bluuebunny/crossref_metadata_2025 huggingface dataset:
Silencing of microRNA-517a induces oxidative stress injury in melanoma cells via inactivation of the JNK signaling pathway by upregulating CDKN1C
Authors: Yang Chao , Yan Zeqiang , Hu Fen , Wei Wei , Sun Zhihua , Xu Wei
Published: January 2020

Background

Melanoma is notoriously resistant to current treatments, and less than 25% of metastatic melanoma cases respond to existing therapies. Growing evidence has shown that microRNAs (miRNAs) play a vital role in the prognosis of melanoma. MiR-517a has been implicated in many types of cancer; however, its expressional features and potential biological functions in melanoma remain unclear. The present study aimed to investigate the possible effects of miR-517a on oxidative stress (OS) in melanoma cells.

Methods

miR-517a expression in melanoma was determined using RT-qPCR. After treatment with different concentrations of H2O2, cell viability was determined in order to identify the most appropriate H2O2 concentration. Through loss and gain of function experiments, the interactions between miR-517a, the cyclin dependent kinase inhibitor 1C (CDKN1C) and the c-Jun NH2-terminal kinase (JNK) signaling pathway, as well as their roles in OS of melanoma cells were identified. Moreover, the expression of Cleaved Caspase-3, extent of ERK1/2 phosphorylation, Bax/Bcl-2 ratio, levels of T-AOC, ROS and MDA, and SOD activity were also tested. Finally, melanoma cell viability and apoptosis were detected.

Results

MiR-517a was upregulated, while CDKN1C was downregulated in melanoma tissues and cells. MiR-517a targets CDKN1C and consequently reduced its expression. Inhibition of miR-517a was shown to increase Cleaved Caspase-3 expression, Bax/Bcl-2 ratio, levels of ROS and MDA, as well as cell apoptosis but decrease extent of ERK1/2 phosphorylation, T-AOC levels, SOD activity, along with cell proliferation and mitochondrial membrane potential.

Conclusions

Overall, silencing miR-517a results in upregulated CDKN1C expression, and inhibited JNK signaling pathway activation, consequently promoting OS in melanoma cells.
The heterogeneous clinical and pathological landscapes of metastatic Braf-mutated colorectal cancer
Authors: Fanelli Giuseppe Nicolò , Dal Pozzo Carlo Alberto , Depetris Ilaria , Schirripa Marta , Brignola Stefano , Biason Paola , Balistreri Mariangela , Dal Santo Luca , Lonardi Sara , Munari Giada , Loupakis Fotios , Fassan Matteo
Published: January 2020

Colorectal cancer (CRC) is a complex and molecularly heterogeneous disease representing one of the most frequent causes of cancer-related death worldwide. About 8–15% of CRCs harbor a mutation inBRAFgene, a proto-oncogene involved in cell proliferation, differentiation and survival through the MAPK signaling cascade. The acquisition ofBRAFmutation is an early event in the “serrated” CRC carcinogenetic pathway and is associated with specific and aggressive clinico-pathological and molecular features. Despite that the presence ofBRAFmutation is a well-recognized negative prognostic biomarker in metastatic CRC (mCRC), a great heterogeneity in survival outcome characterizes these patients, due to the complex, and still not completely fully elucidated, interactions between the clinical, genetic and epigenetic landscape ofBRAFmutations. Because of the great aggressiveness ofBRAF-mutated mCRCs, only 60% of patients can receive a second-line chemotherapy; so intensive combined and tailored first-line approach could be a potentially effective strategy, but to minimize the selective pressure of resistant clones and to reduce side effects, a better stratification of patients bearingBRAFmutations is needed.
Effect of group versus individual antenatal care on uptake of intermittent prophylactic treatment of malaria in pregnancy and related malaria outcomes in Nigeria and Kenya: analysis of data from a pragmatic cluster randomized trial
Authors: Noguchi Lisa , Grenier Lindsay , Kabue Mark , Ugwa Emmanuel , Oyetunji Jaiyeola , Suhowatsky Stephanie , Onguti Brenda , Orji Bright , Whiting-Collins Lillian , Adetiloye Oniyire
Published: January 2020

Background

Every year, malaria in pregnancy contributes to approximately 20% of stillbirths in sub-Saharan Africa and 10,000 maternal deaths globally. Most eligible pregnant women do not receive the minimum three recommended doses of intermittent preventive treatment with Sulfadoxine–pyrimethamine (IPTp-SP). The objective of this analysis was to determine whether women randomized to group antenatal care (G-ANC) versus standard antenatal care (ANC) differed in IPTp uptake and insecticide-treated nets (ITN) use.

Methods

Prospective data were analysed from the G-ANC study, a pragmatic, cluster randomized, controlled trial that investigated the impact of G-ANC on various maternal newborn health-related outcomes. Data on IPTp were collected via record abstraction and difference between study arms in mean number of doses was calculated by t test for each country. Data on ITN use were collected via postpartum interview, and difference between arms calculated using two-sample test for proportions.

