bluuebunny/crossref_metadata_2025 huggingface dataset:
Summer net community production in the northern Chukchi Sea: Comparison between 2017 and 2020
Authors: Kwon Soyeon , Lee Inhee , Park Keyhong , Cho Kyoung-Ho , Jung Jinyoung , Park Taewook , Lee Youngju , Jeon Chanhyung , Seo Seongbong , Hahm Doshik
Published: November 2022

The Arctic Ocean environment is drastically changing because of global warming. Although warming-induced processes, such as the decrease in sea-ice extent and freshening of the surface layer, have the potential to alter primary production, the changes that will likely occur in their production and their mechanisms are still poorly understood. To assess the potential changes in net community production, which is a measure of biological carbon pump, in response to climate change, we observed the O2/Ar at the surface of the northern Chukchi Sea in the summers of 2017 and 2020. The net community production (NCP) estimates that we derived from O2/Ar measurements were largely in the range of 1 – 11 mmol O2 m-2 d-1 in the northern Chukchi and Beaufort Seas, close to the lower bounds of the values in the global oceans. The average NCP of 1.5 ± 1.7 mmol O2 m-2 d-1 in 2020 was substantially lower than 7.1 ± 7.4 mmol O2 m-2 d-1 in 2017, with the most pronounced decrease occurring in the ice-free region of the northern Chukchi Sea; the NCP of the ice-free region in 2020 was only 12% of that in 2017. The decrease in NCP in 2020 was accompanied by a lower salinity of > 2, which resulted in shallower mixed layer depths and stronger stratification. We speculated that the anomalously low pressure near the east Russian coast and the lack of strong winds contributed to the strong stratification in 2020. With a continuing decrease in the extent of sea ice, the northern Chukchi Sea will likely experience earlier phytoplankton blooms and nitrate exhaustion. Unless winds blow strong enough to break the stratification, the biological pump in late summer is likely to remain weak.
Application of visual placement of a nasojejunal indwelling feeding tube in intensive care unit patients receiving mechanical ventilation
Authors: Chen Yuequn , Tian Xin , Liu Cheng , Zhang Liqin , Xv Yueyuan , Xv Shuang
Published: November 2022

Background

Compared with nasogastric nutrition, nasojejunal nutrition may prevent some complications of critically ill patients by maintaining better nutritional status, and blind placement of nasojejunal dwelling feeding tubes is widely used. However, the visual placement seems to be safer and more effective than the blind placement, and is still seldom reported.

Objective

We tried to develop visual placement of a nasojejunal feeding tube in intensive care unit patients.

Methods

A total of 122 patients receiving mechanical ventilation were admitted to the Department of Critical Care Medicine of the Fifth Affiliated Hospital of Wenzhou Medical University and received the placement of nasojejunal feeding tubes. These patients were randomly and evenly assigned into two groups, one group receiving visual placement of nasojejunal dwelling feeding tubes and another group receiving blind placement. Actual tube placement was confirmed by X-ray. The primary outcome included the success rates of first placement of feeding tubes. The secondary outcome included the time of tube placement, complications, the total cost, heart rates and respiratory rates.

Results

The primary outcome showed that the success rates of first placement were 96.70% (59 cases/61 cases) in the visual placement group, and two cases failed due to pyloric stenosis and gastroparesis. The success rates were 83.6% (51 cases/61 cases) in the blind placement group and 10 cases failed due to either wrong placement or retrograde tube migration. The success rates in the visual placement group were higher than that in the blind placement group (P = 0.015). The secondary outcome showed that the time of tube placement in the visual placement group was shorter than that in the blind placement group (P < 0.0001). The cost of tube placement in the visual placement group was higher than that in the blind placement group (P < 0.0001). The statistical differences in complications, heart and respiratory rates were insignificant between the two groups (P > 0.05).

Conclusion

Compared with the blind placement, the visual placement shortened the time of nasojejunal tube placement and increased success rates of first placement. The visual placement was more efficient, easy to operate, safe, and has potential clinical applications.
Preoperative plasma visfatin may have a dual effect on the occurrence of postoperative delirium
Authors: Kang Ning , Yang Ning , Zhao Kaixuan , Li Zhengqian , Zhang Wenchao , Han Yongzheng , Liu Kaixi , Song Yanan , Chen Lei , Li Yue , Hong Jingshu , Li Yitong , Guo Xiangyang , Wang Geng , Yuan Yi
Published: November 2022

Background

Visfatin is considered to be a “novel pro-inflammatory cytokine.” Neuroinflammatory response is one of the important mechanisms of postoperative delirium (POD). The relationship between preoperative plasma visfatin and POD is unclear.

Objective

To investigate the relationship between preoperative plasma visfatin concentrations and POD (primary outcome) in older hip fracture patients and to explore whether it affects POD through inflammatory factors.

Materials and methods

This prospective cohort study enrolled 176 elderly patients who were scheduled for hip fracture surgery. Preoperative plasma was collected on the morning of surgery, and visfatin levels were measured. Interleukin (IL)-1 and IL-6 were measured using patients’ plasma collected on the first day after surgery. We used the 3-min diagnostic interview for Confusion Assessment Method-defined delirium (3D-CAM) twice daily within the 2 days after surgery to assess whether POD had occurred. Restricted cubic splines and piecewise regression were used to explore the relationship between preoperative plasma visfatin concentrations and POD, and further mediation analysis was used to verify whether visfatin plays a role in POD through regulating inflammatory factors.

