bluuebunny/crossref_metadata_2025 huggingface dataset:
Lysosomal dysfunction and autophagy blockade contribute to autophagy-related cancer suppressing peptide-induced cytotoxic death of cervical cancer cells through the AMPK/mTOR pathway
Authors: Yang Yang , Wang Qi , Song Dongjian , Zen Ruirui , Zhang Lei , Wang Yingjun , Yang Heying , Zhang Da , Jia Jia , Zhang Jiao , Wang Jiaxiang
Published: September 2020

Background

Autophagy is an intracellular process through which intracellular components are recycled in response to nutrient or growth factor deficiency to maintain homeostasis. We identified the peptide autophagy-related cancer-suppressing peptide (ARCSP), a potential antitumor peptide that disrupts intracellular homeostasis by blocking autophagic flux and causes cytotoxic death.

Methods

The proliferative ability of ARCSP-treated cervical cancer cells was examined by the CCK8, EdU, and colony formation assays. The TUNEL assay was used to detect apoptosis. Mitochondrial function was evaluated based on the mitochondrial membrane potential. Autophagic flux was detected by immunofluorescence and confocal microscopy. The autophagy-related proteins AMPK, Raptor, mTOR, p62, LC3B, atg7, Rab7, LAMP1, LAMP2, and cathepsin D were detected by Immunoblotting. The antitumor effect of ARCSP was explored in vivo by establishing a transplant tumor model in nude mice.

Results

The results demonstrated that ARCSP induced cell death and inhibited proliferation. ARCSP induced AMPK/mTOR activation, resulting in the accumulation of the proteins LC3B, p62 and Atg7. ARCSP also blocked autophagosome-lysosome fusion by inhibiting endosomal maturation and increasing the lysosomal pH. The accumulation of nonfused autophagosomes exacerbated cytotoxic death, whereas knocking down Atg7 reversed the cytotoxic death induced by ARCSP. ARCSP-treated cells exhibited increased cytotoxic death after cotreatment with an autophagy inhibitor (Chloroquine CQ). Furthermore, the tumors of ARCSP-treated nude mice were significantly smaller than those of untreated mice.

Conclusions

Our findings demonstrate that ARCSP, a novel lethal nonfused autophagosome inducer, might cause mitochondrial dysfunction and autophagy-related cytotoxic death and is thus a prospective agent for cancer therapy.
CD14+CD16− monocytes are the main precursors of osteoclasts in rheumatoid arthritis via expressing Tyro3TK
Authors: Xue Jimeng , Xu Liling , Zhu Huaqun , Bai Mingxin , Li Xin , Zhao Zhen , Zhong Hua , Cheng Gong , Li Xue , Hu Fanlei , Su Yin
Published: September 2020

Background

Monocytes as precursors of osteoclasts in rheumatoid arthritis (RA) are well demonstrated, while monocyte subsets in osteoclast formation are still controversial. Tyro3 tyrosine kinase (Tyro3TK) is a member of the receptor tyrosine kinase family involved in immune homeostasis, the role of which in osteoclast differentiation was reported recently. This study aimed to compare the osteoclastic capacity of CD14+CD16+ and CD14+CD16− monocytes in RA and determine the potential involvement of Tyro3TK in their osteoclastogenesis.

Methods

Osteoclasts were induced from CD14+CD16+ and CD14+CD16− monocyte subsets isolated from healthy control (HC) and RA patients in vitro and evaluated by tartrate-resistant acid phosphatase (TRAP) staining. Then, the expression of Tyro3TK on CD14+CD16+ and CD14+CD16− monocyte subsets in the peripheral blood of RA, osteoarthritis (OA) patients, and HC were evaluated by flow cytometry and qPCR, and their correlation with RA patient clinical and immunological features was analyzed. The role of Tyro3TK in CD14+CD16− monocyte-mediated osteoclastogenesis was further investigated by osteoclast differentiation assay with Tyro3TK blockade.

Results

The results revealed that CD14+CD16− monocytes were the primary source of osteoclasts. Compared with HC and OA patients, the expression of Tyro3TK on CD14+CD16− monocytes in RA patients was significantly upregulated and positively correlated with the disease manifestations, such as IgM level, tender joint count, and the disease activity score. Moreover, anti-Tyro3TK antibody could inhibit Gas6-mediated osteoclast differentiation from CD14+CD16− monocytes in a dose-dependent manner.

Conclusions

These findings indicate that elevated Tyro3TK on CD14+CD16− monocytes serves as a critical signal for osteoclast differentiation in RA.
In vivo animal models confirm an increased virulence potential and pathogenicity of the NAP1/RT027/ST01 genotype within the Clostridium difficile MLST Clade 2
Authors: Orozco-Aguilar Josué , Alfaro-Alarcón Alejandro , Acuña-Amador Luis , Chaves-Olarte Esteban , Rodríguez César , Quesada-Gómez Carlos
Published: September 2020

Background

Based on MLST analyses the global population of C. difficile is distributed in eight clades, of which Clade 2 includes the “hypervirulent” NAP1/RT027/ST01 strain along with various unexplored sequence types (STs).

