bluuebunny/crossref_metadata_2025 huggingface dataset:
Diversion Colitis and Probiotic Stimulation: Effects of Bowel Stimulation Prior to Ileostomy Closure
Authors: Rodríguez-Padilla Ángela , Morales-Martín Germán , Pérez-Quintero Rocío , Rada-Morgades Ricardo , Gómez-Salgado Juan , Ruiz-Frutos Carlos
Published: June 2021

Background: Diversion colitis is a non-specific inflammation of a defunctionalised segment of the colon after a temporary stoma has been performed. This inflammation is associated with a change in the colonic flora.

Aim: To evaluate the efficacy and safety of preoperative stimulation of the efferent loop with probiotics prior to closure of the protective ileostomy in patients operated on colorectal carcinoma and its effect on diversion colitis. A prospective, randomised, double-blind, controlled study is carried out.

Methods: Patients who underwent surgery for colorectal carcinoma with protective ileostomy pending reconstructive surgery and with diversion colitis as diagnosis are included. Randomised and divided into two groups. Histological and endoscopic changes were evaluated after stimulation, after restorative surgery and during the short-term follow-up after surgery.

Results: Patients in CG were distributed according to the endoscopic index of severity in pre-stimulation/post-stimulation as follows: severe n = 9/9 (25.7%), moderate n = 23/23 (65.7%), and mild n = 3/3 (8.6%); compared to the distribution in SG, severe n = 9/0 (26.5/0%), moderate n = 23/3 (67.6/8.8%), mild n = 2/19 (5.9/55.9%) and normal colonoscopy in 0/12 patients (0/35.3%).

Conclusion: Probiotic stimulation of the efferent loop is a safe and effective method, managing to reduce both macroscopic and microscopic colitis, as well as a decrease in symptoms in the short term after reconstructive surgery.
Saudi Familial Hypercholesterolemia Patients With Rare LDLR Stop Gain Variant Showed Variable Clinical Phenotype and Resistance to Multiple Drug Regimen
Authors: Awan Zuhier Ahmed , Rashidi Omran M. , Al-Shehri Bandar Ali , Jamil Kaiser , Elango Ramu , Al-Aama Jumana Y. , Hegele Robert A. , Banaganapalli Babajan , Shaik Noor A.
Published: June 2021

Familial hypercholesterolemia (FH), a well-known lipid disease caused by inherited genetic defects in cholesterol uptake and metabolism is underdiagnosed in many countries including Saudi Arabia. The present study aims to identify the molecular basis of severe clinical manifestations of FH patients from unrelated Saudi consanguineous families. Two Saudi families with multiple FH patients fulfilling the combined FH diagnostic criteria of Simon Broome Register, and the Dutch Lipid Clinic Network (DLCN) were recruited. LipidSeq, a targeted resequencing panel for monogenic dyslipidemias, was used to identify causative pathogenic mutation in these two families and in 92 unrelated FH cases. Twelve FH patients from two unrelated families were sharing a very rare, pathogenic and founder LDLR stop gain mutation i.e., c.2027delG (p.Gly676Alafs*33) in both the homozygous or heterozygous states, but not in unrelated patients. Based on the variant zygosity, a marked phenotypic heterogeneity in terms of LDL-C levels, clinical presentations and resistance to anti-lipid treatment regimen (ACE inhibitors, β-blockers, ezetimibe, statins) of the FH patients was observed. This loss-of-function mutation is predicted to alter the free energy dynamics of the transcribed RNA, leading to its instability. Protein structural mapping has predicted that this non-sense mutation eliminates key functional domains in LDLR, which are essential for the receptor recycling and LDL particle binding. In conclusion, by combining genetics and structural bioinformatics approaches, this study identified and characterized a very rare FH causative LDLR pathogenic variant determining both clinical presentation and resistance to anti-lipid drug treatment.
Bather Shedding as a Source of Human Fecal Markers to a Recreational Beach
Authors: Li Dong , Van De Werfhorst Laurie C. , Steets Brandon , Ervin Jared , Murray Jill L. S. , Devarajan Naresh , Holden Patricia A.
Published: June 2021

Microbial source tracking (MST) can identify and locate surf zone fecal indicator bacteria (FIB) sources. However, DNA-based fecal marker results may raise new questions, since FIB and DNA marker sources can differ. Here, during 2 years of summertime (dry season) MST for a Goleta, California recreational beach, surf zone FIB were mainly from gulls, yet low level human-associated DNA-based fecal marker (HF183) was detected in 25 and 14% of surf zone water samples, respectively. Watershed sources were hypothesized because dry weather creek waters had elevated FIB, and runoff-generating rain events mobilized human (and dog) fecal markers andSalmonellaspp. into creeks, with human marker HF183 detected in 40 and 50% of creek water samples, dog markers detected in 70 and 50% of samples, andSalmonellaspp. in 40 and 33.3% of samples, respectively over 2 years. However, the dry weather estuary outlet was bermed in the first study year; simultaneously, creek fecal markers and pathogens were lower or similar to surf zone results. Although the berm breached in the second year, surf zone fecal markers stayed low. Watershed sediments, intertidal beach sands, and nearshore sediments were devoid of HF183 and dog-associated DNA markers. Based on dye tests and groundwater sampling, beach sanitary sewers were not leaking; groundwater was also devoid of HF183. Offshore sources appeared unlikely, since FIB and fecal markers decreased along a spatial gradient from the surf zone toward nearshore and offshore ocean waters. Further, like other regional beaches, surf zone HF183 corresponded significantly to bather counts, especially in the afternoons when there were more swimmers. However, morning detections of surf zone HF183 when there were few swimmers raised the possibility that the wastewater treatment plant (WWTP) offshore outfall discharged HF183 overnight which transported to the surf zone. These findings support that there may be lowest achievable limits of surf zone HF183 owing to several chronic and permanent, perhaps diurnal, low concentration sources.
Variation in Soil Microbial Communities Along an Elevational Gradient in Alpine Meadows of the Qilian Mountains, China
Authors: Duan Yulong , Lian Jie , Wang Lilong , Wang Xuyang , Luo Yongqing , Wang Wanfu , Wu Fasi , Zhao Jianhua , Ding Yun , Ma Jun , Li Yulin , Li Yuqiang
Published: June 2021