Results

Data from 1075 women and 419 women from Nigeria and Kenya, respectively, were analysed: 535 (49.8%) received G-ANC and 540 (50.2%) received individual ANC in Nigeria; 211 (50.4%) received G-ANC and 208 (49.6%) received individual ANC in Kenya. Mean number of IPTp doses received was higher for intervention versus control arm in Nigeria (3.45 versus 2.14, p < 0.001) and Kenya (3.81 versus 2.72, p < 0.001). Reported use of ITN the previous night was similarly high in both arms for mothers in Nigeria and Kenya (over 92%). Reported ITN use for infants was higher in the intervention versus control arm in Nigeria (82.7% versus 75.8%, p = 0.020).

Conclusions

G-ANC may support better IPTp-SP uptake, possibly related to better ANC retention. However, further research is needed to understand impact on ITN use.

Trial registration Pan African Clinical Trials Registry, May 2, 2017 (PACTR201706002254227).
Long non-coding RNA UCA1 promotes malignant phenotypes of renal cancer cells by modulating the miR-182-5p/DLL4 axis as a ceRNA
Authors: Wang Wei , Hu Wentao , Wang Ya , An Yong , Song Lei , Shang Panfeng , Yue Zhongjin
Published: January 2020

Background

Accumulating literatures have indicated that long non-coding RNAs (lncRNAs) are potential biomarkers that play key roles in tumor development and progression. Urothelial cancer associated 1 (UCA1) is a novel lncRNA that acts as a potential biomarker and is involved in the development of cancers. However, the molecular mechanism of UCA1 in renal cancer is still needed to further explore.

Methods

The relative expression level of UCA1 was determined by Real-Time qPCR in a total of 88 patients with urothelial renal cancer and in different renal cancer cell lines. Loss-of-function experiments were performed to investigate the biological roles of UCA1 and miR-182-5p on renal cancer cell proliferation, migration, apoptosis and tumorigenicity. Comprehensive transcriptional analysis, dual-luciferase reporter assay and western blot etc. were performed to explore the molecular mechanisms underlying the functions of UCA1.

Results

In this study, we found that UCA1 was significantly up-regulated in renal cancer. Moreover, increased UCA1 expression was positively correlated with differentiation and advanced TNM stage. Further experiments demonstrated that knockdown of UCA1 inhibited malignant phenotypes and Notch signal path of renal cancer cells, and miR-182-5p was reverse function as UCA1. UCA1 functioned as a miRNA sponge to positively regulate the expression of Delta-like ligand 4(DLL4) through sponging miR-182-5p and subsequently promoted malignant phenotypes of renal cancer cells, thus UCA1 playing an oncogenic role and miR-182-5p as an antioncogenic one in renal cancer pathogenesis.

Conclusion

UCA1-miR-182-5p-DLL4 axis is involved in proliferation and progression of renal cancer. Thus, this study demonstrated that UCA1 plays a critical regulatory role in renal cancer cell and UCA1 may serve as a potential diagnostic biomarker and therapeutic target of renal cancer.
Physical resistance training-induced changes in lipids metabolism pathways and apoptosis in prostate
Authors: Teixeira Giovana Rampazzo , Mendes Leonardo Oliveira , Veras Allice Santos Cruz , Thorpe Hayley Hope Allyssa , Fávaro Wagner José , de Almeida Chuffa Luiz Gustavo , Pinheiro Patrícia Fernanda Felipe , Martinez Francisco Eduardo
Published: January 2020

Background

Altered lipid metabolism is an important characteristic of neoplastic cells, with androgens and growth factors being major regulatory agents of the lipid metabolism process. We investigated the effect of physical resistance training on lipid metabolism and apoptosis in the adult Wistar rat prostate.

Methods

Two experimental groups represented sedentary and physical resistance training. Three days per week for 13 weeks, rats performed jumps in water carrying a weight load strapped to their chests as part of a physical resistance exercise protocol. Two days after the last training session, rats were anesthetized and sacrificed for blood and prostate analysis.

Results

Physical exercise improved feeding efficiency, decreased weight gain, regulated the serum-lipid profile, and modulated insulin-like growth factor-1 (IGF-1) and free testosterone concentration. Furthermore, upregulation of cluster of differentiation 36 (CD36), sterol regulatory element binding protein-1 (SREBP-1), sterol regulatory element-binding protein cleavage-activating protein (SCAP), and reduced lysosome membrane protein (LIMPII) expression were also observed in the blood and prostates of trained rats. Consistent with these results, caspase-3 expression was upregulating and the BCL-2/Bax index ratio was decreased in trained rats relative to sedentary animals.

Conclusions

In this work, physical resistance training can alter lipid metabolism and increase markers of apoptosis in the prostate, suggesting physical resistance training as a potential novel therapeutic strategy for treating prostate cancer.
Mid- to long-term effects of two different biological reconstruction techniques for the treatment of humerus osteosarcoma involving caput humeri
Authors: Yao Weitao , Cai Qiqing , Wang Jiaqiang , Hou Jingyu
Published: January 2020

Background

The proximal humerus is one of the most common sites of primary or metastatic malignant tumors. Reconstruction of the shoulder after tumor resection is controversial and challenging. When intra-articular resection is performed, biological reconstruction (osteoarticular allograft and autologous bone implantation) may be the first choice rather than prosthetic reconstruction.

Objective

To observe the mid- to long-term effects of oncologic, reconstructive, and functional outcomes of two different biological reconstruction methods for resection of humerus osteosarcoma involving caput humeri.