Methods

To clarify whether this clinically relevant phenotype is a widespread feature of C. difficile Clade 2, we used the murine ileal loop model to compare the in vivo pro-inflammatory (TNF-α, IL-1β, IL-6) and oxidative stress activities (MPO) of five Clade 2 clinical C. difficile isolates from sequence types (STs) 01, 41, 67, and 252. Besides, we infected Golden Syrian hamsters with spores from these strains to determine their lethality, and obtain a histological evaluation of tissue damage, WBC counts, and serum injury biomarkers (LDH, ALT, AST, albumin, BUN, creatinine, Na+, and Cl−). Genomic distances were calculated using Mash and FastANI to explore whether the responses were dictated by phylogeny.

Results

The ST01 isolate tested ranked first in all assays, as it induced the highest overall levels of pro-inflammatory cytokines, MPO activity, epithelial damage, biochemical markers, and mortality measured in both animal models. Statistically indistinguishable or rather similar outputs were obtained for a ST67 isolate in tests such as tissue damage, neutrophils count, and lethal activity. The results recorded for the two ST41 isolates tested were of intermediate magnitude and the ST252 isolate displayed the lowest pathogenic potential in all animal experiments. This ordering matched the genomic distance of the ST01 isolate to the non-ST01 isolates.

Conclusions

Despite their close phylogenic relatedness, our results demonstrate differences in pathogenicity and virulence levels in Clade 2 C. difficile strains, confirm the high severity of infections caused by the NAP1/RT027/ST01 strain, and highlight the importance of C. difficile typing.
Linking chemical and disease entities to ontologies by integrating PageRank with extracted relations from literature
Authors: Ruas Pedro , Lamurias Andre , Couto Francisco M.
Published: September 2020

Background

Named Entity Linking systems are a powerful aid to the manual curation of digital libraries, which is getting increasingly costly and inefficient due to the information overload. Models based on the Personalized PageRank (PPR) algorithm are one of the state-of-the-art approaches, but these have low performance when the disambiguation graphs are sparse.

Findings

This work proposes a Named Entity Linking framework designated by Relation Extraction for Entity Linking (REEL) that uses automatically extracted relations to overcome this limitation. Our method builds a disambiguation graph, where the nodes are the ontology candidates for the entities and the edges are added according to the relations established in the text, which the method extracts automatically. The PPR algorithm and the information content of each ontology are then applied to choose the candidate for each entity that maximises the coherence of the disambiguation graph. We evaluated the method on three gold standards: the subset of the CRAFT corpus with ChEBI annotations (CRAFT-ChEBI), the subset of the BC5CDR corpus with disease annotations from the MEDIC vocabulary (BC5CDR-Diseases) and the subset with chemical annotations from the CTD-Chemical vocabulary (BC5CDR-Chemicals). The F1-Score achieved by REEL was 85.8%, 80.9% and 90.3% in these gold standards, respectively, outperforming baseline approaches.

Conclusions

We demonstrated that RE tools can improve Named Entity Linking by capturing semantic information expressed in text missing in Knowledge Bases and use it to improve the disambiguation graph of Named Entity Linking models. REEL can be adapted to any text mining pipeline and potentially to any domain, as long as there is an ontology or other knowledge Base available.
Neurologically asymptomatic cerebral oligometastatic prostate carcinoma metastasis identified on [Ga]Ga-THP-PSMA PET/CT
Authors: Ross M. I. , Bird N. , Mendichovszky I. A. , Rimmer Y. L.
Published: September 2020

Background

Brain metastases from prostate cancer are rare and usually only occur in the context of widespread systemic disease. This is the first case report of a solitary brain oligometastasis, in a neurologically intact prostate cancer patient with no other systemic disease, detected using [68Ga]Ga-THP-PSMA PET/CT and only the second one using a PSMA-based radiopharmaceutical.

Case presentation

We report the case of a prostate cancer patient presenting 5 years after robot-assisted laparoscopic prostatectomy with biochemical recurrence, no neurological symptoms, and in the absence of metastatic lesions in the body on conventional imaging. A solitary cerebral metastasis was detected using [68Ga]Ga-THP-PSMA PET/CT, surgically resected, leading to a drop in serum PSA and a good recovery.

Conclusion

In this case, [68Ga]Ga-THP-PSMA PET/CT resulted in a major change in clinical management and avoided additional morbidity associated with delayed diagnosis and treatment. This report demonstrates the importance of considering the presence of metastatic disease outside the conventional locations of prostate cancer spread, as well as the importance of ensuring comprehensive [68Ga]Ga-PSMA PET/CT coverage from vertex to upper thighs.
Mode of progression after radioembolization in patients with colorectal cancer liver metastases
Authors: van Roekel Caren , Jongen Jennifer M. J. , Smits Maarten L. J. , Elias Sjoerd G. , Koopman Miriam , Kranenburg Onno , Borel Rinkes Inne H. M. , Lam Marnix G. E. H.
Published: September 2020

Background

Radioembolization is an established treatment modality in colorectal cancer patients with liver-dominant disease in a salvage setting. Selection of patients who will benefit most is of vital importance. The aim of this study was to assess response (and mode of progression) at 3 months after radioembolization and the impact of baseline characteristics.

Methods

Three months after radioembolization with either yttrium-90 resin/glass or holmium-166, anatomic response, according to RECIST 1.1, was evaluated in 90 patients. Correlations between baseline characteristics and efficacy were evaluated. For more detailed analysis of progressive disease as a dismal clinical entity, distinction was made between intra- and extrahepatic progression, and between progression of existing metastases and new metastases.