Results

The incidence of POD was 18.2%. A J-shaped association was observed between preoperative plasma visfatin levels and POD. The risk of POD decreased within the lower visfatin concentration range up to 37.87 ng/ml, with a hazard ratio of 0.59 per 5 ng/ml [odds ratio (OR) = 0.59, 95% confidence interval (CI) = 0.37–0.95], but the risk increased above this concentration (P for non-linearity < 0.001, with a hazard ratio of 1.116 per 10 ng/ml; OR = 1.10, 95% CI = 1.02–1.23). Mediation effect analysis showed that when the plasma visfatin concentration was higher than 37.87 ng/ml, the effect of visfatin on POD was mediated by IL-6 (p < 0.01). A significant indirect association with postoperative plasma IL-6 was observed between preoperative plasma visfatin and POD (adjusted β = 0.1%; 95% CI = 4.8∼38.9%; p < 0.01).

Conclusion

Visfatin is the protective factor in POD when the preoperative plasma visfatin concentration is below 37.87 ng/ml, but when it exceeds 37.87 ng/ml, the visfatin concentration is a risk factor for POD, which is mediated by postoperative plasma IL-6. The results suggest that preoperative visfatin may have a dual effect on the POD occurrence.

Clinical trial registration

[www.ClinicalTrials.gov], identifier [ChiCTR21 00052674].
Giant cell arteritis: A population-based retrospective cohort study exploring incidence and clinical presentation in Canterbury, Aotearoa New Zealand
Authors: Lyne Suellen A. , Ruediger Carlee , Lester Susan , Chapman Peter T. , Shanahan Ernst Michael , Hill Catherine L. , Stamp Lisa
Published: November 2022

Background/aim

To determine the epidemiology and clinical features of giant cell arteritis (GCA) in Canterbury, Aotearoa New Zealand, with a particular focus on extra-cranial large vessel disease.

Methods

Patients with GCA were identified from radiology and pathology reports, outpatient letters and inpatient hospital admissions in the Canterbury New Zealand from 1 June 2011 to 31 May 2016. Data was collected retrospectively based on review of electronic medical records.

Results

There were 142 cases of GCA identified. 65.5% of cases were female with a mean age of 74.2 years. The estimated population incidence for biopsy-proven GCA was 10.5 per 100,000 people over the age of 50 and incidence peaked between 80 and 84 years of age. 10/142 (7%) people were diagnosed with large vessel GCA, often presenting with non-specific symptoms and evidence of vascular insufficiency including limb claudication, vascular bruits, blood pressure and pulse discrepancy, or cerebrovascular accident. Those with limited cranial GCA were more likely to present with the cardinal clinical features of headache and jaw claudication. Patients across the two groups were treated similarly, but those with large vessel disease had greater long-term steroid burden. Rates of aortic complication were low across both groups, although available follow-up data was limited.

Conclusion

This study is the first of its kind to describe the clinical characteristics of large vessel GCA in a New Zealand cohort. Despite small case numbers, two distinct subsets of disease were recognized, differentiating patients with cranial and large vessel disease. Our results suggest that utilization of an alternative diagnostic and therapeutic approach may be needed to manage patients with large vessel disease.
Gut microbiota profile of COVID-19 patients: Prognosis and risk stratification (MicroCOVID-19 study)
Authors: Nobre José Guilherme , Delgadinho Mariana , Silva Carina , Mendes Joana , Mateus Vanessa , Ribeiro Edna , Costa Diogo Alpuim , Lopes Miguel , Pedroso Ana Isabel , Trigueiros Frederico , Rodrigues Maria Inês , de Sousa Cristina Lino , Brito Miguel
Published: November 2022

Background

Gut microbiota is intrinsically associated with the immune system and can promote or suppress infectious diseases, especially viral infections. This study aims to characterize and compare the microbiota profile of infected patients with SARS-CoV-2 (milder or severe symptoms), non-infected people, and recovered patients. This is a national, transversal, observational, multicenter, and case–control study that analyzed the microbiota of COVID-19 patients with mild or severe symptoms at home, at the hospital, or in the intensive care unit, patients already recovered, and healthy volunteers cohabiting with COVID-19 patients. DNA was isolated from stool samples and sequenced in a NGS platform. A demographic questionnaire was also applied. Statistical analysis was performed in SPSS.

Results

Firmicutes/Bacteroidetes ratios were found to be significantly lower in infected patients (1.61 and 2.57) compared to healthy volunteers (3.23) and recovered patients (3.89). Furthermore, the microbiota composition differed significantly between healthy volunteers, mild and severe COVID-19 patients, and recovered patients. Furthermore, Escherichia coli, Actinomyces naeslundii, and Dorea longicatena were shown to be more frequent in severe cases. The most common COVID-19 symptoms were linked to certain microbiome groups.

