bluuebunny/crossref_metadata_2025 huggingface dataset:
Gait kinematics of the hip, pelvis, and trunk associated with external hip adduction moment in patients with secondary hip osteoarthritis: toward determination of the key point in gait modification
Authors: Tateuchi Hiroshige , Akiyama Haruhiko , Goto Koji , So Kazutaka , Kuroda Yutaka , Ichihashi Noriaki
Published: January 2020

Background

A larger daily cumulative hip loading, which is the product of the external hip adduction moment (HAM) impulse during gait and the number of steps per day has been identified as a factor associated with the progression of secondary hip osteoarthritis (OA). The cause of the increased HAM impulse in patients with hip OA has not been identified. The purpose of this study was to identify the gait parameters associated with HAM impulse during gait in patients with secondary hip OA.

Methods

Fifty-five patients (age 22–65 years) with mild-to-moderate secondary hip OA participated in this cross-sectional study. The HAM impulse during gait was measured using a three-dimensional gait analysis system. To identify the gait parameters associated with HAM impulse, hierarchical multiple regression analysis was performed. The first model (basic model) included body weight and stance phase duration. The second models included gait parameters (gait speed; ground reaction force [GRF] in frontal plane; and hip, pelvic, and trunk angle in frontal plane) and hip pain in addition to the basic model.

Results

Body weight and stance phase duration explained 61% of the variance in HAM impulse. In the second model, which took into account body weight and stance phase duration, hip adduction angle (9.4%), pelvic tilt (6.5%), and trunk lean (3.2%) in addition to GRF explained the variance in the HAM impulse. Whereas larger hip adduction angle and pelvic tilt toward the swing limb were associated with a larger HAM impulse, larger trunk lean toward the stance limb was associated with smaller HAM impulse.

Conclusion

In patients with excessive hip adduction and pelvic tilt toward the swing limb during gait, gait modification may contribute to the reduction of hip joint loading.
Near-infrared auto-fluorescence spectroscopy combining with Fisher’s linear discriminant analysis improves intraoperative real-time identification of normal parathyroid in thyroidectomy
Authors: Liu Junsong , Wang Xiaoxia , Wang Rui , Xu Chongwen , Zhao Ruimin , Li Honghui , Zhang Shaoqiang , Yao Xiaobao
Published: January 2020

Background

To evaluate the efficacy of a sensitive, real-time tool for identification and protection for parathyroid glands during thyroidectomy.

Methods

Near-infrared (NIR) auto-fluorescence was measured intraoperatively from 20 patients undergoing thyroidectomy. Spectra were measured from suspicious parathyroid glands and surrounding neck tissues during the operation with a NIR fluorescence system. Fast frozen sections were performed on the suspicious parathyroid glands. Accuracy was evaluated by comparison with histology and NIR identification. Data were attracted for Fisher’s linear discriminant analysis.

Results

The auto-fluorescence intensity of parathyroid was significantly higher than that of thyroid, fat and lymph node. The peak intensity of auto-fluorescence from parathyroid was 5.55 times of that from thyroid at the corresponding wave number. Of the 20 patients, the parathyroid was accurately detected and identified in 19 patients by NIR system, compared with their histologic results. One suspicious parathyroid did not exhibit typical spectra, and was proved to be fat tissue by histology. The NIR auto-fluorescence method had a 100% sensitivity of parathyroid glands identification and a high accuracy of 95%. The positive predictive value was 95%. The parathyroid gland have specific auto-fluorescence spectrum and can be separated from the other three samples through the Fisher’s linear discriminant analysis.

Conclusions

NIR auto-fluorescence spectroscopy can accurately identify normal parathyroid gland during thyroidectomy. The Fisher’s linear discriminant analysis demonstrated the specificity of the NIR auto-fluorescence of parathyroid tissue and its efficacy in parathyroid discrimination.
Synovial sarcoma of the floor of the mouth: a rare case report
Authors: Wang Yannan , Zhu Feiya , Wang Kai
Published: January 2020

Background

Head and neck Synovial sarcoma (SS) accounts for 3–10% of all total body SS. It is rare to find it in the oral cavity, especially on the floor of the mouth.

Case presentation

We present a 44-year-old Chinese male, who had been misdiagnosed as fibroadenoma, with a swelling on the right submandibular region for more than 3 months. The radiology examinations and the pathology results indicate the diagnosis of SS of the floor of the mouth.

