follow-up was excluded from this analysis. Overall, 26(81%) of tumors had OR and 23(72%) had CR. Mean TD of 253 Gy predicted OR with 92% sensitivity and 83% specificity (area under the curve (AUC = 0.929, p < 0.001). Mean TD of 337 Gy predicted CR with 83% sensitivity and 89% specificity (AUC = 0.845, p < 0.001). Mean NTLD of 81Gy and 87 Gy predicted grade 3 AE’s with 100% sensitivity and 100% specificity in the non-segmental cohort at 3- and 6-month post Y90, respectively.
Conclusion:
In patients with HCC undergoing resin-based Y90, there are dose response and dose toxicity thresholds directly affecting outcomes.
Seasonal Monitoring of Microbial Activity Using Conventional Approaches in a Full-Scale Urban Biological Wastewater Treatment Plant
Authors: Demirbilek Deniz , İpek Ubeyde , Yetiş Ülkü
Published: November 2022

Activated sludge processes contains various groups of microorganisms with different metabolic properties, which are responsible for contaminants removal. Therefore, it is important to elucidate the general structure and functional properties of biomass in activated sludge processes. For this purpose, a full-scale domestic biological wastewater treatment plant in Tunceli (Turkey), Tunceli WWTP, was monitored to observe seasonal variations in process performance and biomass properties for a year. It was observed that nitrifying bacteria developed abundantly in the rainy and cool spring season as they were suppressed in summer because their large losses took placed due to an environment containing high alkalinity values. In September, aerobic heterotrophic, nitrify, denitrify, and anaerobic activities increased. It can be said that mature biomass contained young and active levels in an environment in which the sludge volume index (SVI) value increased to 196 mL/g. As a result of the improvement in the structural and functional properties of biomass, the nitrogen removal efficiency reached to 99%. Throughout whole study, the structural improvement observed in biomass reflected in its removal activity. The amount of biomass and removal activity decreased with the abundance of organic matter in the influent at the period in which biomass was closer to being categorized in the aged sludge class. The results showed that as the lowest mixed liquid volatile suspended solids (MLVSS) value of the year was 400 mg/L in November, MLVSS value reached the highest amount (1,400 mg/L) in December which aerobic heterotrophic activity accelerated with a decrease in organic matter level.
Posteroanterior scout view of pediatric patients using computed tomography: Validation using pediatric anthropomorphic phantoms
Authors: Arao Keiko , Masuda Takanori , Funama Yoshinori , Nakaura Takeshi , Sato Tomoyasu , Masuda Shouko , Oku Takayuki , Gotanda Rumi , Imaizumi Hiromasa , Arao Shinichi , Ono Atsushi , Hiratsuka Junichi , Awai Kazuo
Published: November 2022

Background: To compare the effect of obtaining the anteroposterior scout view (APSV) with that of posteroanterior scout view (PASV) on mammary gland dose in pediatric patients.
Methods: We used a pediatric anthropomorphic phantom with a 64 detector-row computed tomography (CT) scanner using the APSV or PASV protocol of the chest. A real-time skin dosimeter was placed on the scanner gantry and pasted onto the phantom surfaces of the right and left mammary glands. We compared the real-time skin dosimeter values in the right and left mammary glands between the APSV and PASV protocols at different tube voltages.
Results: Compared with APSV, it is possible to reduce the exposure dose by approximately 80% using PASV at different tube voltages (p < 0.05).
Conclusion: Obtaining the PASV was helpful in reducing the mammary gland dose by approximately 80% in pediatric patients than that of APSV without deteriorating the image quality of the main scan.
Exploration of KIR Genes and Hematological-related Diseases in Chinese Han Population: a Multi-center Retrospective Analysis
Authors: Li Ye-Mo , Li Yu-Xia , Hu Xiao-Zhuang , Li Dai-Yang , An Lin , Yuan Zhi-Yang , Liu Zhong-Liang , Du Ke-Ming , Zheng Zhong-Zheng
Published: November 2022

The function of natural killer (NK) cells has previously been implicated in hematopoietic-related diseases. Killer immunoglobulin-like receptors (KIR) play an important role in NK cells after hematopoietic stem cell transplantation. To explore the immunogenetic predisposition of hematopoiesis-related diseases, herein, a multi-center retrospective study in China was conducted, analyzing and comparing 2519 patients with hematopathy (mainly, acute lymphoblastic leukemia, acute myeloid leukemia, aplastic anemia, and myelodysplastic syndrome) to 18108 individuals without known pathology. Genotyping was performed by polymerase chain reaction with specific sequence primers (PCR-SSP). As a result, we discovered four genes including KIR2DL5 (OR: 0.74, 95% CI: 0.59–0.93; Pc = 0.0405), 2DS1 (OR: 0.74, 95% CI: 0.59–0.93; Pc = 0.0405), 2DS3 (OR: 0.58, 95% CI: 0.41–0.81; Pc = 0.0180), and 3DS1 (OR: 0.74, 95% CI: 0.58–0.94; Pc = 0.0405) to be protective factors that significantly reduce the risk of aplastic anemia. Our findings offer new approaches to immunotherapy for hematological-related diseases. As these therapies mature, they are promising to be used alone or in combination with current treatments to help to make hematopathy a manageable disease.
Biomarkers of GPC3, DCP and VEGF in Hepatocellular Carcinoma: Early Diagnostic and Prognostic Significance in the Chinese Population
Authors: Zhu Yangbo , Qin Jiayi , Ye Ziqi , Zhou Lin , Ling Qi
Published: November 2022

