bluuebunny/crossref_metadata_2025 huggingface dataset:
Eating behavior in patients with smell loss
Authors: Liu David T. , Prem Bernhard , Sharma Gunjan , Kaiser Julia , Besser Gerold , Mueller Christian A.
Published: November 2022

Background

The objective of this study was to determine how clinical characteristics and validated quality of life (QoL)-measures are associated with eating behavior in patients with olfactory dysfunction (OD).

Methods

For this cross-sectional study, 150 OD patients of different causes were retrospectively recruited. Olfactory function was measured using the Sniffin’ Sticks (TDI), while olfactory-related QoL was evaluated with the Questionnaire of OD negative and positive statements (QOD-NS and QOD-PS). The importance of olfaction was measured using the Importance of Olfaction Questionnaire (IOQ). The Dutch Eating Behavior Questionnaire (DEBQ) assessed eating behavior based on emotional, external, and restrained eating. Associations were sought between eating behavior metrics (as dependent variables) with clinical characteristics and olfactory-related outcome measures.

Results

Emotional, external, and restrained eating behavior deviating from normative standards were reported in 54%, 71.3%, and 68% of patients, respectively. Multivariate regression modeling revealed that emotional eating was associated with age (ß = –0.227, p = 0.032), the body mass index (BMI, ß = 0.253, p = 0.005), the TDI (ß = 0.190, p = 0.046), and the QOD-NS (ß = 0.203, p = 0.049). External eating was associated with OD duration (ß = 0.291, p = 0.005), the TDI (ß = 0.225, p = 0.018), the QOD-PS (ß = –0.282, p = 0.008), and the IOQ (ß = 0.277, p = 0.004). Restrained eating was associated with age (ß = 0.216, p = 0.033), the BMI (ß = 0.257, p = 0.003), male gender (ß = –0.263, p = 0.002), and the IOQ (ß = 0.332, p < 0.001).

Conclusion

Clinical characteristics and olfactory outcome measures differentially impact eating styles in OD patients. Our study’s results highlight the importance of considering unfavorable changes in eating behavior during clinical counseling.
Molecular mechanism and potential therapeutic targets of liver metastasis from gastric cancer
Authors: Li Difeng , Zhang Xin , Jiang Lili
Published: November 2022

Gastric cancer (GC) is characterized by high invasion and poor prognosis. The occurrence of liver metastasis seriously affects advanced GC prognosis. In recent years, great progress has been made in the field of GC liver metastasis. The abnormal expression of related genes leads to the occurrence of GC liver metastasis through metastasis cascades. The changes in the liver microenvironment provide a pre-metastasis condition for GC cells to colonize and grow. The development of several potential therapeutic targets might provide new therapeutic strategies for its treatment. Therefore, we reviewed the regulatory mechanism of abnormal genes mediating liver metastasis, the effect of liver resident cells on liver metastasis, and potential therapeutic targets, hoping to provide a novel therapeutic option to improve the quality of life and prognosis of GC patients with liver metastasis.
Risk prediction of pancreatic cancer using AI analysis of pancreatic subregions in computed tomography images
Authors: Javed Sehrish , Qureshi Touseef Ahmad , Gaddam Srinivas , Wang Lixia , Azab Linda , Wachsman Ashley Max , Chen Wansu , Asadpour Vahid , Jeon Christie Younghae , Wu Beichien , Xie Yibin , Pandol Stephen Jacob , Li Debiao
Published: November 2022

Early detection of Pancreatic Ductal Adenocarcinoma (PDAC) is complicated as PDAC remains asymptomatic until cancer advances to late stages when treatment is mostly ineffective. Stratifying the risk of developing PDAC can improve early detection as subsequent screening of high-risk individuals through specialized surveillance systems reduces the chance of misdiagnosis at the initial stage of cancer. Risk stratification is however challenging as PDAC lacks specific predictive biomarkers. Studies reported that the pancreas undergoes local morphological changes in response to underlying biological evolution associated with PDAC development. Accurate identification of these changes can help stratify the risk of PDAC. In this retrospective study, an extensive radiomic analysis of the precancerous pancreatic subregions was performed using abdominal Computed Tomography (CT) scans. The analysis was performed using 324 pancreatic subregions identified in 108 contrast-enhanced abdominal CT scans with equal proportion from healthy control, pre-diagnostic, and diagnostic groups. In a pairwise feature analysis, several textural features were found potentially predictive of PDAC. A machine learning classifier was then trained to perform risk prediction of PDAC by automatically classifying the CT scans into healthy control (low-risk) and pre-diagnostic (high-risk) classes and specifying the subregion(s) likely to develop a tumor. The proposed model was trained on CT scans from multiple phases. Whereas using 42 CT scans from the venous phase, model validation was performed which resulted in ~89.3% classification accuracy on average, with sensitivity and specificity reaching 86% and 93%, respectively, for predicting the development of PDAC (i.e., high-risk). To our knowledge, this is the first model that unveiled microlevel precancerous changes across pancreatic subregions and quantified the risk of developing PDAC. The model demonstrated improved prediction by 3.3% in comparison to the state-of-the-art method that considers the global (whole pancreas) features for PDAC prediction.
Remarkable response to alectinib for metastatic papillary thyroid cancer with STRN-ALK fusion: A case report
Authors: Zhu Lucheng , Ma Shenglin , Xia Bing
Published: November 2022