Methods

This was a retrospective study of 13 consecutive patients who underwent humeral reconstruction of osteosarcoma including caput humeri using osteoarticular allograft (n = 7) and tumor bone inactivated and reimplantation (TBIR, n = 6) in our clinic between 2007 and 2017. Patients’ general information, resection and reconstruction techniques, oncological and functional outcomes, and complications were collected and evaluated. Different complications of implantations were compared and analyzed for the different biological methods.

Results

The study included ten males and three females with an average age of 19.15 years. The operation time was about 3.65 h with an average blood loss of 631 ml. The resection tumor bones were 13–45 cm (23.54 cm on average). The mean follow-up period was 5.27 years. The shoulder movement was 10–70° (average, 44.00°) in abduction, 0–30° (average, 14.17°) in flexion, and 0–20° (average, 11.90°) in extention at the last follow-up. The complications included fracture in four TBIR patients and two allograft patients with an average of 2.67 years postoperation. Fracture rate was higher and appeared time was earlier in TBIR patients than in allograft patients (p = 0.04); caput humeri absorption occurred in all seven allograft patients and three TBIR patients at an average of 3.10 years after surgery; severe graft bone resorption appeared in five TBIR patients and two allograft patients at an average of 2.57 years of follow-up.

Conclusions

Humerus biological reconstruction involving caput humeri was associated with a high complication rate and acceptable limb function in the mid to long term. New combined biological methods should be explored and adopted in the future.
The impact of a global health elective on CanMEDS competencies and future practice
Authors: Lanys Ashley , Krikler Gena , Spitzer Rachel F.
Published: January 2020

Background

There is evidence that participating in global health electives generates positive educational outcomes and personal benefits for medical trainees. The objective of this study was to examine the effect and impact that a global health elective has on CanMEDS competencies and anticipated future practice.

Results

The medical expert, collaborator, leader, scholar, and professional CanMEDS competencies were self-perceived to be strongly impacted through this elective. A total of 94% of participants indicated it increased their strengths as a medical expert and leader, 82% indicated a major impact on the scholar competency, 88% of participants reported a strong impact as a professional, and 76% of participants indicated that it strongly impacted them as a collaborator. The majority of participants continue to have involvement in global health, and 88% of respondents found this elective to be influential on their current practice and beliefs.

Conclusions

These results suggest that individuals who participated in this global health elective perceived value in their experience. These findings support our hypothesis that participation in this global health elective would generate self-perceived positive impacts. Global health electives may provide an opportunity for physicians to expand on their CanMEDS competencies and become more proficient in caring for diverse patient populations.
Disruption of Midkine gene reduces traumatic brain injury through the modulation of neuroinflammation
Authors: Takada Seiya , Sakakima Harutoshi , Matsuyama Takahiro , Otsuka Shotaro , Nakanishi Kazuki , Norimatsu Kosuke , Itashiki Yuki , Tani Akira , Kikuchi Kiyoshi
Published: January 2020

Background

Midkine (MK) is a multifunctional cytokine found upregulated in the brain in the presence of different disorders characterized by neuroinflammation, including neurodegenerative disorders and ischemia. The neuroinflammatory response to traumatic brain injury (TBI) represents a key secondary injury factor that can result in further neuronal injury. In the present study, we investigated the role of endogenous MK in secondary injury, including neuroinflammation, immune response, and neuronal apoptosis activity, after TBI.

Methods

Wild type (Mdk+/+) and MK gene deficient (Mdk−/−) mice were subjected to fluid percussion injury for TBI models and compared at 3, 7, and 14 days after TBI, in terms of the following: brain tissue loss, neurological deficits, microglia response, astrocytosis, expression of proinflammatory M1 and anti-inflammatory M2 microglia/macrophage phenotype markers, and apoptotic activity.

Results

As opposed to Mdk+/+ mice, Mdk−/− mice reported a significantly reduced area of brain tissue loss and an improvement in their neurological deficits. The ratios of the Iba1-immunoreactive microglia/macrophages in the perilesional site were significantly decreased in Mdk−/− than in the Mdk+/+ mice at 3 days after TBI. However, the ratios of the glial fibrillary acidic protein immunoreactive area were similar between the two groups. The M1 phenotype marker (CD16/32) immunoreactive areas were significantly reduced in Mdk−/− than in the Mdk+/+ mice. Likewise, the mRNA levels of the M1 phenotype markers (TNF-α, CD11b) were significantly decreased in Mdk−/− mice than in Mdk+/+ mice. Furthermore, flow cytometry analysis identified the M2 markers, i.e., CD163+ macrophages cells and arginase-1+ microglia cells, to be significantly higher in Mdk−/− than in Mdk+/+ mice. Finally, the ratios of apoptotic neurons were significantly decreased in the area surrounding the lesion in Mdk−/− than in Mdk+/+ mice following TBI.

Conclusion

Our findings suggest that MK-deficiency reduced tissue infiltration of microglia/macrophages and altered their polarization status thereby reducing neuroinflammation, neuronal apoptosis, and tissue loss and improving neurological outcomes after TBI. Therefore, targeting MK to modulate neuroinflammation may represent a potential therapeutic strategy for TBI management.
Risk factors for lung metastasis at presentation with malignant primary osseous neoplasms: a population-based study
Authors: Xie Lin , Huang Weibo , Wang Hongli , Zheng Chaojun , Jiang Jianyuan
Published: January 2020

Background

Large population-based studies of risk factor for lung metastases at the presentation with primary osseous neoplasms are lacking and necessary. We aim to examine potential risk factors of lung metastases at presentation with primary osseous neoplasms using Surveillance, Epidemiology, and End Results (SEER) database tool.