Results

Forty-two patients (47%) had extrahepatic disease (up to five ≥ 1 cm lung nodules, and ≤ 2 cm lymph nodes) at baseline. No patients showed complete response, 5 (5.5%) patients had partial response, 16 (17.8%) had stable disease, and 69 (76.7%) had progressive disease. Most progressive patients (67/69; 97%) had new metastases (intra-hepatic N = 11, extrahepatic N = 32; or both N = 24). Significantly fewer patients had progressive disease in the group of patients presenting without extrahepatic metastases at baseline (63% versus 93%; p = 0.0016). Median overall survival in patients with extrahepatic disease was 6.5 months, versus 10 months in patients without extrahepatic disease at baseline (hazard ratio 1.79, 95%CI 1.24–2.57).

Conclusions

Response at 3-month follow-up and survival were heavily influenced by new metastases. Patients with extrahepatic disease at baseline had a worse outcome compared to patients without.
Considering the societal perspective in economic evaluations: a systematic review in the case of depression
Authors: Duevel Juliane Andrea , Hasemann Lena , Peña-Longobardo Luz María , Rodríguez-Sánchez Beatriz , Aranda-Reneo Isaac , Oliva-Moreno Juan , López-Bastida Julio , Greiner Wolfgang
Published: September 2020

Background

Depressive disorders are associated with a high burden of disease. However, due to the burden posed by the disease on not only the sufferers, but also on their relatives, there is an ongoing debate about which costs to include and, hence, which perspective should be applied. Therefore, the aim of this paper was to examine whether the change between healthcare payer and societal perspective leads to different conclusions of cost-utility analyses in the case of depression.

Methods

A systematic literature search was conducted to identify economic evaluations of interventions in depression, launched on Medline and the Cost-Effectiveness Registry of the Tufts University using a ten-year time horizon (2008–2018). In a two-stepped screening process, cost-utility studies were selected by means of specified inclusion and exclusion criteria. Subsequently, relevant findings was extracted and, if not fully stated, calculated by the authors of this work.

Results

Overall, 53 articles with 92 complete economic evaluations, reporting costs from healthcare payer/provider and societal perspective, were identified. More precisely, 22 estimations (24%) changed their results regarding the cost-effectiveness quadrant when the societal perspective was included. Furthermore, 5% of the ICURs resulted in cost-effectiveness regarding the chosen threshold (2% of them became dominant) when societal costs were included. However, another four estimations (4%) showed the opposite result: these interventions were no longer cost-effective after the inclusion of societal costs.

Conclusions

Summarising the disparities in results and applied methods, the results show that societal costs might alter the conclusions in cost-utility analyses. Hence, the relevance of the perspectives chosen should be taken into account when carrying out an economic evaluation. This systematic review demonstrates that the results of economic evaluations can be affected by different methods available for estimating non-healthcare costs.
Autophagy and its role in regeneration and remodeling within invertebrate
Authors: Song Qian , Liu Hongjin , Zhen Hui , Zhao Bosheng
Published: September 2020

Background

Acting as a cellular cleaner by packaging and transporting defective proteins and organelles to lysosomes for breakdown, autophagic process is involved in the regulation of cell remodeling after cell damage or cell death in both vertebrate and invertebrate. In human, limitations on the regenerative capacity of specific tissues and organs make it difficult to recover from diseases. Comprehensive understanding on its mechanism within invertebrate have strong potential provide helpful information for challenging these diseases.

Method

In this study, recent findings on the autophagy function in three invertebrates including planarian, hydra and leech with remarkable regenerative ability were summarized. Furthermore, molecular phylogenetic analyses of DjATGs and HvATGs were performed on these three invertebrates compared to that of Saccharomyces cerevisiae, Caenorhabditis elegans, Drosophila melanogaster, Mus musculus and Homo sapiens.

Results

In comparison with Scerevisiae, C elegans, D melanogaster, M musculus and human, our analysis exhibits the following characteristics of autophagy and its function in regeneration within invertebrate. Phylogenetical analysis of ATGs revealed that most autophagy-related genes (ATGs) were highly similar to their homologs in other species, which indicates that autophagy is a highly conservative biological function in both vertebrate and invertebrate. Structurally, almost all the core amino acids necessary for the function of ATG8 in mammal were observed in invertebrate HvATG8s and DjATG8s. For instance, ubiquitin-like domain as a signature structure in each ATG8, was observed in all ATG8s in three invertebrates. Basically, autophagy plays a key role in the regulation of regeneration in planarian. DjATG8-2 and DjATG8-3 associated with mTOR signaling pathway are sophisticated in the invertebrate tissue/organ regeneration. Furthermore, autophagy is involved in the pathway of neutralization of toxic molecules input from blood digestion in the leech.