Conclusion

We can conclude that microbiota composition is significantly affected by SARS-CoV-2 infection and may be used to predict COVID-19 clinical evolution. Therefore, it will be possible to better allocate healthcare resources and better tackle future pandemics.
Biocontrol efficacy of Bacillus velezensis strain YS-AT-DS1 against the root-knot nematode Meloidogyne incognita in tomato plants
Authors: Hu Yanfeng , You Jia , Wang Yu , Long Yong , Wang Siru , Pan Fengjuan , Yu Zhenhua
Published: November 2022

Root-knot nematodes (RKNs; Meloidogyne spp.), one of the most economically important plant-parasitic nematodes (PPNs), cause severe yield and quality losses in agriculture annually. The application of biological control agents is an environmentally safe and effective approach to control RKNs. Here, we report the genomic characteristics of a Bacillus velezensis strain YS-AT-DS1 (Bv-DS1) isolated from the tidal soil, revealing that it has a 4.73 Mb circular chromosome with an average GC-content of 46.43%, 3,977 genes, 86 tRNAs, and 27 rRNAs, and contains secondary metabolite clusters for producing antimicrobial compounds. In vitro assays indicated that Bv-DS1 has not only antagonistic activities against fungal pathogens, but also shows nematicidal activity, with a mortality rate of 71.62% mortality rates in second-stage juvenile (J2s) Meloidogyne incognita. We then focused on the biocontrol efficiency of Bv-DS1 against M. incognita in pot assays. Preinoculation with Bv-DS1 enhanced tomato growth, and significantly reduced the infection rate of J2s, and the number of galls and egg masses on tomato roots. The underlying mechanism in Bv-DS1-induced resistance to M. incognita was further investigated through split-root experiments, and analysing the expression of the genes related to jasmonic acid (JA), salicylic acid (SA), and the tonoplast intrinsic protein (TIP). The results indicated that Bv-DS1 could not activate host systemic-induced resistance (ISR) in the split-root system of tomatoes. Additionally, the expression of JA- (LOX D and MC) and SA- (PAL2 and PR) responsive genes did not change in Bv-DS1-pretreated plants at 3 and 14 days after nematode inoculation. The presented data showed that JA-and SA-dependent pathways were not required for the biocontrol action of the Bv-DS1 against RKN. The TIP genes, responsible for transport of water and small substrates in plants, have previously been shown to negatively regulate the parasitism of PPNs. Surprisingly, Bv-DS1 compromised the downregulation of TIP1.1 and TIP1.3 by M. incognita. Together, our data suggest that Bv-DS1 exhibits a dual effect on plant growth promotion and protection against RKN, possibly related to the regulation of water and solute transport via TIPs. Thus, the Bv-DS1 strain could be used as a biocontrol agent for RKN control in sustainable agriculture.
The European Prevention of Alzheimer's Dementia Programme: An Innovative Medicines Initiative-funded partnership to facilitate secondary prevention of Alzheimer's disease dementia
Authors: Saunders Stina , Gregory Sarah , Clement Matthew H. S. , Birck Cindy , Geyten Serge van der , Ritchie Craig W.
Published: November 2022

Introduction

Tens of millions of people worldwide will develop Alzheimer's disease (AD), and only by intervening early in the preclinical disease can we make a fundamental difference to the rates of late-stage disease where clinical symptoms and societal burden manifest. However, collectively utilizing data, samples, and knowledge amassed by large-scale projects such as the Innovative Medicines Initiative (IMI)-funded European Prevention of Alzheimer's Dementia (EPAD) program will enable the research community to learn, adapt, and implement change.

Method

In the current article, we define and discuss the substantial assets of the EPAD project for the scientific community, patient population, and industry, describe the EPAD structure with a focus on how the public and private sector interacted and collaborated within the project, reflect how IMI specifically supported the achievements of the above, and conclude with a view for future.

Results

The EPAD project was a €64-million investment to facilitate secondary prevention of AD dementia research. The project recruited over 2,000 research participants into the EPAD longitudinal cohort study (LCS) and included over 400 researchers from 39 partners. The EPAD LCS data and biobank are freely available and easily accessible via the Alzheimer's Disease Data Initiative's (ADDI) AD Workbench platform and the University of Edinburgh's Sample Access Committee. The trial delivery network established within the EPAD program is being incorporated into the truly global offering from the Global Alzheimer's Platform (GAP) for trial delivery, and the almost 100 early-career researchers who were part of the EPAD Academy will take forward their experience and learning from EPAD to the next stage of their careers.

Discussion

Through GAP, IMI-Neuronet, and follow-on funding from the Alzheimer's Association for the data and sample access systems, the EPAD assets will be maintained and, as and when sponsors seek a new platform trial to be established, the learnings from EPAD will ensure that this can be developed to be even more successful than this first pan-European attempt.
Preliminary evidence of safety and effectiveness of Loxoprofen Sodium Cataplasm combined with physiotherapy for myofascial pain syndrome treatment: A randomized controlled pilot clinical trial
Authors: Zhou Xuewen , Li Xuelian , Wang Ziyang , Huang Dong
Published: November 2022

Background

Myofascial pain syndrome (MPS) is one of the most common causes of chronic skeletal muscle pain, which is closely related to skeletal muscle myofascial trigger point (MTRP). Since there is no first-line treatment for MPS, we investigated Loxoprofen Sodium Cataplasm combined with physiotherapy as a non-invasive therapy in patients at different levels to a protocol with superior efficacy that is safe and easy to promote. Moreover, this treatment could represent an alternative therapeutic strategy for low-income patients to a safer, more convenient, and more economical treatment scheme.

Methods

A randomized clinical study was aimed at evaluating the safety and efficacy of Loxoprofen Sodium Cataplasm combined with physiotherapy in patients diagnosed with MPS in the pain clinic. We screened 100 patients with MPS, and using a computer-generated random allocation sequence, we stratified patients in a ratio of 2:1:1:1 (A: B: C: D) to one of the four treatment groups. Group A received Loxoprofen Sodium Cataplasm combined with extracorporeal shock wave therapy (ESWT) and transcutaneous electrical nerve stimulation (TENS). Group B received Loxoprofen Sodium Cataplasm alone. Group C received physiotherapy alone. Group D received Flurbiprofen Cataplasm combined with physiotherapy. After 2 weeks of treatment, the overall efficiency and secondary assessment indicators, including visual analog scale (VAS) scores, chronic soft tissue injury (CSTI) scores, Oswestry Disability Index (ODI) scores, or Northwick Park Neck Pain Questionnaire (NPQ) scores, were evaluated before and after treatment to analyze the difference in efficacy of each group.

