bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimal use of SGLT2 inhibitors in diabetic kidney transplant recipients
Authors: Pham Phuong-Thu T. , Pham Phuong-Chi T.
Published: November 2022

Sodium-glucose cotransporter 2 inhibitor (SGLT2i), a glucosuric agent initially approved for use as an antidiabetic agent, was unexpectedly found to confer cardio-and reno-protective effects in individuals with or without type 2 diabetes mellitus. Despite mounting evidence suggesting that SGLT2i provides cardio- and reno-protective benefits in both diabetic and non-diabetic and in chronic kidney disease (CKD) patients in the general population, reservations for its use in the transplant setting persist due to concerns for increased risk of genital mycotic and urinary tract infections. A comprehensive review of the literature on the efficacy and safety of SGLT2i use in diabetic kidney transplant recipients is herein presented followed by authors’ opinion on its optimal use in this patient population.
Higher comorbidity burden is associated with lower self-reported quality of life after stroke
Authors: Heinze Marlene , Lebherz Lisa , Rimmele David Leander , Frese Marc , Jensen Märit , Barow Ewgenia , Lettow Iris , Kriston Levente , Gerloff Christian , Härter Martin , Thomalla Götz
Published: November 2022

Introduction

This study assesses the association of comorbidity burden and polypharmacy with self-reported quality of life after stroke.

Patients and methods

We performed a post-hoc analysis of a prospective, single-center, observational study of outcome evaluation by patient-reported outcome measures in stroke clinical practice. Consecutive patients with acute ischemic stroke (AIS) were enrolled and self-reported health–related quality of life (HrQoL) was assessed 90 days after acute stroke using the Patient-reported Outcomes Measurement Information System 10-Question Short-Form (PROMIS-10). Comorbidities at baseline were assessed by the Charlson Comorbidity Index (CCI). Polypharmacy was defined as medication intake of ≥5 at baseline. We used linear regression analysis to study the association of CCI, polypharmacy and other clinical covariates with HrQoL after stroke.

Results

Of 781 patients (median age 76 years, 48.4% female) enrolled, 30.2% had a CCI Score ≥2, and 31.5% presented with polypharmacy. At follow up, 71 (9.1%) had died. In 409 (52.4%) reached for outcome evaluation, Global Physical Health T-Score was 43.8 ± 10 and Global Mental Health T-Score was 43.5 ± 8.76, indicating lower HrQoL than the average population. A CCI Score ≥2, higher NIHSS Score, female sex, dependency on others for dressing, toileting and mobility before index stroke, atrial fibrillation and hypertension were independent predictors of worse physical and mental health outcomes, while polypharmacy was not.

Conclusion

In patients with AIS, high comorbidity burden and polypharmacy are frequent. Comorbidity burden at admission is independently associated with worse self-reported physical and mental health three months after stroke.
Multi-omics integration reveals a six-malignant cell maker gene signature for predicting prognosis in high-risk neuroblastoma
Authors: Yan Zijun , Liu Qiming , Cao Ziyang , Wang Jinxia , Zhang Hongyang , Liu Jiangbin , Zou Lin
Published: November 2022

Background

Neuroblastoma is the most common extracranial solid tumor of childhood, arising from the sympathetic nervous system. High-risk neuroblastoma (HRNB) remains a major therapeutic challenge with low survival rates despite the intensification of therapy. This study aimed to develop a malignant-cell marker gene signature (MMGS) that might serve as a prognostic indicator in HRNB patients.

Methods

Multi-omics datasets, including mRNA expression (single-cell and bulk), DNA methylation, and clinical information of HRNB patients, were used to identify prognostic malignant cell marker genes. MMGS was established by univariate Cox analysis, LASSO, and stepwise multivariable Cox regression analysis. Kaplan–Meier (KM) curve and time-dependent receiver operating characteristic curve (tROC) were used to evaluate the prognostic value and performance of MMGS, respectively. MMGS further verified its reliability and accuracy in the independent validation set. Finally, the characteristics of functional enrichment, tumor immune features, and inflammatory activity between different MMGS risk groups were also investigated.

Results

We constructed a prognostic model consisting of six malignant cell maker genes (MAPT, C1QTNF4, MEG3, NPW, RAMP1, and CDT1), which stratified patients into ultra-high-risk (UHR) and common-high-risk (CHR) group. Patients in the UHR group had significantly worse overall survival (OS) than those in the CHR group. MMGS was verified as an independent predictor for the OS of HRNB patients. The area under the curve (AUC) values of MMGS at 1-, 3-, and 5-year were 0.78, 0.693, and 0.618, respectively. Notably, functional enrichment, tumor immune features, and inflammatory activity analyses preliminarily indicated that the poor prognosis in the UHR group might result from the dysregulation of the metabolic process and immunosuppressive microenvironment.

Conclusion

This study established a novel six-malignant cell maker gene prognostic model that can be used to predict the prognosis of HRNB patients, which may provide new insight for the treatment and personalized monitoring of HRNB patients.
Ataxia with oculomotor apraxia type 2 caused by a novel homozygous mutation in SETX gene, and literature review
Authors: Chen Shuaishuai , Du Juping , Jiang Huihua , Zhao Weibo , Wang Na , Ying Anna , Li Jun , Chen Shiyong , Shen Bo , Zhou Yuanlin
Published: November 2022

Objectives

Autosomal recessive inherited ataxia with oculomotor apraxia type 2 (AOA2), caused by SETX gene mutations, is characterized by early-onset, progressive cerebellar ataxia, peripheral neuropathy, oculomotor apraxia and elevated serum α-fetoprotein (AFP). This study aimed to expand and summarize the clinical and genetic characteristics of SETX variants related to AOA2.