Methods

We collected patients diagnosed with primary osseous neoplasms between 2010 and 2015 from the SEER database. Patients were divided into two groups: patients with lung metastases or patients without lung metastases. Patient characteristics such as age, sex, race, tumor size, histologic types, histologic grade, and lung metastasis were collected. Univariate and multivariate logistic regression analyses were applied to determine which characteristics were risk factors for lung metastasis at diagnosis.

Results

A total of 4459 patients were collected, and 507 patients had lung metastases at presentation. Data on age, race, gender, primary site, grade, tumor size, and histology types were enrolled into the multivariate logistic analysis. Higher grade (OR = 5.197, 95% CI 3.328 to 8.117), histology type (Ewing sarcoma: OR = 1.432, 95% CI 1.020 to 2.009; osteosarcoma: OR = 1.597, 95% CI, 1.073 to 2.377), and larger tumor size (≥ 5 cm: OR = 3.528, 95% CI 2.370 to 5.251) were associated with an increased risk of lung metastasis at presentation.

Conclusion

Histology types (osteosarcoma and Ewing sarcoma) were related to a higher risk of lung metastases in primary osseous neoplasms patients. Patients with osteosarcoma and lager tumors or higher tumor grade were associated with higher possibility of lung metastases. Patients with Ewing sarcoma and larger tumors have more tendency of lung metastases. These patients are supposed to receive chest CT scans at the presentation with primary osseous neoplasms.
Co-existence of hepatocellular carcinoma and cystic echinococcosis
Authors: Bo Ran , Yasen Aimaiti , Shao Yingmei , Zhang Wenbao , Lin Renyong , Jiang Tiemin , Wen Hao , Xiao Hui , Aji Tuerganaili
Published: January 2020

Purpose

Co-existence of hepatocellular carcinoma (HCC) and cystic echinococcus (CE) is extremely rare. Echinococcus granulosus may exhibit a protective effect against cancer. Herein, this study aimed to evaluate the possible effects of echinococcal infection on HCC patients.

Methods

Three thousand three hundred hepatic CE patients and 815 HCC patients were retrospectively reviewed between January 2010 and December 2018 in Xinjiang, China, and these patients were 1:5 matched according to their sex, age and tumor TMN stage, and only 13 patients coexisted both CE and HCC. Preoperative ultrasonography (US), computed tomography (CT), liver magnetic resonance imaging (MRI) and dot immune-gold filtration assay (DIGFA) were used for preoperative identification and intraoperative specimens from liver resections were pathologically examined for further confirmation. Survival time was analyzed through Cox proportional hazard model analysis.

Results

The co-existing incidence rate of two diseases was 0.39%. For these concurrent cases, HCC was all at the advanced stage and CE lesions were inactive. Median survival time for HCC patients was 6 month (1–17). However, it was 8 month (3–90) for the co-existing cases and was much longer than the median survival time of HCC patients (P<0.05), which was closely associated with tumor size, location, TMN stage and hydatid size, location, classification. Four of the patients underwent surgical intervention and their median survival time was 17 month (3–68).

Conclusions

Echinococcus granulosus may elicit a protective effect against the development and progression of HCC, while more basic and clinical researches are needed.
Towards definitions of time-sensitive conditions in prehospital care
Authors: Wibring Kristoffer , Magnusson Carl , Axelsson Christer , Lundgren Peter , Herlitz Johan , Andersson Hagiwara Magnus
Published: January 2020

Background

Prehospital care has changed in recent decades. Advanced assessments and decisions are made early in the care chain. Patient assessments form the basis of a decision relating to prehospital treatment and the level of care. This development imposes heavy demands on the ability of emergency medical service (EMS) clinicians properly to assess the patient. EMS clinicians have a number of assessment instruments and triage systems available to support their decisions. Many of these instruments are based on vital signs and can sometimes miss time-sensitive conditions. With this commentary, we would like to start a discussion to agree on definitions of temporal states in the prehospital setting and ways of recognising patients with time-sensitive conditions in the most optimal way.

Main body

There are several articles discussing the identification and management of time-sensitive conditions. In these articles, neither definitions nor terminology have been uniform. There are a number of problems associated with the definition of time-sensitive conditions. For example, intoxication can be minor but also life threatening, depending on the type of poison and dose. Similarly, diseases like stroke and myocardial infarction can differ markedly in terms of severity and the risk of life-threatening complications. Another problem is how to support EMS clinicians in the early recognition of these conditions. It is well known that many of them can present without a deviation from normal in vital signs. It will most probably be impossible to introduce specific decision support tools for every individual time-sensitive condition. However, there may be information in the type and intensity of the symptoms patients present. In future, biochemical markers and machine learning support tools may help to identify patients with time-sensitive conditions and predict mortality at an earlier stage.