Background: Glypican-3 (GPC3), des-γ-carboxyprothrombin (DCP) and vascular endothelial growth factor (VEGF) are potential biomarkers for the early diagnosis and prognosis of hepatocellular carcinoma (HCC), especially in AFP negative patients. However, their sensitivity and accuracy as biomarkers are still needed to be compared and verified by large clinical samples in Chinese population.
Methods: ELISA was used to evaluate the GPC3, DCP and VEGF in the serum of 136 HCC patients, 47 liver cirrhosis patients and 46 healthy controls. Meanwhile, the risk factors and mortality for HCC recurrence were also investigated to obtain some prognostic variables according to the histopathological evaluation and follow-up data.
Results: The GPC3 and VEGF serum levels were significantly sensitive and specific compared with those of AFP and DCP for the diagnosis of HCC based on cut-off values. Compared with VEGF, the maximum area under the curve (AUC) of serum GPC3 level indicated most accurately in the diagnosis of HCC. In addition, GPC3 level was increased in 50.6% (39 / 77) of HCC patients with negative serum AFP. The risk factors for recurrence were high serum levels of tumor biomarkers, including DCP (>350 mAu/ml) and VEGF (>112 pg/ml) which were significantly higher in patients with microvascular invasion (MVI) than in those without MVI (P<0.01). Moreover, the expression of VEGF in various types of tumor invasion was also significantly different (P < 0.05, type 3 vs. type 1).
Conclusions: Serum GPC3 and VEGF levels have the potential to be effective biomarkers for the early diagnosis of HCC, especially for these with normal serum AFP. Serum DCP and VEGF levels would be non-invasive prognostic biomarker substitute for tumor invasiveness and MVI, which were tightly correlated with postoperative recurrence of HCC.
Evolution of surface-borne vibrational communication in fungus-growing ant societies
Authors: Murakami Takahiro , Sakamoto Hironori , Higashi Seigo
Published: November 2022

In ants, chemical communication, through pheromones for example, was thought to be the main communication tool in ant societies; however, a major question is whether chemical substances alone can control highly differentiated social behaviours. In this study, we focused on the surface-borne vibrational signals of fungus-growing ants, key organisms in the Neotropical ecosystem, and conducted a detailed analysis of the signals. Our results indicate that in fungus-growing ants, vibrational communication is a much more frequent and critical factor than previously believed. The frequency of vibrational signal recordings from the ants were found to be significantly correlated with social structure complexity. Structural analysis indicated that both the area and number of slits in the stridulatory organs were significantly correlated with body size. The ability of leaf-cutting ants to maintain fungus gardens was significantly lower in the vibration-inhibited group than in the pheromone secretion-inhibited group. These results suggest that ants that have become more communicative may induce altruistic behaviours and create more complex societies. The findings of this study may be applicable not only to social evolution studies but also for effectively controlling ant behaviours.
Similarity Matching of Medical Question Based on Siamese Network
Authors: Li Qing , He Song
Published: November 2022

Background
With the rapid development of the medical industry and the gradual increase in people's awareness of their health, the use of the Internet for medical question and answer, to obtain more accurate medical answers. It is necessary to first calculate the similarity of the questions asked by users, which further matches professional medical answers.
Method
This paper focuses on building a bidirectional gated recurrent unit(BiGRU) deep learning model based on Siamese network for medical interrogative similarity matching, using Word2Vec word embedding tool for word vector processing of ethnic-medical corpus, and introducing an attention mechanism and convolutional neural network. Bidirectional gated recurrent unit extracts contextual semantic information and long-distance dependency features of interrogative sentences; introducing an attention mechanism can give higher weight to keywords in interrogative sentences and further improve the recognition of similar words in interrogative sentences; Convolutional neural network takes into account the local information of interrogative sentences and can capture local position invariance, allowing feature extraction for words of different granularity through convolutional operations; By comparing the Euclidean distance, cosine distance and Manhattan distance to calculate the spatial distance of medical interrogatives, the Manhattan distance produced the best similarity result.
Result
Based on the ethnic medical question dataset constructed in this paper, the accuracy and F1-score reached 97.24% and 97.98%, which is a significant improvement compared to several other models.
Conclusion
By comparing with other models, the model proposed in this paper has better performance and achieve accurate matching of similar semantic question data of ethnic medicine.
Autosomal recessive bestrophinopathy combined with neurofibromatosis type 1 in a patient
Authors: Zhao Bo , Chen Lian , Zhang Peng , He Ke , Lei Min , Zhang Juan
Published: November 2022

Background

Neurofibromatosis type 1 (NF1) is a multisystem genetic disorder that may affect multiple systems of the body. Autosomal recessive bestrophinopathy (ARB) is a rare retinal dystrophy caused by autosomal recessively mutations in bestrophin 1 (BEST1) gene. So far, we have not retrieved any case report of the same patient with both NF1 and BEST1 gene mutations.