The patient only had a surgical operation, without radiotherapy and chemotherapy. At the first follow-up, the patient exhibited no clinical or radiographic complications, and the patient was asymptomatic on subsequent visits.

Conclusions

Misdiagnosis results the delay of diagnosis and treatment of SS. Immunohistological analysis might be the most important tool to confirm the diagnosis of SS.
Cyclic compression emerged dual effects on the osteogenic and osteoclastic status of LPS-induced inflammatory human periodontal ligament cells according to loading force
Authors: Jia Ru , Yi Yingjie , Liu Jie , Pei Dandan , Hu Bo , Hao Huanmeng , Wu Linyue , Wang Zhenzhen , Luo Xiao , Lu Yi
Published: January 2020

Background

Appropriate mechanical stimulation is essential for bone homeostasis in healthy periodontal tissues. While the osteogenesis and osteoclast differentiation of inflammatory periodontal ligament cells under different dynamic loading has not been yet clear. The aim of this study is to clarify the inflammatory, osteogenic and pro-osteoclastic effects of different cyclic stress loading on the inflammatory human periodontal ligament cells (hPDLCs).

Methods

hPDLCs were isolated from healthy premolars and cultured in alpha minimum Eagle’s medium (α-MEM). Lipopolysaccharides (LPS) were used to induce the inflammation state of hPDLCs in vitro. Determination of LPS concentration for the model of inflammatory periodontium was based on MTT and genes expression analysis. Then the cyclic stress of 0, 0–50, 0–90 and 0–150 kPa was applied to the inflammatory hPDLCs for 5 days respectively. mRNA and protein levels of osteogenic, osteoclastic and inflammation-related markers were examined after the treatment.

Results

MTT and RT-PCR results showed that 10 μg/ml LPS up-regulatedTNF-α, IL-1β, IL-6, IL-8andMCP-1mRNA levels (P < 0.05) and did not affect the cell viability (P > 0.05). The excessive loading of stress (150 kPa) with or without LPS strongly increased the expression of inflammatory-related markersTNF-α,IL-1β,IL-6,IL-8,MCP-1(P < 0.05) and osteoclastic markersRANKL,M-CSF,PTHLHandCTSKcompared with other groups (P < 0.05), but had no significant effect on osteogenic genes. While 0–90 kPa cyclic pressure could up-regulate the expression of osteogenic genesALP, COL-1,RUNX2, OCN, OPNandOSXin the healthy hPDLSCs.

Conclusions

Collectively, it could be concluded that 0–150 kPa was an excessive stress loading which accelerated both inflammatory and osteoclastic effects, while 0–90 kPa may be a positive factor for the osteogenic differentiation of hPDLCs in vitro.
Knowledge and practice of adolescent females about menstruation and menstruation hygiene visiting a public healthcare institute of Quetta, Pakistan
Authors: Michael Judy , Iqbal Qaiser , Haider Sajjad , Khalid Adnan , Haque Naheed , Ishaq Rabia , Saleem Fahad , Hassali Mohamed Azmi , Bashaar Mohammad
Published: January 2020

Background

The current study is aimed to assess menstruation-related knowledge and practices of adolescent females visiting a public health care institute of Quetta city, Pakistan.

Methods

A questionnaire-based cross-sectional survey was conducted. Nine hundred and twenty three female adolescents attending general out-patient departments of Mohtarma Shaheed Benazir Bhutto Hospital Quetta, Balochistan, was approached for data collection. Based on the objectives of the study, descriptive analysis was conducted and SPSS v. 21.0 was used for the data analysis.

Results

Demographic characteristics revealed that the mean age of the respondents was 15 years. Mothers’ (67%) were the main source of menstruation-related information. Majority (77.7%) of our respondents never had a class or session regarding menstruation-related education in their schools. About (44%) knew that menstruation is a physiological phenomenon while 60.2% knew that menstrual blood comes from the vagina. Nearly 40% of our study respondents missed their schools because of menarche. The use of absorbent material was frequent (90%) among the adolescent females and (68.7%) used commercially available sanitary napkins/pads. Although majority of the respondents (58.2%) were not taking baths during menstruation, 80.5% do cleaned their genitalia with water during menstruation.

