bluuebunny/crossref_metadata_2025 huggingface dataset:
The Role of Gut and Airway Microbiota in Pulmonary Arterial Hypertension
Authors: Huang Linlin , Zhang Hongdie , Liu Yijun , Long Yang
Published: July 2022

Pulmonary arterial hypertension (PAH) is a severe clinical condition that is characterized pathologically by perivascular inflammation and pulmonary vascular remodeling that ultimately leads to right heart failure. However, current treatments focus on controlling vasoconstriction and have little effect on pulmonary vascular remodeling. Better therapies of PAH require a better understanding of its pathogenesis. With advances in sequencing technology, researchers have begun to focus on the role of the human microbiota in disease. Recent studies have shown that the gut and airway microbiota and their metabolites play an important role in the pathogenesis of PAH. In this review, we summarize the current literature on the relationship between the gut and airway microbiota and PAH. We further discuss the key crosstalk between the gut microbiota and the lung associated with PAH, and the potential link between the gut and airway microbiota in the pathogenesis of PAH. In addition, we discuss the potential of using the microbiota as a new target for PAH therapy.
Extraversion Is Associated With Lower Brain Beta-Amyloid Deposition in Cognitively Normal Older Adults
Authors: Oh Hwamee
Published: July 2022

Emerging evidence suggests that some personality traits may link to the vulnerability to or protection for Alzheimer’s disease (AD). A causal mechanism underlying this relationship, however, remains largely unknown. Using 18F-Florbetaben positron emission tomography (PET) binding to beta-amyloid (Aβ) plaques, a pathological feature of AD, and functional magnetic resonance imaging (fMRI), we investigated pathological and functional correlates of extraversion and neuroticism in a group of healthy young and older subjects. We quantified the level of brain Aβ deposition in older individuals. Brain activity was measured in young adults using a task-switching fMRI paradigm. When we correlated personality scores of extraversion and neuroticism with these pathological and functional measures, higher extraversion, but not neuroticism, was significantly associated with lower global Aβ measures among older adults, accounting for age and sex. This association was present across widespread brain regions. Among young subjects, higher extraversion was associated with lower activity during task switching in the anterior cingulate cortex, left anterior insular cortex, left putamen, and middle frontal gyrus bilaterally, while higher neuroticism was associated with increased activity throughout the brain. The present results suggest that possibly via efficient neuronal activity, extraversion, one of the lifelong personality traits, may confer the protective mechanism against the development of Aβ pathology during aging.
A New Antiviral Regimen Against SARS-CoV-2 Based on Nanoviricide’s Biopolymer (NV-CoV-2)
Authors: Chakraborty Ashok , Diwan Anil , Barton Randall , Arora Vinod , Thakur Yogesh , Chiniga Vijetha , Tatake Jay , Pandey Rajesh , Holkar Preetam , Holkar Neelam , Pond Bethany
Published: July 2022

NV-CoV-2, a nanoviricide composed of covalently attached polyethylene glycol and alkyl pendants that are designed to bind free virion particles of multiple strains of coronaviruses in a broad-spectrum manner at multiple points. The binding interaction is like a nano-velcro-tape and may cause a lipid–lipid fusion between nanoviricide micelle and the lipid envelope of the virus. A nanoviricide can encapsulate the virus and dismantle it without any involvement of the host immune system, ultimately disabling the infectibility of the host cells. Thus, it may be expected to count a stronger and synergistic antiviral effect by combining NV-CoV-2 with other anti-coronavirus regimens like remdesivir. Furthermore, some ligands similar to the SARS-CoV S-protein are designed by molecular modeling and attached to the nanoviricide at the same site as where the cognate cellular receptor, ACE2, binds. As a result, a competitive binding inhibition may occur. A nanoviricide can encapsulate other antiviral compounds and protect them from serum-mediated degradation in vivo. This makes the antiviral compounds available for a longer period of time to interact with RNA polymerase and inhibit it. Altogether, a multipoint antiviral efficacy can be achieved with our nanoviricide, NV-CoV-2.
Somatosensory Deficits After Stroke: Insights From MRI Studies
Authors: Lv Qiuyi , Zhang Junning , Pan Yuxing , Liu Xiaodong , Miao Linqing , Peng Jing , Song Lei , Zou Yihuai , Chen Xing
Published: July 2022

Somatosensory deficits after stroke are a major health problem, which can impair patients' health status and quality of life. With the developments in human brain mapping techniques, particularly magnetic resonance imaging (MRI), many studies have applied those techniques to unravel neural substrates linked to apoplexy sequelae. Multi-parametric MRI is a vital method for the measurement of stroke and has been applied to diagnose stroke severity, predict outcome and visualize changes in activation patterns during stroke recovery. However, relatively little is known about the somatosensory deficits after stroke and their recovery. This review aims to highlight the utility and importance of MRI techniques in the field of somatosensory deficits and synthesizes corresponding articles to elucidate the mechanisms underlying the occurrence and recovery of somatosensory symptoms. Here, we start by reviewing the anatomic and functional features of the somatosensory system. And then, we provide a discussion of MRI techniques and analysis methods. Meanwhile, we present the application of those techniques and methods in clinical studies, focusing on recent research advances and the potential for clinical translation. Finally, we identify some limitations and open questions of current imaging studies that need to be addressed in future research.
Interictal Cognitive Performance in Children and Adolescents With Primary Headache: A Narrative Review
Authors: Tarantino Samuela , Proietti Checchi Martina , Papetti Laura , Ursitti Fabiana , Sforza Giorgia , Ferilli Michela Ada Noris , Moavero Romina , Monte Gabriele , Capitello Teresa Grimaldi , Vigevano Federico , Valeriani Massimiliano
Published: July 2022