Bacterial, archaeal, and eukaryota diversity in mountainous areas varies along elevational gradients, but details remain unclear. Here, we use a next-generation sequencing method based on 16S/18S rRNA to reveal the soil microbial diversity and community compositions of alpine meadow ecosystems along an elevation span of nearly 2,000 m (1,936–3,896 m) in China’s Qilian Mountains. Both bacterial and eukaryota diversity increased linearly with increasing elevation, whereas archaeal diversity increased, but not significantly. The diversity patterns of several phyla in the bacterial, archaeal, and eukaryota communities were consistent with the overall elevational trend, but some phyla did not follow this pattern. The soil microbial community compositions were shaped by the coupled effects of regional climate and local soil properties. Intradomain links were more important than interdomain links in the microbial network of the alpine meadows, and these links were mostly positive. The bacteria formed more connections than either archaea or eukaryota, but archaea may be more important than bacteria in building the soil microbial co-occurrence network in this region. Our results provide new visions on the formation and maintenance of soil microbial diversity along an elevational gradient and have implications for microbial responses to climate change in alpine ecosystems.
Resting-State Functional Connectivity Signatures of Apathy in Community-Living Older Adults
Authors: Jang Jung Yun , Han S. Duke , Yew Belinda , Blanken Anna E. , Dutt Shubir , Li Yanrong , Ho Jean K. , Gaubert Aimée , Nation Daniel A.
Published: June 2021

Apathy predicts poor outcomes in older adults, and its underlying neural mechanism needs further investigation. We examined the association between symptoms of apathy and functional connectivity (FC) in older adults without stroke or dementia. Participants included 48 individuals (mean age = 70.90) living independently in the community, who underwent resting-state fMRI and completed the Apathy Evaluation Scale (AES). Seed-to-voxel analysis (cluster-level p-FDR <0.05, voxel threshold p < 0.001) tested the association between AES scores and the whole-brain FC of brain regions involved in reward- and salience-related processing. We found that AES scores were negatively associated with FC of the right insula cortex and right anterior temporal regions (124 voxels, t = −5.10) and FC of the left orbitofrontal cortex and anterior cingulate regions (160 voxels, t = −5.45), and were positively associated with FC of the left orbitofrontal cortex and left lateral prefrontal (282 voxels, t = 4.99) and anterior prefrontal (123 voxels, t = 4.52) regions. These findings suggest that apathy in older adults may reflect disruptions in neural connectivity involved in reward- and salience-related processing.
A Narrative Review of Cerebellar Malfunctions and Sleep Disturbances
Authors: Song Bijia , Zhu Jun-Chao
Published: June 2021

Cerebellar malfunctions significantly impact the regulation of the sleep–wakefulness transition. The possible mechanism for this effect is still unknown. Evidence on the role of cerebellar processing in the sleep–wake cycle is derived mainly from animal studies, and clinical management of the sleep–wake cycle is also challenging. The purpose of this review is to investigate the role of cerebellar activity during normal sleep and the association between cerebellar dysfunction and sleep disorders. Large-scale, multicenter trials are still needed to confirm these findings and provide early identification and intervention strategies to improve cerebellar function and the sleep quality of patients.
Introducing Plant-Based Mediterranean Diet as a Lifestyle Medicine Approach in Latin America: Opportunities Within the Chilean Context
Authors: Figueroa Catalina , Echeverría Guadalupe , Villarreal Grisell , Martínez Ximena , Ferreccio Catterina , Rigotti Attilio
Published: June 2021

Latin America is experiencing a significant epidemiological and nutritional transition, with a trend toward higher incidence of food-related chronic diseases. In this context, Lifestyle Medicine (LM) is a growing field focused on assisting individuals in adopting healthy behaviors for the prevention and treatment of these chronic diseases, including, among other pillars, a great emphasis on healthy eating. There is also a growing interest worldwide in environmental sustainability of dietary patterns, with increasing concern about their effects on planetary health. In this context, whole-food, plant-based diets -such as the Mediterranean diet (MD)- have emerged as a solution for both healthier eating and lowering environmental impact. Yet in order to be effective at these goals and achieve a high adherence to any nutritional prescription, the sociocultural reality of the community or population where we aim to practice must also be taken into account. In this review, we specifically highlight the plant-based MD as a LM-contextualized dietary pattern that is adaptable, applicable, and sustainable within the Chilean context and has the potential to address the current trend of chronic diseases in our country.
The Association Between Dietary Inflammatory Index and Parathyroid Hormone in Adults With/Without Chronic Kidney Disease
Authors: Qin Zheng , Yang Qinbo , Liao Ruoxi , Su Baihai
Published: June 2021

Aims: We aimed to assess the association between dietary inflammation index (DII) with parathyroid hormone (PTH) and hyperparathyroidism (HP) in adults with/without chronic kidney disease (CKD).

Methods: Data were obtained from the 2003–2006 National Health and Nutrition Examination Survey (NHANES). The participants who were <18 years old, pregnant, or missing the data of DII, PTH, and CKD were excluded. DII was calculated based on a 24-h dietary recall interview for each participant. Weighted multivariable regression analysis and subgroup analysis were conducted to estimate the independent relationship between DII with PTH and the HP in the population with CKD/non-CKD.