Conclusion

It may be of great value for prehospital clinicians to be able to describe time-sensitive conditions. Today, neither definitions nor terminology are uniform. Our hope is that this commentary will initiate a discussion on the issue aiming at definitions of time-sensitive conditions in prehospital care and how they should be recognised in the most optimal fashion.
An integrated intervention for chronic care management in rural Nepal: protocol of a type 2 hybrid effectiveness-implementation study
Authors: Schwarz Dan , Dhungana Santosh , Kumar Anirudh , Acharya Bibhav , Agrawal Pawan , Aryal Anu , Baum Aaron , Choudhury Nandini , Citrin David , Dangal Binod , Dhimal Meghnath , Gauchan Bikash , Gupta Tula , Halliday Scott , Karmacharya Biraj , Kishore Sandeep , Koirala Bhagawan , Kshatriya Uday , Levine Erica , Maru Sheela , Rimal Pragya , Sapkota Sabitri , Schwarz Ryan , Shrestha Archana , Thapa Aradhana , Maru Duncan
Published: January 2020

Background

In Nepal, the burden of noncommunicable, chronic diseases is rapidly rising, and disproportionately affecting low and middle-income countries. Integrated interventions are essential in strengthening primary care systems and addressing the burden of multiple comorbidities. A growing body of literature supports the involvement of frontline providers, namely mid-level practitioners and community health workers, in chronic care management. Important operational questions remain, however, around the digital, training, and supervisory structures to support the implementation of effective, affordable, and equitable chronic care management programs.

Methods

A 12-month, population-level, type 2 hybrid effectiveness-implementation study will be conducted in rural Nepal to evaluate an integrated noncommunicable disease care management intervention within Nepal’s new municipal governance structure. The intervention will leverage the government’s planned roll-out of the World Health Organization’s Package of Essential Noncommunicable Disease Interventions (WHO-PEN) program in four municipalities in Nepal, with a study population of 80,000. The intervention will leverage both the WHO-PEN and its cardiovascular disease-specific technical guidelines (HEARTS), and will include three evidence-based components: noncommunicable disease care provision using mid-level practitioners and community health workers; digital clinical decision support tools to ensure delivery of evidence-based care; and training and digitally supported supervision of mid-level practitioners to provide motivational interviewing for modifiable risk factor optimization, with a focus on medication adherence, and tobacco and alcohol use. The study will evaluate effectiveness using a pre–post design with stepped implementation. The primary outcomes will be disease-specific, “at-goal” metrics of chronic care management; secondary outcomes will include alcohol and tobacco consumption levels.

Discussion

This is the first population-level, hybrid effectiveness-implementation study of an integrated chronic care management intervention in Nepal. As low and middle-income countries plan for the Sustainable Development Goals and universal health coverage, the results of this pragmatic study will offer insights into policy and programmatic design for noncommunicable disease care management in the future.

Trial registration

ClinicalTrials.gov,NCT04087369. Registered on 12 September 2019.
Association between metabolic syndrome and prognosis of breast cancer: a meta-analysis of follow-up studies
Authors: Li Peiting , Wang Tianying , Zeng Chen , Yang Meng , Li Gang , Han Jiang , Wu Wei
Published: January 2020

Background

Metabolic syndrome (MetS) has been suggested to be a risk factor for many cancers, including breast cancer. However, it remains unclear whether MetS predicts poor prognosis in women with breast cancer. A meta-analysis was performed to summarize the association between MetS and clinical outcome in women with breast cancer.

Methods

Cohort studies were identified by search of PubMed and Embase databases. A random-effect model incorporating the potential heterogeneity was applied to pool the results. Subgroup analyses according to the ethnicity and study design were performed.

Results

Nine cohort studies with 17,892 women with breast cancer were included. Pooled results showed that MetS was significantly associated with an increased risk of breast cancer recurrence (adjusted risk ratio [RR] = 1.52, 95%, p = 0.02). Subgroup analyses showed that MetS was independently associated with increased recurrence of breast cancer in Caucasians (adjusted RR = 1.75, p = 0.02), but not in Asians (adjusted RR = 1.07, p = 0.81), and MetS was associated with a trend of increased risk of breast cancer recurrence in both the prospective and retrospective studies. Although we failed to show a significant association between MetS and breast cancer related deaths (adjusted RR = 1.24, p = 0.41), MetS was associated with increased risk of all-cause deaths in these patients (adjusted RR = 1.80, p < 0.001).

Conclusions

MetS may predict the risk of cancer recurrence and mortality in women with breast cancer, particularly in Caucasians.
Analysis of risk factors for carotid intima-media thickness in patients with type 2 diabetes mellitus in Western China assessed by logistic regression combined with a decision tree model
Authors: Zhou Yuan-Yuan , Qiu Hong-Mei , Yang Ying , Han Yuan-Yuan
Published: January 2020

Background

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in patients with type 2 diabetes (T2DM). Carotid intima-media thickness (CIMT) is considered a preclinical stage of atherosclerosis. Therefore, it is necessary to identify the related risk factors for CIMT to facilitate the early prevention of CVD. Previous studies have shown that visceral fat area (VFA) is a risk factor for T2DM and CVD. However, few studies have focused on the effects of VFA on CIMT associated with T2DM. Moreover, considering that the body fat distribution shows regional and racial heterogeneity, the purpose of this study was to investigate the predictive value of VFA and other risk factors for CIMT associated with T2DM in Western China.

Methods

In a cross-sectional study, a total of 1372 patients with T2DM were divided into the CIMT (−) group (n = 965) and the CIMT (+) group (n = 407) based on CIMT values. In addition to the univariate analyses, logistic regression analysis and a decision tree model were simultaneously performed to establish a correlation factor model for CIMT.