Results

All groups were well tolerated with no reported adverse events. Significant treatment differences in the change from baseline in overall efficiency (primary efficacy endpoint) (P = 0.0078) were observed in subjects of groups A and C.

Conclusion

Showing valuable data of efficacy in primary and secondary endpoints, Loxoprofen Sodium Cataplasm combined with physiotherapy is superior in the treatment of MPS.

Trial registration number

https://www.chictr.org.cn/ (ChiCTR2100054756).
Edge detection networks inspired by neural mechanisms of selective attention in biological visual cortex
Authors: Zhang Zhenguang , Lin Chuan , Qiao Yakun , Pan Yongcai
Published: November 2022

Edge detection is of great importance to the middle and high-level vision task in computer vision, and it is useful to improve its performance. This paper is different from previous edge detection methods designed only for decoding networks. We propose a new edge detection network composed of modulation coding network and decoding network. Among them, modulation coding network is the combination of modulation enhancement network and coding network designed by using the self-attention mechanism in Transformer, which is inspired by the selective attention mechanism of V1, V2, and V4 in biological vision. The modulation enhancement network effectively enhances the feature extraction ability of the encoding network, realizes the selective extraction of the global features of the input image, and improves the performance of the entire model. In addition, we designed a new decoding network based on the function of integrating feature information in the IT layer of the biological vision system. Unlike previous decoding networks, it combines top-down decoding and bottom-up decoding, uses down-sampling decoding to extract more features, and then achieves better performance by fusing up-sampling decoding features. We evaluated the proposed method experimentally on multiple publicly available datasets BSDS500, NYUD-V2, and barcelona images for perceptual edge detection (BIPED). Among them, the best performance is achieved on the NYUD and BIPED datasets, and the second result is achieved on the BSDS500. Experimental results show that this method is highly competitive among all methods.
Sea cucumber (Acaudina leucoprocta) peptides extended the lifespan and enhanced antioxidant capacity via DAF-16/DAF-2/SOD-3/OLD-1/PEPT-1 in Caenorhabditis elegans
Authors: Wu Yue , Yang Jingjuan , Xu Chengmei , Li Qiuqi , Ma Yage , Zhao Shenglan , Zhuang Jiachen , Shen Fei , Wang Qianqian , Feng Fengqin , Zhang Xi
Published: November 2022

The sea cucumber peptides (SCPs) from Acaudina leucoprocta were derived from the patented bio-enzyme digestion technology and the molecular weight of obtained SCPs was < 10 kDa. In this study, we investigated the possible anti-aging effects of SCPs on the model of Caenorhabditis elegans and the underlying mechanisms. SCPs extend the average lifespan of nematodes by 31.46%. SCPs enhance the anti-stress capacity of C. elegans by improving heat resistance and mobility, Also, the accumulated potential oxidative stress inducers like lipofuscin and reactive oxygen species (ROS) were reduced to 40.84 and 71.43%. In addition, SCPs can increase the antioxidant capacity in nematodes by enhancing the activity of SOD and CAT and reducing MDA accumulation in nematodes to 32.44%. Mechanistically, SCPs could mediate DAF-16/DAF-2/SOD-3/OLD-1/PEPT-1 axis to improve antioxidant capacity and extend lifespan in nematodes. Taken together, these findings provide a direction for the anti-aging effects of sea cucumber peptides and new insights into the further purifications of SCPs and future research on aging.
Lenvatinib as second-line treatment in patients with unresectable hepatocellular carcinoma: A retrospective analysis
Authors: Qin He-nan , Ning Zhen , Sun Rui , Jin Chen-xing , Guo Xin , Wang A-man , Liu Ji-wei
Published: November 2022

Objective

The purpose of this study is to determine the efficacy and safety of lenvatinib as second-line therapy in Chinese patients with unresectable hepatocellular carcinoma (HCC).

Methods

We performed a retrospective analysis of Chinese patients with unresectable HCC who received second-line treatment of lenvatinib at three institutions from November 2018 to February 2022. Demographic and clinicopathologic characteristics, data on the treatment regimens were obtained from medical records. Tumor response was evaluated every 4-6 weeks by modified Response Evaluation Criteria in Solid Tumors (mRECIST).

Results

In total, 50 patients with unresectable HCC who received second-line treatment of lenvatinib were enrolled in this study. The objective response rate (ORR) was 18.0% and the disease control rate (DCR) was 74.0%, respectively. The duration of response (DoR) was 6.0 months. The median progression-free survival (PFS) and overall survival (OS) were 5.0 and 8.5 months, respectively. Patients who received ICIs combined with anti-angiogenic inhibitors as first-line therapy, achieving CR/PR at first-line therapy, with PFS≥6months at first-line therapy had a higher DCR. Univariate and multivariate analysis showed that AFP (ng/ml)<400, absence of extrahepatic metastasis, Child-Pugh A, tumor number<3, ICIs combined with anti-angiogenic inhibitors as first-line therapy, CR/PR to first-line therapy, and PFS≥6months at first-line therapy were independent factors of favorable PFS. Univariate analysis showed that absence of extrahepatic metastasis, tumor number<3, ICIs combined with anti-angiogenic inhibitors as first-line therapy, and PFS≥6months at first-line therapy were significantly associated with longer OS. Multivariate analysis showed that absence of extrahepatic metastasis, Child-Pugh A, tumor number<3, CR/PR to first-line therapy and PFS≥6months at first-line therapy were independent prognostic factors of OS. The majority of AEs were grade 1-2, and were reversible. Grade 3/4 AEs occurred in 12 patients (24.0%) and were mostly connected with hand-foot skin reactions (10.0%), and 10 patients had lenvatinib dose reductions. Two toxicity-related treatment interruptions were attributed to grade 3 hand-foot skin reaction, and grade 4 proteinuria, respectively.