Results: A total of 7,679 participants were included with the median DII of −0.24 (−2.20 to 1.80) and a mean PTH level of 43.42 ± 23.21 pg/ml. The average PTH was 45.53 ± 26.63 pg/ml for the participants in the highest tertile group compared with 41.42 ± 19.74 pg/ml in the lowest tertile group (P < 0.0001). The rate of HP was 11.15% overall, while the rate in the highest DII tertile was 13.28 and 8.60% in the lowest DII tertile (P < 0.0001). The participants with CKD tended to have higher PTH levels compared with their counterparts (61.23 ± 45.62 vs. 41.80 ± 19.16 pg/ml, P < 0.0001). A positive association between DII scores and PTH was observed (β = 0.46, 95% CI: 0.25, 0.66, P ≤ 0.0001), and higher DII was associated with an increased risk of HP (OR = 1.05, 95% CI: 1.02, 1.08, P = 0.0023). The results from subgroup analysis indicated that this association was similar in the participants with different renal function, gender, age, BMI, hypertension, and diabetes statuses and could also be appropriate for the population with CKD.

Conclusions: Higher consumption of a pro-inflammatory diet appeared to cause a higher PTH level and an increased risk of HP. Anti-inflammatory dietary management may be beneficial to reduce the risk of HP both in the population with and without CKD.
INSTIGO Trial: Evaluation of a Plasma Protein Profile as a Predictive Biomarker for Metastatic Relapse of Triple Negative Breast Cancer
Authors: Veyssière Hugo , Lusho Sejdi , Molnar Ioana , Kossai Myriam , Bernadach Maureen , Abrial Catherine , Bidet Yannick , Radosevic-Robin Nina , Durando Xavier
Published: June 2021

Background

Triple negative breast cancer (TNBC) accounts for 10-20% of breast cancers but has no specific therapy. While TNBC may be more sensitive to chemotherapy than other types of breast cancer, it has a poor prognosis. Most TNBC relapses occur during the five years following treatment, however predictive biomarkers of metastatic relapse are still lacking. High tumour-infiltrating lymphocytes (TILs) levels before and after neo-adjuvant chemotherapy (NAC) are associated with lower relapse risk and longer survival but TILs assessment is highly error-prone and still not introduced into the clinic. Therefore, having reliable biomarker of relapse, but easier to assess, remains essential for TNBC management. Searching for such biomarkers among serum/plasma proteins, circulating tumoral DNA (ctDNA) and blood cells appear relevant.

Methods

This single-centre and prospective study aims to discover predictive biomarkers of TNBC relapse and particularly focuses on plasma proteins. Blood samples will be taken at diagnosis, on the day of first-line or post-NAC surgery, on the day of radiotherapy start, then 6 months and one year after radiotherapy. A blood sample will be taken at the time of metastatic relapse diagnosis. Blood samples will be used for circulating protein quantification, blood cell counts and circulating tumour DNA quantification. A tumour RNA signature, based on the analysis of the RNA expression of 6 genes, will also be tested from the initial biopsy taken routinely. In NAC patients, TILs quantity will be assessed on TNBC pre-treatment biopsy and surgical specimen.

Ethics and Dissemination

INSTIGO belongs to category 2 interventional research on humans. This study has been approved by the SUD-EST IV ethics committee and is conducted in accordance with the Declaration of Helsinki and General Data Protection Regulation (GDPR). Study findings will be published in peer-reviewed medical journals.

Clinical Trial Registration

ClinicalTrials.gov, identifier NCT04438681.
Comparison of Diagnostic Performance of Spread Through Airspaces of Lung Adenocarcinoma Based on Morphological Analysis and Perinodular and Intranodular Radiomic Features on Chest CT Images
Authors: Qi Lin , Li Xiaohu , He Linyang , Cheng Guohua , Cai Yongjun , Xue Ke , Li Ming
Published: June 2021

Object

STAS is associated with poor differentiation, KRAS mutation and poor recurrence-free survival. The aims of this study are to evaluate the ability of intra- and perinodular radiomic features to distinguish STAS at non-contrast CT.

Patients and Methods

This retrospective study included 216 patients with pathologically confirmed lung adenocarcinoma (STAS+, n = 56; STAS−, n = 160). Texture-based features were extracted from intra- and perinodular regions of 2, 4, 6, 8, 10, and 20 mm distances from the tumor edge using an erosion and expansion algorithm. Traditional radiologic features were also analyzed including size, consolidation tumor ratio (CTR), density, shape, vascular change, cystic airspaces, tumor–lung interface, lobulation, spiculation, and satellite sign. Nine radiomic models were established by using the eight separate models and a total of the eight VOIs (eight-VOI model). Then the prediction efficiencies of the nine radiomic models were compared to predict STAS of lung adenocarcinomas.

Results

Among the traditional radiologic features, CTR, unclear tumor–lung interface, and satellite sign were found to be associated with STAS significantly, and the AUCs were 0.796, 0.677, and 0.606, respectively. Radiomic model of combined tumor bodies and all the distances of perinodular areas (eight-VOI model) had better predictive efficiency for predicting STAS+ lung adenocarcinoma. The AUCs of the eight-VOI model in the training and verification sets were 0.907 (95%CI, 0.862–0.947) in the training set, and 0.897 (95%CI, 0.784–0.985) in the testing set, and 0.909 (95%CI, 0.863–0.949) in the external validation set, and the diagnostic accuracy in the external validation set was 0.849.