Primary headache is a very common and disabling disease. The burden of pain and recurrent attacks may lead to a poor quality of life, anxiety and depression. An increased risk of low functioning and curricular performances in young patients with primary headache has been described. The mechanisms underlying the relationship between migraine and poor school achievement may be various and could be a reflection of weak cognitive skills. Data concerning the cognitive functioning in the free pain interval in pediatric age are under-investigated and results are far from conclusive. The present review article suggests that, though considered a benign disease, pediatric migraine may be associated to altered neuropsychological functioning in the interictal phase. Although children and adolescents with migraine generally have a normal intelligence, they may show a not homogeneous cognitive profile, characterized by possible difficulties in verbal skills, in particular comprehension abilities. Pediatric primary headache may present altered neuropsychological functioning involving attentional resources, processing speed and memory, particularly verbal memory. Given the impact that this disease can have on school performance and the tendency to persist from childhood to adulthood, a cognitive screening in young patients affected by primary headache is pivotal. Additional neuropsychological research using more homogenous methods is needed.
Development, Reliability, and Validity of the Preschool Learning Skills Scale: A Tool for Early Identification of Preschoolers at Risk of Learning Disorder in Mainland China
Authors: Yao Mengmeng , Wang Jing , Liu Panting , Guo Yanru , Xie Yachun , Zhang Lei , Su Nan , Li Yanwei , Yu Dongchuan , Hong Qin , Chi Xia
Published: July 2022

Background

Early identification of children at risk of learning disorders (LD) may mitigate the adverse effects of delayed intervention by guiding children to receive preventive services at an earlier age. However, there is no assessment tool for the early identification of children at risk of LD in Mainland China. Therefore, this study aimed to create a Chinese version of the Preschool Learning Skills Scale and investigate its validity and reliability.

Methods

Firstly, a pilot scale was designed based on literature review and expert review. Secondly, a pre-survey of the pilot scale was conducted. In phase 3, a formal survey was carried out to test the reliability and validity of the scale by involving 2,677 preschool children from 7 kindergartens. Data were collected using a checklist for demographic characteristics, the preschool learning skills scale, the Behavior Rating Inventory of Executive Function-Preschool Version (BRIEF-P), and Conners' Rating Scales.

Results

The final scale included 38 items under seven factors. The reliability and validity tests confirmed that the Cronbach's alpha, split-half reliability, and test–retest reliability coefficients of the scale were 0.946, 0.888, and 0.941, respectively. The Spearman correlations of factor-total score ranged from 0.685 to 0.876. The results of criterion-related validity showed a direct and significant association between the preschool learning skills scale with the BRIEF-P (r = 0.641, P < 0.001) and the cognitive problems factor of Conners' Rating Scales (r = 0.564, P < 0.001). The model had a good fit (χ2/df = 3.489, RMSEA = 0.047, RMR = 0.024, CFI = 0.912, TLI = 0.900, and IFI = 0.912). Multigroup confirmatory factor analysis supported the structural and measurement invariance on the preschool learning skills scale across gender and grade.

Conclusions

The developed preschool learning skills scale has good reliability and validity, indicating that the scale can be used to identify preschool children at risk of LD and can be recommended for use in clinical research and practice.
Case Report: Spontaneous Postpartum Quadruple Cervicocephalic Arterial Dissection With a Heterozygous COL5A1 Variant of Unknown Significance
Authors: Imamura Takeaki , Omura Takaki , Sasaki Nobuo , Arino Satoshi , Nohara Haruna , Saito Akira , Ichinose Maki , Yamaguchi Kazumasa , Kojima Naoki , Inagawa Hiroshi , Takahashi Katsutoshi , Unno Toshiyuki , Morisaki Hiroko , Ishikawa Osamu , Yoshikawa Gakushi , Okada Yasusei
Published: July 2022

Pregnancy-associated cervicocephalic arterial dissection is rare, and its pathophysiology remains poorly understood. Despite the hypothesized contribution to pathogenesis, connective tissue diseases and genetic factors are rarely identified in clinical cases. We describe a case of postpartum arterial dissection involving all four cervicocephalic arteries resulting in acute cerebral infarction. The patient underwent successful endovascular thrombectomy and angioplasty and recovered fully without sequelae. Genetic screening for connective tissue diseases identified a heterozygous missense COL5A1 variant with unknown clinical significance. Two genetically related family members later developed arterial abnormalities, and one of them tested positive for the same COL5A1 gene variant as our patient, while the other was scheduled for genetic testing. The extensive clinical presentation of our patient and the prevalence of arterial abnormalities in her family warrant further assessment of the association between the identified COL5A1 gene variant and the pathogenesis of arterial dissections.
Pain-Related Factors and Their Impact on Quality of Life in Chinese Patients With Amyotrophic Lateral Sclerosis
Authors: An Ran , Wu Yuan , Li Yi , Li Xin , Ai Shaolong , Xu Yanming , He Chengqi
Published: July 2022

Objectives

Pain is considered a common symptom in amyotrophic lateral sclerosis (ALS). However, the results of studies on pain in ALS are limited and inconsistent. The aim of our study was to comprehensively evaluate the potential factors of pain and effects on quality of life (QoL) in patients with ALS from China.