Little is known about the efficacy of alectinib for papillary thyroid cancer with STRN-ALK fusion. A 64-year-old female presented with metastatic papillary thyroid cancer, widespread to lungs, mediastinal lymph nodes and brain 20 years after surgery. Disease progression still occurred after radioactive iodine therapy, chemotherapy, and radiotherapy. Tissue obtained from left cervical lymph node confirmed metastatic papillary thyroid cancer. Molecular profiling from re-biopsy tissue identified an STRN-ALK fusion rearrangement. After multidisciplinary discussion, alectinib was administered to the patient. Treatment was well tolerated, and follow-up images confirmed a partial response. ALK occurs rarely, with limited data suggesting the efficacy of ALK inhibitors in thyroid cancer. We presented the first case of a patient with PTC and STRN-ALK fusion to be treat effectively with alectinib.
Histomorphological transformation from non-small cell lung carcinoma to small cell lung carcinoma after targeted therapy or immunotherapy: A report of two cases
Authors: Liu Hao , Chen Li-Hong , Zhang Zhi-Hui , Wang Ning , Zhuang Si-Hui , Chen Hao , Du Jin , Pang Li-Juan , Qi Yan
Published: November 2022

Molecular targeting and immunotherapy provide durable responses for advanced lung cancer clinical therapy in many patients. However, the mechanisms of occurrence of progressive disease and resistance to targeted therapy and immunotherapy have not been elucidated. Herein, we report two cases of small cell transformation of non-small cell lung cancer (NSCLC) after targeted therapy or immunotherapy. The first case was a 63-year-old female patient presenting with cough and expectoration. Left lung invasive adenocarcinoma was diagnosed after left lung tumor biopsy. After epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) targeted therapy for almost 2 years, disease progression and symptom aggravation were observed. Pathological and immunohistochemical staining results after biopsy revealed small cell lung cancer (SCLC). The second case was a 75-year-old male patient diagnosed with stage IV squamous cell carcinoma of the lung, who received carboplatin/paclitaxel adjuvant chemotherapy and pembrolizumab treatment with partial response. Disease progression and metastasis occurred within 15 cycles of immunotherapy. Computed tomography revealed a lower left lung tumor. Cytological examination of lung lavage fluid and biopsy under thoracoscope revealed SCLC. In conclusion, histological transformation to SCLC is a potential mechanism of NSCLC resistance to targeted therapy or immunotherapy. During treatment, clinicians should monitor serum tumor markers or genome sequencing, particularly in patients with disease progression, as this may be beneficial for early detection of SCLC transformation. Repeated biopsy can be performed if necessary, and the therapeutic regimen can be adjusted in a timely manner according to the results of molecular pathological tests for personalization and whole-process management.
Endoscopic resection of upper gastrointestinal lymphangioma: A single-center experience
Authors: Shi Ziyu , Huang Xue , Li Keliang , Tu Qiuyue , Liu Dan , Zhao Lixia , Yang Huiyu , Li Deliang , Zhao Yue , Zhang Jiyu , Li Muhan , Liu Bingrong
Published: November 2022

Objective

Lymphagioma, which in most cases as benign tumors, occurs in head, neck, axilla, and mediastinum. Lymphangioma is exceedingly rare in the upper gastrointestinal tract including esophagus, stomach, and duodenum. However, the clinical characteristics, natural history, and recurrence rate after endoscopic resection remain unclear. This study aims to evaluate the characteristic findings and assess the efficacy of endoscopic techniques in the management of this disease.

Methods

In this systematic retrospective analysis, we evaluated all 24 cases of upper gastrointestinal lymphangioma resected by endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) and diagnosed by histopathology at our hospital from January 2012 to May 2021. We analyzed the results of endoscopy, endoscopic ultrasonography (EUS), CT, histologic examination, and follow-up assessments.

Results

9 male and 15 female patients with esophageal lymphangioma were enrolled in this study, with a mean age of 54.17 ± 11.60 years (range 30-71 years). The lesions’ size varied from 2.20 to 40.10 mm, with the median size of 7.83 mm. All patients were evaluated preoperatively, whose endoscopic appearance typically appears as dilated lymphatic channels beneath the surface epithelium of the protrude mucosal or sub-mucosal lesion. Endoscopic ultrasonography revealed the presence of a honeycomb-like or grid-like mass with a heterogeneous echo pattern, and a clear boundary between the lesion and the muscularis propria layer may be helpful for the primary diagnosis of this disease. 22 patients underwent EMR and 2 patient were treated with ESD. Histologic examination revealed that the lesions contained many dilated lymphatic vessels, which confirmed the initial diagnosis of lymphangioma in all patients. No major adverse events were found during the operation or a median follow-up of 43 months (range 13–92).

Conclusions

Endoscopic ultrasonography has important clinical value for the primary diagnosis of lymphangioma in the upper gastrointestinal tract. This study also suggests that endoscopic resection should be considered as a more minimally invasive, safe, feasible, and effective therapeutic option comparing to laparoscopic surgery.
Case report: A mesocolic lymphangioma in a 14-year-old child resected by laparoscopic surgery
Authors: Feng Xuping , Chen Xinyang , Feng Qingbo , Liu Xiaoyin , Li Hancong , Chen Hao , Cai Zhaolun , Li Jiaxin
Published: November 2022

Introduction

Cystic lymphangioma is a benign malformation tumor of the lymphatic system. Its location is variable, and mesocolic localization remains extremely rare.

Case presentation

We report a case of right mesocolon giant cystic lymphangioma in a previously healthy 14-year-old boy who was successfully managed through a minimally invasive laparoscopic excision. The patient presented with 8 months of dull abdominal pain, sporadic, located on the peri-umbilicus, exacerbated for a month. An abdominal computed tomography (CT) revealed a large, multiseptated cystic mass on the right mesocolon. Right mesocolic excision using a laparoscope was performed on this patient. He was discharged on the fifth day without complications. Recurrence was not detected in three months of follow-up.