Case presentation

An 8-year-old female patient with café-au-lait spots, freckling on skin presented to our ophthalmology clinic for routine ophthalmological examination. Her best corrected visual acuity (BCVA) was 20/20 in both eyes. Slit-lamp examination of both eyes revealed few yellowish-brown dome-shaped Lisch nodules over the iris surface. Fundus examination was notable for bilateral confluent yellowish subretinal deposits at macula, few yellow flecks at temporal retina, and cup-to-disc ratio of 0.2. Optical coherence tomography (OCT) revealed subretinal fluid (SRF) involving the fovea, elongated photoreceptor outer segments and mild intraretinal fluid (IRF) at bilateral macula. Fundus autofluorescence demonstrated hyperfluorescence in the area corresponding to the subretinal deposits. Whole-exome sequencing and Sanger sequencing were used to investigate genetic mutation in the patient and her parents. A BEST1 gene heterozygous missense c.604C > T (p.Arg202Trp) was identified in the patient and her mother. Also, the patient carries an NF1 nonsense mutation c.6637C > T (p.Gln2213*) with the mosaic generalized phenotype. There were no visual impairments or obvious neurological, musculoskeletal, behavioral or other symptoms in this patient, so she was managed conservatively and advised to follow up regularly for a long time.

Conclusions

ARB and NF1, which are caused by two different pathogenic gene mutations, have rarely coexisted in the same patient. The discovery of pathogenic gene mutations may play a crucial role in more accurate diagnostics and genetic consultations for individuals and their families.
Calcium ions improve organic carbon stability in bauxite residue through alkaline minerals
Authors: Xue Shengguo , Zhang Yufei , Jiang Jun , Li Feng , Guo Xuyao , Zhu Feng , Chen Hualin , Wu Yujun
Published: November 2022

Purpose
The interaction of minerals and organic matter significantly affects the stability of organic carbon, which is key to the rehabilitation of bauxite residue. However, due to the microscopic structure of minerals and the chemical composition of dissolved organic matter (DOM), the interaction mechanism between alkaline minerals and DOM in the presence of calcium ions that are widely used as amendments is still poorly understood.
Methods
In this work, the adsorption mechanism of organic matter by sodalite and cancrinite in the presence of calcium ions was investigated by fourier transform infrared spectroscopy (FTIR), excitation-emission matrix fluorescence (EEMs), thermogravimetric analysis (TG-DSC) and atomic force microscope (AFM).
Results
The calcium ions can act as bridges to connect the negative sites on the mineral surface with the polysaccharide functional groups of organic matter, thus allowing the DOM to enter the pore channels of mineral structure to sequester organic carbon via ligand-exchange and/or electrostatic interactions. Furthermore, DOM located in the pore structure within cancrinite may be better protected due to physical isolation. The 3D view of the interacted minerals-organic matter assemblages provided visual evidence that the adsorption sites distributed on the surface of cancrinite increased by the action of calcium ions, with different adsorption capacity of individual sites for DOM.
Conclusions
The calcium ions enhance the ability of alkaline minerals to trap dissolved organic carbon, and the work highlighted the significance of organo-mineral associations in the microscopic mineral structure for the organic carbon sequestration in the revegetation process of bauxite residue disposal areas.
Knowledge and Practice of Third Year Degree Nursing Students Regarding Postpartum Depression at a University: Windhoek, Namibia.
Authors: Kadhila Joseph Galukeni Joseph , Moongo Winnie Rauha
Published: November 2022

Postpartum depressions (PPD) are common, affecting at least 10% of mothers. PPD is a common illness, the global prevalence being 10–15%. The prevention, detection and treatment of postpartum depression (PPD) are of great importance because PPD without care may cause many problems. Postpartum depressions are serious because of their impact on mother-baby relationships and on the Childs’ Development. However, these depressions seem very insufficiently diagnosed and treated. Methodology: In this study a quantitative descriptive research design was adopted. Descriptive research design is useful as it helps to obtain information that describes the existing phenomena by asking individuals about their perceptions, attitudes and values. The design reports things the way they are. In this regard, the descriptive research design was used to achieve the main objective of the study which is to assess the knowledge and practice of third year degree nursing students at a University, Windhoek Namibia, regarding postpartum depression. Result: Participant have good knowledge on, knowledge and practice regarding postpartum depression. An analysis of student’s knowledge about whether physical stress can predispose a woman to PPD revealed that clearly more than half of participants (89.6%, n = 60) agreed, while only 9.0% (n = 6) of the participants chosen neutral and 1.5%(n = 1) disagreed that physical stress can predisposes a woman to PPD. Conclusion: Descriptive analysis was conducted to compare the knowledge of study participants on postpartum depression. In addition, it shows that only few students who’s disagreed that smoking can predispose woman to PPD. The study revealed that the majority of the participant agreed that physical stress can predispose a woman to PPD. Overall, the study results revealed that above average of the 3rd year nursing students has good knowledge on postpartum depression.
The concept of detection of dynamic lung hyperinflation using cardiopulmonary exercise testing
Authors: Kominami Kazuyuki
Published: November 2022