Results

Univariate analyses showed that sex, smoking status, age, heart rate, systolic blood pressure (SBP), diastolic blood pressure (DBP), height, weight, body mass index (BMI), waist circumference, hip circumference, waist-hip ratio, VFA, subcutaneous fat area, and the levels of 2-h C-peptide, serum creatinine, urea nitrogen and uric acid were significantly different between the two groups (all p < 0.05). Smoking, increased VFA, female sex and increased BMI were risk factors in the logistic regression analyses (OR = 5.759, OR = 1.364, OR = 2.239, OR = 1.186, respectively). In the decision tree model, smoking was the root node, followed by sex, waist circumference, VFA and chronic kidney disease (CKD) in order of importance.

Conclusions

In addition to smoking, sex and BMI, VFA has a significant effect on CIMT associated with T2DM in the Chinese Han population in Western China. In addition, the decision tree model could help clinicians make more effective decisions, with its simplicity and intuitiveness, making it worth promoting in future medical research.

Trial registration ChiCTR, ChiCTR1900027739. Registered 24 November 2019-Retrospectively registered, http://www.chictr.org.cn/index.aspx.
Profiling parvalbumin interneurons using iPSC: challenges and perspectives for Autism Spectrum Disorder (ASD)
Authors: Filice Federica , Schwaller Beat , Michel Tanja M. , Grünblatt Edna
Published: January 2020

Autism spectrum disorders (ASD) are persistent conditions resulting from disrupted/altered neurodevelopment. ASD multifactorial etiology—and its numerous comorbid conditions—heightens the difficulty in identifying its underlying causes, thus obstructing the development of effective therapies. Increasing evidence from both animal and human studies suggests an altered functioning of the parvalbumin (PV)-expressing inhibitory interneurons as a common and possibly unifying pathway for some forms of ASD. PV-expressing interneurons (short: PVALB neurons) are critically implicated in the regulation of cortical networks’ activity. Their particular connectivity patterns, i.e., their preferential targeting of perisomatic regions and axon initial segments of pyramidal cells, as well as their reciprocal connections, enable PVALB neurons to exert a fine-tuned control of, e.g., spike timing, resulting in the generation and modulation of rhythms in the gamma range, which are important for sensory perception and attention.

New methodologies such as induced pluripotent stem cells (iPSC) and genome-editing techniques (CRISPR/Cas9) have proven to be valuable tools to get mechanistic insight in neurodevelopmental and/or neurodegenerative and neuropsychiatric diseases. Such technological advances have enabled the generation of PVALB neurons from iPSC. Tagging of these neurons would allow following their fate during the development, from precursor cells to differentiated (and functional) PVALB neurons. Also, it would enable a better understanding of PVALB neuron function, using either iPSC from healthy donors or ASD patients with known mutations in ASD risk genes. In this concept paper, the strategies hopefully leading to a better understanding of PVALB neuron function(s) are briefly discussed. We envision that such an iPSC-based approach combined with emerging (genetic) technologies may offer the opportunity to investigate in detail the role of PVALB neurons and PV during “neurodevelopment ex vivo.”
Acute kidney injury and hepatitis associated with energy drink consumption: a case report
Authors: Al Yacoub Raed , Luczkiewicz Debra , Kerr Christopher
Published: January 2020

Introduction

In the USA, energy drinks are commonly consumed among adults. The side effects of these drinks are not well studied but consumers have reported multiple adverse events to the US Food and Drug Administration including acute kidney injury and acute hepatitis.

Case presentation

A 62-year-old white woman presented with progressive weakness, fatigue, confusion, and delirium secondary to acute kidney injury and acute hepatitis associated with excessive energy drink use. Clinical improvement occurred with supportive care and discontinuation of energy drinks, with resolution of acute kidney injury and progressive improvement of liver function. The defined mechanism of injury is unknown but thought due to energy drink ingredients.

Conclusion

Multiple cases of energy drink-induced acute kidney injury or acute hepatitis are reported in the literature but this case is the first to report them simultaneously. Ingredients and presumed doses to cause these events are outlined in this case report.
EphrinB2 overexpression enhances osteogenic differentiation of dental pulp stem cells partially through ephrinB2-mediated reverse signaling
Authors: Wang Wen , Yuan Changyong , Geng Tengyu , Liu Yi , Zhu Shaoyue , Zhang Chengfei , Liu Zongxiang , Wang Penglai
Published: January 2020

Background

Alveolar bone loss is a frequent occurrence. Dental pulp stem cells (DPSCs) which have invasive accessibility and high osteogenic potential is a promising source for cell-based bone regeneration. EphrinB2 is involved in bone homeostasis and osteogenesis. The aim of this study was to investigate the effect and mechanism of ephrinB2 overexpression on osteogenic differentiation of DPSCs and bone defect repair.

Methods

EphrinB2 expression was analyzed during osteogenic induction of human DPSCs (hDPSCs). Endogenous ephrinB2 expression in hDPSCs was then upregulated using EfnB2 lentiviral vectors. The effect of ephrinB2 overexpression on osteogenic differentiation capacity of hDPSCs was investigated in vitro, and activation of ephrinB2-EphB4 bidirectional signaling in ephrinB2-overexpressing hDPSCs was detected. In vivo, a canine alveolar bone defect model was established and canine DPSCs (cDPSCs) were cultured, characterized, EfnB2-tranfected, and combined with a PuraMatrix scaffold. Micro-CT analysis was performed to evaluate the therapeutic effect of ephrinB2-overexpressing cDPSCs on bone defect repair.