Conclusions

The recent investigations on autophagy in invertebrate including planarian, hydra and leech suggest that autophagy is evolutionally conserved from yeast to mammals. The fundamental role of its biological function in the invertebrate contributing to the regeneration and maintenance of cellular homeostasis in these three organisms could make tremendous information to confront life threatening diseases in human including cancers and cardiac disorders.
Low-complexity decoding of LDPC codes using reduced-set WBF-based algorithms
Authors: Haddadi Sadjad , Farhang Mahmoud , Derakhtian Mostafa
Published: September 2020

We propose a method to substantially reduce the computational complexity of iterative decoders of low-density parity-check (LDPC) codes which are based on the weighted bit-flipping (WBF) algorithm. In this method, the WBF-based decoders are modified so that the flipping function is calculated only over a reduced set of variable nodes. An explicit expression for the achieved complexity gain is provided and it is shown that for a code of block length N, the decoding complexity is reduced from O(N2) to O(N). Moreover, we derive an upper bound for the difference in the frame error rate of the reduced-set decoders and the original WBF-based decoders, and it is shown that the error performances of the two decoders are essentially the same.
Modeling the effects of contact tracing on COVID-19 transmission
Authors: Traoré Ali , Konané Fourtoua Victorien
Published: September 2020

In this paper, a mathematical model for COVID-19 that involves contact tracing is studied. The contact tracing-induced reproduction number $\mathcal{R}_{q}$

R
q

and equilibrium for the model are determined and stabilities are examined. The global stabilities results are achieved by constructing Lyapunov functions. The contact tracing-induced reproduction number $\mathcal{R}_{q}$

R
q

is compared with the basic reproduction number $\mathcal{R}_{0}$

R
0

for the model in the absence of any intervention to assess the possible benefits of the contact tracing strategy.
A collaborative scheduling strategy for IoV computing resources considering location privacy protection in mobile edge computing environment
Authors: Pang Meiyu , Wang Li , Fang Ningsheng
Published: September 2020

This paper proposes a collaborative scheduling strategy for computing resources of the Internet of vehicles considering location privacy protection in the mobile edge computing environment. Firstly, a multi area multi-user multi MEC server system is designed, in which a MEC server is deployed in each area, and multiple vehicle user equipment in an area can offload computing tasks to MEC servers in different areas by a wireless channel. Then, considering the mobility of users in Internet of vehicles, a vehicle distance prediction based on Kalman filter is proposed to improve the accuracy of vehicle-to-vehicle distance. However, when the vehicle performs the task, it needs to submit the real location, which causes the problem of the location privacy disclosure of vehicle users. Finally, the total cost of communication delay, location privacy of vehicles and energy consumption of all users is formulated as the optimization goal, which take into account the system state, action strategy, reward and punishment function and other factors. Moreover, Double DQN algorithm is used to solve the optimal scheduling strategy for minimizing the total consumption cost of system. Simulation results show that proposed algorithm has the highest computing task completion rate and converges to about 80% after 8000 iterations, and its performance is more ideal compared with other algorithms in terms of system energy cost and task completion rate, which demonstrates the effectiveness of our proposed scheduling strategy.
Same-day antiretroviral treatment (ART) initiation and associated factors among HIV positive people in Northwest Ethiopia: baseline characteristics of prospective cohort
Authors: Moges Nurilign Abebe , Adesina Olubukola Adeponle , Okunlola Micheal A. , Berhane Yemane
Published: September 2020

Background

Despite a well-established fact that same-day or rapid ART initiation after a positive HIV test result is vital for faster viral suppression and for prevention of further sexual transmissions of HIV, there is a paucity of evidence on the uptake of same-day ART initiation among newly HIV diagnosed people in Northwest, Ethiopia.

Methods

A cross-sectional study was conducted between December 1st, 2018 and July 30, 2019. About 759 newly HIV diagnosed adults were recruited from 24 health facilities. Data were collected using interviewer-administered questionnaire. Data were entered using EPI-Data and exported to SPSS and STATA software for further analysis. Bivariate logistic regression was used to select candidate variables atp-value less than 0.25 for multivariate logistic regression. Then adjusted odds ratio with 95% Confidence Interval (CI) at p-value of less than 0.05 was used to declare the statistical associations between the dependent and independent variables.

Result

Magnitude of same-day ART initiation was 318 (41.90%)[(95% CI, 38.2–45.20%)]. Factors associated with same-day ART initiation were: Patients resided in West Gojjam Zone were 2.04 times more likely to initiate same-day ART compared to those in Bahir Dar city administration [AOR = 2.04 (1.04–3.97)], patients in the health centers were 3.06 times more likely to initiate same-day ART initiation compared to those in the hospitals [AOR = 3.06 (1.90–4.92)] and Patients who were diagnosed their HIV status at the same health facility where they linked for ART were 2.16 times more likely to initiate ART at the same-day of diagnosis [AOR = 2.16 (91.24–3.74)]. Moreover, patients with no opportunistic infection [AOR = 2.08 (1.04–4.19)] and pregnant women [AOR = 3.97 (1.78–8.87)] were more likely to initiate ART same-day of diagnosis.

Conclusions

Same-day ART initiation was low among HIV patients in Ethiopia. Patients attending their treatment at hospitals and those from big city (Bahir Dar) were less likely to initiate same-day ART. Clinical factors such as having opportunistic infections and non-pregnancy status affected the immediate initiation of treatment. HIV positive people who seek care in hospitals and those tested HIV positive from another health facilities in which they did not intend to continue their ART follow-up care need special attention.
Current situation and distribution equality of public health resource in China
Authors: Yao Honghui , Zhan Chaohong , Sha Xinping
Published: September 2020

Background

The public health system has been developed in China for several years while no research explores its distribution. This research aims to describe the variation and equality of public health allocation from 2013 to 2018 and explore the source of inequality.

Methods

Data in this research was obtained from the China Health Statistics Yearbook 2014 to 2019 and the China Statistical Yearbook 2019. Four indicators were chosen in describing the development and current situation of the public health system. Three of them were used to evaluate allocation equality. 31 provinces were categorized into western, middle, and eastern groups based on geographical and economic conditions. Total allocation equality, inter- and intra-difference were all measured by the Theil index.