Methods

The biochemical parameters, electromyogram and radiological findings of the patient were evaluated. Whole-exome sequencing (WES) was performed on the patient using next-generation sequencing (NGS), the variants were confirmed by Sanger sequencing and the pathogenicity of the variants was classified according to the American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines. We reviewed 57 studies of AOA2 patients with SETX mutations and collected clinical and genetic information.

Results

The patient was a 40-year-old Chinese woman who primarily presented with numbness and weakness of the lower limbs in her teenage years. She had elevated AFP, increased serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) and decreased anti-Müllerian hormone (AMH) levels. We identified a novel homozygous missense mutation of the SETX gene, c.7118 C>T (p. Thr2373Ile), in the patient via Whole-exome and Sanger sequencing. The variant was located in the DNA/RNA helicase domain and is highly conserved. The protein prediction analysis verified the SETX variant as a damaging alteration and ACMG/AMP guidelines classified it as likely pathogenic. Through a literature review, we identified 229 AOA2 cases with SETX variants, and among the variants, 156 SETX variants were exonic. We found that 107 (46.7%) patients were European, 50 (21.8%) were African and 48 (21.0%) were Asian. Among the Asian patients, five from two families were Mainland Chinese. The main clinical features were cerebellar ataxia (100%), peripheral neuropathy (94.6%), cerebellar atrophy (95.3%) and elevated AFP concentration (92.0%). Most reported SETX mutations in AOA2 patients were missense, frameshift and nonsense mutations.

Conclusion

We discovered a novel homozygous variant of the SETX gene as a cause of AOA2 in the current patient and expanded the genotypic spectrum of AOA2. Moreover, the clinical features of AOA2 and genetic findings in SETX were assessed in reported cohorts and are summarized in the present study.
Naringenin, a citrus flavanone, enhances browning and brown adipogenesis: Role of peroxisome proliferator-activated receptor gamma
Authors: Bae Jiyoung , Yang Yang , Xu Xinyun , Flaherty Jamie , Overby Haley , Hildreth Kelsey , Chen Jiangang , Wang Shu , Zhao Ling
Published: November 2022

Identifying functional brown adipose tissue (BAT) has provided new hope for obesity treatment and prevention. Functional BAT includes classical BAT and brown-like adipose tissue converted from white adipose tissue. By promoting thermogenesis (i.e., heat production) via uncoupling protein 1 (UCP1), functional BAT can increase energy expenditure and aid obesity treatment and prevention. Naringenin (NAR) is a flavanone primarily found in citrus fruits. NAR has been reported to decrease body weight, increase energy expenditure in treated mice, and promote browning in human adipocytes. Here, we examined the effects of NAR on 3T3-L1 adipocytes’ browning and β-adrenergic agonist isoproterenol (ISO)-stimulated thermogenic activation and classical murine brown adipogenesis. In addition, we demonstrated the signaling pathways and involvement of peroxisome proliferator-activated receptor gamma (PPARγ) in the process. We found that NAR did not increase Ucp1 mRNA expression at the basal (i.e., non-ISO stimulated) condition. Instead, it enhanced Ucp1 and Pgc-1α up-regulation and thermogenesis under ISO-stimulated conditions in 3T3-L1 adipocytes. NAR promoted protein kinase A (PKA) activation and phosphorylation of p38 MAPK downstream of ISO stimulation and activated PPARγ. Pharmacological inhibition of either PKA or p38 and PPARγ knockdown attenuated Ucp1 up-regulation by NAR. Moreover, NAR promoted brown adipogenesis by increasing lipid accumulation, brown marker expression, and thermogenesis in murine brown adipocytes, which was also attenuated by PPARγ knockdown. Together, our results suggest that NAR may promote the development of functional BAT in part through PPARγ activation. NAR’s role in combating human obesity warrants further investigation.
Vitamin E concentration in breast milk in different periods of lactation: Meta-analysis
Authors: Xi Yuandi , Wang Xianyun , Liu Kuo , Zhang Huanmei , Ren Xiangnan , Zhao Ai , Yang Yuexin , Lai Jianqiang , Xiao Rong
Published: November 2022

Objective

This study systematized information about vitamin E concentration in healthy breast milk during different stages of lactation in order to support the strategies of protecting postpartum women and infants.

Methods

Studies published before April 30th, 2021, which detected vitamin E concentration in breast milk of healthy women by High Performance Liquid Chromatography (HPLC) or Ultra High Performance Liquid Chromatographic (UHPLC), were evaluated. The databases of CNKI (Chinese), WanFang Data (Chinese), VIP (Chinese), PubMed, Cochrane Library, Web of Science and Embase were searched. The random effect models were used to conduct meta-analysis by the statistical software package Stata 14.0.

Results

In all 4,791 searched publications, 53 with full text were selected, which included 46 descriptive studies, 1 case-control study, 1 non-randomized controlled trial, and 5 randomized controlled trials. The pooled mean of vitamin E concentration was 10.57 mg α-TE/L (95%CI 8.94–12.20) in colostrum, 4.03 mg α-TE/L (95%CI 3.29–4.77) in transitional milk and 3.29 mg α-TE/L (95%CI 2.95–3.64) in mature milk. Subgroup analysis showed that vitamin E concentration of colostrum in Asian countries was lower than that in Western countries in colostrum and transitional milk.