Conclusion

Radiomic features from intra- and perinodular regions of nodules can best distinguish STAS of lung adenocarcinoma.
Automatic Pancreatic Ductal Adenocarcinoma Detection in Whole Slide Images Using Deep Convolutional Neural Networks
Authors: Fu Hao , Mi Weiming , Pan Boju , Guo Yucheng , Li Junjie , Xu Rongyan , Zheng Jie , Zou Chunli , Zhang Tao , Liang Zhiyong , Zou Junzhong , Zou Hao
Published: June 2021

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancer types worldwide, with the lowest 5-year survival rate among all kinds of cancers. Histopathology image analysis is considered a gold standard for PDAC detection and diagnosis. However, the manual diagnosis used in current clinical practice is a tedious and time-consuming task and diagnosis concordance can be low. With the development of digital imaging and machine learning, several scholars have proposed PDAC analysis approaches based on feature extraction methods that rely on field knowledge. However, feature-based classification methods are applicable only to a specific problem and lack versatility, so that the deep-learning method is becoming a vital alternative to feature extraction. This paper proposes the first deep convolutional neural network architecture for classifying and segmenting pancreatic histopathological images on a relatively large WSI dataset. Our automatic patch-level approach achieved 95.3% classification accuracy and the WSI-level approach achieved 100%. Additionally, we visualized the classification and segmentation outcomes of histopathological images to determine which areas of an image are more important for PDAC identification. Experimental results demonstrate that our proposed model can effectively diagnose PDAC using histopathological images, which illustrates the potential of this practical application.
Radiomics Analysis of Contrast-Enhanced CT Predicts Survival in Clear Cell Renal Cell Carcinoma
Authors: Yan Lei , Yang Guangjie , Cui Jingjing , Miao Wenjie , Wang Yangyang , Zhao Yujun , Wang Ning , Gong Aidi , Guo Na , Nie Pei , Wang Zhenguang
Published: June 2021

Purpose

To develop and validate the radiomics nomogram that combines clinical factors and radiomics features to estimate overall survival (OS) in patients with clear cell renal cell carcinoma (ccRCC), and assess the incremental value of radiomics for OS estimation.

Materials and Methods

One hundred ninety-four ccRCC cases were included in the training cohort and 188 ccRCC patients from another hospital as the test cohort. Three-dimensional region-of-interest segmentation was manually segmented on multiphasic contrast-enhanced abdominal CT images. Radiomics score (Rad-score) was calculated from a formula generated via least absolute shrinkage and selection operator (LASSO) Cox regression, after which the association between the Rad-score and OS was explored. The radiomics nomogram (clinical factors + Rad-score) was developed to demonstrate the incremental value of the Rad-score to the clinical nomogram for individualized OS estimation, which was then evaluated in relation to calibration and discrimination.

Results

Rad-score, calculated using a linear combination of the 11 screened features multiplied by their respective LASSO Cox coefficients, was significantly associated with OS. Calibration curves showed good agreement between the OS predicted by the nomograms and observed outcomes. The radiomics nomogram presented higher discrimination capability compared to clinical nomogram in the training (C-index: 0.884; 95% CI: 0.808–0.940 vs. 0.803; 95% CI: 0.705–0.899, P < 0.05) and test cohorts (C-index: 0.859; 95% CI: 0.800–0.921 vs. 0.846; 95% CI: 0.777–0.915, P < 0.05).

Conclusions

The radiomics nomogram may be used for predicting OS in patients with ccRCC, and radiomics is useful to assist quantitative and personalized treatment.
ASRGL1 Correlates With Immune Cell Infiltration in Hepatocellular Carcinoma and Can Serve as a Prognostic Biomarker
Authors: Xue Cailin , Gao Peng , Cui Xiaohan , Zhang Xudong , Lei Jin , Li Renzhi , Zhu Chunfu , Qin Xihu
Published: June 2021

Background

The enzyme L-asparaginase (ASRGL1) catalyzes the hydrolysis of L-asparagine (Asn) to L-aspartic acid (Asp) and ammonia. Numerous studies have shown a strong correlation between ASRGL1 expression and tumorigenesis. However, the expression and biological function of ASRGL1 in hepatocellular carcinoma (HCC) are still unclear.

Methods

We explored the mRNA expression of ASRGL1 in HCC using the HCCDB, Oncomine, and TIMER 2.0 databases. Western blotting and immunohistochemical analyses were also used to determine the mRNA expression of ASRGL1 in HCC. LinkedOmics was used to analyze the genes co-expressed with ASRGL1 and regulators including kinases, miRNAs, and transcription factors. The Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of the co-expressed genes were also investigated using LinkedOmics. The correlation between ASRGL1 expression and immune infiltrates was analyzed using the TIMER 2.0 and Gene Expression Profiling Interactive Analysis (GEPIA) databases. The effects of ASRGL1 expression on patient outcome were investigated using the UALCAN and GEPIA databases, and the Kaplan–Meier plotter. c-Bioportal was used to explore the mutations of ASRGL1 in HCC.

Results

Compared with the adjacent tissues, ASRGL1 was upregulated in HCC. High ASRGL1 expression in HCC indicated poor relapse-free survival, progression-free survival, disease-specific survival, and overall survival. The expression of ASRGL1 was significantly correlated with infiltrating levels of B cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells in HCC.