Conclusion

Cystic lymphangiomas in the mesocolon are rare benign neoplasms that pose diagnostic challenges. Complete resection is the optimal option for diagnostic confirmation and recurrence prevention. Laparoscopic surgery is feasible for children with mesocolic lymphangioma.
Tumor and microenvironmental mechanisms of resistance to immunomodulatory drugs in multiple myeloma
Authors: Chen Lucia Y. , Gooding Sarah
Published: November 2022

Resistance to immunomodulatory drugs (IMiDs®) is a major cause of treatment failure, disease relapse and ultimately poorer outcomes in multiple myeloma (MM). In order to optimally deploy IMiDs and their newer derivates CRBN E3 ligase modulators (CELMoDs®) into future myeloma therapeutic regimens, it is imperative to understand the mechanisms behind the inevitable emergence of IMiD resistance. IMiDs bind and modulate Cereblon (CRBN), the substrate receptor of the CUL4CRBNE3 ubiquitin ligase, to target novel substrate proteins for ubiquitination and degradation. Most important of these are IKZF1 and IKZF3, key MM survival transcription factors which sustain the expression of myeloma oncogenes IRF4 and MYC. IMiDs directly target MM cell proliferation, but also stimulate T/NK cell activation by their CRBN-mediated effects, and therefore enhance anti-MM immunity. Thus, their benefits in myeloma are directed against tumor and immune microenvironment – and in considering the mechanisms by which IMiD resistance emerges, both these effects must be appraised. CRBN-dependent mechanisms of IMiD resistance, includingCRBNgenetic aberrations, CRBN protein loss and CRBN-substrate binding defects, are beginning to be understood. However, only a proportion of IMiD-resistant cases are related to CRBN and therefore additional mechanisms, which are currently less well described, need to be sought. These include resistance within the immune microenvironment. Here we review the existing evidence on both tumor and immune microenvironment mechanisms of resistance to IMiDs, pose important questions for future study, and consider how knowledge regarding resistance mechanism may be utilized to guide treatment decision making in the clinic.
The effect of neoadjuvant chemotherapy on the tumor immune microenvironment in gastrointestinal tumors
Authors: Wang Yujie , Gao Peng , Hao Zhibin , Chen Ling , Li Xiaoxiao , Jiao Yuan , Liu Jingyu , Li Jie , Zhang Yingyi , Peng Xiaobo , Ning Beifang , Zhan Xianbao
Published: November 2022

In recent years, numerous studies have demonstrated that the tumor immune microenvironment (TIME) is capable of regulating the growth of tumors, and tumor-infiltrating immune cells in the TIME can affect the prognosis and treatment responses of patients. Consequently, therapies targeting these immune cells have emerged as important antitumor treatments. As a crucial componet of the perioperative treatment of malignant tumors, neoadjuvant chemotherapy (NACT) can improve the surgical resection rate and prognosis of patients and is a suitable clinical model to evaluate the effect of chemotherapy on the TIME. To provide a rationale for developing valid combinational therapies, this review summarizes the impact of NACT on the TIME, the relationship between tumor-infiltrating immune cells and treatment responses of patients, and the prognostic value of these infiltrating immune cells.
Machine learning identifies characteristics molecules of cancer associated fibroblasts significantly correlated with the prognosis, immunotherapy response and immune microenvironment in lung adenocarcinoma
Authors: Wang Qian , Zhang Xunlang , Du Kangming , Wu Xinhui , Zhou Yexin , Chen Diang , Zeng Lin
Published: November 2022

Background

Lung adenocarcinoma (LUAD) is a highly lethal disease with a dramatic pro-fibrocytic response. Cancer-associated fibroblasts (CAFs) have been reported to play a key role in lung adenocarcinoma.

Methods

Marker genes of CAFs were obtained from the Cell Marker website. Single sample gene set enrichment analysis (ssGSEA) was used for CAFs quantification. R and GraphPad Prism software were utilized for all analysis. Quantitative real-time PCR (qRT-PCR) was utilized to detect the RNA level of specific molecules.

Results

Based on the ssGSEA algorithm and obtained CAFs markers, the LUAD patients with low- and high-CAFs infiltration were successfully identified, which had different response patterns to immunotherapy. Through the machine learning algorithm – LASSO logistic regression, we identified 44 characteristic molecules of CAFs. Furthermore, a prognosis signature consisting of seven characteristic genes was established, which showed great prognosis prediction ability. Additionally, we found that patients in the low-risk group might have better outcomes when receiving immunotherapy of PD-1, but not CTLA4. Also, the biological enrichment analysis revealed that immune response-related pathways were significantly associated with CAFs infiltration. Meanwhile, we investigated the underlying biological and microenvironment difference in patients with high- and low-risk groups. Finally, we identified that AMPD1 might be a novel target for LUAD immunotherapy. Patients with a high level of AMPD1 were correlated with worse responses to immunotherapy. Moreover, immunohistochemistry showed that the protein level of AMPD1 was higher in lung cancer. Results of qRT-PCR demonstrated that AMPD1 was upregulated in A549 cells compared with BEAS-2B. Meanwhile, we found that the knockdown of AMPD4 can significantly reduce the expression of CTLA4 and PDCD1, but not CD274 and PDCD1LG2.