Conclusion

This study confirms the efficacy and safety of lenvatinib as second-line therapy after progression on sorafenib or ICIs combined with anti-angiogenic inhibitors.
Progression of hepatocellular carcinoma after radiofrequency ablation: Current status of research
Authors: Wu Shilun , Li Zhuxin , Yao Changyu , Dong Shuying , Gao Jun , Ke Shan , Zhu Ruhang , Huang Sen , Wang Shaohong , Xu Li , Ye Chen , Kong Jian , Sun Wenbing
Published: November 2022

Hepatocellular carcinoma (HCC) remains an important disease for health care systems in view of its high morbidity, mortality, and increasing incidence worldwide. Radiofrequency ablation (RFA) is preferred to surgery as a local treatment for HCC because it is safer, less traumatic, less painful, better tolerated, causes fewer adverse reactions, and allows more rapid postoperative recovery. The biggest shortcoming of RFA when used to treat HCC is the high incidence of residual tumor, which is often attributed to the vascular thermal deposition effect, the wide infiltration zone of peripheral venules, and the distance between satellite foci and the main focus of the cancer. Recurrence and progression of the residual tumor is the most important determinant of the prognosis. Therefore, it is important to be aware of the risk of recurrence and to improve the efficacy of RFA. This review summarizes the relevant literature and the possible mechanisms involved in progression of HCC after RFA. Current studies have demonstrated that multimodal treatments which RFA combined with other anti-cancer approaches can prevent progression of HCC after RFA.
Integrated systemic analysis of FAM72A to identify its clinical relevance, biological function, and relationship to drug sensitivity in hepatocellular carcinoma
Authors: Zhou Qi , Chen Lingjun , Yang Luo , Zhou Haoxiong , Chen Yan , Guo Yunwei
Published: November 2022

Background

The family with sequence similarity 72 member A (FAM72A) protein has been identified as an effector of multiple pathological processes in many cancers. The value of FAM72A in HCC remains largely unknown.

Methods

Data from TCGA-LIHC, ICGC-LIRI-JP, IMvigor210, cBioPortal, GeneMANIA, and TIMER were processed and visualized to explore the association between FAM72A and the prognosis, stemness phenotype, mutational burden, immune cell infiltration, and drug sensitivity in HCC patients. Potential pathways were also revealed. Furthermore, we experimentally verified the results in vivo and in vitro using immunohistochemistry, western blotting, and CCK-8 assays.

Results

First, FAM72A mRNA expression was significantly upregulated in HCC. High FAM72A expression was independently associated with a poor prognosis. Experimental validation confirmed that FAM72A was remarkably overexpressed in HCC patients and mice. Moreover, FAM72A knockdown suppressed HCC cell proliferation. In addition, the frequency of TP53 mutations was significantly higher in the high FAM72A expression group. Subsequently, the enrichment analysis revealed that FAM72A was closely related to immune processes and mTOR pathways. Silencing FAM72A increased the expression levels of mTOR in HCC cell lines. The FAM72A-mTOR pathway was strongly associated with a poor prognosis for patients with HCC. Patients with high FAM72A expression levels might be more resistant to sorafenib. Furthermore, the expression of FAM72A and mTOR was significantly associated with the abundance of some tumor-infiltrating immune cells, especially CD4+ T cells. Finally, patients with high levels of FAM72A and mTOR were more sensitive to immunotherapy.

Conclusions

FAM72A, a member of the FAM72 family, might be a prognostic and immunotherapeutic target for HCC patients.
The role of IL-35 and IL-37 in breast cancer – potential therapeutic targets for precision medicine
Authors: Ma Yuntao , Su He , Wang Xuyun , Niu Xiangdong , Che Yang , Hambly Brett D. , Bao Shisan , Wang Xiaopeng
Published: November 2022

Breast cancer is still a major concern due to its relatively poor prognosis in women, although there are many approaches being developed for the management of breast cancer. Extensive studies demonstrate that the development of breast cancer is determined by pro versus anti tumorigenesis factors, which are closely related to host immunity. IL-35 and IL-37, anti-inflammatory cytokines, play an important role in the maintenance of immune homeostasis. The current review focuses on the correlation between clinical presentations and the expression of IL-35 and IL-37, as well as the potential underlying mechanism during the development of breast cancer in vitro and in vivo. IL-35 is inversely correlated the differentiation and prognosis in breast cancer patients; whereas IL-37 shows dual roles during the development of breast cancer, and may be breast cancer stage dependent. Such information might be useful for both basic scientists and medical practitioners in the management of breast cancer patients.
Macular hole and vitreous hemorrhage subsequent to stereotactic hypofractionated radiotherapy for choroidal melanoma: A case report and review of the literature
Authors: Zhou Xiaoyin , Ishikawa Hiroto , Gomi Fumi
Published: November 2022