Participants and Methods

Patients were eligible if they fulfilled the criteria of probable and definitive ALS according to the revised El Escorial criteria. Pain was assessed by the Brief Pain Inventory (BPI). Disease severity, sleep quality, fatigue, anxiety, depression, and quality of life (QoL) were evaluated in ALS patients by the ALS Functional Rating Scale-revised (ALSFRS-R) and ALS severity scale (ALSSS), Pittsburgh Sleep Quality Index (PSQI), Fatigue Severity Scale (FSS), Hamilton Anxiety Rating Scale (HARS), Hamilton Depression Rating Scale (HDRS) and McGill Quality of Life Questionnaire (MQOL). Then, the clinical characteristics of ALS patients with pain were compared with those without pain. Last, associated factors of pain, as well as impact on QoL in Chinese ALS patients, were assessed.

Results

A total of 86 ALS patients were included. ALS patients with pain tended to have higher FSS scores and poorer QoL. The FSS score and ALSSS [lower extremity (LE) + upper extremity (UE)] were associated with pain in ALS patients. The ALS Functional Rating Scale-revised (ALSFRS-R), Pain Severity Index (PSI), HARS and HDRS scores were significantly associated with both the physical and psychological domains of QoL.

Conclusion

Our study was the first to comprehensively evaluate factors associated with pain in Chinese ALS patients, finding that fatigue can be a risk factor for pain and ALSSS (LE + UE) score was related with pain intensity. Additionally, we identified the adverse effects of ALSSS (LE + UE), HARS and HDRS scores on QoL in Chinese ALS patients.
Five-Year Outcomes After Endovascular Treatment for Large Vessel Occlusion Stroke
Authors: Gong Changxiong , Huang Jiacheng , Kong Weilin , Li Fengli , Liu Chang , Yang Jie , Liu Shuai , Qiu Zhongming , Lin Min , Guo Zhangbao , Yan Zhizhong , Huang Xianjun , Zhang Shuai , Ling Wentong , Zhou Peiyang , Wang Zhen , Liu Yong , Xue Dongzhang , Zhong Yaoyi , Yang Shu , Wan Yue , Fang Jiayang , Huang Wenguo , Liu Huihui , Luo Jun , Li Rongzhong , Wen Changming , Fu Xinmin , Tu Mingyi , Wang Li , Tian Xiguang , Peng Huiyuan , Wu Zhilin , Zeng Guoyong , Zi Wenjie , Yang Qingwu
Published: July 2022

Background

The long-term outcomes of acute large vessel occlusion (LVO) in anterior circulation treated by endovascular treatment (EVT) remains to be determined. The aim of this study was to assess the 5-year outcomes of patients with LVO who underwent EVT.

Methods

This study was an observational, nationwide registry of consecutive patients with acute LVO who received EVT in 28 comprehensive stroke centers in China. The primary outcome was the proportion of favorable outcome [modified Rankin Scale score (mRS) 0–2] at 5 years. Secondary outcomes included proportions of patients with excellent outcome (mRS 0–1), all-cause mortality and risk of stroke recurrence at 5 years.

Results

A total of 807 patients were included into the study and had 90-day follow-up data, 657 patients had 5-year follow-up data. At 90 days, 218 patients (27.0%) had an excellent outcome, 349 patients (43.2%) had a favorable functional outcome. 199 patients (24.7%) died. At 5 years, 190 patients (28.9%) had an excellent outcome, 261 patients (39.7%) had a favorable functional outcome, 317 patients (48.2%) died and 129 (28.2%) had stroke recurrence. Because of missing 5-year follow-up data, among available 269 patients who achieved functional independence at 90 days, 208 (77.3%) maintained favorable outcome, 19 (7.1%) had disability (mRS 3–5) and 42 (15.6%) died at 5 years. Furthermore, among available 189 patients with mRS 3–5 at 90 days, 53 (28.0%) patients achieved favorable functional outcome, 60 (31.7%) patients maintained unfavorable functional outcome and 76 (40.2%) patients died within 5 years. Multivariate analyses identified that younger age [odds ratio (OR): 0.96; 95% CI, 0.93–0.99; P = 0.009], lower mRS at 90 days (OR: 0.15; 95% CI, 0.10–0.23; P < 0.001) and absence of stroke recurrence (OR: 0.001; 95% CI, 0.000–0.006; P < 0.001) were significantly associated with favorable outcome at 5 years. Advanced age (OR: 1.06, 95% CI, 1.04–1.08; P < 0.001), higher mRS at 90 days (OR: 0.84; 95% CI, 0.73–0.98; P = 0.021) and atrial fibrillation (OR: 1.63; 95% CI, 1.02–2.60; P = 0.04) were independent factors for stroke recurrence.

Conclusion

Our results indicated that the beneficial effect of EVT in patients with acute LVO can be sustained during the course of at least 5 years. Reducing the risk of stroke recurrence by anticoagulation for atrial fibrillation may be a crucial strategy to improve long-term outcome.
The Effects of Food Taxes and Subsidies on Promoting Healthier Diets in Iranian Households
Authors: Mokari-Yamchi Amin , Omidvar Nasrin , Tahamipour Zarandi Morteza , Eini-Zinab Hassan
Published: July 2022

Background and Aim

Price, as a key driver of food purchasing, has an important role in determining the consumer demand. This study is aimed to estimate the effect of food taxes and subsidies on purchasing patterns of Iranian households (HHs).

Methods

This study was performed in two phases. In phase one, a two-round Delphi study was conducted to determine and prioritize food-related fiscal policies; and in the second phase, using the Iranian Household Income and Expenditure Survey (HIES), we estimated an almost ideal demand system (AIDS) and simulated changes in purchases, nutrient intake, and consumer welfare under six different policy scenarios: (1) 20% subsidy on vegetables, (2) 20% subsidy on fruits, (3) 30% subsidy on legumes, (4) 25% tax on sugar and sweets, (5) 30% tax on sweetened beverages, and (6) 30% tax on hydrogenated oil and animal fats.