Conclusion

We comprehensively explored the role of CAFs and its characteristics molecules in LUAD immunotherapy and developed an effective signature to indicate patients prognosis and immunotherapy response. Moreover, AMPD1 was identified as a novel target for lung cancer immunotherapy.
Adjuvant chemoradiotherapy does not improve outcomes in patients with fistula-associated anal adenocarcinoma undergoing abdominoperineal resection
Authors: Wang Min , Xiang Yu , Wang Yunshan , Zhang Jiayi , Zhao Haoran , Wang Can , Qiao Lichao , Yang Bolin
Published: November 2022

Objective

Abdominoperineal resection (APR) is currently established as a standard treatment regimen for fistula-associated anal adenocarcinoma (FAAA), however, the efficacy of chemoradiotherapy (CRT) remains unclear. The aim of this study is to evaluate the role of CRT in patients with FAAA treated with APR through single-center experience and literature review.

Methods

A retrospective review was performed on patients with FAAA consecutive treated in our institution from 2005 to 2022. In addition, a systematic literature search was performed using PubMed and MEDLINE. All patients with FAAA who received APR in our institution and reported in the literature were included and divided into three categories for statistical analysis: APR alone (APR group), neoadjuvant therapy combined APR (CRT+APR group), and APR combined postoperative therapy (APR+CRT group).

Results

Fifteen patients with FAAA were identified from our retrospective charts review. At a median follow-up time of 18 months, the recurrence-free survival rate was 53.3% and the survival rate was 73.3%. Eight patients underwent APR and 6 received postoperative chemotherapy. Among them, one died, one developed recurrence and the remaining six patients were alive with disease free. We found 37 publications describing 62 patients with FAAA treated with APR. Clinical data from these articles were analyzed together with the 8 cases in our institution. The overall survival rates were 94.1%, 70.8%, and 38.5% at 1-, 3-, 5-years respectively. Combining (neo)adjuvant therapy did not appear to improve outcomes in FAAA treated with APR (CRT+APR vs. APR, p=0.977; APR+CRT vs. APR, p=0.351). Lymph node involvement was shown to be significantly associated with poor outcomes by multivariate analysis (p=0.020).

Conclusions

For patients with FAAA without lymph node involvement, APR is adequate to control disease and the addition of CRT does not appear to prolong survival.
Contouring lumbosacral plexus nerves with MR neurography and MR/CT deformable registration technique
Authors: Cao Xi , Gao Xian-Shu , Li Wei , Liu Peilin , Qin Shang-Bin , Dou Yan-Bin , Li Hong-Zhen , Shang Shiyu , Gu Xiao-Bin , Ma Ming-Wei , Qi Xin , Xie Mu , Wang Dian
Published: November 2022

Purpose

It is difficult to contour nerve structures with the naked eye due to poor differentiation between the nerve structures with other soft tissues on CT images. Magnetic resonance neurography (MRN) has the advantage in nerve visualization. The purpose of this study is to identify one MRN sequence to better assist the delineation of the lumbosacral plexus (LSP) nerves to assess the radiation dose to the LSP using the magnetic resonance (MR)/CT deformable coregistration technique.

Methods

A total of 18 cases of patients with prostate cancer and one volunteer with radiation-induced lumbosacral plexopathy (RILSP) were enrolled. The data of simulation CT images and original treatment plans were collected. Two MRN sequences (Lr_NerveVIEW sequence and Cs_NerveVIEW sequence) were optimized from a published MRN sequence (3D NerveVIEW sequence). The nerve visualization ability of the Lr_NerveVIEW sequence and the Cs_NerveVIEW sequence was evaluated via a four-point nerve visualization score (NVS) scale in the first 10 patients enrolled to determine the better MRN sequence for assisting nerve contouring. Deformable registration was applied to the selected MRN sequence and simulation CT images to get fused MR/CT images, on which the LSP was delineated. The contouring of the LSP did not alter treatment planning. The dosimetric data of the LSP nerve were collected from the dose–volume histogram in the original treatment plans. The data of the maximal dose (Dmax) and the location of the maximal radiation point received by the LSP structures were collected.

Results

The Cs_NerveVIEW sequence gained lower NVS scores than the Lr_NerveVIEW sequence (Z=-2.887, p=0.004). The LSP structures were successfully created in 18 patients and one volunteer with MRN (Lr_NerveVIEW)/CT deformable registration techniques, and the LSP structures conformed with the anatomic distribution. In the patient cohort, the percentage of the LSP receiving doses exceeding 50, 55, and 60 Gy was 68% (12/18), 33% (6/18), and 17% (3/18), respectively. For the volunteer with RILSP, the maximum irradiation dose to his LSP nerves was 69 Gy.

Conclusion

The Lr_NerveVIEW MRN sequence performed better than the Cs_NerveVIEW sequence in nerve visualization. The dose in the LSP needs to be measured to understand the potential impact on treatment-induced neuropathy.
Application basis of combining antiangiogenic therapy with radiotherapy and immunotherapy in cancer treatment
Authors: Yuan Meng , Zhai Yirui , Hui Zhouguang
Published: November 2022

How to further optimize the combination of radiotherapy and immunotherapy is among the current hot topics in cancer treatment. In addition to adopting the preferred dose-fractionation of radiotherapy or the regimen of immunotherapy, it is also very promising to add antiangiogenic therapy to this combination. We expound the application basis of cancer radiotherapy combined with immunotherapy and antiangiogenic therapy.
Prenatal case report of Barth syndrome caused by novel TAFAZZIN mutation: Clinical characteristics of fetal dilated cardiomyopathy with ascites
Authors: Zhao Xuliang , Li Xu , Sun Weiwei , Jia Jian-an , Yu Min , Tian Ruixia
Published: November 2022