Choroidal melanoma is the leading primary intraocular tumor with potentially fatal outcomes in adults. The coexistence of choroidal melanoma and a macular hole is extremely rare, and treatment strategies and information on the prognosis of associated complications are currently lacking. We report the first case of choroidal melanoma complicated with a macular hole and vitreous hemorrhage after stereotactic hypofractionated radiotherapy in Japan, and review the relevant literature in relation to the possible mechanisms, treatment strategies, and outcomes. An 83-year-old male with choroidal melanoma was treated with stereotactic hypofractionated radiotherapy in January 2021. Five months later, a full-thickness macular hole developed, followed by an acute massive vitreous hemorrhage about 2 weeks later. Following confirmation of tumor regression, the patient underwent a pars plana vitrectomy and internal limiting membrane peeling. The macular hole was closed postoperatively and the patient’s best-corrected visual acuity improved to 20/125. There was no evidence of intraocular tumor dissemination or distant metastases during follow-up. A systematic literature search only identified 10 previous cases of choroidal melanoma with a macular hole in eight reports worldwide, mainly in females. Macular edema may be the primary cause of macular hole formation in these cases. Most patients who underwent vitrectomy for complications after tumor regression achieved a good prognosis. The development of a macular hole is a rare complication associated with choroidal melanoma. Anterior-posterior traction of posterior vitreous detachment and secondary macular edema may have contributed to the formation of the macular hole in the current case.
Anlotinib in patients with medullary thyroid carcinoma with negative prognostic factors: A sub-analysis based on the ALTER01031 study
Authors: Zhao Jingzhu , Chi Yihebali , Hu Chuanxiang , Chen Xiaohong , Ge Minghua , Zhang Yuan , Guo Zhuming , Wang Jun , Chen Jie , Zhang Jiewu , Cheng Ying , Li Zhendong , Liu Hui , Qin Jianwu , Zhu Jingqiang , Cheng Ruochuan , Xu Zhengang , Li Dapeng , Tang Pingzhang , Gao Ming , Zheng Xiangqian
Published: November 2022

Background

Medullary thyroid carcinoma (MTC) is a rare type of thyroid cancer; however, it accounted for 13.4% of the disease-specific mortalities. ALTER01031 (NCT02586350) was a randomised, placebo-controlled phase 2b trial that evaluated the efficacy and safety of anlotinib in locally advanced or metastatic MTC. This post hoc analysis aimed to evaluate the efficacy and safety of anlotinib in older patients and those with bone metastases using ALTER01031.

Methods

In ALTER01031, anlotinib significantly prolonged the median progression-free survival (PFS) from 11.1 months to 20.7 months compared with placebo in the whole population. Patients who were older (≥ 50 years) or had bone metastases were selected. PFS and overall survival (OS) were estimated and compared between patients receiving anlotinib or placebo in each subgroup. A sub-analysis of tumour response and safety was also performed.

Results

Patients with older age or bone metastases experienced rapid disease progression as the median PFS was 6.8 months and 7.0 months respectively in the placebo group. Anlotinib significantly improved the median PFS to 17.5 months (P = 0.002) and 20.7 months (P = 0.029) with hazard ratio (HR) of 0.31 (95% CI, 0.15–0.68) and 0.44 (95% CI, 0.20–0.94) compared with placebo. Significant benefit in OS was observed in patients with older age after a longer follow-up (HR = 0.47 [95% CI, 0.22–0.99], P = 0.041). The safety profile of these subgroups was similar to that of the entire population.

Conclusion

This sub-analysis demonstrated significant survival benefits and favourable safety of anlotinib in patients with MTC who had old age or bone metastases, supporting the feasibility of anlotinib in these patients.
The potential impact of melanosomal pH and metabolism on melanoma
Authors: You Jaewon , Yusupova Maftuna , Zippin Jonathan H.
Published: November 2022

Melanin is synthesized in melanocytes and is transferred into keratinocytes to block the effects of ultraviolet (UV) radiation and is important for preventing skin cancers including melanoma. However, it is known that after melanomagenesis and melanoma invasion or metastases, melanin synthesis still occurs. Since melanoma cells are no longer involved in the sun tanning process, it is unclear why melanocytes would maintain melanin synthesis after melanomagenesis has occurred. Aside from blocking UV-induced DNA mutation, melanin may provide other metabolic functions that could benefit melanoma. In addition, studies have suggested that there may be a selective advantage to melanin synthesis in melanoma; however, mechanisms regulating melanin synthesis outside the epidermis or hair follicle is unknown. We will discuss how melanosomal pH controls melanin synthesis in melanocytes and how melanosomal pH control of melanin synthesis might function in melanoma. We will also discuss potential reasons why melanin synthesis might be beneficial for melanoma cellular metabolism and provide a rationale for why melanin synthesis is not limited to benign melanocytes.
RUNX2 facilitates aggressiveness and chemoresistance of triple negative breast cancer cells via activating MMP1
Authors: Si Wentao , Xu Xiaodan , Wan Lijuan , Lv Fengxu , Wei Wei , Xu Xiaojun , Li Wei , Huang Dabing , Zhang Leisheng , Li Feifei
Published: November 2022