Results

EphrinB2 was upregulated after osteogenic induction of hDPSCs. EphrinB2 overexpression enhanced osteogenic differentiation capacity of hDPSCs in vitro. Moreover, p-ephrinB2 instead of p-EphB4 was upregulated by ephrinB2 overexpression, and activation of ephrinB2-mediated reverse signaling promoted osteogenic differentiation of hDPSCs. In a canine bone defect model, ephrinB2 overexpression in cDPSCs significantly improved trabecular bone volume per tissue volume (BV/TV) and trabecular thickness, as demonstrated by radiographic analysis.

Conclusions

EphrinB2 overexpression enhanced osteogenic potential of DPSCs partially via upregulation of ephrinB2-mediated reverse signaling and effectively promoted alveolar bone defect repair.
TGF-β/SMAD signaling regulation of mesenchymal stem cells in adipocyte commitment
Authors: Li Sheng-Nan , Wu Jia-Fa
Published: January 2020

Adipocytes arising from mesenchymal stem cells (MSCs) requires MSC adipocyte commitment and differentiation of preadipocytes to mature adipocytes. Several signaling and some cytokines affect the adipogenesis of MSCs. This review focuses on the roles of TGF-β/SMAD signaling in adipocyte commitment of MSCs. BMP4 and BMP7 signaling are sufficient to induce adipocyte lineage determination of MSCs. The roles of BMP2, TGF-β, and myostatin signaling in this process are unclear. Other TGF-β/SMAD signaling such as BMP3 and BMP6 signaling have almost no effect on commitment because of limited research available, while GDF11 signaling inhibits adipocyte commitment in human MSCs. In this review, we summarize the available information on TGF-β/SMAD signaling regulation of MSCs in adipocyte commitment. Deeper study of this commitment mechanism will offer new approaches in treating obesity, diabetes mellitus, and obesity-related metabolism syndrome.
The use of micro-costing in economic analyses of surgical interventions: a systematic review
Authors: Potter Shelley , Davies Charlotte , Davies Gareth , Rice Caoimhe , Hollingworth William
Published: January 2020

Background

Compared with conventional top down costing, micro-costing may provide a more accurate method of resource-use assessment in economic analyses of surgical interventions, but little is known about its current use. The aim of this study was to systematically-review the use of micro-costing in surgery.

Methods

Comprehensive searches identified complete papers, published in English reporting micro-costing of surgical interventions up to and including 22nd June 2018. Studies were critically appraised using a modified version of the Consensus on Health Economic Criteria (CHEC) Checklist. Study demographics and details of resources identified; methods for measuring and valuing identified resources and any cost-drivers identified in each study were summarised.

Results

A total of 85 papers were identified. Included studies were mainly observational comparative studies (n = 42, 49.4%) with few conducted in the context of a randomised trial (n = 5, 5.9%). The majority of studies were single-centre (n = 66, 77.6%) and almost half (n = 40, 47.1%) collected data retrospectively. Only half (n = 46, 54.1%) self-identified as being ‘micro-costing’ studies. Rationale for the use of micro-costing was most commonly to compare procedures/techniques/processes but over a third were conducted specifically to accurately assess costs and/or identify cost-drivers. The most commonly included resources were personnel costs (n = 76, 89.4%); materials/disposables (n = 76, 89.4%) and operating-room costs (n = 62,72.9%). No single resource was included in all studies. Most studies (n = 72, 84.7%) identified key cost-drivers for their interventions.

Conclusions

There is lack of consistency regarding the current use of micro-costing in surgery. Standardising terminology and focusing on identifying and accurately costing key cost-drivers may improve the quality and value of micro-costing in future studies.

Trial registration

PROSPERO registrationCRD42018099604.
ATM, ATR and DNA-PKcs kinases—the lessons from the mouse models: inhibition ≠ deletion
Authors: Menolfi Demis , Zha Shan
Published: January 2020

DNA damage, especially DNA double strand breaks (DSBs) and replication stress, activates a complex post-translational network termed DNA damage response (DDR). Our review focuses on three PI3-kinase related protein kinases—ATM, ATR and DNA-PKcs, which situate at the apex of the mammalian DDR. They are recruited to and activated at the DNA damage sites by their respective sensor protein complexes—MRE11/RAD50/NBS1 for ATM, RPA/ATRIP for ATR and KU70–KU80/86 (XRCC6/XRCC5) for DNA-PKcs. Upon activation, ATM, ATR and DNA-PKcs phosphorylate a large number of partially overlapping substrates to promote efficient and accurate DNA repair and to coordinate DNA repair with other DNA metabolic events (e.g., transcription, replication and mitosis). At the organism level, robust DDR is critical for normal development, aging, stem cell maintenance and regeneration, and physiological genomic rearrangements in lymphocytes and germ cells. In addition to endogenous damage, oncogene-induced replication stresses and genotoxic chemotherapies also activate DDR. On one hand, DDR factors suppress genomic instability to prevent malignant transformation. On the other hand, targeting DDR enhances the therapeutic effects of anti-cancer chemotherapy, which led to the development of specific kinase inhibitors for ATM, ATR and DNA-PKcs. Using mouse models expressing kinase dead ATM, ATR and DNA-PKcs, an unexpected structural function of these kinases was revealed, where the expression of catalytically inactive kinases causes more genomic instability than the loss of the proteins themselves. The spectrum of genomic instabilities and physiological consequences are unique for each kinase and depends on their activating complexes, suggesting a model in which the catalysis is coupled with DNA/chromatin release and catalytic inhibition leads to the persistence of the kinases at the DNA lesion, which in turn affects repair pathway choice and outcomes. Here we discuss the experimental evidences supporting this mode of action and their implications in the design and use of specific kinase inhibitors for ATM, ATR and DNA-PKcs for cancer therapy.
Design and implementation of intelligent accounting data analysis platform based on industrial cloud computing
Authors: Ting Wang , Liu Yang
Published: January 2020