Conclusions

Vitamin E concentration in breast milk decreased during lactation until the mature milk was produced. The vitamin E concentration of colostrum in Asian countries was evidently lower than that in Western countries. The vitamin E concentration in mature milk is similar in different regions. The concentration of vitamin E in breast milk started to be stable from about 2 to 3 weeks postpartum until 4 or 6 months postpartum, but it needs additional evidence to support.
Promotion effect of the blend containing 2'-FL, OPN and DHA on oligodendrocyte progenitor cells myelination in vitro
Authors: Xie Qinggang , Zhang Youbo , Zhang Jinlan , Cui Dongying , Zhou Qile , Guo Mingruo
Published: November 2022

During early neurodevelopment of infant, myelination plays an essential role in brain connectivity and emergence of behavioral and cognitive function. Early life nutrition is an important factor to shape myelination and consequently cognitive appearance. To analyze the effects of additive nutrients, including 2'-fucosyllactose (2'-FL), osteopontin (OPN), docosahexaenoic acid (DHA), on neurocognitive function and brain structure, the current study evaluated the effects of different composition of breast milk nutrients on oligodendrocyte progenitor cells (OPCs) myelination with a neural primary cell model in vitro. The study showed that the three nutrients promoted the proliferation, maturation and differentiation of OPCs into mature oligodendrocytes (OLs) in each phage of the cell growth, and the effect of the nutrients blend is obviously stronger than that of the nutrient treatment alone, showing a synergistic effect in promotion of OPCs. The results of this experiment clarified the effects of 2′-FL OPN and DHA to promote myelination development of neural cells, and laid an experimental basis for further optimization of infant formula.
Impact of textual warnings on emotional brain responses to ultra-processed food products
Authors: Fernandes Thayane Ferreira da Costa , Ferreira Naiane Beatriz , Campagnoli Rafaela Ramos , Gomes Fabio da Silva , Braga Filipe , David Isabel Antunes , Lobo Isabela
Published: November 2022

Background and objectives

Ultra-processed food products (UPF) have been associated with numerous non-communicable diseases. Despite this, the addictive nature of UPF, and the aggressive marketing strategies used to promote them, has created a strong emotional connection between UPF and consumers, and supports their increasing UPF global consumption. In view of the emotional link that consumers often have with UPF, modulating emotional reactions to UPF (by using strategies such as textual warnings) is important in changing consumers’ behavior. Since emotions are better understood by assessing individuals’ implicit reactions, we conducted an electroencephalographic study applying the event-related potential technique to investigate whether textual warnings were able to modulate the brain responses to UPF stimuli.

Materials and methods

Twenty-six participants (19 women) viewed pictures of UPF preceded by a warning sentence about the health risks of consuming UPF or a control sentence while the electroencephalogram was recorded. In addition, the participants rated the picture in respect of pleasantness, arousal, and intention to consume. As emotions are associated with motivational circuits in the brain, we focused on a well-known event-related potential brain marker of the motivational relevance associated with emotional stimuli, namely late positive potential (LPP).

Results

The late positive potential amplitude was larger for pictures depicting UPF under the warning condition compared to the control condition, a result that was accompanied by lower pleasantness ratings during the warning condition (compared to the control).

Conclusion

Textual warnings about the negative health consequences of consuming UPF changed the emotional responses toward UPF, possibly increasing the motivation to avoid UPF. These results shed new light on the impact of textual warnings on UPF-evoked emotions.
Traditional Chinese medicine Tongxie Yaofang treating irritable bowel syndrome with diarrhea and type 2 diabetes mellitus in rats with liver-depression and spleen-deficiency: A preliminary study
Authors: Xu Weidong , Zhang Zhiyi , Lu Ye , Li Mengxi , Li Jiayao , Tao Wenhua
Published: November 2022

Tongxie Yaofang (TXYF), a Traditional Chinese Medicine (TCM) with four components as follows: Rhizoma Atractylodis Macrocephalae (baizhu), Radix Paeoniae Alba (baishao), Pericarpium Citri Reticulatae (chenpi) and Radix Saposhnikovia Divaricata (fangfeng), benefits irritable bowel syndrome (IBS). Nonetheless, proofs of this formula ameliorating D-IBS and T2DM are required. This research aimed at investigating the efficacy of TXYF in treating inflammation in rats with D-IBS and T2DM using animal models. In this study, gavage with high-fat diet, fasciculation, and senna was given to develop rat models with target diseases. To determine intestinal inflammations, major inflammatory factors, and intestinal permeability proteins, H&E staining, ELISA, and immunohistochemistry methods were employed, respectively. This study also utilized Western blot to discover potential inflammatory targets. Results of this research illustrates that TXYF treatment reduced the level of TNF-α, IL-1β, and IL-6, and raised the IL-10 concentration in liver-depressed spleende ficient rats with D-IBS and T2DM, indicating controlled inflammatory reactions. Staining analysis also showed improved disease states of animal models. Furthermore, efficient rebounds of claudin-1, an intestinal permeability-associated protein, were detected. Moreover, TXYF may treat D-IBS and T2DM in rats via the rage pathway.
Association between modes of delivery and postpartum dietary patterns: A cross-sectional study in Northwest China
Authors: Zhao Lingxi , Wang Lianlian , Wang Wenling , Shi Zumin , Zhu Yuzhao , Li Shengping , Wang Tiankun , Su Yu , Li Zhourong , Wen Yaqi , Zhang Laixi , Xu Qi , Sharma Manoj , Zhao Yong
Published: November 2022

Objective

Puerperae’ dietary patterns (DPs) during the puerperium may be influenced by the mode of delivery, but population studies on this topic are scarce. This study aims to explore the relationship between DPs and different modes of delivery among puerperae.