Barth syndrome (BTHS) is a rare X-linked recessive genetic disease, which appears in infancy with myocardial and skeletal muscle diseases, neutropenia, growth retardation, and other clinical features. TAFAZZIN is the pathogenic gene of BTHS, which encodes the tafazzin protein of the inner membrane of the mitochondria, a phosphatidyltransferase involved in cardiolipin remodeling and functional maturation. At present, BTHS has been widely reported, but prenatal cases are rare. We report a 24+4-week fetus with clinical manifestations including left ventricular insufficiency and ascites. After induced labor, whole exome sequencing detection of fetal skin tissue showed that TAFAZZIN had the mutation c.311A > C/p.His104Pro and that his mother was the carrier. This His104Pro mutation has hitherto not been reported, and it is rated as likely to be pathogenic according to the American College of Medical Genetics and Genetics guidelines. Molecular dynamics and protein expression experiments on the His104Pro mutation showed that the stability of the local protein structure and protein expression were reduced. In conclusion, the case presented in this study enriches our knowledge of the TAFAZZIN mutation spectrum and suggests that His104Pro may lead to cardiac structural abnormalities in the early embryo. The possibility of BTHS should be considered when an abnormal cardiac structure or ascites appear in a prenatal ultrasound.
Approaches to SARS-CoV-2 and other vaccinations in children with a history of multisystem inflammatory syndrome (MIS-C): An international survey
Authors: Minoia Francesca , Lucioni Federica , Heshin-Bekenstein Merav , Vastert Sebastiaan , Kessel Christoph , Uziel Yosef , Lamot Lovro , Ruperto Nicolino , Gattorno Marco , Bracaglia Claudia , Toplak Natasa
Published: November 2022

Background

Following the Coronavirus Disease-19 (COVID-19) pandemic outbreaks, the hyperinflammatory condition termed Multisystem Inflammatory Syndrome in Children (MIS-C) became a healthcare issue worldwide. Since December 2020 the mRNA vaccine against SARS-CoV-2 has become available with a good safety profile. However, evidence regarding safety and vaccination strategies in children with previous MIS-C is still lacking. The aim of our study was to investigate the current approach of international centers to anti-SARS-CoV-2 and other vaccinations in children with a history of MIS-C.

Methods

Physicians who care for patients with MIS-C were invited to anonymously complete a 15-question, web-based survey. The survey was open from October 6 to December 31, 2021.

Results

A total of 290 replies from 236 centers in 61 countries were collected. Most respondents (86%) were pediatric rheumatologists. The anti-SARS-CoV-2 vaccine was available in 85% of the countries. Sixty-seven centers (28%) in 22 countries already vaccinated MIS-C patients without adverse reactions in most cases (89%). Six reported complications: 2 not specified, 3 mild symptoms and 1 reported a MIS-C-like reaction. Most centers (84%) favored vaccinating MIS-C patients against SARS-CoV-2, after 3–6 months (40%), 6–12 months (52%) or >12 months (8%). The survey revealed broad heterogeneity of responses among healthcare providers within the same country and within the same center. The variable with the greatest impact on the decision not to vaccinate MIS-C patients was the current lack of evidence (51%), followed by patient/parent objection (40%). The most relevant parameters in the vaccination strategy were time from MIS-C episode (78%), immunosuppressive treatment (35%), SARS-CoV-2 serologic status (32%), and MIS-C features (31%). Almost all centers favored continuing regular vaccination with non-live (99%) and live (93%) vaccines; however, with high variability in suggested timelines.

Conclusion

To date, the experience of the international pediatric rheumatology community in vaccinating MIS-C patients against SARS-CoV-2 is overall reassuring. However, lack of evidence causes broad heterogeneity in vaccination strategy worldwide.
Multicenter, randomized controlled trial of traditional Japanese medicine, kakkonto with shosaikotokakikyosekko, for mild and moderate coronavirus disease patients
Authors: Takayama Shin , Namiki Takao , Arita Ryutaro , Ono Rie , Kikuchi Akiko , Ohsawa Minoru , Saito Natsumi , Suzuki Satoko , Nakae Hajime , Kobayashi Seiichi , Yoshino Tetsuhiro , Ishigami Tomoaki , Tanaka Koichiro , Nochioka Kotaro , Takagi Airi , Mimura Masaru , Yamaguchi Takuhiro , Ishii Tadashi , Hisanaga Akito , Mitani Kazuo , Ito Takashi
Published: November 2022

The traditional Japanese (Kampo) medicine, kakkonto with shosaikotokakikyosekko, has antiviral and anti-inflammatory effects. In this randomized trial, patients with mild and moderate coronavirus disease (COVID-19) were randomly allocated to the control group receiving conventional treatment for symptom relief such as antipyretics and antitussives or the Kampo group receiving mixed extract granules of kakkonto (2.5 g) and shosaikotokakikyosekko (2.5 g) three times a day for 14 days in addition to conventional treatment. The main outcome was the number of days until total symptom relief. The secondary outcome was the number of days until each symptom’s relief and whether the disease progressed to respiratory failure. We enrolled a total of 161 patients (Kampo group, n = 81; control group, n = 80). The results from Kaplan–Meier estimates of symptom relief showed that there are no significant differences between the groups. However, covariate-adjusted cumulative incidence of fever relief considering competitive risk showed that the recovery was significantly faster in the Kampo group than in the control group (HR 1.76, 95% CI 1.03–3.01). Additionally, the risk of disease progression to moderate COVID-19 requiring oxygen inhalation was lower in the Kampo group than in the control group (Risk Difference −0.13, 95% CI −0.27–0.01). No significant drug-related side effects were observed. Kakkonto with shosaikotokakikyosekko is effective for fever relief with suppression of disease progression in COVID-19 patients.