Results

The highest calorie reduction was detected in sugar and sweets tax, which has resulted in 949.67, 971.68, and 1,148.03 kilocalories decrease in energy intake per Adult Male Equivalent (AME) in all HHs, low-income HHs, and high-income HHs, respectively. In terms of welfare changes, high-income HHs will experience a lower change in welfare (−0.81 to 0.11%) relative to their income when compared with low-income HHs (−0.88 to 0.28%) due to fiscal policies.

Conclusion

Fiscal policies in Iran can be a potential way to improve dietary choices. The findings provide essential information for decision makers for the implementation of food-related fiscal policies.
The Association of Salt Intake and Non-alcoholic Fatty Liver Disease in People With Type 2 Diabetes: A Cross-Sectional Study
Authors: Takahashi Fuyuko , Hashimoto Yoshitaka , Kaji Ayumi , Sakai Ryosuke , Kawate Yuka , Okamura Takuro , Kitagawa Noriyuki , Okada Hiroshi , Nakanishi Naoko , Majima Saori , Osaka Takafumi , Senmaru Takafumi , Ushigome Emi , Hamaguchi Masahide , Fukui Michiaki
Published: July 2022

Objectives

Non-alcoholic fatty liver disease (NAFLD), which has a close relationship with type 2 diabetes (T2D), is related to salt intake in the general population. In contrast, the relationship between salt intake and the presence of NAFLD in patients with T2D has not been clarified.

Methods

Salt intake (g/day) was assessed using urinary sodium excretion, and a high salt intake was defined as an intake greater than the median amount of 9.5 g/day. Hepatic steatosis index (HSI) ≥ 36 points was used to diagnosed NAFLD. Odds ratios of high salt intake to the presence of NAFLD were evaluated by logistic regression analysis.

Results

The frequency of NAFLD was 36.5% in 310 patients with T2D (66.7 ± 10.7 years old and 148 men). The patients with high salt intake had a higher body mass index (25.0 ± 4.0 vs. 23.4 ± 3.8 kg/m2, p < 0.001) than those with low salt intake. HSI in patients with high salt intake was higher than that in patients with low salt intake (36.2 ± 6.2 vs. 34.3 ± 5.5 points, p = 0.005). In addition, the presence of NALFD in patients with high salt intake was higher than that in patients with low salt intake (44.5% vs. 28.4%, p = 0.005). High salt intake was associated with the prevalence of NAFLD [adjusted odds ratio, 1.76 (95% confidence interval: 1.02–3.03), p = 0.043].

Conclusion

This cross-sectional study revealed that salt intake is related to the prevalence of NAFLD in patients with T2D.
Antibacterial and Biofilm Degradation Effects of Hungarian Honeys Linked With Botanical Origin, Antioxidant Capacity and Mineral Content
Authors: Farkas Ágnes , Balázs Viktória Lilla , Kõszegi Tamás , Csepregi Rita , Kerekes Erika , Horváth Györgyi , Szabó Péter , Gaál Krisztián , Kocsis Marianna
Published: July 2022

The aim of the study was to assess the impact of four unifloral honeys on the food-borne pathogens Pseudomonas aeruginosa and Staphylococcus aureus, by analyzing the honeys’ antibacterial and biofilm degradation effects, as well as their antioxidant activity and element content. Linden and milkweed honeys represented light colored honeys, while goldenrod and chestnut honeys the darker ones. The botanical origin of the honeys and the relative frequency of their pollen types were established with melissopalynological analysis. The antioxidant capacities were calculated by two single electron transfer based methods (TRC – Total Reducing Capacity and TEAC – Trolox Equivalent Antioxidant Capacity) and a hydrogen atom transfer based assay (ORAC – Oxygen Radical Absorbance). The amount of four main macro- and two microelements was quantified. The antibacterial activity was determined by minimum inhibitory concentration (MIC) and membrane degradation assays. Furthermore, the biofilm degradation power of the samples was studied as well. The light colored linden honey with the lowest TRC and TEAC, but with the highest ORAC antioxidant activity and high element content showed the best antibacterial and biofilm degradation effects. Meanwhile, the dark colored chestnut honey with significantly higher single electron transfer based antioxidant capacities, with high element content, but lower ORAC showed significantly higher MIC and lower membrane degradation activity than linden honey. In case of biofilm degradation, both honey types gave similarly high inhibitory effect. Goldenrod honey was similarly effective regarding its MIC properties like chestnut honey, but had significantly lower antioxidant potential and ability to disrupt bacterial membranes and biofilms. Milkweed honey was the honey type with the lowest bioactivity and element content. The honeys, unequivocally characterized by their antioxidant characters and element content, displayed different antibacterial and biofilm degradation effects. In addition, some honey traits were found to be good predictors of the antimicrobial potential of honeys: ORAC assay showed correlation with the MIC values of both bacteria, and strict correlation was found between the mineral content and the antibiofilm activity of the studied honeys. Our studies indicate that unifloral honeys, such as linden and chestnut honeys, are plant-derived products with great potential as antimicrobial agents in food preservation, exhibiting remarkable antibacterial activity against food-borne pathogens.
Dehydroepiandrosterone (DHEA) Sensitizes Irinotecan to Suppress Head and Neck Cancer Stem-Like Cells by Downregulation of WNT Signaling
Authors: Li Li-Jie , Li Chien-Hsiu , Chang Peter Mu-Hsin , Lai Tsung-Ching , Yong Chen-Yin , Feng Sheng-Wei , Hsiao Michael , Chang Wei-Min , Huang Chi-Ying F.
Published: July 2022

Purpose

Current treatment options for head and neck squamous cell carcinoma (HNSCC) are limited, especially for cases with cancer stem cell-induced chemoresistance and recurrence. The WNT signaling pathway contributes to maintenance of stemness via translocation of β-catenin into the nucleus, and represents a promising druggable target in HNSCC. Dehydroepiandrosterone (DHEA), a steroid hormone, has potential as an anticancer drug. However, the potential anticancer mechanisms of DHEA including inhibition of stemness, and its therapeutic applications in HNSCC remain unclear.