Methods

A cross-sectional study was conducted on 3,345 parturients in Lanzhou, China. The postpartum food intake was measured by a food frequency questionnaire (FFQ). Factor analysis was used to determine the DPs. Multiple linear regression was employed to examine the association between the mode of delivery and DP.

Results

In this study, two DPs, i.e., traditional and modern DPs, were identified. Traditional DP was characterized by high energy-adjusted intake of tubers, coarse cereals, rice, whole grains, fishery products, and eggs. Modern DP included a high intake of coffee, non-sugary drinks, wine, tea, and fishery products. Compared with participants with vaginal delivery (reference category), cesarean section had an inverse association with modern DP (β: −0.11, 95% CI: −0.36, −0.09). A significant interaction was found between education level, monthly household income, alcohol drinking, and modes of delivery. The inverse association between cesarean section and modern DP or the intake of coffee was significant among puerperae with higher or lower monthly household income. However, the inverse association between cesarean section and traditional DP was only found among puerperae with higher monthly household income. Moreover, among the participants with high education, cesarean section was positively associated with intake of vegetables.

Conclusion

Cesarean puerperae with higher levels of education and those with lower and higher monthly household income had less unhealthy foods intake than those who had vaginal delivery. They need to be accounted for in educational programs and interventions focused on healthy diet recommendations in puerperium.
Radiomics nomogram based on multi-parametric magnetic resonance imaging for predicting early recurrence in small hepatocellular carcinoma after radiofrequency ablation
Authors: Zhang Xiaojuan , Wang Chuandong , Zheng Dan , Liao Yuting , Wang Xiaoyang , Huang Zhifeng , Zhong Qun
Published: November 2022

Background

There are few studies on the application of radiomics in the risk prediction of early recurrence (ER) after radiofrequency ablation (RFA). This study evaluated the value of a multi-parametric magnetic resonance imaging (MRI, mpMRI)-based radiomics nomogram in predicting ER of small hepatocellular carcinoma (HCC) after RFA.

Materials and methods

A retrospective analysis was performed on 90 patients with small HCC who were treated with RFA. Patients were divided into two groups according to recurrence within 2 years: the ER group (n=38) and the non-ER group (n=52). Preoperative T1WI, T2WI, and contrast-enhanced MRI (CE-MRI) were used for radiomic analysis. Tumor segmentation was performed on the images and applied to extract 1316 radiomics features. The most predictive features were selected using analysis of variance + Mann–Whitney, Spearman’s rank correlation test, random forest (importance), and least absolute shrinkage and selection operator analysis. Radiomics models based on each sequence or combined sequences were established using logistic regression analysis. A predictive nomogram was constructed based on the radiomics score (rad-score) and clinical predictors. The predictive efficiency of the nomogram was evaluated using the area under the receiver operating characteristic curve (AUC). Decision curve analysis (DCA) was used to evaluate the clinical efficacy of the nomogram.

Results

The radiomics model mpMRI, which is based on T1WI, T2WI, and CE-MRI sequences, showed the best predictive performance, with an AUC of 0.812 for the validation cohort. Combined with the clinical risk factors of albumin level, number of tumors, and rad-score of mpMRI, the AUC of the preoperative predictive nomogram in the training and validation cohorts were 0.869 and 0.812, respectively. DCA demonstrated that the combined nomogram is clinically useful.

Conclusions

The multi-parametric MRI-based radiomics nomogram has a high predictive value for ER of small HCC after RFA, which could be helpful for personalized risk stratification and further treatment decision-making for patients with small HCC.
Ensemble learning based on efficient features combination can predict the outcome of recurrence-free survival in patients with hepatocellular carcinoma within three years after surgery
Authors: Wang Liyang , Wu Meilong , Zhu Chengzhan , Li Rui , Bao Shiyun , Yang Shizhong , Dong Jiahong
Published: November 2022

Preoperative prediction of recurrence outcome in hepatocellular carcinoma (HCC) facilitates physicians’ clinical decision-making. Preoperative imaging and related clinical baseline data of patients are valuable for evaluating prognosis. With the widespread application of machine learning techniques, the present study proposed the ensemble learning method based on efficient feature representations to predict recurrence outcomes within three years after surgery. Radiomics features during arterial phase (AP) and clinical data were selected for training the ensemble models. In order to improve the efficiency of the process, the lesion area was automatically segmented by 3D U-Net. It was found that the mIoU of the segmentation model was 0.8874, and the Light Gradient Boosting Machine (LightGBM) was the most superior, with an average accuracy of 0.7600, a recall of 0.7673, a F1 score of 0.7553, and an AUC of 0.8338 when inputting radiomics features during AP and clinical baseline indicators. Studies have shown that the proposed strategy can relatively accurately predict the recurrence outcome within three years, which is helpful for physicians to evaluate individual patients before surgery.
Image-guided percutaneous ablation for lung malignancies
Authors: Shang Youlan , Li Ge , Zhang Bin , Wu Yuzhi , Chen Yanjing , Li Chang , Zhao Wei , Liu Jun
Published: November 2022

Image-guided percutaneous lung ablation has proven to be an alternative and effective strategy in the treatment of lung cancer and other lung malignancies. Radiofrequency ablation, microwave ablation, and cryoablation are widely used ablation modalities in clinical practice that can be performed along or combined with other treatment modalities. In this context, this article will review the application of different ablation strategies in lung malignancies.
A phase I/II escalation trial design T-RAD: Treatment of metastatic lung cancer with mRNA-engineered T cells expressing a T cell receptor targeting human telomerase reverse transcriptase (hTERT)
Authors: Maggadóttir Sólrún Melkorka , Kvalheim Gunnar , Wernhoff Patrik , Sæbøe-Larssen Stein , Revheim Mona-Elisabeth , Josefsen Dag , Wälchli Sébastien , Helland Åslaug , Inderberg Else Marit
Published: November 2022