Clinical Trial Registration:https://jrct.niph.go.jp/en-latest-detail/jRCTs021200020, identifier [jRCTs021200020]
Arachidonate 15-lipoxygenase type B: Regulation, function, and its role in pathophysiology
Authors: Benatzy Yvonne , Palmer Megan A. , Brüne Bernhard
Published: November 2022

As a lipoxygenase (LOX), arachidonate 15-lipoxygenase type B (ALOX15B) peroxidizes polyenoic fatty acids (PUFAs) including arachidonic acid (AA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and linoleic acid (LA) to their corresponding fatty acid hydroperoxides. Distinctive to ALOX15B, fatty acid oxygenation occurs with positional specificity, catalyzed by the non-heme iron containing active site, and in addition to free PUFAs, membrane-esterified fatty acids serve as substrates for ALOX15B. Like other LOX enzymes, ALOX15B is linked to the formation of specialized pro-resolving lipid mediators (SPMs), and altered expression is apparent in various inflammatory diseases such as asthma, psoriasis, and atherosclerosis. In primary human macrophages, ALOX15B expression is associated with cellular cholesterol homeostasis and is induced by hypoxia. Like in inflammation, the role of ALOX15B in cancer is inconclusive. In prostate and breast carcinomas, ALOX15B is attributed a tumor-suppressive role, whereas in colorectal cancer, ALOX15B expression is associated with a poorer prognosis. As the biological function of ALOX15B remains an open question, this review aims to provide a comprehensive overview of the current state of research related to ALOX15B.
Receptor activator of nuclear factor-κB ligand-mediated osteoclastogenesis signaling pathway and related therapeutic natural compounds
Authors: Qu Zechao , Zhang Bo , Kong Lingbo , Gong Yining , Feng Mingzhe , Gao Xiangcheng , Wang Dong , Yan Liang
Published: November 2022

Osteoclast is a hematopoietic precursor cell derived from the mononuclear macrophage cell line, which is the only cell with bone resorption function. Its abnormal activation can cause serious osteolysis related diseases such as rheumatoid arthritis, Paget’s disease and osteoporosis. In recent years, the adverse effects caused by anabolic anti-osteolytic drugs have increased the interest of researchers in the potential therapeutic and preventive effects of natural plant derivatives and natural compounds against osteolytic diseases caused by osteoclasts. Natural plant derivatives and natural compounds have become major research hotspots for the treatment of osteolysis-related diseases due to their good safety profile and ability to improve bone. This paper provides an overview of recent advances in the molecular mechanisms of RANKL and downstream signaling pathways in osteoclast differentiation, and briefly outlines potential natural compounds with antiosteoclast activity and molecular mechanisms.
Effectiveness and safety of treating carotid atherosclerotic plaques with the method of nourishing qi, promoting blood circulation and expelling phlegm: A systematic review and meta-analysis
Authors: Li Jia , Du Yuying , Cai Chao , Liu Fuming
Published: November 2022

Objectives: This meta-analysis aimed at evaluating the effectiveness and safety of Chinese medicine (TCM), which nourished qi, promoted blood circulation, and expelled phlegm (YQHXZT), in treating carotid atherosclerosis (CAS) from an immunological perspective.

Background: The incidence of CAS has been increasing and tends to be younger. Although western medicine is effective, there are some limitations. TCM has certain advantages over the multichannel and multitarget treatment strategies in slowing down the process of CAS. However, there is no comprehensive review in this field.

Methods: Nine databases were searched from January, 2012, to September, 2022. After applying the inclusion and exclusion criteria to the RCTs, research quality evaluation and data extraction were conducted, and a meta-analysis of the articles was performed. The GRADE was used to assess the quality of the evidence.

Results: Fourteen RCTs involving 1,191 patients were identified. The results indicated that the experimental group was more effective in improving carotid intima-media thickness (CIMT)[SMD = −0.97, 95%CI(−.30,−0.65), p < 0.00001], reducing carotid plaque area [SMD = −1.98, 95%CI(−3.06,−0.89), p = 0.0003], lowering hs-CRP [SMD = −1.33, 95%CI(−1.59,-1.06), p < 0.00001] and LDL-C levels [SMD = −0.60, 95%CI(−0.83,-0.38), p < 0.00001]. Moreover, the experimental group was superior to peak systolic blood flow velocity (PSV) [SMD = −0.37, 95%CI(−0.59,−0.16), p = 0.0007], clinical efficacy [RR = 1.64, 95% CI (1.39, 1.94), p < 0.00001] and plaque area efficacy [RR = 1.36, 95% CI (1.22, 1.52), p < 0.0001]. The adverse reactions were not statistically significant in the two groups [RD = -0.01, 95% CI (-0.04.0.01), p = 0.17]. The results of grade evaluation suggested that the outcome indicators LDL-C, hs-CRP, plaque area efficacy, PSV, and adverse events were moderate. CIMT, plaque reduction area, and TCM clinical efficacy were low-quality.

Conclusion: The combination of YQHXZT can alleviate the process of CAS by inhibiting the thickening of CIMT, reducing plaque area and lowering hs-CRP and LDL-C levels. The mechanism may possibly be related to reducing lipid deposition and inhibiting the inflammatory response. Besides, the combination did not increase the risk of adverse effects. However, more well-designed RCTs are needed in the future.