Methods

Firstly, SRB assay and sphere formation assay were used to examine cellular viability and cancer stem cell-like phenotype, respectively. The expressions of stemness related factors were measured by RT-qPCR and western blotting. The luciferase reporter assay was applied to evaluate transcriptional potential of stemness related pathways. The alternations of WNT signaling pathway were measured by nuclear translocation of β-catenin, RT-qPCR and western blotting. Furthermore, to investigate the effect of drugs in vivo, both HNSCC orthotopic and subcutaneous xenograft mouse models were applied.

Results

We found that DHEA reduced HNSCC cell viability, suppressed sphere formation, and inhibited the expression of cancer-stemness markers, such as BMI-1 and Nestin. Moreover, DHEA repressed the transcriptional activity of stemness-related pathways. In the WNT pathway, DHEA reduced the nuclear translocation of the active form of β-catenin and reduced the protein expression of the downstream targets, CCND1 and CD44. Furthermore, when combined with the chemotherapeutic drug, irinotecan (IRN), DHEA enhanced the sensitivity of HNSCC cells to IRN as revealed by reduced cell viability, sphere formation, expression of stemness markers, and activation of the WNT pathway. Additionally, this combination reduced in vivo tumor growth in both orthotopic and subcutaneous xenograft mouse models.

Conclusion

These findings indicate that DHEA has anti-stemness potential in HNSCC and serves as a promising anticancer agent. The combination of DHEA and IRN may provide a potential therapeutic strategy for patients with advanced HNSCC.
Imaging-Based Deep Graph Neural Networks for Survival Analysis in Early Stage Lung Cancer Using CT: A Multicenter Study
Authors: Lian Jie , Long Yonghao , Huang Fan , Ng Kei Shing , Lee Faith M. Y. , Lam David C. L. , Fang Benjamin X. L. , Dou Qi , Vardhanabhuti Varut
Published: July 2022

Background

Lung cancer is the leading cause of cancer-related mortality, and accurate prediction of patient survival can aid treatment planning and potentially improve outcomes. In this study, we proposed an automated system capable of lung segmentation and survival prediction using graph convolution neural network (GCN) with CT data in non-small cell lung cancer (NSCLC) patients.

Methods

In this retrospective study, we segmented 10 parts of the lung CT images and built individual lung graphs as inputs to train a GCN model to predict 5-year overall survival. A Cox proportional-hazard model, a set of machine learning (ML) models, a convolutional neural network based on tumor (Tumor-CNN), and the current TNM staging system were used as comparison.

Findings

A total of 1,705 patients (main cohort) and 125 patients (external validation cohort) with lung cancer (stages I and II) were included. The GCN model was significantly predictive of 5-year overall survival with an AUC of 0.732 (p < 0.0001). The model stratified patients into low- and high-risk groups, which were associated with overall survival (HR = 5.41; 95% CI:, 2.32–10.14; p < 0.0001). On external validation dataset, our GCN model achieved the AUC score of 0.678 (95% CI: 0.564–0.792; p < 0.0001).

Interpretation

The proposed GCN model outperformed all ML, Tumor-CNN, and TNM staging models. This study demonstrated the value of utilizing medical imaging graph structure data, resulting in a robust and effective model for the prediction of survival in early-stage lung cancer.
Case Report: Rare Acute Abdomen: Focal Nodular Hyperplasia With Spontaneous Rupture
Authors: Si Ying , Sun Bo , Zhao Ting , Xiao Ke , Zhao Dong-Xia , Huang Yong-Mao
Published: July 2022

Focal nodular hyperplasia (FNH) of the liver is a benign lesion characterized by hypertrophic nodules with central star-shaped fibrous scars. The etiology and pathogenesis of FNH are not completely understood. A 43-year-old man was hospitalized because of acute abdominal pain. Emergency computed tomography(CT) showed hepatic tumor rupture and bleeding. The patient’s condition improved following arteriographic embolization to stop bleeding. Laparotomy confirmed spontaneous rupture and hemorrhage of focal hyperplasia and the patient remains asymptomatic after an uneventful recovery. FNH with spontaneous rupture and bleeding is extremely rare. Currently, there is no unified management standard for FNH and most previous studies recommend observation and follow-up. We recommend consideration of surgical treatment of cases with spontaneous rupture and bleeding.
Gut Microbes in Gynecologic Cancers: Causes or Biomarkers and Therapeutic Potential
Authors: Han Mengzhen , Wang Na , Han Wenjie , Ban Meng , Sun Tao , Xu Junnan
Published: July 2022

The human intestine is home to a variety of microorganisms. In healthy populations, the intestinal flora shares a degree of similarity and stability, and they have a role in the metabolism, immunological response, and physiological function of key organs. With the rapid advent of high-throughput sequencing in recent years, several researchers have found that dysbiosis of the human gut microflora potentially cause physical problems and gynecological malignancies among postmenopausal women. Besides, dysbiosis hinders tumor treatment. Nonetheless, the importance of maintaining homeostatic gut microbiota and the effective use of probiotics in the treatment of gynecological malignancies should not be disregarded. Moreover, intestinal flora regulation and the involvement of probiotics as well as associated biologically active substances in gynecological malignancies could be an adjuvant treatment modality related to surgery and chemoradiotherapy in the future. Herein, this article aims to review the potential relationship between gut microorganisms and postmenopausal status as well as gynecologic malignancies; then the relationship between gut microbes and early screening as well as therapeutic aspects. Also, we describe the role of probiotics in the prevention, treatment, and prognosis of gynecologic malignancies.
The Prognostic Value of Adjuvant Chemotherapy in Colon Cancer With Solitary Tumor Deposit
Authors: Lin Qiangkang , Zhou Huizhen , Shi Si , Lin Jixu , Yan Wangxin
Published: July 2022

Purpose

The aim of this study is to investigate the survival benefit of adjuvant chemotherapy in patients with colon cancer with the solitary tumor deposit (TD).