Background

Adoptive cellular therapy (ACT) with genetically modified T cells aims to redirect T cells against resistant cancers through introduction of a T cell receptor (TCR). The Radium-4 TCR was isolated from a responding patient in a cancer vaccination study and recognizes the enzymatic component of human Telomerase Reverse Transcriptase (hTERT) presented on MHC class II (HLA-DP04). hTERT is a constitutively overexpressed tumor-associated antigen present in most human cancers, including non-small-cell lung cancer (NSCLC), which is the second most common type of cancer worldwide. Treatment alternatives for relapsing NSCLC are limited and survival is poor. To improve patient outcome we designed a TCR-based ACT study targeting hTERT.

Methods

T-RAD is a phase I/II study to evaluate the safety and efficacy of Radium-4 mRNA electroporated autologous T cells in the treatment of metastatic NSCLC with no other treatment option. Transient TCR expression is applied for safety considerations. Participants receive two intravenous injections with escalating doses of redirected T cells weekly for 6 consecutive weeks. Primary objectives are safety and tolerability. Secondary objectives include progression-free survival, time to progression, overall survival, patient reported outcomes and overall radiological response.

Discussion

Treatment for metastatic NSCLC is scarce and new personalized treatment options are in high demand. hTERT is a tumor target applicable to numerous cancer types. This proof-of-concept study will explore for the first time the safety and efficacy of TCR mRNA electroporated autologous T cells targeting hTERT. The T-RAD study will thus evaluate an attractive candidate for future immunotherapy of solid tumors.
Thrombosis and lymphocyte subsets of COVID-19 omicron BA.2 variant patients with cancer
Authors: Yin Jiaxin , Cong Xiaofeng , Wang Nanya , Song Wei , Guan Yanjie , Zhang Yiqun , Li Zhi , Liu Ziling
Published: November 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused an ongoing global pandemic of COVID-19. It has been found that COVID-19 has an influence on the changes of blood coagulation parameters and the high incidence of thrombosis. Changchun experienced the epidemic of the Omicron BA.2 variant SARS-CoV-2 in March 2022 in China. Once infected, BA.2 spreads rapidly and most of them are asymptomatic. The purpose of this study is to research venous thrombosis and laboratory changes (including PLT, PT, APTT, DD, FDP, CRP, WBC, IL-6 and lymphocyte subsets) among 92 cancer patients with COVID-19 and 73 COVID-19 patients with non-cancer by Mann-Whitney U and Chi-square test. It was found that the levels of D-dimer, FDP, CRP and IL-6 in cancer patients were significantly higher than those in the COVID-19 cohort. There were 9 (9.8%) cancer patients and 2 (2.7%) non-cancer patients found VTE, with no significant difference. The results showed that WBC, lymphocytes and B cells in cancer patients were significantly lower than those in the other group. Prophylactic anticoagulation was recommended for cancer patients with high risk factors, while paying attention to the occurrence of bleeding events. The detection of leukocyte classification, D-dimer, prothrombin time and fibrinogen at different time points are helpful for the diagnosis and anticoagulation of COVID-19 patients with cancer.
Research landscape and trends of lung cancer radiotherapy: A bibliometric analysis
Authors: Liu Yanhao , Jiang Shu , Lin Yaru , Yu Haiming , Yu Lan , Zhang Xiaotao
Published: November 2022

Background

radiotherapy is one of the major treatments for lung cancer and has been a hot research area for years. This bibliometric analysis aims to present the research trends on lung cancer radiotherapy.

Method

On August 31, 2022, the authors identified 9868 articles on lung cancer radiotherapy by the Web of Science (Science Citation Indexing Expanded database) and extracted their general information and the total number of citations. A bibliometric analysis was carried out to present the research landscape, demonstrate the research trends, and determine the most cited papers (top-papers) as well as top-journals on lung cancer radiotherapy. After that, the authors analyzed the recent research hotspots based on the latest publications in top-journals.

Results

These 9868 papers were cited a total of 268,068 times. “Durvalumab after chemoradiotherapy in stage III non–small-cell lung cancer” published in 2017 by Antonia et al.was the most cited article (2110 citations). Among the journals, New England Journal of Medicine was most influential. Moreover, J. Clin. Oncol. and Int. J. Radiat. Oncol. Biol. Phys. was both influential and productive. Corresponding authors represented the USA (2610 articles) and China mainland (2060 articles) took part in most publications and articles with corresponding authors from Netherlands were most cited (46.12 citations per paper). Chemoradiotherapy was the hottest research area, and stereotactic body radiotherapy has become a research hotspot since 2006. Radiotherapy plus immunotherapy has been highly focused since 2019.