Systematic review registration: CRD42022360529, https://www.crd.york.ac.uk/prospero/
Financial crisis prediction based on multilayer supervised network analysis
Authors: Qiu Lu , Su Rongpei , Wang Zhouwei
Published: November 2022

Financial crisis prediction is essential in preventing financial problems as its monitoring indicators help regulators judge the probability of future crises. In this context, the activities of the scientific community have been focused on the dynamics of single/multiple sequences and utilized unsupervised/supervised methods for financial crisis prediction. It is noteworthy that the cross-correlation between the risks of multiple economic entities makes financial network analysis paramount in crisis prediction. Focusing on this point, we propose a multilayer supervised network analysis (MSNA) method to train the multilayer network, and select the most suitable layer for financial crisis prediction. Specifically, we use 37 crucial stock market indices from 4 continents to create successive multilayer financial networks with 120-day windows and 1-day step by Pearson cross-correlation (PCC), variance decompositions (VD), transfer entropy (TE), minimum spanning tree (MST), directed MST (DMST), planar maximally filtered graph (PMFG) and directed PMFG (DPMFG) methods. Based on the multilayer network, we embed the graph neural network classification (GNNC) model and train the dynamic multilayer networks at each window scale (240,120, and 60 days). Finally, we conclude that the accuracy of the short window (60 days) is significantly higher than that of the long window. The network constructed by PCC with MST is the most suitable for short sequence (60 days) crisis prediction (AUC = 0.959), and the network constructed by TE with DMST is the most suitable for long sequence (240 days) crisis prediction (AUC = 0.772).
On-field low-frequency fatigue measurement after repeated drop jumps
Authors: Ridard Jade , Rozand Vianney , Millet Guillaume Y. , Lapole Thomas
Published: November 2022

Purpose: Monitoring fatigue is now commonly performed in athletes as it can directly impact performance and may further increase the risk of injury or overtraining syndrome. Among the exercise-induced peripheral alterations, low-frequency fatigue (LFF) assessment is commonly restricted to in-lab studies. Measuring LFF on-field would allow athletes and coaches to assess muscle fatigability on a regular basis. The aim of the present study was therefore to validate a new portable device allowing quadriceps LFF assessment in the field.

Methods: LFF was assessed in 15 active and healthy participants before (PRE) and after (POST) a series of drop jumps. LFF was assessed, thanks to a dedicated device recording evoked force to muscle submaximal electrical low- and high-frequency stimulation. Changes in the low- to high-frequency force ratio (further referred to as Powerdex® value) were compared to the changes in the ratio of evoked force induced by paired-pulse femoral nerve electrical stimulation at 10 and 100 Hz (i.e., DB10/DB100 ratio). Maximal voluntary contraction (MVC) and voluntary activation (VA) were also measured.

Results: MVC decreased (p < 0.001), whereas VA was not affected by the fatiguing task (p = 0.14). There was a decrease in the DB10/DB100 ratio (from 96.4% to 67.3%, p < 0.001) as well as in the Powerdex value (from 74.0% to 55.7%, p < 0.001). There was no significant difference between POST values (expressed in percentage of PRE values) of the DB10/DB100 ratio and Powerdex (p = 0.44), and there was a significant correlation between the changes in Powerdex® and DB10/DB100 (r = 0.82, p < 0.001).

Conclusion: The on-field device we tested is a valid tool to assess LFF after a strenuous exercise consisting of repeated drop jumps as it evidences the presence of LFF similarly to a lab technique. Such a device can be used to monitor muscle fatigability related to excitation–contraction in athletes.
Phenolic profiles and antioxidant activity in different organs of Sinopodophyllum hexandrum
Authors: Liu Wei , Zhang Zheng , Zhang Tong , Qiao Qi , Hou Xiaogai
Published: November 2022

Sinopodophyllum hexandrum is a perennial anti-cancer medicinal plant as unique phytochemical composition podophyllotoxin, and it has special effects on the treatments of pneumonic, cervical and testicular cancers. Besides the podophyllotoxin, phenolic substances play a key role in the clinical practice. However, few reports were available in terms of the phenolic compositions and antioxidant activity. In this work, main phenolic compounds were quantified by RP-HPLC in seven organs from S. hexandrum. Simultaneously, the sodium borohydride/chloranil-based (SBC) method and the Folin-Ciocalteau colorimetric method were used to determine total flavonoids and total phenols contents, respectively. The antioxidant activity of the different organs was further assessed by three methods (DPPH method, ABTS method and FRAP method). Phenolic compositions/total flavonoids contents/total phenols contents/antioxidant activity was observed to have significant differences among different organs (P<0.05), but have a consistent changing rule viz. rhizome>root>fruit>flower>leaf>stem>petiole. Furthermore, a correlation analysis was employed and indicated that a positive correlation existed between phenolic compositions contents and antioxidant activity. Obviously, rhizome had high phenolic compositions contents and strong antioxidant activity with the low DPPHIC50 value of 23.52 μg/mL, high ABTS value of 1137.82 μmol equiv. Trolox/g and high FRAP value of 685.76 μmol equiv. Trolox/g. Therefore, rhizome is recommended as a preponderant medicinal part, and root is proposed as an alternative raw material resource for natural antioxidant agents in functional food, medicine and chemicals. This study can provide a new insight into the utilization extension of S. hexandrum resources.
Plant responses to high temperature and drought: A bibliometrics analysis
Authors: Cui Yong , Ouyang Shengnan , Zhao Yongju , Tie Liehua , Shao Changchang , Duan Honglang
Published: November 2022