Results

All indicators showed a stably upwards trend except for the number of public health institutions. The allocation gap of the public health institution per km2 was larger than that per 10,000 capita. Theil index of three indicators continually rose from 2013 to 2018 and the inequality of public health institutions allocation was the highest one. The western region had the highest Theil index in technical personnel and beds allocation. Among the three regions, the western region contributed most to inequality.

Conclusions

The public health workforces and institutions are still under the requirement of the National Medical and Health Service System Plan. From 2013 to 2018, the equality of public health resources stably decreases, which is mainly contributed by the internal difference within the western region. Further research should be done to explore the possible cause of the results. Problems founded in this research should be solved by multisectoral cooperation.
Theoretical background of innovation in services in small and medium-sized enterprises: literature mapping
Authors: de Oliveira Sousa Saymon Ricardo , da Silva Wesley Vieira , da Veiga Claudimar Pereira , Zanini Roselaine Ruviaro
Published: September 2020

The aim of this study was to map the innovation of services in small and medium-sized enterprises, as reported on the Web of Science and SCOPUS databases, using a structured review, involving 121 papers published between 1946 and 2019. There has been an increase in the number of studies in recent years, covering 23 countries on six continents, with the UK representing 48.78% of the studies. Patterns in the use of methods applied in research were identified, as well as a conceptual structure of the field. The main areas of science were finance, marketing, energy, and green engineering. The study makes an original contribution to the literature, highlighting the interest in the expansion of knowledge among the academic community, in addition to enabling a deeper analysis of the relation between the evaluated constructs.
Endothelial glycocalyx shedding in the acute respiratory distress syndrome after flu syndrome
Authors: Benatti Maira Nilson , Fabro Alexandre Todorovic , Miranda Carlos Henrique
Published: September 2020

Background

Scientific evidence indicates that endothelial glycocalyx (EG) shedding contributes to the pathophysiological installation of acute respiratory distress syndrome (ARDS) after bacterial sepsis. The aim was to evaluate the EG shedding in ARDS installation after flu syndrome.

Methods

This cross-sectional study included patients with flu syndrome during the influenza outbreak divided into two groups: patients with and without ARDS. Healthy subjects without flu syndrome were included in a control group. We measured EG damage biomarkers (hyaluronan, syndecan-1) and endothelial cell injury biomarker (soluble thrombomodulin) during the first medical evaluation. Histological assessment of the perimeter of the hyaline membrane and the number of neutrophils infiltrated in the alveolar septum was performed in patients who died.

Results

ARDS group had 30 patients (44 ± 16 years old, 57% men), the non-ARDS group had 36 patients (39 ± 17 years old, 42% men), and the control group had 35 individuals (44 ± 9 years old, 51% men). Hyaluronan levels were significantly higher in the ARDS group than the two groups [31 ng/ml (interquartile range-IQR 12–56) vs. 5 ng/ml (IQR 3–10) vs. 5 ng/ml (IQR 2–8); p < 0.0001]. Hyaluronan levels above 19 ng/ml in patients with flu syndrome were associated with a significant increase in 28-day mortality rate: relative risk (RR): 6.95; (95% confidence interval 1.88–25.67); p = 0.0017. A positive correlation was observed between hyaline membrane perimeter and soluble thrombomodulin levels (r = 0.89; p = 0.05) as well as between the number of neutrophils in the alveolar septum and hyaluronan levels (r = 0.89; p = 0.05).

Conclusions

Evidence of EG shedding was found in ARDS established after flu syndrome.
REC8 suppresses tumor angiogenesis by inhibition of NF-κB-mediated vascular endothelial growth factor expression in gastric cancer cells
Authors: Liu Miao , Xu Wanfu , Su Mingmin , Fan Pingsheng
Published: September 2020

Background

Tumor angiogenesis is an essential event for tumor growth and metastasis. It has been showed that REC8, a component of the meiotic cohesion complex, played a vital role in Epithelial-Mesenchymal Transition (EMT) in gastric cancer. However, the role of REC8 in gastric cancer angiogenesis remains to be identified.

Results

Inhibition of REC8 expression in gastric cancer cells contributed to tumor angiogenesis in the gastric cancer microenvironment. The clinical analysis demonstrated that the loss of REC8 in gastric cancer with enrichment of MVD. Depletion of REC8 expression in gastric cancer cells significantly increased tube formation of human umbilical vein endothelial cells (HUVECs), which is attributed to enhancement of vascular endothelial growth factor (VEGF) secretion caused by REC8 slicing. While addition of neutralizing antibody targeted VEGF into supernatant drastically reversed the effect of REC8 loss in gastric cancer cells on tube formation. Mechanistic analyses indicated that ablation of REC8 promotes nuclear factor-κB (NF-κB) p65 activity and its downstream gene VEGF expression, leading to tube formation.

Conclusions

These results demonstrated a novel REC8 function that suppressed tumor angiogenesis and progression by attenuation of VEGF in gastric cancer microenvironment.
Identification of dental implants using deep learning—pilot study
Authors: Takahashi Toshihito , Nozaki Kazunori , Gonda Tomoya , Mameno Tomoaki , Wada Masahiro , Ikebe Kazunori
Published: September 2020

Background

In some cases, a dentist cannot solve the difficulties a patient has with an implant because the implant system is unknown. Therefore, there is a need for a system for identifying the implant system of a patient from limited data that does not depend on the dentist’s knowledge and experience. The purpose of this study was to identify dental implant systems using a deep learning method.