Conclusions

This bibliometric analysis comprehensively and quantitatively presents the research trends and hotspots based on 9868 relevant articles, and further suggests future research directions. The researchers can benefit in selecting journals and in finding potential collaborators. This study can help researchers gain a comprehensive picture of the research landscape, historical development, and recent hotspots in lung cancer radiotherapy and can provide inspiration for future research.
Aplastic anemia and paroxysmal nocturnal hemoglobinuria in children and adults in two centers of Northern Greece
Authors: Gavriilaki Eleni , Tragiannidis Athanasios , Papathanasiou Maria , Besikli Sotiria , Karvouni Paraskevi , Douka Vassiliki , Paphianou Eleni , Hatzipantelis Emmanuel , Papaioannou Giorgos , Athanasiadou Anastasia , Marvaki Anastasia , Panteliadou Alkistis-Kira , Vardi Anna , Batsis Ioannis , Syrigou Antonia , Mallouri Despina , Lalayanni Chrysavgi , Sakellari Ioanna
Published: November 2022

Bone marrow failure (BMF) syndromes are a group of various hematological diseases with cytopenia as a main common characteristic. Given their rarity and continuous progress in the field, we aim to provide data considering the efficiency and safety of the therapeutic methods, focusing on the treatment of aplastic anemia(AA) and paroxysmal nocturnal hemoglobinuria (PNH). We enrolled consecutive patients diagnosed with BMF in two referral centers of Northern Greece from 2008 to 2020. We studied 43 patients with AA (37 adults and 6 children/adolescents) and 6 with classical PNH. Regarding classical PNH, 4 patients have received eculizumab treatment with 1/4 presenting extravascular hemolysis. Among 43 patients with aplastic anemia, PNH clones were detected in 11. Regarding patients that did not receive alloHCT (n=15), 14/15 were treated with ATG and cyclosporine as first line, with the addition of eltrombopag in patients treated after its approval (n=9). With a median follow-up of 16.7 (1.8-56.2) months from diagnosis, 12/14 (85.7%) are alive (4-year OS: 85.1%). AlloHCT was performed in 28 patients. Five patients developed TA-TMA which did not resolve in 3/5 (all with a pre-transplant PNH clone). With the follow-up among survivors reaching 86.3 (6.3-262.4) months, 10-year OS was 56.9%, independently associated with PNH clones after adjusting for age (p=0.024). In conclusion, our real-world experience confirms that novel treatments are changing the field of BMF syndromes. Nevertheless, there is still an unmet need to personalize algorithms in this field.
Heparin binding epidermal growth factor–like growth factor is a prognostic marker correlated with levels of macrophages infiltrated in lung adenocarcinoma
Authors: Van Hiep Nguyen , Sun Wei-Lun , Feng Po-Hao , Lin Cheng-Wei , Chen Kuan-Yuan , Luo Ching-Shan , Dung Le Ngoc , Van Quyet Hoang , Wu Sheng-Ming , Lee Kang-Yun
Published: November 2022

Background

The interactions between tumor cells and the host immune system play a crucial role in lung cancer progression and resistance to treatment. The alterations of EGFR signaling have the potential to produce an ineffective tumor-associated immune microenvironment by upregulating a series of immune suppressors, including inhibitory immune checkpoints, immunosuppressive cells, and cytokines. Elevated Heparin-binding EGF-like growth factor (HB-EGF) expression, one EGFR ligand correlated with higher histology grading, worse patient prognosis, and lower overall survival rate, acts as a chemotactic factor. However, the role of heparin-binding epidermal growth factor-like growth factor (HB-EGF) in the accumulation of immune cells in the tumor microenvironment remains unclear.

Methods

The clinical association of HB-EGF expression in lung cancer was examined using the Gene Expression Omnibus (GEO) repository. HB-EGF expression in different cell types was determined using single-cell RNA sequencing (scRNA-seq) dataset. The correlation between HB-EGF expression and cancer-immune infiltrated cells was investigated by performing TIMER and ClueGo pathways analysis from TCGA database. The chemotaxis of HB-EGF and macrophage infiltration was investigated using migration and immunohistochemical staining.

Results

The high HB-EGF expression was significantly correlated with poor overall survival in patients with lung adenocarcinoma (LUAD) but not lung squamous cell carcinoma (LUSC). Moreover, HB-EGF expression was correlated with the infiltration of monocytes, macrophages, neutrophils, and dendritic cells in LUAD but not in LUSC. Analysis of scRNA-seq data revealed high HB-EGF expression in lung cancer cells and myeloid cells. Results from the pathway analysis and cell-based experiment indicated that elevated HB-EGF expression was associated with the presence of macrophage and lung cancer cell migration. HB-EGF was highly expressed in tumors and correlated with M2 macrophage infiltration in LUAD.

Conclusions

HB-EGF is a potential prognostic marker and therapeutic target for lung cancer progression, particularly in LUAD.
The modified shrinkage classification modes could help to guide breast conserving surgery after neoadjuvant therapy in breast cancer
Authors: Bi Zhao , Qiu Peng-Fei , Yang Tao , Chen Peng , Song Xian-Rang , Zhao Tong , Zhang Zhao-Peng , Wang Yong-Sheng
Published: November 2022

Purpose

The traditional shrinkage classification modes might not suitable for guiding breast conserving surgery (BCS) after neoadjuvant therapy (NAT). Aim was to explore the modified shrinkage classification modes to guide BCS after NAT.

Methods

From April 2010 to 2018, 104 patients were included. All patients underwent MRI examinations before and after NAT. Residual tumors were removed and divided into more than 30 tissue blocks at 5-mm intervals. After performing routine procedures for paraffin-embedded histology, we made semiserial sections (6-μm thick). The MRI and pathology 3D models were reconstructed with 3D-DOCTOR software. Combined with traditional shrinkage modes and efficacy of NAT, we derived modified shrinkage classification modes which oriented by BCS purpose: modified concentric shrinkage modes (MCSM) and modified non concentric shrinkage modes (MNCSM). The MCSM means the longest diameter of residual tumor was less than 50% and ≤2cm in comparison with the primary tumor before NAT. Other shrinkage modes were classified as MNCSM.