Conclusion

Our findings suggest that ASRGL1 is overexpressed in HCC and that ASRGL1 expression was significantly correlated with immune infiltration in HCC and prognosis. Therefore, ASRGL1 may serve as a biomarker for the early diagnosis and treatment of HCC.
Secondary Hemophagocytic Lymphohistiocytosis With Epstein–Barr Virus-Associated Transformed Follicular Lymphoma: A Case Report and Literature Review
Authors: Xu Huan , Xu Xia , Cui Guohui , Fang Jun , Chen Wanxin , Xue Mei , Jin Runming , Chen Hongbo , Zhang Lu , Hu Yu
Published: June 2021

A 58-year-old male was admitted to our hospital due to lasting fever, progressive lymphadenopathy and bicytopenia, with a previously histological diagnosis of follicular lymphoma grade 3a with Epstein–Barr virus-encoded RNA positive one month ago. A second biopsy of axillary lymph node revealed concurrent diffuse large B-cell lymphoma with Epstein–Barr virus-encoded RNA positive. Another diagnosis of hemophagocytic lymphohistiocytosis secondary to Epstein–Barr virus positive diffuse large B-cell lymphoma was further concluded by clinical manifestation, laboratory test and atypical lymphocytes in peripheral-blood smear. After a pulse of steroid pre-phase treatment, the patient’s clinical condition deteriorated and died in two weeks. The presence of Epstein–Barr virus infection in patients with follicular lymphoma is associated with more aggressive clinical course and increased risk of high-grade transformation. Hemophagocytic lymphohistiocytosis in response to Epstein–Barr virus infection or lymphoma remains fatal. Early diagnosis and initiation of treatment may improve the outcome.
Survival, Chemotherapy and Chemosensitivity Predicted by CTC Cultured In Vitro of SCLC Patients
Authors: Ju Lixia , Yang Juan , Zhai Changyun , Chai Shuizhen , Dong Zhiyi , Li Minghua
Published: June 2021

Purpose

The prognosis for small cell lung cancer (SCLC) patients receiving later-line treatment is very poor and there is still no standard treatments after the second-line setting. Analyzing the susceptibility of chemotherapeutic drugs with circulating tumor cells (CTCs) cultured in vitro may contribute to optimize the therapeutic regimen. However, so far CTCs have been barely used for studying their chemosensitivity due to the lack of technology to obtain wholly intact and viable CTCs.

Methods

Based on a retrospective study of the therapeutic response of 99 patients with unresectable SCLC, the CTC count in 14 SCLC patients was detected before and after chemotherapy to evaluate its role as a potential marker of response. Furthermore, the drug susceptibility of CTCs cultured in vitro obtained from ClearCell FX® System was tested and the therapy response was evaluated.

Results

All of the 99 patients received the first-line chemotherapy and the objective response rate (ORR) was 74.7%. A total of 36 patients received the second-line therapy and the average duration was 2.6 months, and only 11 cases out of them received the third-line therapy but no one responded. The change of CTC counts was identified to be correlated with therapy response. However all the five SCLC patients who were administered with the drugs according to the drug susceptibility test of CTCs for two cycles underwent progression of disease.

Conclusion

The results showed that the responses of chemotherapy are very poor in later lines and the drug susceptibility test using CTCs primary cultured in vitro may not benefit the improvement of therapeutic regimen of SCLC patients.
68Ga-FAPI-04 Versus 18F-FDG PET/CT in the Detection of Hepatocellular Carcinoma
Authors: Wang Hao , Zhu Wenwei , Ren Shuhua , Kong Yanyan , Huang Qi , Zhao Jun , Guan Yihui , Jia Huliang , Chen Jinhong , Lu Lu , Xie Fang , Qin Lunxiu
Published: June 2021

Background

Fibroblast activation protein (FAP) is commonly expressed in activated stromal fibroblasts in various epithelial tumours. Recently, 68Ga-FAPI-04 has been used for tumour imaging in positron emission tomography/computed tomography (PET/CT). This study aimed to compare the diagnostic performances of 68Ga-FAPI-04 PET/CT and 18F-FDG PET/CT in hepatocellular carcinoma (HCC), and to assess factors associated with 68Ga-FAPI-04 uptake in HCC.

Materials and Methods

Twenty-nine patients with suspiciously HCC who received both 18F-FDG and 68Ga-FAPI-04 PET/CT were included in this retrospective study. The results were interpreted by two experienced nuclear medicine physicians independently. The maximum and mean standardized uptake values (SUVmax and SUVmean) were measured in the lesions and liver background, respectively. The tumour-to-background ratio (TBR) was then calculated as lesion’s SUVmax divided by background SUVmean.

Results

A total of 35 intrahepatic lesions in 25 patients with HCC were finally involved in the statistical analysis. 68Ga-FAPI-04 PET/CT showed a higher sensitivity than 18F-FDG PET/CT in detecting intrahepatic HCC lesions (85.7% vs. 57.1%, P = 0.002), including in small (≤ 2 cm in diameter; 68.8% vs. 18.8%, P = 0.008) and well- or moderately-differentiated (83.3% vs. 33.3%, P = 0.031) tumors. SUVmax was comparable between 68Ga-FAPI-04 and 18F-FDG (6.96 ± 5.01 vs. 5.89 ± 3.38, P > 0.05), but the TBR was significantly higher in the 68Ga-FAPI-04 group compared with the 18F-FDG group (11.90 ± 8.35 vs. 3.14 ± 1.59, P < 0.001). SUVmax and the TBR in 68Ga-FAPI-04 positive lesions were associated with tumour size (both P < 0.05), but not the remaining clinical and pathological features (all P > 0.05).