Methods

A dataset of 1282 panoramic radiograph images with implants were used for deep learning. An object detection algorithm (Yolov3) was used to identify the six implant systems by three manufactures. To implement the algorithm, TensorFlow and Keras deep-learning libraries were used. After training was complete, the true positive (TP) ratio and average precision (AP) of each implant system as well as the mean AP (mAP), and mean intersection over union (mIoU) were calculated to evaluate the performance of the model.

Results

The number of each implant system varied from 240 to 1919. The TP ratio and AP of each implant system varied from 0.50 to 0.82 and from 0.51 to 0.85, respectively. The mAP and mIoU of this model were 0.71 and 0.72, respectively.

Conclusions

The results of this study suggest that implants can be identified from panoramic radiographic images using deep learning-based object detection. This identification system could help dentists as well as patients suffering from implant problems. However, more images of other implant systems will be necessary to increase the learning performance to apply this system in clinical practice.
Assessment of hepatic fibrosis and steatosis by vibration-controlled transient elastography and controlled attenuation parameter versus non-invasive assessment scores in patients with non-alcoholic fatty liver disease
Authors: Mansour Ahmed M. F. , Bayoumy Essam M. , ElGhandour Ahmed M. , El-Talkawy Mohamed Darwish , Badr Sameh M. , Ahmed Ahmed El-Metwally
Published: September 2020

Background

Non-alcoholic fatty liver disease (NAFLD) is regarded as the most common liver disease in the twenty-first century, and a condition leaving individuals at increased risk of extra-hepatic morbidity. Liver biopsy has long been regarded as the gold standard for diagnosis and prognostication of patients with NAFLD. However, due to its invasive nature and potential complications (e.g., bleeding), other methods for non-invasive laboratory and radiological assessment of hepatic steatosis and fibrosis in NAFLD have evolved and include scores such as AST/Platelet Ratio Index (APRI), Fibrosis-4 (FIB-4) score, NAFLD fibrosis score (NFS), and fatty liver index (FLI), in addition to radiological methods such as transient elastography (TE), which is a well-validated non-invasive ultrasound-based technique for assessment of hepatic fibrosis. Recently, novel development of controlled attenuation parameter (CAP) in TE allowed simultaneous assessment of hepatic steatosis. This provided a chance to assess both hepatic fibrosis and steatosis in the same setting and without any unwanted complications. This study aimed at assessing the role of TE and CAP versus other non-invasive assessment scores for liver fibrosis and steatosis in patients with NAFLD.

Results

This study included 90 patients diagnosed with NAFLD based on abdominal ultrasonography, body mass index, and serum liver enzymes. All patients were assessed with TE and non-invasive scores (APRI score, FIB-4 score, NFS, and FLI). There was a highly significant positive correlation between fibrosis and steatosis grades assessed by TE and other non-invasive respective scores. Both TE and CAP achieved acceptable sensitivity and specificity compared to other non-invasive assessment methods.

Conclusions

TE with CAP can be used as a screening method for patients suspected with NAFLD or patients without a clear indication for liver biopsy. CAP allows a non-invasive method of assessment of hepatic steatosis in patients with NAFLD.
Circadian Rhythms and the Gastrointestinal Tract: Relationship to Metabolism and Gut Hormones
Authors: Martchenko Alexandre , Martchenko Sarah E , Biancolin Andrew D , Brubaker Patricia L
Published: September 2020

Circadian rhythms are 24-hour biological rhythms within organisms that have developed over evolutionary time due to predefined environmental changes, mainly the light-dark cycle. Interestingly, metabolic tissues, which are largely responsible for establishing diurnal metabolic homeostasis, have been found to express cell-autonomous clocks that are entrained by food intake. Disruption of the circadian system, as seen in individuals who conduct shift work, confers significant risk for the development of metabolic diseases such as type 2 diabetes and obesity. The gastrointestinal (GI) tract is the first point of contact for ingested nutrients and is thus an essential organ system for metabolic control. This review will focus on the circadian function of the GI tract with a particular emphasis on its role in metabolism through regulation of gut hormone release. First, the circadian molecular clock as well as the organization of the mammalian circadian system is introduced. Next, a brief overview of the structure of the gut as well as the circadian regulation of key functions important in establishing metabolic homeostasis is discussed. Particularly, the focus of the review is centered around secretion of gut hormones; however, other functions of the gut such as barrier integrity and intestinal immunity, as well as digestion and absorption, all of which have relevance to metabolic control will be considered. Finally, we provide insight into the effects of circadian disruption on GI function and discuss chronotherapeutic intervention strategies for mitigating associated metabolic dysfunction.
Digenic Variants in the FGF21 Signaling Pathway Associated with Severe Insulin Resistance and Pseudoacromegaly
Authors: Stone Stephen I , Wegner Daniel J , Wambach Jennifer A , Cole F Sessions , Urano Fumihiko , Ornitz David M
Published: September 2020