Results

According to traditional shrinkage modes, 50 (48.1%) cases were suitable for BCS;while 70 (67.3%) cases were suitable for BCS according to the modified shrinkage modes (p=0.007). The consistency of MRI 3D reconstruction in assessing modified shrinkage classification modes was 93.2%, while it was 61.5% when assessing traditional shrinkage modes. Multivariate analysis showed that primary tumor stage, mammographic malignant calcification, molecular subtypes and nodal down-staging after NAT were independent predictors of modified shrinkage modes (all p<0.05). A nomogram was created based on these four predictors. With a median follow-up time of 77 months, the recurrence/metastasis rate in the MCSM and MNCSM group was 7.1% and 29.4%, respectively.

Conclusion

Modified shrinkage classification modes could help to guide the individualized selection of BCS candidates and scope of resection after NAT. MRI 3D reconstruction after NAT could accurately predict modified shrinkage modes and extent of residual tumor.
Diagnostic value of multiple diagnostic methods for lymph node metastases of papillary thyroid carcinoma: A systematic review and meta-analysis
Authors: Wang Si-Rui , Li Qiao-Li , Tian Feng , Li Jun , Li Wen-Xiao , Chen Ming , Sang Tian , Cao Chun-Li , Shi Li-Nan
Published: November 2022

Objective

This study compared the diagnostic value of various diagnostic methods for lymph node metastasis (LNM) of papillary thyroid carcinoma (PTC) through network meta-analysis.

Methods

In this experiment, databases such as CNKI, Wanfang, PubMed, and Web of Science were retrieved according to the Cochrane database, Prisma, and NMAP command manual. A meta-analysis was performed using STATA 15.0, and the value of the surface under the cumulative ranking curve (SUCRA) was used to determine the most effective diagnostic method. Quality assessments were performed using the Cochrane Collaboration’s risk of bias tool, and publication bias was assessed using Deeks’ funnel plot.

Results

A total of 38 articles with a total of 6285 patients were included. A total of 12 diagnostic methods were used to study patients with LNM of PTC. The results showed that 12 studies were direct comparisons and 8 studies were indirect comparisons. According to the comprehensive analysis of the area of SUCRA, US+CT(86.8) had the highest sensitivity, FNAC had the highest specificity (92.4) and true positive predictive value (89.4), and FNAC+FNA-Tg had higher negative predictive value (99.4) and accuracy (86.8). In the non-invasive method, US+CT had the highest sensitivity, and the sensitivity (SEN) was [OR=0.59, 95% confidence interval (CI): (0.30, 0.89]. Among the invasive methods, the combined application of FNAC+FNA-Tg had higher diagnostic performance. The sensitivity was [OR=0.62, 95% CI: (0.26, 0.98)], the specificity (SPE) was [OR=1.12, 95% CI: (0.59, 1.64)], the positive predictive value was [OR=0.98, 95% CI: (0.59, 1.37)], the negative predictive value was [OR=0.64, 95% CI (0.38, 0.90)], and the accuracy was [OR=0.71, 95% CI: (0.31, 1.12)].

Conclusion

In the non-invasive method, the combined application of US+CT had good diagnostic performance, and in the invasive method, the combined application of FNAC+FNA-Tg had high diagnostic performance, and the above two methods were recommended.
Clinical characteristics, prognostic factors, and predictive model for elderly primary spinal tumor patients who are difficult to tolerate surgery or refuse surgery
Authors: Huang Zhangheng , Zhao Zhen , Wang Yu , Wu Ye , Guo Chuan , Kong Qingquan
Published: November 2022

Background

As a rare tumor, surgery is the best treatment for primary spinal tumors. However, for elderly patients who cannot undergo surgery, the prognosis is often difficult to evaluate. The purpose of this study was to identify the risk factors that may lead to death and predict the prognosis of elderly patients with primary spinal tumors who have not undergone surgical treatment.

Methods

In this study, 426 patients aged 60 years or older diagnosed with a primary spinal tumor between 1975 and 2015 were selected and included from the Surveillance, Epidemiology, and End Results database. A retrospective analysis was performed by using the Cox regression algorithm to identify independent prognostic factors. A nomogram model was developed based on the results. Multiple evaluation methods (calibration curve, receiver operating characteristic curve, and decision curve analyses) were used to evaluate and validate the performance of the nomogram.

Results

A nomogram was developed, with age, histological type, and stage as independent prognostic factors. The results indicated that the prognostic risk tended to increase significantly with age and tumor spread. Osteosarcoma was found to have the most prominent risk prognosis in this patient group, followed by chondrosarcoma and chordoma. The area under the curve and the C-index of the model were both close to or greater than 0.7, which proved the high-differentiation ability of the model. The calibration curve and decision curve analyses showed that the model had high predictive accuracy and application value.