Methods

The primary study outcomes used in this study were colon cancer–specific survival (CSS) and overall survival (OS). The differences of the distribution of categorical variables in patients with colon cancer with the solitary TD according to adjuvant chemotherapy administration were tested using the Pearson’s chi-square test. The Kaplan–Meier method was utilized to evaluate CSS and OS. Hazard ratio (HR) and 95% confidence interval (CI) were calculated on the basis of Cox regression models to assess the prognostic value of different demographic and clinicopathological characteristics.

Results

A total of 877 patients with TanyN1cM0 colon cancer with solitary TD were identified in our analysis. It was found that OS (75.4% vs. 42.8% for 5-year OS rate, p < 0.001) and CSS (82.9% vs. 69.3% for 5-year CSS rate, p < 0.001) of patients with colon cancer with adjuvant chemotherapy administration were significantly better than those without adjuvant chemotherapy administration. Multivariate Cox survival analyses revealed that the overall and colon cancer–specific mortality risks of patients with adjuvant chemotherapy administration were decreased by 64.4% (HR = 0.356, 95% CI = 0.265–0.479, p < 0.001) and 57.4% (HR = 0.426, 95% CI = 0.286–0.634, p < 0.001) compared with those without adjuvant chemotherapy administration, respectively.

Conclusions

Adjuvant chemotherapy administration could significantly improve OS and CSS in patients with colon cancer with the solitary TD. This is the first study to investigate and demonstrate the survival benefit of adjuvant chemotherapy in patients with colon cancer with the solitary TD.
Changes in Cancer Mortality by Race and Ethnicity Following the Implementation of the Affordable Care Act in California
Authors: Martinez Maria Elena , Gomez Scarlett L. , Canchola Alison J. , Oh Debora L. , Murphy James D. , Mehtsun Winta , Yabroff K. Robin , Banegas Matthew P.
Published: July 2022

Although Affordable Care Act (ACA) implementation has improved cancer outcomes, less is known about how much the improvement applies to different racial and ethnic populations. We examined changes in health insurance coverage and cancer-specific mortality rates by race/ethnicity pre- and post-ACA. We identified newly diagnosed breast (n = 117,738), colorectal (n = 38,334), and cervical cancer (n = 11,109) patients < 65 years in California 2007-2017. Hazard rate ratios (HRR) and 95% confidence intervals (CI) were calculated using multivariable Cox regression to estimate risk of cancer-specific death pre- (2007-2010) and post-ACA (2014-2017) and by race/ethnicity [American Indian/Alaska Natives (AIAN); Asian American; Hispanic; Native Hawaiian or Pacific Islander (NHPI); non-Hispanic Black (NHB); non-Hispanic white (NHW)]. Cancer-specific mortality from colorectal cancer was lower post-ACA among Hispanic (HRR = 0.82, 95% CI = 0.74 to 0.92), NHB (HRR = 0.69, 95% CI = 0.58 to 0.82), and NHW (HRR = 0.90; 95% CI = 0.84 to 0.97) but not Asian American (HRR = 0.95, 95% CI = 0.82 to 1.10) patients. We observed a lower risk of death from cervical cancer post-ACA among NHB women (HRR = 0.68, 95% CI = 0.47 to 0.99). No statistically significant differences in breast cancer-specific mortality were observed for any racial or ethnic group. Cancer-specific mortality decreased following ACA implementation for colorectal and cervical cancers for some racial and ethnic groups in California, suggesting Medicaid expansion is associated with reductions in health inequity.
Telomere Attrition With Concomitant hTERT Overexpression Involved in the Progression of Gastric Cancer May Have Prognostic and Clinical Implications in High-Risk Population Group From North India
Authors: Mushtaq Ifra , Bhat Gh Rasool , Rah Bilal , Besina Syed , Zahoor Sheikh , Wani Muneer A. , Shah Mubashir A. , Bashir Sadaf , Farooq Muzamil , Rather Rafiq A. , Afroze Dil
Published: July 2022

Genetic instabilities exacerbated by the dysfunction of telomeres can lead to the development of cancer. Nearly 90% of all human malignancies are linked with telomere dysregulation and overexpression of telomerase, an enzyme that catalyzes the synthesis of telomeric DNA repeats at the ends of chromosomes. The burden of gastric cancer continues to inflict a deterring impact on the global health scenario, accounting for over one million new cases in 2020. The disease is asymptomatic in its early stages of progression, which is attributed to the poor prognosis and overall surge in mortality rate worldwide. Exploiting telomere physiology can provide extensive mechanistic insight into telomere-associated gastric cancer progression and its use as a target in a variety of therapeutic interventions. In this study, we aimed to evaluate the clinical implications of c-Myc, human telomerase reverse transcriptase (hTERT) expression, and telomere length in patients with gastric cancer. A total of 57 gastric cancer cases and adjacent controls were included in the study. RT-PCR and immunohistochemistry were used to assess the expression levels of c-Myc and hTERT. The relative telomere length was measured by MMQPCR using the Cawthon method. Our results indicated that the shorter telomere and increased hTERT expression were associated with gastric cancer progression. The study also highlighted the role of short telomeres and increased expression of hTERT in gastric cancer progression and its association with various etiological risk factors, transcriptional activators, and overall survival among the ethnic Kashmiri population of North India.
Predicting Adverse Radiation Effects in Brain Tumors After Stereotactic Radiotherapy With Deep Learning and Handcrafted Radiomics
Authors: Keek Simon A. , Beuque Manon , Primakov Sergey , Woodruff Henry C. , Chatterjee Avishek , van Timmeren Janita E. , Vallières Martin , Hendriks Lizza E. L. , Kraft Johannes , Andratschke Nicolaus , Braunstein Steve E. , Morin Olivier , Lambin Philippe
Published: July 2022