Insulin-mediated pseudoacromegaly (IMPA) is a rare disease of unknown etiology. Here we report a 12-year-old female with acanthosis nigricans, hirsutism, and acromegalic features characteristic of IMPA. The subject was noted to have normal growth hormone secretion, with extremely elevated insulin levels. Studies were undertaken to determine a potential genetic etiology for IMPA. The proband and her family members underwent whole exome sequencing. Functional studies were undertaken to validate the pathogenicity of candidate variant alleles. Whole exome sequencing identified monoallelic, predicted deleterious variants in genes that mediate fibroblast growth factor 21 (FGF21) signaling, FGFR1 and KLB, which were inherited in trans from each parent. FGF21 has multiple metabolic functions but no known role in human insulin resistance syndromes. Analysis of the function of the FGFR1 and KLB variants in vitro showed greatly attenuated ERK phosphorylation in response to FGF21, but not FGF2, suggesting that these variants act synergistically to inhibit endocrine FGF21 signaling but not canonical FGF2 signaling. Therefore, digenic variants in FGFR1 and KLB provide a potential explanation for the subject’s severe insulin resistance and may represent a novel category of insulin resistance syndromes related to FGF21.
Neuroleptic Malignant Syndrome Secondary to Quetiapine in Critical Care: A Case Report
Authors: Nestor C. , O’Brien D. , Dwyer R.
Published: September 2020

Quetiapine, an atypical antipsychotic, is widely used to treat delirium in intensive care units (ICUs). Studies demonstrate its efficacy and favorable safety profile. We report a case of an elderly patient who developed clinical and biochemical evidence of neuroleptic malignant syndrome (NMS) 5 days after quetiapine was commenced. Signs of NMS resolved after discontinuation of quetiapine and administration of dantrolene. Quetiapine-induced NMS has occurred with long-term use in the elderly in the outpatient setting. However, NMS has not previously been reported after treatment of ICU delirium. NMS is an important complication to consider before prescribing quetiapine in the ICU.
Inside ILSI: How Coca-Cola, Working through Its Scientific Nonprofit, Created a Global Science of Exercise for Obesity and Got It Embedded in Chinese Policy (1995–2015)
Authors: Greenhalgh Susan
Published: September 2020

Context: Industry influence on health science and policy is a critical issue of our day. In 2015 the New York Times revealed that Coca-Cola paid scientists to form a Global Energy Balance Network promoting the notion that exercise, not dietary restraint, is the solution to the obesity epidemic—a claim few accept. This article examines the organizational dynamics and policy process behind Coke's efforts to sway obesity policy—globally and in China, a critical market—during 1995–2015.

Methods: In-depth, qualitative research during 2013–18 involved 10 weeks of fieldwork in Beijing, interviews with 25 leading experts, analysis of newsletters documenting all major obesity-related activities in China, interviews with 10 Euro-American experts, and extensive internet research on all major actors.

Findings: This article tells two intertwined stories (institutional dynamics, science making and policy making) at global and local-Chinese levels. Coke succeeded in redirecting China's obesity science and policy to emphasize physical activity. Key to its success was the industry-funded global nonprofit International Life Sciences Institute (ILSI). Beneath ILSI's public narrative of unbiased science and no policy advocacy lay a maze of hidden channels companies used to advance their interests. Working through those channels, Coca-Cola influenced China's science making and policy making during every phase in the policy process, from framing the issues to drafting official policy.

Conclusions: Though China is exceptional, ILSI promoted exercise globally, suggesting potentially significant impacts in other ILSI-branch countries.
Case Report: Multifocal non-invasive follicular thyroid neoplasm with papillary-like nuclear features presenting in a female child
Authors: Abdou Asmaa Gaber , Aiad Hayam , Asaad Nancy
Published: September 2020

Non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) was introduced as a separate entity by the World Health Organization in 2017 with strict inclusion and exclusion criteria.  Most NIFTP cases have been reported in adults and few cases have been diagnosed in children. Here, we present a classic case of NIFTP affecting a 10-year old female child. We also review previous reports of NIFTP in children regarding size, focality, nodal metastasis, recurrence, type of operation and follow-up data. The present report adds a new case of NIFTP in the paediatric age group characterized by multifocality, absence of nodal invasion and indolent course until last follow-up, recommending less aggressive management.
Immunohistochemical analysis of stem cells from human exfoliated deciduous teeth seeded in carbonate apatite scaffold for the alveolar bone defect in Wistar rats (Rattus novergicus)
Authors: Saskianti Tania , Nugraha Alexander Patera , Prahasanti Chiquita , Ernawati Diah Savitri , Suardita Ketut , Riawan Wibi
Published: September 2020

Background: Stem cells from human exfoliated deciduous teeth (SHED) seeded in carbonate apatite scaffold (CAS) may have multiple functions that could be used to regenerate the alveolar bone defects. The purpose of this study is to examine the ability of SHED and CAS in alveolar bone defects using an immunohistochemical analysis.

Methods: ten three-month-old healthy male Wistar rats (R. novergicus) that weighed between 150–250 grams (g) were used as animal models. A simple blind random sampling method was used to select the sample that was assigned to the study group for CAS and SHED seeded in CAS (n=5). The animal study model of the alveolar bone was established by extracting the anterior mandible teeth. Rodent anesthesia was applied to relieve the pain during the procedure for all test animals. Immunohistochemistry was performed after seven days to facilitate the examination of the receptor activator of NF-κβ ligand (RANKL), osteoprotegrin (OPG), transforming growth factor-β (TGF-β), vascular endothelial growth factor (VEGF), runt-related transcription factor 2 (RUNX2), alkaline phosphatase (ALP), osteocalcin, and osteopontin expression. The data was analyzed using the unpaired t-test (p<0.01) and Pearson’s correlation test (p<0.05).