Conclusions

We successfully established a practical nomogram to assess the prognosis of elderly patients with primary spinal tumors who have not undergone surgical treatment, providing a scientific basis for clinical management.
Laparoscopic electrochemotherapy for the treatment of hepatocellular carcinoma: Technological advancement
Authors: Trotovsek Blaz , Hadzialjevic Benjamin , Cemazar Maja , Sersa Gregor , Djokic Mihajlo
Published: November 2022

Electrochemotherapy is an effective treatment modality for hepatocellular carcinoma (HCC). Electrochemotherapy for HCC was initially used in the setting of open surgery. Recently, with the development of newer electrodes, percutaneous approaches have also been performed. However, laparoscopic application of electrochemotherapy for HCC has not yet been described. Two patients with unresectable HCC were enrolled in the study. The first patient was not suitable for the percutaneous approach because the tumor was located close to the gallbladder. He also had symptomatic gallstones. The second patient had HCC in close proximity to the stomach and was therefore not suitable for percutaneous access or any other ablative technique. Thus, the laparoscopic approach was chosen, using newly developed Stinger electrodes for the application of electric pulses. After intravenous administration of bleomycin, several sets of electric pulses were delivered to the whole tumor mass in both patients. Ultrasonographically, the coverage of the whole tumor was verified, as described previously. Cholecystectomy was also performed in the first patient. Follow-up abdominal computed tomography showed a complete response of the treated lesions in both patients. Minimally invasive laparoscopic electrochemotherapy is safe, feasible and effective method for the treatment of HCC. It could be used in patients in whom the percutaneous approach is unsafe (proximity to other organs) and in patients with concomitant symptomatic gallstones in whom cholecystectomy is already indicated. This technological approach thus allows broader and minimally invasive clinical applicability of electrochemotherapy.
Automatic detection of pain using machine learning
Authors: Winslow Brent D. , Kwasinski Rebecca , Whirlow Kyle , Mills Emily , Hullfish Jeffrey , Carroll Meredith
Published: November 2022

Pain is one of the most common symptoms reported by individuals presenting to hospitals and clinics and is associated with significant disability and economic impacts; however, the ability to quantify and monitor pain is modest and typically accomplished through subjective self-report. Since pain is associated with stereotypical physiological alterations, there is potential for non-invasive, objective pain measurements through biosensors coupled with machine learning algorithms. In the current study, a physiological dataset associated with acute pain induction in healthy adults was leveraged to develop an algorithm capable of detecting pain in real-time and in natural field environments. Forty-one human subjects were exposed to acute pain through the cold pressor test while being monitored using electrocardiography. A series of respiratory and heart rate variability features in the time, frequency, and nonlinear domains were calculated and used to develop logistic regression classifiers of pain for two scenarios: (1) laboratory/clinical use with an F1 score of 81.9% and (2) field/ambulatory use with an F1 score of 79.4%. The resulting pain algorithms could be leveraged to quantify acute pain using data from a range of sources, such as ECG data in clinical settings or pulse plethysmography data in a growing number of consumer wearables. Given the high prevalence of pain worldwide and the lack of objective methods to quantify it, this approach has the potential to identify and better mitigate individual pain.
Case report: A giant bilateral inguinal hernia requiring artificial mesh and multi-stage surgery in infancy; hernioplasty with silo placement to prevent acute compartment syndrome
Authors: Nakagawa Yoichi , Makita Satoshi , Uchida Hiroo , Hinoki Akinari , Shirota Chiyoe , Sumida Wataru , Amano Hizuru , Okamoto Masamune , Takimoto Aitaro , Yasui Akihiro , Ogata Seiya , Takada Shunya , Kato Daiki , Gohda Yousuke , Yaohui Guo
Published: November 2022

Hernioplasty for giant inguinal hernias can cause abdominal compartment syndrome (ACS) in adults but rarely does in infants. We encountered a case of a giant bilateral inguinal hernia in infancy complicated by ACS after hernioplasty. Silo placement via a skin incision effectively treated ACS, after which the abdominal wall was safely closed. Hernioplasty performed early in the clinical course can help expand the abdominal cavity and avoid ACS. Thus, hernioplasty should be performed earlier if the hernia size in the flank space gradually increases.
In utero antidepressant exposure not associated with ADHD in the offspring: A case control sibling design
Authors: Hartwig C. A. M. , Robiyanto R. , de Vos S. , Bos J. H. J. , van Puijenbroek E. P. , Hak E. , Schuiling-Veninga C. C. M.
Published: November 2022

Recent studies have reported an association between antidepressant (AD) use during pregnancy and the risk to develop attention-deficit/hyperactivity disorder (ADHD) in the offspring. However, the association might be confounded by risk factors in the pregnant parent. To control for unmeasured factors between pregnancies carried by the same parent, we set up a case-control sibling study using the University of Groningen prescription database IADB.nl. Children receiving medication for ADHD (cases) before the age of 16 years were matched to siblings not receiving such medication (controls). Exposure was defined as at least two prescriptions for any AD during pregnancy, i.e., the period of 39 weeks before the birth date of the offspring. Secondary analyses were performed to assess the effects of the degree of exposure (the amount of Defined Daily Doses) and the type of AD exposed to. Univariate and multivariate logistic regression was used to estimate odds ratios (ORs) with corresponding 95% confidence intervals (CI). In total, 2,833 children (1,304 cases and 1,529 controls) were included in the analysis. Exposure rate to ADs among cases and controls was 2.2% and 2.4%, respectively. After adjusting for the birth date of the child (as a proxy for the date of pregnancy), age of the pregnant parent at birth, use of psychostimulants, opioids, and antiepileptic drugs by the pregnant parent in the 15 months before birth of the child, an adjusted OR of 1.11 (95% CI 0.67–1.83) was found for the risk of ADHD in the offspring when exposed in utero to ADs. This indicates no increased risk of ADHD in offspring following in utero exposure to ADs. The secondary analyses revealed no statistically significant associations either. The present study provides further evidence that an association between in utero AD exposure and ADHD in offspring might not exist. This perceived association may be caused (at least partially) by confounding by indication. The extent to which depression in the pregnant parent could cause mental disorders such as ADHD in offspring, and the mechanisms involved, should be investigated in further studies.