Introduction

There is a cumulative risk of 20–40% of developing brain metastases (BM) in solid cancers. Stereotactic radiotherapy (SRT) enables the application of high focal doses of radiation to a volume and is often used for BM treatment. However, SRT can cause adverse radiation effects (ARE), such as radiation necrosis, which sometimes cause irreversible damage to the brain. It is therefore of clinical interest to identify patients at a high risk of developing ARE. We hypothesized that models trained with radiomics features, deep learning (DL) features, and patient characteristics or their combination can predict ARE risk in patients with BM before SRT.

Methods

Gadolinium-enhanced T1-weighted MRIs and characteristics from patients treated with SRT for BM were collected for a training and testing cohort (N = 1,404) and a validation cohort (N = 237) from a separate institute. From each lesion in the training set, radiomics features were extracted and used to train an extreme gradient boosting (XGBoost) model. A DL model was trained on the same cohort to make a separate prediction and to extract the last layer of features. Different models using XGBoost were built using only radiomics features, DL features, and patient characteristics or a combination of them. Evaluation was performed using the area under the curve (AUC) of the receiver operating characteristic curve on the external dataset. Predictions for individual lesions and per patient developing ARE were investigated.

Results

The best-performing XGBoost model on a lesion level was trained on a combination of radiomics features and DL features (AUC of 0.71 and recall of 0.80). On a patient level, a combination of radiomics features, DL features, and patient characteristics obtained the best performance (AUC of 0.72 and recall of 0.84). The DL model achieved an AUC of 0.64 and recall of 0.85 per lesion and an AUC of 0.70 and recall of 0.60 per patient.

Conclusion

Machine learning models built on radiomics features and DL features extracted from BM combined with patient characteristics show potential to predict ARE at the patient and lesion levels. These models could be used in clinical decision making, informing patients on their risk of ARE and allowing physicians to opt for different therapies.
BNIP3 Upregulation Characterizes Cancer Cell Subpopulation With Increased Fitness and Proliferation
Authors: Zhu Yanyan , Chen Bowang , Yan Junya , Zhao Wendi , Dou Pengli , Sun Na , Wang Yaokai , Huang Xiaoyun
Published: July 2022

BNIP3 is a BH3-only protein with both pro-apoptotic and pro-survival roles depending on the cellular context. It remains unclear how BNIP3 RNA level dictates cell fate decisions of cancer cells. Here, we undertook a quantitative analysis of BNIP3 expression and functions in single-cell datasets of various epithelial malignancies. Our results demonstrated that BNIP3 upregulation characterizes cancer cell subpopulations with increased fitness and proliferation. We further validated the upregulation of BNIP3 in liver cancer 3D organoid cultures compared with 2D culture. Taken together, the combination of in silico perturbations using public single-cell datasets and experimental cancer modeling using organoids ushered in a new approach to address cancer heterogeneity.
Flavokawain A Reduces Tumor-Initiating Properties and Stemness of Prostate Cancer
Authors: Song Liankun , Mino Merci , Yamak Jana , Nguyen Vyvyan , Lopez Derron , Pham Victor , Fazelpour Ali , Le Vinh , Fu Dongjun , Tippin Matthew , Uchio Edward , Zi Xiaolin
Published: July 2022

We have previously demonstrated the in vivo chemopreventive efficacy of flavokawain A (FKA), a novel chalcone from the kava plant, in prostate carcinogenesis models. However, the mechanisms of the anticarcinogenic effects of FKA remain largely unknown. We evaluated the effect of FKA on prostate tumor spheroid formation by prostate cancer stem cells, which were sorted out from CD44+/CD133+ prostate cancer cells 22Rv1 and DU145. FKA treatment significantly decreased both the size and numbers of the tumor spheroids over different generations of spheroid passages. In addition, the dietary feeding of FKA-formulated food to Nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice bearing CD44+/CD133+ 22Rv1 xenograft tumors resulted in a significant reduction of tumor growth compared to those fed with vehicle control food–fed mice. Furthermore, the expression of stem cell markers, such as Nanog, Oct4, and CD44, were markedly downregulated in both tumor spheroids and tumor tissues. We also observed that FKA inhibits Ubc12 neddylation, c-Myc, and keratin-8 expression in both CD44+/CD133+ prostate tumor spheroids and xenograft tumors. Our results suggest that FKA can reduce the tumor-initiating properties and stemness of prostate cancer, which provides a new mechanism for the chemoprevention efficacy of FKA.
Colon Sparing Endoscopic Full-Thickness Resection for Advanced Colorectal Lesions: Is It Time for Global Adoption?
Authors: Wu Zhong-Wei , Ding Chao-Hui , Song Yao-Dong , Cui Zong-Chao , Bi Xiu-Qian , Cheng Bo
Published: July 2022