Breast cancer remains the most common malignancy in women and constantly threatens the lives of patients worldwide. State-of-the-art renewal has indicated the involvement of RUNX-associated transcription factor 2 (RUNX2) in tumorigenesis and cancer progression, yet the detailed information during breast cancer is largely obscure. Herein, we took advantage of breast cancer cell lines and in vivo tumorigenicity test as well as multifaceted phenotypic analyses (e.g., RNA-sequencing, ChIP and qRT-PCR assay) to verify the pathogenic mechanism of RUNX2 in triple negative breast cancer aggressiveness and chemoresistance. Strikingly, the proliferation, migration, invasion and chemoresistance of resistant cell lines in triple negative breast cancer was effectively suppressed by RUNX2 silencing, and the in vivo tumorigenicity was significantly weakened as well. Furthermore, with the aid of transcriptomic and bioinformatic analyses, we found MMP1 was highly expressed in triple negative breast cancer (TNBC) and showed a strong correlation with the poor prognosis of the patients, which was consistent with the expression pattern of RUNX2. Finally, by conducting ChIP and qRT-PCR assessment, we verified that RUNX2 functioned via directly binding to the specific motifs in the promoter of MMP1 and thus activating the transcriptional process. Collectively, our data demonstrated the facilitating effect of RUNX2 during triple negative breast cancer progression by directly orchestrating the expression of MMP1, which supplied overwhelming new references for RUNX2-MMP1 axis serving as a novel candidate for breast cancer diagnosis and treatment.
Importance of quadratus lumborum muscle trigger point injection and prolotherapy technique for lower back and buttock pain
Authors: Sirh Soo-Ji , Sirh So-Woon , Mun Hah-Yong , Sirh Heon-Man
Published: November 2022

Background

Low back pain is a heterogeneous disease. Myofascial pain and enthesopathy of the quadratus lumborum muscle are important causes of lower back and/or buttock pain. However, a concrete, safe, and effective injection technique for the treatment of trigger points and enthesopathy in the quadratus lumborum muscle has not yet been developed.

Objectives

We aimed to evaluate the importance of the quadratus lumborum muscle and introduce an effective landmark-based blind injection technique for treating quadratus lumborum trigger points and enthesopathy.

Methods

Adult patients (n = 17) with lower back and/or buttock pain were placed in the lateral decubitus position. Next, we delicately palpated the quadratus lumborum muscle to accurately locate its lesions, including trigger points, taut bands, and tendon lesions, after five key landmarks had been identified. A newly designed 60–90-mm, 28G thin hypodermic needle was inserted at the tender points. The needle was typically advanced until its tip touched the transverse process to treat myofascial trigger points and tendon lesions in the iliolumbar and lumbocostal fibers, excluding superficial trigger points of the iliocostal fibers. Subsequently, lidocaine (0.5%) or a mixture of lidocaine (0.5%) and dextrose (12.5–15%) was injected.

Results

The pretreatment visual analog scale score for all 17 patients decreased from ≥4–8/10 (mean 5.588) to 0–1/10 (mean 0.294) after completion of all treatments. The total number of treatments was one to four in acute and subacute cases and two to eight in chronic cases. The mean follow-up period was 73.5 days (treatment period: range, 4 to 43 days + at least 60 days of follow-up).

Conclusions

Herein, we describe for the first time a landmark-based integrated injection technique for the treatment of trigger points and myofascial pain in the quadratus lumborum; this technique is safe, effective, and can be used with or without steroids, fluoroscopy, or ultrasound guidance.
Severity of illness and organ dysfunction scoring systems in pediatric critical care: The impacts on clinician's practices and the future
Authors: Recher Morgan , Leteurtre Stéphane , Canon Valentine , Baudelet Jean Benoit , Lockhart Marguerite , Hubert Hervé
Published: November 2022

Severity and organ dysfunction (OD) scores are increasingly used in pediatric intensive care units (PICU). Therefore, this review aims to provide 1/ an updated state-of-the-art of severity scoring systems and OD scores in pediatric critical care, which explains 2/ the performance measurement tools and the significance of each tool in clinical practice and provides 3/ the usefulness, limits, and impact on future scores in PICU. The following two pediatric systems have been proposed: the PRISMIV, is used to collect data between 2 h before PICU admission and the first 4 h after PICU admission; the PIM3, is used to collect data during the first hour after PICU admission. The PELOD-2 and SOFApediatric scores were the most common OD scores available. Scores used in the PICU should help clinicians answer the following three questions: 1/ Are the most severely ill patients dying in my service: a good discrimination allow us to interpret that there are the most severe patients who died in my service. 2/ Does the overall number of deaths observed in my department consistent with the severity of patients? The standard mortality ratio allow us to determine whether the total number of deaths observed in our service over a given period is in adequacy with the number of deaths predicted, by considering the severity of patients on admission? 3/ Does the number of deaths observed by severity level in my department consistent with the severity of patients? The calibration enabled us to determine whether the number of deaths observed according to the severity of patients at PICU admission in a department over a given period is in adequacy with the number of deaths predicted, according to the severity of the patients at PICU admission. These scoring systems are not interpretable at the patient level. Scoring systems are used to describe patients with PICU in research and evaluate the service's case mix and performance. Therefore, the prospect of automated data collection, which permits their calculation, facilitated by the computerization of services, is a necessity that manufacturers should consider.
Different profiles of lipoprotein particles associate various degrees of cardiac involvement in adolescents with morbid obesity
Authors: Siurana José M. , Sabaté-Rotés Anna , Amigó Núria , Martínez-Micaelo Neus , Arciniegas Larry , Riaza Lucia , Mogas Eduard , Rosés-Noguer Ferran , Ventura Paula S. , Yeste Diego
Published: November 2022

Introduction

Dyslipidemia secondary to obesity is a risk factor related to cardiovascular disease events, however a pathological conventional lipid profile (CLP) is infrequently found in obese children. The objective is to evaluate the advanced lipoprotein testing (ALT) and its relationship with cardiac changes, metabolic syndrome (MS) and inflammatory markers in a population of morbidly obese adolescents with normal CLP and without type 2 diabetes mellitus, the most common scenario in obese adolescents.