Conclusions

68Ga-FAPI-04 PET/CT is more sensitive than 18F-FDG PET/CT in detecting HCC lesions, and 68Ga-FAPI-04 uptake is correlated mainly with tumour size.
TGF-β1 Induces Immune Escape by Enhancing PD-1 and CTLA-4 Expression on T Lymphocytes in Hepatocellular Carcinoma
Authors: Bao Shixiang , Jiang Xiaopei , Jin Shuai , Tu Peipei , Lu Jingtao
Published: June 2021

Primary liver cancer (PLC) is one of the most common types of cancer worldwide. Hepatocellular carcinoma (HCC) accounts for approximately 90% of PLC cases. The HCC microenvironment plays an important role in the occurrence and development of HCC. Immunotherapy for the HCC microenvironment has become an effective treatment strategy. T lymphocytes are an important part of the HCC microenvironment, and programmed cell death 1 (PD-1) and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) are the main immunosuppressive molecules of T lymphocytes. Transforming growth factor β1 (TGF-β1) can inhibit the immune function of T lymphocytes and promote the occurrence and development of tumors. However, few studies have explored whether TGF-β1 can upregulate the expression of PD-1 and CTLA-4 on T cells. In this study, we showed that TGF-β1 upregulated the expression of PD-1 and CTLA-4 on T lymphocytes and attenuated the cytotoxicity of T lymphocytes for HCC cells in vitro and in vivo. In addition, TGF-β1 increased the apoptosis of T lymphocytes induced by HCC cells. Finally, we found that the mechanism by which TGF-β1 upregulates the expression of PD-1 and CTLA-4 on T lymphocytes may be related to the calcineurin-nuclear factor of activated T cells 1 (CaN/NFATc1) pathway. This study will provide some experimental basis for liver cancer immunotherapy based on the tumor microenvironment.
Expression and Role of Heparan Sulfated Proteoglycans in Pancreatic Cancer
Authors: Furini Simone , Falciani Chiara
Published: June 2021

Pancreatic cancer is a lethal condition with poor outcomes and an increasing incidence. The unfavourable prognosis is due to the lack of early symptoms and consequent late diagnosis. An effective method for the early diagnosis of pancreatic cancer is therefore sought by many researchers in the field. Heparan sulfated proteoglycan-related genes are often expressed differently in tumors than in normal tissues. Alteration of the tumor microenvironment is correlated with the ability of heparan sulfated proteoglycans to bind cytokines and growth factors and eventually to influence tumor progression. Here we discuss the importance of glypicans, syndecans, perlecan and extracellular matrix modifying enzymes, such as heparanases and sulfatases, as potential diagnostics in pancreatic cancer. We also ran an analysis on a multidimensional cancer genomics database for heparan sulfated proteoglycan-related genes, and report altered expression of some of them.
A New Prognostic Risk Signature of Eight Ferroptosis-Related Genes in the Clear Cell Renal Cell Carcinoma
Authors: Chen Ji , Zhan Yating , Zhang Rongrong , Chen Bo , Huang Junting , Li Chunxue , Zhang Wenjie , Wang Yajing , Gao Yuxiang , Zheng Jianjian , Li Yeping
Published: June 2021

Clear cell renal cell carcinoma (ccRCC) is the most common renal cell carcinoma and has poor prognosis in the locally advanced stage. Ferroptosis, a relatively new type of cell death, has gained significant attention in recent years. This study aimed to explore the prognostic value of ferroptosis-related genes (FRGs) in ccRCC. In this study, 50 differentially expressed FRGs between ccRCC and adjacent normal kidney tissues were identified, 26 of them correlated with overall survival (OS) (P <0.05). Eight optimal FRGs were selected by Lasso regression and multivariate Cox regression analysis, and used to construct a new prognostic risk signature to predict the prognosis of ccRCC patients. In addition, the signature passed the validation of prognostic survival analyses by a significant margin, and the risk score was identified as an independent prognostic marker via Cox regression analyses. Further studies indicated that the signature was significantly correlated with immune cell infiltration. Moreover, the levels of eight FRGs were examined in ccRCC. Collectively, the 8-FRG prognostic risk signature helps the clinicians predict the prognosis and OS of the patients, and standardize prognostic assessments.
Activated PI3Kinase Delta Syndrome—A Multifaceted Disease
Authors: Thouenon Romane , Moreno-Corona Nidia , Poggi Lucie , Durandy Anne , Kracker Sven
Published: June 2021

Autosomal dominant gain-of-function mutations in the PIK3CD gene encoding the catalytic subunit p110δ of phosphoinositide 3-kinase-δ (PI3K-δ) or autosomal dominant loss-of-function mutations in the PIK3R1 gene encoding the p85α, p55α and p50α regulatory subunits cause Activated PI3-kinase-δ syndrome (APDS; referred as type 1 APDS and type 2 APDS, respectively). Consequences of these mutations are PI3K-δ hyperactivity. Clinical presentation described for both types of APDS patients is very variable, ranging from mild or asymptomatic features to profound combined immunodeficiency. Massive lymphoproliferation, bronchiectasis, increased susceptibility to bacterial and viral infections and, at a lesser extent, auto-immune manifestations and occurrence of cancer, especially B cell lymphoma, have been described for both types of APDS patients. Here, we review clinical presentation and treatment options as well as fundamental immunological and biological features associated to PI3K-δ increased signaling.
Loureirin B Exerts its Immunosuppressive Effects by Inhibiting STIM1/Orai1 and KV1.3 Channels
Authors: Shi Shujuan , Zhao Qianru , Ke Caihua , Long Siru , Zhang Feng , Zhang Xu , Li Yi , Liu Xinqiao , Hu Hongzhen , Yin Shijin
Published: June 2021