Global climate change is expected to further increase the frequency and severity of extreme events, such as high temperature/heat waves as well as drought in the future. Thus, how plant responds to high temperature and drought has become a key research topic. In this study, we extracted data from Web of Science Core Collections database, and synthesized plant responses to high temperature and drought based on bibliometric methods using software of R and VOSviewer. The results showed that a stabilized increasing trend of the publications (1199 papers) was found during the period of 2008 to 2014, and then showed a rapid increase (2583 papers) from year 2015 to 2021. Secondly, the top five dominant research fields of plant responses to high temperature and drought were Plant Science, Agroforestry Science, Environmental Science, Biochemistry, and Molecular Biology, respectively. The largest amount of published article has been found in the Frontiers in Plant Science journal, which has the highest global total citations and H-index. We also found that the journal of Plant Physiology has the highest local citations. From the most cited papers and references, the most important research focus was the improvement of crop yield and vegetation stress resistance. Furthermore, “drought” has been the most prominent keyword over the last 14 years, and more attention has been paid to “climate change” over the last 5 years. Under future climate change, how to regulate growth and development of food crops subjected to high temperature and drought stress may become a hotspot, and increasing research is critical to provide more insights into plant responses to high temperature and drought by linking plant above-below ground components. To summarize, this research will contribute to a comprehensive understanding of the past, present, and future research on plant responses to high temperature and drought.
Root colonization by the endophytic fungus Piriformospora indica shortens the juvenile phase of Piper nigrum L. by fine tuning the floral promotion pathways
Authors: Lekshmi R. S. , Sora S. , Anith K. N. , Soniya E. V.
Published: November 2022

Piriformospora indica, the mutualistic biotrophic root colonizing endosymbiotic fungus belonging to the order Sebacinales, offers host plants various benefits and enhances its growth and performance. The effect of colonization of P. indica in Piper nigrum L. cv. Panniyur1 on growth advantages, floral induction and evocation was investigated. Growth and yield benefits are credited to the alteration in the phytohormone levels fine-tuned by plants in response to the fungal colonization and perpetuation. The remarkable upregulation in the phytohormone levels, as estimated by LC- MS/MS and quantified by qRT-PCR, revealed the effectual contribution by the endophyte. qRT-PCR results revealed a significant shift in the expression of putative flowering regulatory genes in the photoperiod induction pathway (FLOWERING LOCUS T, LEAFY, APETALA1, AGAMOUS, SUPPRESSOR OF CONSTANS 1, GIGANTEA, PHYTOCHROMEA, and CRYPTOCHROME1) gibberellin biosynthetic pathway genes (GIBBERELLIN 20-OXIDASE2, GIBBERELLIN 2-OXIDASE, DELLA PROTEIN REPRESSOR OF GA1-3 1) autonomous (FLOWERING LOCUS C, FLOWERING LOCUS VE, FLOWERING LOCUS CA), and age pathway (SQUAMOSA PROMOTER LIKE9, APETALA2). The endophytic colonization had no effect on vernalization (FLOWERING LOCUS C) or biotic stress pathways (SALICYLIC ACID INDUCTION DEFICIENT 2, WRKY family transcription factor 22). The data suggest that P. nigrum responds positively to P. indica colonization, affecting preponement in floral induction as well as evocation, and thereby shortening the juvenile phase of the crop.
Risk factors and preventive strategies for post-traumatic stress disorder in neonatal intensive care unit
Authors: Di Chiara Maria , Laccetta Gianluigi , Gangi Sara , De Santis Benedetta , Spiriti Caterina , Attenni Martina , Bertolaso Laura , Boscarino Giovanni , De Nardo Maria Chiara , Ciambra Gianluca , Parisi Pasquale , Terrin Gianluca
Published: November 2022

Background

Preterm birth and admission to the neonatal intensive care unit (NICU) could induce post-traumatic stress disorder (PTSD). PTSD is an important factor to focus on, as it is associated with parental mental health difficulties and with changes in caregiving quality such as increased intrusiveness, reduced sensitivity, and increased attachment insecurity for the child.

Aims

We aimed to study the main risk factors, in the early life of newborns, and preventive measures for PTSD in parents of neonates hospitalized in the NICU.

Methods

We included parents of preterm newborns, consecutively admitted to the NICU of the University La Sapienza of Rome. The presence of PTSD following preterm birth and NICU admission was assessed using the Clinician-administered PTSD scale (CAPS) at enrollment and at 28–30 days following NICU admission or the moment of discharge. We also evaluated the Family Environment Scale which measures the social environment of all types of families; the Parental Stressor Scale which measures parental anxiety and stress; the Spielberger State-Trait Anxiety Inventory consisting of two parts measuring the State (response to present situation) and Trait (pre-disposition to be anxious) anxieties separately, and the Beck Depression Inventory Second Edition assessing depressive symptoms.

Results

We found, in a multivariate analysis, that the gestational age of newborns admitted to NICU significantly (β = 2.678; p = 0.040) influences the occurrence of PTSD. We found that the cases showed significantly (β = 2.443; p = 0.020) more pathological Parental Stressor Scale sights and sounds scores compared to controls. The early Kangaroo-Care (KC) significantly (β = −2.619; p = 0.015) reduces the occurrence of PTSD.

Conclusion

Post-traumatic stress disorder in parents of preterm newborns is a pathological condition that should be properly managed, in the very first days after birth. The NICU environment represents a main risk factor for PTSD, whereas KC has been demonstrated to have a protective role in the occurrence of PTSD.
The work design contribution to educational workers' sustainable wellbeing and performance patterns
Authors: Pérez-Nebra Amalia Raquel , Viana Brenda Soares , Lira Eva , Martín-Hernandez Pilar , Gracia-Pérez María Luisa , Gil-Lacruz Marta
Published: November 2022

Brazilian education faces difficulties relating to performance and illness, suggesting that the characteristics of the work can affect both variables. This study aims to describe the work characteristics that increase the odds of having happy–productive patterns in education workers. A total of 4,598 employees of the Secretariat of Education of the Federal District (SEEDF) participated in the research, answering questionnaires about work design (Brazilian version, with 18 factors), wellbeing (containing three factors), and performance. The results showed that task, social, and contextual characteristics increase the probability of being in the happy–productive pattern, and specifically, Social Support, Feedback from Others, Task Significance, Task Identity, and Autonomy, in this order, should be considered for intervention purposes.