Background
Dynamic lung hyperinflation (DLH) caused by air trapping, which increases residual air volume, is a common cause of shortness of breath on exertion in chronic obstructive pulmonary disease (COPD). DLH is commonly evaluated by measuring the decrease in maximal inspiratory volume during exercise, or using the hyperventilation method. However, only a few facilities perform these methods, and testing opportunities are limited. Therefore, we investigated the possibility of visually and qualitatively detecting DLH using data from a cardiopulmonary exercise test (CPET).
Methods
Four men who underwent symptom-limiting CPET were included in this study, including a male patient in his 60s with confirmed COPD, a 50s male long-term smoker, and two healthy males in their 20s and 70s, respectively. We calculated the difference between the inspiratory tidal volume (TV I) and expiratory tidal volume (TV E) per breath (TV E-I) from the breath-by-breath data of each CPET and plotted it against the time axis.
Results
No decrease in TV E-I was observed in either of the healthy males. However, in the patient with COPD and long-term smoker, TV E-I began to decrease soon after the start of exercise.
Conclusion
These results indicate that DLH can be visually detected using CPET data. However, this study was a validation of a very limited number of cases, and a comparison with existing evaluation methods and verification of disease specificity are required.
Differentiation of Enteric Neural Crest Cells Transplanted From Sox10-venus Mouse Embryonic Stem Cells Into the Gut of the Endothelin Receptor B Null Mouse Model
Authors: Fujiwara Naho , Miyahara Katsumi , Nakazawa-Tanaka Nana , Oishi Yoshie , Akazawa Chihiro , Tada Norihiro , Yamataka Atsuyuki
Published: November 2022

Purpose
Failure of enteric neural crest-derived cells (ENCCs) to correctly colonize the embryonic gut results in Hirschsprung’s disease (HD). Embryonic stem cells (ESCs) have the potential to differentiate into all tissue-specific cells and lineages, including ENCCs. We investigated the cellular differentiation of ESCs from Sox10-Venus + mice into both control and endothelin receptor-B knockout (Ednrb KO) mouse gut to assess each region.
Methods
We established ESCs from Sox10-Venus + mice. These cells were cultured for two days, then selected and co-cultured with either a dissociated control or Sox10-Venus – Ednrb KO mouse gut (both small intestine and colon) on embryonic day (E) 13.5. Four days later, cells were immunolabeled for Tuj1 and visualized using confocal microscopy.
Results
Confocal microscopy revealed that transplanted Sox10-Venus + cells from ESCs migrated extensively within the host gut. Moreover, Tuj1-positive neurites were detected in the transplanted ESCs. Tuj1 expression was significantly decreased in aganglionic HD colon compared to controls (p<0.05) and the HD small intestine (p<0.05).
Conclusions
This study demonstrated that an appropriate host environment is crucial for normal and complete colonization of the gut. Further investigations are required to confirm whether modifying this environment can improve the results of this model.
Metformin Regulates Autophagy to Attenuate Mitochondrial Dysfunction in High Glucose-stimulated H9C2 Cardiomyocytes via the AMPKα/Sirt1/Parkin Signaling Axis
Authors: Zhang Zhiliang , Ling Yesheng , Huang Zhuoshan , Zhong Junlin , Chen Qian , Liu Jinlai , Tang Xixiang , Peng Long
Published: November 2022

Purpose: Mitophagy reduces mitochondrial dysfunction and
accumulation of reactive oxygen species (ROS) to prevent myocardial
injury in diabetic cardiomyopathy (DCM). Accumulated studies have
confirmed that metformin enhances autophagy to maintain
mitochondrial homeostasis and scavenge ROS. However, whether and
how metformin regulates mitophagy in cardiomyocytes remain
unclear.

Methods: Diabetic cardiomyopathy was modeled in H9c2
Cardiomyocytes treated with high glucose (30 mM) . Then high
Glucose-stimulated H9C2 cells were exposed to metformin, AMPKα
inhibitor and Sirt1 inhibitor for 24 h. Mitochondrial dysfunction
and mitophagy were detected by fluorescent probe
2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA), mitochondrial
membrane potential(MMP), flow cytometry and western blot.

Resluts: We found that the protein expression of Parkin, ROS
level, and mitochondrial membrane potential showed dynamic changes
in H9C2 cells under the stimulation of high glucose. Importantly,
metformin enhanced mitophagy, scavenged ROS, improved mitochondrial
function and inhibited apoptosis in H9C2 cells treated with high
glucose. Mechanistically, metformin increased the protein
expression of p-AMPKα, Sirt1, Parkin, and LC3-II in H9C2 cells
after a high glucose challenge. Depletion of AMPKα and Sirt1
abolished the increase of protein levels of Parkin and LC3-II and
mitophagy levels induced by metformin.

Conclusion: Our data indicated that metformin improves
mitochondrial dysfunction of H9C2 cells under hyperglycemia by
activating AMPKα/Sirt1/Parkin-mediated mitophagy, which provides
novel evidence for the treatment of DCM.
Osteoid Osteoma of the Quadrilateral plate of acetabulum: A case report on an unusual cause of hip pain
Authors: Virk Jagandeep Singh , Sanga Sunil , Chawla Manju , Rana Shaleen , Bhaker Poonam
Published: November 2022