Loureirin B (LrB) is a constituent extracted from traditional Chinese medicine Resina Draconis. It has broad biological functions and an impressive immunosuppressive effect that has been supported by numerous studies. However, the molecular mechanisms underlying Loureirin B-induced immune suppression are not fully understood. We previously reported that Loureirin B inhibited KV1.3 channel, calcium ion (Ca2+) influx, and interleukin-2 (IL-2) secretion in Jurkat T cells. In this study, we applied CRISPR/Cas9 to edit KV1.3 coding gene KCNA3 and successfully generated a KV1.3 knockout (KO) cell model to determine whether KV1.3 KO was sufficient to block the Loureirin B-induced immunosuppressive effect. Surprisingly, we showed that Loureirin B could still inhibit Ca2+ influx and IL-2 secretion in the Jurkat T cells in the absence of KV1.3 although KO KV1.3 reduced about 50% of Ca2+ influx and 90% IL-2 secretion compared with that in the wild type cells. Further experiments showed that Loureirin B directly inhibited STIM1/Orai1 channel in a dose-dependent manner. Our results suggest that Loureirin B inhibits Ca2+ influx and IL-2 secretion in Jurkat T cells by inhibiting both KV1.3 and STIM1/Orai1 channels. These studies also revealed an additional molecular target for Loureirin B-induced immunosuppressive effect, which makes it a promising leading compound for treating autoimmune diseases.
Identification of the Target for a Transition Metal-α-Amino Acid Complex Antibiotic Against Mycobacterium smegmatis
Authors: Karpin George W. , Merola Joseph S. , Falkinham Joseph O.
Published: June 2021

Spontaneous mutants of Mycobacterium smegmatis strain mc2155 resistant to 1-PG (iridium-L-phenylglycine complex), an antimycobacterial antibiotic, were isolated. Based on the discovery that some 1-PG-resistant mutants (1-PGR) were also resistant to high concentrations of clarithromycin (≥250 μg/ml), but no other anti-mycobacterial antibiotics, the 23S rRNA region spanning the peptidyl transferase domain was sequenced and mutations shown to be localized in the peptidyl transferase domain of the 23S rRNA gene. Measurements showed that 1-PG bound to ribosomes isolated from the 1-PG-sensitive parental strain, but the ribosome binding values for the 1-PGR mutant reduced.
Negotiating the Descriptive–Normative Frontier of Complexity Research in the Anthropocene
Authors: Leach Michael C.
Published: June 2021

This mini-review article offers a commentary on a singular analytical problem faced by legal scholars who use complexity theory and methods in legal research on climate change and the “Anthropocene”. It positions such research as a subset of complexity scholarship in law, which is generally faced with the methodological and analytical challenge of negotiating and reconciling empirical description with normative prescription. It argues that this challenge is particularly acute for legal scholars writing on climate change and the Anthropocene. Using examples from scholars writing about “Earth systems law,” it demonstrates how a heavy reliance on complexity-based empirical data as a source material for normative claim-making can distract scholars from important but difficult questions about normative legitimacy and how legal change happens at multiple levels. The special epistemological challenges posed by climate change and the Anthropocene should demand that scholars writing in this domain be especially mindful and explicit on how they link complexity descriptions to the normative claims they make, both for the sake of scientific credibility as well as for the legitimacy and viability of their propositions.
Mild Hypoxia Enhances the Expression of HIF and VEGF and Triggers the Response to Injury in Rat Kidneys
Authors: Xu Yaya , Kong Xiangmei , Li Jiru , Cui Tiantian , Wei Yifan , Xu Jiayue , Zhu Yueniu , Zhu Xiaodong
Published: June 2021

Background

Hypoxia contributes to a cascade of inflammatory response mechanisms in kidneys that result in the development of renal interstitial fibrosis and subsequent chronic renal failure. Nonetheless, the kidney possesses a self-protection mechanism under a certain degree of hypoxia and this mechanism its adaptation to hypoxia. As the hypoxia-inducible factor (HIF)–vascular endothelial growth factor (VEGF) axis is a key pathway for neovascularization, the activation of this axis is a target for renal hypoxia therapies.

Methods

Sprague–Dawley rats were exposed to normobaric hypoxia and subdivided into three groups, namely group A (21% O2), group B (10% O2), and group C (7% O2). Renal tissue samples were processed and analyzed to determine pathological morphological changes, the expression of HIF, VEGF, inflammation factor and vascular density.

Results

We found that as the duration of hypoxia increased, destructive changes in the kidney tissues became more severe in group C (7% O2). In contrast, the increased duration of hypoxia did not exacerbate kidney damage in group B (10% O2). As the hypoxia was prolonged and the degree of hypoxia increased, the expression of HIF-1α increased gradually. As hypoxia time increased, the expression of VEGF increased gradually, but VEGF expression in group B (10% O2) was the highest. Group C (7% O2) had higher levels of IL-6, IL-10, and TNF-alpha. Additionally, the highest vascular density was observed in group B.

Conclusion

These findings suggest that activating the HIF–VEGF signaling pathway to regulate angiogenesis after infliction of hypoxic kidney injury may provide clues for the development of novel CKD treatments.
Genome Wide Association Mapping of Root Traits in the Andean Genepool of Common Bean (Phaseolus vulgaris L.) Grown With and Without Aluminum Toxicity
Authors: Ambachew Daniel , Blair Matthew W.
Published: June 2021