Methods

Prospective case-control research of 42 morbidly obese adolescents and 25 normal-weight adolescents, whose left ventricle (LV) morphology and function had been assessed. The ALT was obtained by proton nuclear magnetic resonance spectroscopy, and the results were compared according to the degree of cardiac involvement – normal heart, mild LV changes, and severe LV changes (specifically LV remodeling and systolic dysfunction) – and related to inflammation markers [highly-sensitive C-reactive protein and glycoprotein A (GlycA)] and insulin-resistance [homeostatic model assessment for insulin-resistance (HOMA-IR)]. A second analysis was performed to compare our results with the predominant ALT when only body mass index and metabolic syndrome criteria were considered.

Results

The three cardiac involvement groups showed significant increases in HOMA-IR, inflammatory markers and ALT ratio LDL-P/HDL-P (40.0 vs. 43.9 vs. 47.1, p 0.012). When only cardiac change groups were considered, differences in small LDL-P (565.0 vs. 625.1 nmol/L, p 0.070), VLDL size and GlycA demonstrated better utility than just traditional risk factors to predict which subjects could present severe LV changes [AUC: 0.79 (95% CI: 0.54–1)]. In the second analysis, an atherosclerotic ALT was detected in morbidly obese subjects, characterized by a significant increase in large VLDL-P, small LDL-P, ratio LDL-P/HDL-P and ratio HDL-TG/HDL-C. Subjects with criteria for MS presented overall worse ALT (specially in triglyceride-enriched particles) and remnant cholesterol values.

Conclusions

ALT parameters and GlycA appear to be more reliable indicators of cardiac change severity than traditional CV risk factors. Particularly, the overage of LDL-P compared to HDL-P and the increase in small LDL-P with cholesterol-depleted LDL particles appear to be the key ALT's parameters involved in LV changes. Morbidly obese adolescents show an atherosclerotic ALT and those with MS present worse ALT values.
Severe pediatric asthma therapy: Dupilumab
Authors: Ferrante Giuliana , Tenero Laura , Piazza Michele , Piacentini Giorgio
Published: November 2022

Severe asthma is a rare disease affecting <5% of children with asthma. This group of patients account for about 50% of the costs of healthcare for children with asthma. Nowadays, several biological agents are available for pediatric severe asthma. One of these is dupilumab, a monoclonal antibody against the Interleukin (IL)-4 receptor α-subunit that acts as an antagonist against both IL-4 and IL-13. Dupilumab binds the subunit of the IL-4 receptor, at the level of the subunit shared by the IL-13 receptor, blocking the inflammatory cascade of these two cytokines and the progression of the Th2-inflammatory pathway. The efficacy and safety of dupilumab have been investigated in recently published randomized controlled trials including pediatric patients with asthma. Currently, its use in asthma is approved in adults, adolescents, and children with severe asthma with type 2 inflammation, that are not controlled in spite of high-dose inhaled corticosteroids plus another maintenance drug. Studies are warranted for the evaluation of long-term treatment with dupilumab, including steroid sparing effect and discontinuation of treatment. Further research should also be planned in order to investigate dupilumab potential ability to interfere with the natural history of atopy since early childhood.
New insight into the management of renal excretion and hyperuricemia: Potential therapeutic strategies with natural bioactive compounds
Authors: Yang Bendong , Xin Meiling , Liang Shufei , Xu Xiaoxue , Cai Tianqi , Dong Ling , Wang Chao , Wang Meng , Cui Yuting , Song Xinhua , Sun Jinyue , Sun Wenlong
Published: November 2022

Hyperuricemia is the result of increased production and/or underexcretion of uric acid. Hyperuricemia has been epidemiologically associated with multiple comorbidities, including metabolic syndrome, gout with long-term systemic inflammation, chronic kidney disease, urolithiasis, cardiovascular disease, hypertension, rheumatoid arthritis, dyslipidemia, diabetes/insulin resistance and increased oxidative stress. Dysregulation of xanthine oxidoreductase (XOD), the enzyme that catalyzes uric acid biosynthesis primarily in the liver, and urate transporters that reabsorb urate in the renal proximal tubules (URAT1, GLUT9, OAT4 and OAT10) and secrete urate (ABCG2, OAT1, OAT3, NPT1, and NPT4) in the renal tubules and intestine, is a major cause of hyperuricemia, along with variations in the genes encoding these proteins. The first-line therapeutic drugs used to lower serum uric acid levels include XOD inhibitors that limit uric acid biosynthesis and uricosurics that decrease urate reabsorption in the renal proximal tubules and increase urate excretion into the urine and intestine via urate transporters. However, long-term use of high doses of these drugs induces acute kidney disease, chronic kidney disease and liver toxicity. Therefore, there is an urgent need for new nephroprotective drugs with improved safety profiles and tolerance. The current systematic review summarizes the characteristics of major urate transporters, the mechanisms underlying the pathogenesis of hyperuricemia, and the regulation of uric acid biosynthesis and transport. Most importantly, this review highlights the potential mechanisms of action of some naturally occurring bioactive compounds with antihyperuricemic and nephroprotective potential isolated from various medicinal plants.