Introduction– Osteoid Osteomas are rare and extremely painful benign bone tumours. They are usually seen in children in the growing age group and young adults. The patients typically complain of bony pain during the night time and usually relieved with rest and salicylates. Osteoid Osteomas are commonly encountered in the limbs with Proximal femur/ Hip region and Tibial diaphysis being the usual locations. Pelvic locations are rare for osteoid osteoma and few cases have been published/ reported in literature.
Case Presentation – A young female with long standing hip pain was diagnosed to have osteoid osteoma in an extremely rare location in her pelvic bone. After careful evaluation of the imaging the lesion was found to be in the Quadrilateral plate/Medial wall of acetabulum. After through pre-surgical planning she underwent the Gold-standard treatment for osteoid osteoma i.e., Computed Tomography (CT)- guided Radiofrequency Ablation (RFA). Immediate post-procedure the patient reported complete relief of her symptoms and has been symptoms-free for the past 2years of follow-up.
Conclusion - A high level of clinical suspicion is warranted to keep osteoid osteoma as a differential diagnosis in a patient presenting with the relevant symptoms. They can be easily missed on Radiographs and CT is a clincher for diagnosis and unusual anatomic sites can harbour the same. A carefully planned Radiofrequency ablation under CT-guidance gives favourable and reliable results for treatment of osteoid osteomas.
Tumor cell density dependent IL-8 secretion induces the fluctuation of Tregs/CD8+ T cells infiltration in hepatocellular carcinoma: one prompt for the existence of density checkpoint
Authors: Yan Mengchao , Yao Jia , Lin Yan , Yan Jun , Xie Ye , Zhou Yongqiang , Wei Jiayun , Li Xun
Published: November 2022

Background
Tumor cell density is a basic pathological feature of solid tumors. Chemotherapy, radiotherapy and targeted therapy reduce tumor cell density, while unrestricted tumor cell proliferation promotes this feature. The impact of tumor cells on the microenvironment during the process of tumor cell density from low to high is still unclear. In this study, we focused on the response mode of key immune cell subsets to tumor cell density in hepatocellular carcinoma (HCC).
Methods
We determined the density of tumor cells and immune cells in the same area by section staining. We identified mediator through PCR, Elisa, 3D culture, co culture, flow cytometry and lentivirus intervention. The mechanism of lactate promotion was verified by lactate test kit, bioinformatic methods, western blot and the above methods. The IL-8/DAPK1/lactate/Tregs axis was verified by the mouse liver cancer model. Tumor mutation burden was calculated from maftools in R.
Results
We found that tumor cell density induced fluctuation in Tregs/CD8+ T cells ratio by secreting IL-8, and IL-8 promoted Tregs infiltration through DAPK1/PK activity/lactate axis. Based on tumor ploidy and mutation burden data, we discussed the potential significance of immune fluctuation in the homeostasis of HCC mutation burden and proposed “density checkpoint” and “entropy model” to describe this phenomenon.
Conclusion
In summary, we report the infiltration mode of Tregs/CD8+ T cells in response to tumor cell density, and the mechanism and significance of this infiltrating mode in HCC. In addition, we provide new theoretical basis for IL-8 as a therapeutic target and the selection of immunotherapy window period in HCC.
Itaconate Inhibits Corticosterone-Induced Necroptosis and Neuroinflammation via Up-regulating Menin in HT22 Cells
Authors: Liang Jin-Yu , Gao Shan , Jiang Jia-Mei , Zhang Pin , Zou Wei , Tang Xiao-Qing , Tang Yi-Yun
Published: November 2022

Corticosterone (CORT) damages hippocampus neurons as well as induces neuroinflammation. Tricarboxylic acid cycle metabolite itaconate has an anti-inflammatory role. Necroptosis acts as programmed cell death triggering neuroinflammation. The deficiency of Menin, a multifunctional scaffold protein, aggravates neuroinflammation. In this study, we explored whether itaconate inhibits CORT-induced neuroinflammation and necroptosis as well as the mediatory role of Menin in this protective effect of itaconate using an exposure of CORT to HT22 hippocampal neuronal cells. The viability of HT22 cells was examined by the Cell Counting Kit 8 (CCK-8). The morphology of HT22 cells was observed by transmission electron microscope (TEM). The expressions of necroptosis-related proteins (p-RIP1/ RIP1, p-RIP3/ RIP3, and p-MLKL/ MLKL) were evaluated by Western blotting. The contents of inflammatory factors were detected by an enzyme-linked immunosorbent assay kit. Our results showed that CORT increases the contents of pro-inflammatory factors (IL-1β, TNF-α) as well as decreases the contents of anti-inflammatory factors (IL4, IL10) in HT22 cells. We also found that CORT increases the expressions of necroptosis-related proteins (p-RIP1/ RIP1, p-RIP3/ RIP3, and p-MLKL/ MLKL) and decreases the cell viability in HT22 cells, indicating that CORT induces necroptosis to HT22 cells. Itaconate improves CORT-induced neuroinflammation and necroptosis. Furthermore, itaconate upregulates the expression of Menin in CORT-exposed HT22 cells. Importantly, silencing Menin abolishes the antagonistic effect of itaconate on CORT-induced necroptosis and neuroinflammation. In brief, these results indicated that itaconate protects HT22 cells against CORT-induced neuroinflammation and necroptosis via upregulating Menin.
Protective effect of urotensin Ⅱ receptor antagonist Urantide and exercise training on doxorubicin-induced cardiotoxicity
Authors: Sun Jing , Zhou Jiedong , Sun Shimin , Lin Hui , Zhang Hanlin , Zhong Zuoquan , Guo HangYuan , Chi Jufang
Published: November 2022