Results: The OPG, RUNX2, TGF-β, VEGF, ALP, osteocalcin, and ostepontin expressions were higher in SHED seeded in CAS than CAS only with a significant difference between the groups (p<0.01). Furthermore, the RANKL expression was lower in SHED seeded in CAS compared to CAS only. There was a strong reverse significant correlation between OPG and RANKL expression (p<0.05).

Conclusions: The number of osteogenic marker expressing cells, such as OPG, RUNX2, TGF-β, VEGF, ALP, osteocalcin, and ostepontin, increased. However, RANKL expression in the alveolar bone defects that were implanted with SHED seeded in CAS did not increase after seven days.
Space-log: a novel approach to inferring gene-gene net-works using SPACE model with log penalty
Authors: Wu Qian (Vicky) , Sun Wei , Hsu Li
Published: September 2020

Gene expression data have been used to infer gene-gene networks (GGN) where an edge between two genes implies the conditional dependence of these two genes given all the other genes. Such gene-gene networks are of-ten referred to as gene regulatory networks since it may reveal expression regulation. Most of existing methods for identifying GGN employ penalized regression withL1 (lasso),L2 (ridge), or elastic net penalty, which spans the range ofL1 toL2 penalty. However, for high dimensional gene expression data, a penalty that spans the range ofL0 andL1 penalty, such as the log penalty, is often needed for variable selection consistency. Thus, we develop a novel method that em-ploys log penalty within the framework of an earlier network identification method space (Sparse PArtial Correlation Estimation), and implement it into a R packagespace-log. We show that thespace-logis computationally efficient (source code implemented in C), and has good performance comparing with other methods, particularly for networks with hubs.Space-logis open source and available at GitHub, https://github.com/wuqian77/SpaceLog
The 21st annual Bioinformatics Open Source Conference (BOSC 2020, part of BCC2020)
Authors: Harris Nomi L. , Cock Peter J.A. , Fields Christopher J. , Hokamp Karsten , Maia Jessica , Munoz-Torres Monica , Taschuk Morgan , Yehudi Yo
Published: September 2020

Launched in 2000 and held every year since, the Bioinformatics Open Source Conference (BOSC) is a volunteer-run meeting coordinated by the Open Bioinformatics Foundation (OBF) that covers open source software development and open science in bioinformatics. Most years, BOSC has been part of the Intelligent Systems for Molecular Biology (ISMB) conference, but in 2018, and again in 2020, BOSC partnered with the Galaxy Community Conference (GCC). This year’s combined BOSC + GCC conference was called the Bioinformatics Community Conference (BCC2020, bcc2020.github.io).

Originally slated to take place in Toronto, Canada, BCC2020 was moved online due to COVID-19. The meeting started with a wide array of training sessions; continued with a main program of keynote presentations, talks, posters, Birds of a Feather, and more; and ended with four days of collaboration (CoFest). Efforts to make the meeting accessible and inclusive included very low registration fees, talks presented twice a day, and closed captioning for all videos. More than 800 people from 61 countries registered for at least one part of the meeting, which was held mostly in the Remo.co video-conferencing platform.
Surveillance of endemic human coronaviruses (HCoV-NL63, OC43 and 229E) associated with childhood pneumonia in Kilifi, Kenya
Authors: Otieno Grieven P. , Murunga Nickson , Agoti Charles N. , Gallagher Katherine E. , Awori Juliet O. , Nokes D. James
Published: September 2020

Introduction: Human coronaviruses (HCoVs) circulate endemically in human populations, often with seasonal variation. We describe the long-term patterns of paediatric disease associated with three of these viruses, HCoV-NL63, OC43 and 229E, in coastal Kenya.

Methods: Continuous surveillance of pneumonia admissions was conducted at the Kilifi county hospital (KCH) located in the northern coastal region of Kenya. Children aged <5 years admitted to KCH with clinically defined syndromic severe or very severe pneumonia were recruited. Respiratory samples were taken and tested for 15 virus targets, using real-time polymerase chain reaction. Unadjusted odds ratios were used to estimate the association between demographic and clinical characteristics and HCoV positivity.

Results: From 2007 to 2019, we observed 11,445 pneumonia admissions, of which 314 (3.9%) tested positive for at least one of the HCoV types surveyed in the study. There were 129 (41.1%) OC43, 99 (31.5%) 229E, 74 (23.6%) NL63 positive cases and 12 (3.8%) cases of HCoV to HCoV coinfection.  Among HCoV positive cases, 47% (n=147) were coinfected with other respiratory virus pathogens. The majority of HCoV cases were among children aged <1 year (66%, n=208), though there was was no change in the proportion infected by age. HCoV-OC43 was predominant of the three HCoV types throughout the surveillance period. Evidence for seasonality was not identified.

Conclusions: Overall, 4% of paediatric pneumonia admissions were associated with three endemic HCoVs, with a high proportion of cases co-occurring with another respiratory virus, no clear seasonal pattern, and with the age-distribution of cases following that of pneumonia admissions (i.e. highest in infants). These observations suggest, at most, a small severe disease contribution of endemic HCoVs in this tropical setting and offer insight into their potential future burden and epidemiological characteristics.