In order to improve the ability of accounting data analysis and statistics, a method of constructing modern accounting data analysis platform based on industrial cloud computing is proposed. The time series model of modern accounting data analysis is constructed by using block bit sequence analysis method, and the association rule characteristic quantity of accounting data is extracted. Combined with cloud computing technology, the modern accounting data analysis platform is constructed, and the fuzzy C-means clustering algorithm is used to realize the clustering of modern accounting data, which can improve the ability of parallel computing and statistical analysis of accounting data. The simulation results show that the intelligent data analysis platform designed makes the statistical analysis ability of accounting data better and the parallel computing efficiency higher.
Whole‐transcriptome sequencing uncovers core regulatory modules and gene signatures of human fetal growth restriction
Authors: Wang Guiying , Yu Jun , Yang Yiwei , Liu Xiaoqin , Zhao Xiaobo , Guo Xudong , Duan Tao , Lu Chenqi , Kang Jiuhong
Published: January 2020

Background

Fetal growth restriction (FGR) contributes the primary cause of perinatal mortality and morbidity with impacts on the long‐term health. To determine the core gene expression network and gene signatures, which in combination with ultrasound confirmation will more effectively differentiate constitutionally normal small for gestational age and pathological FGR groups, we performed RNA sequencing for protein‐coding genes, lncRNAs, and small RNAs in a case–control study of umbilical cord blood.

Results

Five pairs of FGR case and control umbilical cord blood samples were used for RNA sequencing and weighted gene co‐expression network analysis (WGCNA). Results showed that 339 mRNAs, 295 lncRNAs, and 13 miRNAs were significantly differentially expressed between FGR cases and controls. Bioinformatics analysis indicated that these differentially expressed molecules were mainly involved in metabolism, neural, cardiac, and immune systems, and identified 18 WGCNA modules for FGR. Further quantitative verification was performed using umbilical cord blood and maternal peripheral blood from 12 pairs of FGR cases and controls. The logistic regression and receiver operating characteristic curve indicated that RP11_552M6.1, LINC01291, and Asgr1 in umbilical cord blood, while Sfrp2, miR‐432‐5p, and miR‐1306‐3p in maternal peripheral blood had potential significance for FGR.

Conclusions

We comprehensively profiled the whole‐transcriptome landscape of human umbilical cord blood with FGR, constructed the core WGCNA modules, and delineated the critical gene signatures of FGR. These findings provide key insight into intrauterine perturbations and candidate signatures for FGR.
Treating binge eating and food addiction symptoms with low-carbohydrate Ketogenic diets: a case series
Authors: Carmen Matthew , Safer Debra Lynn , Saslow Laura R. , Kalayjian Tro , Mason Ashley E. , Westman Eric C. , Sethi Shebani
Published: January 2020

Background

Many patients with obesity and comorbid binge eating symptoms present with the desire to lose weight. Although some studies suggest that dietary restriction can exacerbate binge eating, others show dietary restriction is associated with significant reductions in binge eating. The effect of a particular type of dieting on binge eating, the ketogenic diet (a high fat, moderate protein, very low carbohydrate diet), is not known.

Case presentations

We report on the feasibility of a low-carbohydrate ketogenic diet initiated by three patients (age 54, 34, and 63) with obesity (average BMI 43.5 kg/m2) with comorbid binge eating and food addiction symptoms. All patients tolerated following the ketogenic diet (macronutrient proportion 10% carbohydrate, 30% protein, and 60% fat; at least 5040 kJ) for the prescribed period (e.g., 6–7 months) and none reported any major adverse effects. Patients reported significant reductions in binge eating episodes and food addiction symptoms including cravings and lack of control as measured by the Binge-Eating Scale, Yale Food Addiction Scale, or Yale-Brown Obsessive-Compulsive Scale modified for Binge Eating, depending on the case. Additionally, the patients lost a range of 10–24% of their body weight. Participants reported maintenance of treatment gains (with respect to weight, binge eating, and food addiction symptoms) to date of up to 9–17 months after initiation and continued adherence to diet.

Conclusions

Although the absence of control cases precludes conclusions regarding the specific role of ketogenic diets versus other forms of dietary restriction, this is the first report to demonstrate the feasibility of prescribing a ketogenic diet for patients with obesity who report binge eating and food addiction symptoms. Further research should seek to reproduce the observed effects in controlled trials as well as to explore potential etiologies.