Doxorubicin (DOX) has a wide antitumor spectrum, but its adverse cardiotoxicity may lead to heart failure. Urotensin II (UⅡ) is the most potent vasoconstrictor in mammals. It plays a role by activating the UII receptor (UT), the orphan G protein-coupled receptor (GPR14), collectively referred to as the UII/UT system. In the new version of "Chinese expert consensus on cardiac rehabilitation of chronic heart failure," it is pointed out that exercise rehabilitation is the cornerstone of cardiac rehabilitation. In this study, in vitro and in vivo assessments were performed using DOX-treated H9C2 cells and rats. It was found that the UT antagonist Urantide and exercise training improved DOX-induced cardiac insufficiency, reduced DOX-induced cardiomyocyte apoptosis, improved the structural disorder of myocardial fibers, and inhibited DOX-induced myocardial fibrosis. Further studies showed that Urantide alleviated DOX-induced cardiotoxicity by downregulating the expression levels of the p38 mitogen-activated protein kinase signaling pathway.
Nomogram-based Survival and Prognosis Prediction for HCC after surgery: analysis of the multi-center patients
Authors: Luo Biyuan , Liu Xianling
Published: November 2022

Objective: Hepatocellular carcinoma(HCC),the most prevalent form of liver cancer, owns high morbidity and mortality. The radical surgery is the preference. It is of great clinical significance to predict the postoperative survival.
Methods: All clinical characteristics of 1187 patients participants from multicenter were collected. We identified several indicators significantly associated with HCC survival through logistic analysis to develop the prediction model. Further analysis revealed the independent predictive capacity of the predictive model. A nomogram comprising the predictive model was established. The decision curve analysis(DCA), receiver operating characteristic (ROC) curve analysis and Kaplan-Meier analysis confirmed the good performance of the predictive model.
Results: As a result, we identified several clinical indicators that were significantly associated with HCC survival through univariate analysis and multivariate analysis. The predictive model was consist of clinical features and tumor characteristics readily obtained after surgery. All the factors above were incorporated into the nomogram and the application of the nomogram gave good discrimination and good calibration. Calibration curves showed a favorable consistency between the predicted probabilities. ROC curve analysis showed that the nomogram had good discrimination both in the training group and validation group, respectively. Moreover, decision curve analysis has been implemented to evaluate and compare prediction nomogram. Kaplan-Meier analysis showed significant differences in prognosis among different risk groups.
Conclusion: The study provides a novel model for predicting HCC patients undergone radical surgery.
Current state and enhancement pathways of biocultural diversity: a systematic review
Authors: Zhao Ye , Zhao Yijun , Wu Chao , Yu Zhaowu
Published: November 2022

A considerable number of field cases and review studies have contributed to the remedial conservation and promotion of the world's biocultural diversity, but few reviews have attempted to systematically and retrospectively analyze the existing studies. Therefore, this study aims to explore the paradigm model and research focus of current BCD studies, to expand the biocultural diversity enhancement pathways, and to reveal the gaps and guide future directions. We used grounded theory as a tool to code 111 high-quality literature abstracts (2010–2022) screened in related fields. We found: (1) the causal conditions for BCD research in the paradigm model are primarily the negative impact of human activities, while the actions and consequences are primarily focused on specific resource conservation, conceptual and approach exploration; (2) the integration of the relevant logic chains yields two major research focuses: biocultural heritage and biocultural approaches; (3) three areas of BCD enhancement pathways are identified: Resources Protection, Academic Integration, and Governance Strategy. We suggest that the BCD research lacks the relevant evaluation system and its application in an urban context, and future efforts should be made in terms of official intervention, concept expansion, and decision-making. This review may provide the theoretical basis for the practice and promotion of BCD in a global context.
Evaluation of Sugar, HMF, pH, and Acidity Content in Some Popular Soft Drinks Sold in Turkey
Authors: Gün Ramazan , Dursun Inan
Published: November 2022

Consumption of soft drinks has been increasing last decades especially amongst children worldwide due to the taste and their relatively cheap prices. It is well-known that high consumption of sugary drinks cause negative effects on human health. It is due to the fact some governments took actions as introducing ‘sugar tax’ on beverages recommended by the World Health Organisation (WHO) aimed to reduce consumption of sugary drinks. This study aims to determine sugar, HMF, pH, and titratable acidity values of soft drinks (n = 25) including fruit (n = 10) and vegetable (n = 1) juices, sodas (n = 4), iced teas (n = 3), energy drinks (n = 3), cokes (n = 2), iced coffee (n = 1), and malt drink (n = 1). All the samples were purchased from chain supermarkets in city of Bingöl, Turkey. HPLC-RID and HPLC-DAD were used to determine sugar profile (glucose, fructose, sucrose, and maltose) and HMF content of the samples respectively. Results showed that total sugar and HMF contents of the samples were found to be ranged from 0.23 to 13.85% and from 0.65 to 27.76 mg/L respectively. In 9 out of 25 samples HMF were not detected. Furthermore, pH and acidity values of the samples were found to be varied from 1.96 to 6.34 and from 0.73 to 22.07 mEq/L, respectively. The samples were then classified based on their total sugar content (from sugar free to very high sugar) and pH erosive capacity (from minimally erosive to extremely erosive).
Colorectal cancer-derived small extracellular vesicles induce TGFβ1-mediated epithelial to mesenchymal transition of hepatocytes
Authors: Pucci Marzia , Moschetti Marta , Urzì Ornella , Loria Marco , Conigliaro Alice , Bella Maria Antonietta Di , Crescitelli Rossella , Bagge Roger Olofsson , Santos Mark F , Puglisi Caterina , Forte Stefano , Lorico Aurelio , Alessandro Riccardo , Fontana Simona
Published: November 2022