The majority of colon lesions are <10 mm in size and are easily resected by endoscopists with appropriate basic training. Lesions ≥10 mm in size are difficult to remove technically and are associated with higher rates of incomplete resection. Currently, the main endoscopic approaches include endoscopic mucosal resection (EMR) for lesions without submucosal invasion, and endoscopic submucosal dissection (ESD) for relatively larger lesions involving the superficial submucosal layer. Both of these approaches have limitations, EMR cannot reliably ensure complete resection for larger tumors and recurrence is a key limitation. ESD reliably provides complete resection and an accurate pathological diagnosis but is associated with risk such as perforation or bleeding. In addition, both EMR and ESD may be ineffective in treating subepithelial lesions that extend beyond the submucosa. Endoscopic full-thickness resection (EFTR) is an emerging innovative endoscopic therapy which was developed to overcome the limitations of EMR and ESD. Advantages include enabling a transmural resection, complete resection of complex colorectal lesions involving the mucosa to the muscularis propria. Recent studies comparing EFTR with current resection techniques and radical surgery for relatively complicated and larger lesion have provided promising results. If the current trajectory of research and development is maintained, EFTR will likely to become a strong contender as an alternative standard of care for advanced colonic lesions. In the current study we aimed to address this need, and highlighted the areas of future research, while stressing the need for multinational collaboration provide the steppingstone(s) needed to bring EFTR to the mainstream.
Case Report: Early-Onset Charcot-Marie-Tooth 2N With Reversible White Matter Lesions Repeatedly Mimicked Stroke or Encephalitis
Authors: Huang Huasheng , Zhang Yu , Yang Mingxiu , Lian Baorong , Guo Rui , Cao Liming
Published: July 2022

Introduction

Charcot-Marie-Tooth (CMT) disease is a rare group of peripheral neuropathies with high clinical and genetic heterogeneity. CMT type 2N (CMT 2N) is a rare subtype of CMT with few clinical reports. The clinical presentation mimics that of other diseases, frequently leading to misdiagnoses. We present a case of CMT 2N with reversible white matter lesions (WMLs), which repeatedly mimicked stroke or encephalitis. We include a literature review to the improve management of this disease.

Case Description

An 8-year-old boy was admitted to the hospital with slurred speech and limb weakness that had persisted for 1 day. Physical examination revealed lethargy, dysarthria, and a positive bilateral Babinski sign. Cerebrospinal fluid (CSF) analysis showed no abnormalities. Brain magnetic resonance imaging (MRI) revealed symmetrical abnormal signal areas in the paraventricular white matter and corpus callosum. The patient was suspected of having viral encephalitis and recovered rapidly after treatment.

He was hospitalized 3 years later for limb weakness, barylalia, and facial paralysis persisting for 1 day. MRI showed an abnormal signal in the bilateral corona radiata. He was suspected of having a stroke or encephalitis. He was completely recovered after treatment.

After a second 3-year span, he was admitted for another stroke-like episode. Physical examination revealed facial-lingual hemiparesis, mild atrophy of the left thenar muscle, decreased muscle strength in the extremities, and disappearance of the tendon reflex. MRI revealed more pronounced abnormal signals in the bilateral centrum semiovale and corpus callosum. Antibodies against autoimmune encephalitis were negative. A nerve conduction velocity (NCV) study showed motor and sensory four-limb nerve demyelination with axonal damage, most notably at the distal end. His symptoms were resolved after active treatment. A follow-up MRI showed the complete disappearance of the abnormal white matter signal. Whole exon sequencing showed a heterozygous mutation [c.2093C > T(p.Ser698Phe)] in the alanyl-tRNA synthetase 1 gene (AARS1). His mutation, clinical features, and electrophysiological testing led to a diagnosis of CMT 2N.

Discussion

Early-Onset CMT 2N with reversible WMLs can often mimic stroke or encephalopathy. Affected individuals may show an atypical posterior reversible encephalopathy syndrome (PRES) on MRI. Careful family history assessment, physical examination, nerve conduction studies, MRIs, and genetic testing are essential for early diagnosis. Further studies are required to confirm these findings.
Fungal Mushrooms: A Natural Compound With Therapeutic Applications
Authors: Chugh Rishi Man , Mittal Pooja , MP Namratha , Arora Tanu , Bhattacharya Tanima , Chopra Hitesh , Cavalu Simona , Gautam Rupesh K.
Published: July 2022

Fungi are extremely diverse in terms of morphology, ecology, metabolism, and phylogeny. Approximately, 130 medicinal activities like antitumor, immunomodulation, antioxidant, radical scavenging, cardioprotective and antiviral actions are assumed to be produced by the various varieties of medicinal mushrooms. The polysaccharides, present in mushrooms like β-glucans, micronutrients, antioxidants like glycoproteins, triterpenoids, flavonoids, and ergosterols can help establish natural resistance against infections and toxins.. Clinical trials have been performed on mushrooms like Agaricus blazei Murrill Kyowa for their anticancer effect, A. blazei Murrill for its antihypertensive and cardioprotective effects, and some other mushrooms had also been evaluated for their neurological effects. The human evaluation dose studies had been also performed and the toxicity dose was evaluated from the literature for number of mushrooms. All the mushrooms were found to be safe at a dose of 2000 mg/kg but some with mild side effects. The safety and therapeutic effectiveness of the fungal mushrooms had shifted the interest of biotechnologists toward fungal nanobiotechnology as the drug delivery system due to the vast advantages of nanotechnology systems. In complement to the vital nutritional significance of medicinal mushrooms, numerous species have been identified as sources of bioactive chemicals. Moreover, there are unanswered queries regarding its safety, efficacy, critical issues that affect the future mushroom medicine development, that could jeopardize its usage in the twenty-first century.