Common bean is one of the most important grain legumes for human diets but is produced on marginal lands with unfavorable soil conditions; among which Aluminum (Al) toxicity is a serious and widespread problem. Under low pH, stable forms of Al dissolve into the soil solution and as phytotoxic ions inhibit the growth and function of roots through injury to the root apex. This results in a smaller root system that detrimentally effects yield. The goal of this study was to evaluate 227 genotypes from an Andean diversity panel (ADP) of common bean and determine the level of Al toxicity tolerance and candidate genes for this abiotic stress tolerance through root trait analysis and marker association studies. Plants were grown as seedlings in hydroponic tanks at a pH of 4.5 with a treatment of high Al concentration (50 μM) compared to a control (0 μM). The roots were harvested and scanned to determine average root diameter, root volume, root surface area, number of root links, number of root tips, and total root length. Percent reduction or increase was calculated for each trait by comparing treatments. Genome wide association study (GWAS) was conducted by testing phenotypic data against single nucleotide polymorphism (SNP) marker genotyping data for the panel. Principal components and a kinship matrix were included in the mixed linear model to correct for population structure. Analyses of variance indicated the presence of significant difference between genotypes. The heritability of traits ranged from 0.67 to 0.92 in Al-treated and reached similar values in non-treated plants. GWAS revealed significant associations between root traits and genetic markers on chromosomes Pv01, Pv04, Pv05, Pv06, and Pv11 with some SNPs contributing to more than one trait. Candidate genes near these loci were analyzed to explain the detected association and included an Al activated malate transporter gene and a multidrug and toxic compound extrusion gene. This study showed that polygenic inheritance was critical to aluminum toxicity tolerance in common beans roots. Candidate genes found suggested that exudation of malate and citrate as organic acids would be important for Al tolerance. Possible cross-talk between mechanisms of aluminum tolerance and resistance to other abiotic stresses are discussed.
Novel Sources of Tolerance to Aluminium Toxicity in Wild Cicer (Cicer reticulatum and Cicer echinospermum) Collections
Authors: Vance Wendy , Pradeep Karthika , Strachan Scott R. , Diffey Simon , Bell Richard W.
Published: June 2021

In acid soils, the toxic form of aluminium, Al3+, significantly inhibits root growth and elongation, leading to less water and nutrient uptake. Previous research had shown differential Al toxicity tolerance among cultivated Cicer arietinum L. (chickpea); however, the potential for developing tolerant cultivars is limited by the narrow genetic diversity of cultivated chickpeas. Recent collections from Turkey of wild Cicer species, Cicer reticulatum, and Cicer echinospermum, have increased the available gene pool significantly, but there has been no large-scale screening of wild Cicer for acid tolerance or Al3+ toxicity tolerance. This study evaluated 167 wild Cicer and 17 Australian chickpea cultivars in a series of screenings under controlled growth conditions. The pH of 4.2 and Al concentrations of 15 and 60 μM Al were selected for large-scale screening based on dose response experiments in a low ionic strength nutrient solution. The change in root length showed better discrimination between tolerant and sensitive lines when compared with shoot and root dry weights and was used as a selection criterion. In a large-scale screening, 13 wild Cicer reticulatum accessions had a higher root tolerance index (≥50%), and eight had higher relative change in root length (≥40%) compared with PBA Monarch, which showed greater tolerance among the Australian domestic cultivars screened. In general, C. reticulatum species were found to be more tolerant than C. echinospermum, while genetic population groups Ret_5, Ret_6, and Ret_7 from Diyarbakir and Mardin Province were more tolerant than other groups. Among C. echinospermum, Ech_6 from the Siv-Diyar collection site of the Urfa Province showed better tolerance than other groups. In this first detailed screening of aluminium toxicity tolerance in the new wild Cicer collections, we identified accessions that were more tolerant than current domestic cultivars, providing promising germplasm for breeding programs to expand chickpea adaptation to acid soils.
Fear From Afar, Not So Risky After All: Distancing Moderates the Relationship Between Fear and Risk Taking
Authors: Mayiwar Lewend , Björklund Fredrik
Published: June 2021

A growing line of research has shown that individuals can regulate emotional biases in risky judgment and decision-making processes through cognitive reappraisal. In the present study, we focus on a specific tactic of reappraisal known asdistancing. Drawing on appraisal theories of emotion and the emotion regulation literature, we examine how distancing moderates the relationship between fear and risk taking and anger and risk taking. In three pre-registered studies (Ntotal= 1,483), participants completed various risky judgment and decision-making tasks. Replicating previous results, Study 1 revealed a negative relationship between fear and risk taking and a positive relationship between anger and risk taking at low levels of distancing. Study 2 replicated the interaction between fear and distancing but found no interaction between anger and distancing. Interestingly, at high levels of distancing, we observed a reversal of the relationship between fear and risk taking in both Study 1 and 2. Study 3 manipulated emotion and distancing by asking participants to reflect on current fear-related and anger-related stressors from an immersed or distanced perspective. Study 3 found no main effect of emotion nor any evidence of a moderating role of distancing. However, exploratory analysis revealed a main effect of distancing on optimistic risk estimation, which was mediated by a reduction in self-reported fear. Overall, the findings suggest that distancing can help regulate the influence of incidental fear on risk taking and risk estimation. We discuss implications and suggestions for future research.
Sleep Monitoring Using WatchPAT Device to Predict Recurrence of Major Depression in Patients at High Risk for Major Depression Disorder Recurrence: A Case Report
Authors: Harlev Daniel , Ravona-Springer Ramit , Nuriel Yonatan , Fruchter Eyal
Published: June 2021

Background: Major depressive disorders are strongly correlated with alterations in sleep pattern and architecture, including changes in the Rapid Eye Movement (REM) phase. However, it is still unknown whether sleep alterations precede other depression-related symptoms, particularly in patients with recurrent depressive episodes at relapse risk.

Case Presentation: We initiated a study aimed at examining the value of ambulatory sleep monitoring using a WatchPAT device, in predicting recurrence of Major depression. Depression was assessed monthly with the Beck Depression Inventory version II (BDI-II). Here we present the case of a 63 years old woman, with a history of recurrent depressive episodes. AT the time of recruitment, she was asymptomatic, she experienced recurrence of Major depression 3 months into the study. We observed a significant reduction of the Rem Latency parameters 5 weeks prior to BDI-II score increase, reflecting major depressive episode recurrence.

Conclusion: Though our results are preliminary, they suggest that ambulatory sleep monitoring can be used as a simple and accessible tool, predicting recurrence of Major Depressive episodes in patients at high risk, thus enabling early treatment intervention.