Background: The liver is the main metastatic site for patients with colorectal cancer (CRC) and represents the most frequent cause of death for patients affected by this cancer. In recent years, a number of studies have highlighted the crucial role played by small extracellular vesicles (sEVs) released by cancer cells in initiating pre-metastatic niche formation in the liver, specifically affecting the activities of non-parenchymal cells as Kupffer cells and hepatic stellate cells, while the role of the hepatocytes still remains unknown. Even if this cell component is the most conspicuous in the liver and it is responsible for several physiological activities of this complex organ, its role in liver metastasis is only partly described and related to tumour cell colonization, while no data is available about its enrolment during the pre-metastatic niche formation.
Methods: sEVs were isolated from SW480 and SW620 CRC cells through differential centrifugation, quantified using the Nanosight technology and characterized by transmission electron microscope and western blot. The presence of TGFβ1 on the surface of CRC_sEVs was assessed by western blot, super-resolution fluorescence microscope, and ELISA. Functional and epithelial to mesenchymal transition (EMT) markers were analyzed through RT PCR, ELISA assay, western blot, and confocal analysis in human healthy hepatocytes (THLE-2 cells) treated with sEVs derived from CRC cells (CRC_sEVs) at different time points.
Results: Our study shows for the first time that CRC_sEVs carrying the transforming growth factor‑β1 (TGFβ1) impair the morphological and functional properties of human healthy hepatocytes by triggering their TGFβ1/SMAD-dependent EMT. These abilities of CRC_sEVs were further confirmed by evaluating the effects elicited on hepatocytes by sEVs isolated from plasma and biopsies from CRC patients.
Conclusions: Since it is known that EMT of hepatocytes leads to the formation of a fibrotic environment, a well-known driver of metastasis, these results suggest that CRC_sEV conditioned hepatocytes could have an active and until now neglected role during the liver metastasis formation.
Modified micro-marsupialization as an alternative treatment for ranulas
Authors: Yildirim Ayhan , Hertach René , Yildirim Ali , Yildirim Vedat
Published: November 2022

The anatomical location of ranulas poses an enormous treatment challenge for the dentist. Due to a number of elementary structures, the regional complexity of the area requires a very high level of expertise on the part of the practitioner. The correction of surgical interventions in this area requires great effort. Although complete excision with removal of the sublingual gland remains the gold standard of treatment, recent literature highlights successful results through simple modification of the conventional technique of granular marsupialization. This micromarsupialization option is minimally invasive and beneficial due to the shorter procedure time, minimal discomfort, and lack of postoperative complications. The following case report highlights the successful management of a case using a modified micro-marsupialization technique in an adult.
The η-secretase-derived APP fragment ηCTF is localized in Golgi, endosomes and extracellular vesicles and contributes to Aβ production
Authors: Afram Elissa , Lauritzen Inger , Bourgeois Alexandre , Manaa Wejdane El , Duplan Eric , Chami Mounia , Valverde Audrey , Bauer Charlotte , Pardossi-Piquard Raphaëlle , Checler Frederic
Published: November 2022

The processing of the amyloid precursor protein (APP) is one of the key events contributing to Alzheimer’s disease (AD) etiology. Canonical cleavages by β- and γ-secretases lead to Aβ production which accumulate in amyloid plaques. Recently, the matrix metalloprotease MT5-MMP, referred to as η-secretase, has been identified as a novel APP cleaving enzyme producing a transmembrane fragment, ηCTF that undergoes subsequent cleavages by α- and β-secretases yielding the Aηα and Aηβ peptides, respectively. The functions and contributions of ηCTF and its related fragments to AD pathology are poorly understood. In this study, we designed a novel immunological probe referred to as ηCTF-NTer antibody that specifically interacts with the N-terminal part of ηCTF targeting ηCTF, Aηα, Aηβ but not C99, C83 and Aβ. We examined the fate and localization of ηCTF fragment in various cell models and in mice. We found that overexpressed ηCTF undergoes degradation in the proteasomal and autophagic pathways and accumulates mainly in the Golgi and in endosomes. Moreover, we observed the presence of ηCTF in small extracellular vesicles (sEVs) purified from neuroblastoma cells or from mouse brains expressing ηCTF. Importantly, the expression of ηCTF in fibroblasts devoid on APP leads to Aβ production demonstrating its contribution to the amyloidogenic pathway. Finally, we observed an ηCTF-like immunoreactivity around amyloid plaques and an age-dependent accumulation of ηCTF in the triple-transgenic mouse AD model. Thus, our study suggests that the ηCTF fragment likely contributes to AD pathology by its exosomal spreading and involvement in Aβ production
Automatic Detection of Circulating Tumor Cells and Cancer Associated Fibroblasts using Deep Learning
Authors: Shen Cheng , Rawal Siddarth , Brown Rebecca , Zhou Haowen , Agarwal Ashutosh , Watson Mark , Cote Richard , Yang Changhuei
Published: November 2022

Circulating tumor cells (CTCs) and cancer-associated fibroblasts (CAFs) from whole blood are emerging as important biomarkers that potentially aid in cancer diagnosis and prognosis. The microfilter technology provides an efficient capture platform for them but is confounded by two challenges. First, uneven microfilter surfaces makes it hard for commercial scanners to obtain images with all cells in-focus. Second, current analysis is labor-intensive with long turnaround time and user-to-user variability. Here we addressed the first challenge through developing a customized imaging system and data pre-processing algorithms. Utilizing cultured cancer and CAF cells captured by microfilters, we showed that images from our custom system are 99.3% in-focus compared to 89.9% from a top-of-the-line commercial scanner. Then we developed a deep-learning-based method to automatically identify tumor cells serving to mimic CTC (mCTC) and CAFs from the uniformly in-focus images. Our deep learning method achieved precision and recall of 94% and 96% for mCTC detection, and 90% and 83% for CAF detection, significantly better than a conventional computer vision method, whose numbers are 92% and 79% for mCTC and 57% and 54% for CAF. Our custom imaging system combined with deep learning cell identification method represents a significant advance on CTC and CAF analysis.
Modular architecture and resilience of structural covariance networks in first-episode antipsychotic-naive psychoses
Authors: Lewis Madison , Santini Tales , Theis Nicholas , Muldoon Brendan , Dash Katherine , Rubin Jonathan , Keshavan Matcheri , Prasad Konasale
Published: November 2022

Structural covariance network (SCN) studies on first-episode antipsychotic-naïve psychosis (FEAP) have examined less granular parcellations on one morphometric feature reporting lower network resilience among other findings. We examined SCNs of volumes, cortical thickness, and surface area using the Human Connectome Project atlas-based parcellation of 358 regions from 79 FEAP and 68 controls to comprehensively characterize the networks using descriptive and perturbational network neuroscience approach. Using graph theoretic methods, we examined network integration, segregation, centrality, community structure, and hub distribution across small-worldness threshold range and correlated them with psychopathology severity. We used simulated nodal “attacks” (removal of nodes and all their edges) to investigate network resilience, and calculated DeltaCon similarity scores and contrasted the removed nodes to characterize the impact of simulated attacks. Compared to controls, FEAP SCN showed higher betweenness centrality (BC) and lower degree in all three morphometric features and disintegrated with fewer attacks with no change in global efficiency. SCNs showed higher similarity score at the first point of disintegration with ≈54% top-ranked BC nodes attacked. FEAP communities consisted of fewer prefrontal, auditory and visual regions. Lower BC, and higher clustering and degree were associated with greater positive and negative symptom severity. Negative symptoms required twice the changes in these metrics. Globally sparse but locally dense network with more higher-importance nodes in FEAP could result in higher communication cost compared to controls. FEAP network disintegration with fewer attacks suggests lower resilience without altering efficiency measure. Greater network disarray underlying negative symptom severity possibly explains the therapeutic challenge.
Comparison and Multivariate Analysis of Radiofrequency and Pulsed Radiofrequency in the Treatment of Postherpetic Neuralgia
Authors: Nie Huiyong , Wang Hui , Yan Shaoyao , Bu Gang , Wang Huan
Published: November 2022

Background: Postherpetic neuralgia(PHN) is the most common complication following herpes zoster. It presents as a persistent or paroxysmal stabbing or burning pain, usually beginning≥3 months after complete healing of the skin lesions. Radiofrequency(RF) and pulsed radiofrequency(PRF), as two minimally invasive interventional techniques, have been clinically validated in the treatment of PHN with good results. However, a comparative effect between the two has not been reported so far. The aim of this cohort study to Compare and multivariate analysis of RF and PRF in the treatment of PHN.
Methods: A total of 164 PHN patients who received RF or PRF from January 2020 to October 2021 were retrospectively analyzed. There were 68 cases in PRF group and 96 cases in RF group. The pain (visual analogue scale, VAS), quality of life (36-Item Short Form Health Survey, SF-36), sleep quality (Athens insomnia scale, AIS) and postoperative complications were evaluated and compared before and after surgery at 1W, 1M, 3M,6M and 12M. The factors that may affect the treatment effect were also analyzed.
Result: The VAS and SF-36 after surgery at 1W, 1M, 3M, 6M and 12M in PRF group and RF group were significantly improved compared with those before operation (P<0.01). VAS decreased more in PRF group than in RF group at 6M after operation (P<0.05).The improvement of mental health SF-36 after surgery at 1W, 3M, 6M and 12M in PRF group was better than that in RF group (P<0.05). The physical functioning of SF-36 in PRF group was significantly higher than that in RF group at 1W, 1M, 3M, 6M and 12M after operation(P<0.01). Social functioning of SF-36 in PRF group increased more after surgery at 3M, 6M and 12M, which was better than that in RF group (P<0.05). In terms of sleep quality, postoperative PRF group and RF group were significantly improved compared with preoperative ones (P<0.01), but there was no significant difference between the two groups. Logistic regression analysis showed that age, gender, preoperative VAS and complications were the possible factors affecting the postoperative outcome.
Conclusion：Both RF and PRF have significant therapeutic effects on PHN. PRF has greater advantages than RF in reducing postoperative pain and improving quality of life. Age, gender, preoperative pain and complications are the possible related factors affecting the efficacy of RF and PRF therapy for PHN.