Conclusion

Female adolescents of our study had certain misconception regarding menstruation because of poor access to health-related education. Education can be provided at healthcare facilities, residential area as well as religious centers. Adolescent reproductive health should be included in the school curriculum; this will influence general reproductive health of females.
Informed consent procedure in a double blind randomized anthelminthic trial on Pemba Island, Tanzania: do pamphlet and information session increase caregivers knowledge?
Authors: Palmeirim Marta S. , Ross Amanda , Obrist Brigit , Mohammed Ulfat A. , Ame Shaali M. , Ali Said M. , Keiser Jennifer
Published: January 2020

Background

In clinical research, obtaining informed consent from participants is an ethical and legal requirement. Conveying the information concerning the study can be done using multiple methods yet this step commonly relies exclusively on the informed consent form alone. While this is legal, it does not ensure the participant’s true comprehension. New effective methods of conveying consent information should be tested. In this study we compared the effect of different methods on the knowledge of caregivers of participants of a clinical trial on Pemba Island, Tanzania.

Methods

A total of 254 caregivers were assigned to receive (i) a pamphlet (n = 63), (ii) an oral information session (n = 62) or (iii) a pamphlet and an oral information session (n = 64) about the clinical trial procedures, their rights, benefits and potential risks. Their post-intervention knowledge was assessed using a questionnaire. One group of caregivers had not received any information when they were interviewed (n = 65).

Results

In contrast to the pamphlet, attending an information session significantly increased caregivers’ knowledge for some of the questions. Most of these questions were either related to the parasite (hookworm) or to the trial design (study procedures).

Conclusions

In conclusion, within our trial on Pemba Island, a pamphlet was found to not be a good form of conveying clinical trial information while an oral information session improved knowledge. Not all caregivers attending an information session responded correctly to all questions; therefore, better forms of communicating information need to be found to achieve a truly informed consent.
What is it like to use a BCI? – insights from an interview study with brain-computer interface users
Authors: Kögel Johannes , Jox Ralf J. , Friedrich Orsolya
Published: January 2020

Background

The neurotechnology behind brain-computer interfaces (BCIs) raises various ethical questions. The ethical literature has pinpointed several issues concerning safety, autonomy, responsibility and accountability, psychosocial identity, consent, privacy and data security. This study aims to assess BCI users’ experiences, self-observations and attitudes in their own right and looks for social and ethical implications.

Methods

We conducted nine semi-structured interviews with BCI users, who used the technology for medical reasons. The transcribed interviews were analyzed according to the Grounded Theory coding method.

Results

BCI users perceive themselves as active operators of a technology that offers them social participation and impacts their self-definition. Each of these aspects bears its own opportunities and risks. BCIs can contribute to retaining or regaining human capabilities. At the same time, BCI use contains elements that challenge common experiences, for example when the technology is in conflict with the affective side of BCI users. The potential benefits of BCIs are regarded as outweighing the risks in that BCI use is considered to promote valuable qualities and capabilities. BCI users appreciate the opportunity to regain lost capabilities as well as to gain new ones.

Conclusions

BCI users appreciate the technology for various reasons. The technology is highly appreciated in cases where it is beneficial in terms of agency, participation and self-definitions. Rather than questioning human nature, the technology can retain and restore characteristics and abilities which enrich our lives.
Development of a targeted client communication intervention to women using an electronic maternal and child health registry: a qualitative study
Authors: Bogale Binyam , Mørkrid Kjersti , O’Donnell Brian , Ghanem Buthaina , Abu Ward Itimad , Abu Khader Khadija , Isbeih Mervett , Frost Michael , Baniode Mohammad , Hijaz Taghreed , Awwad Tamara , Rabah Yousef , Frøen J. Frederik
Published: January 2020

Background

Targeted client communication (TCC) using text messages can inform, motivate and remind pregnant and postpartum women of timely utilization of care. The mixed results of the effectiveness of TCC interventions points to the importance of theory based interventions that are co-design with users. The aim of this paper is to describe the planning, development, and evaluation of a theory led TCC intervention, tailored to pregnant and postpartum women and automated from the Palestinian electronic maternal and child health registry.

Methods

We used the Health Belief Model to develop interview guides to explore women’s perceptions of antenatal care (ANC), with a focus on high-risk pregnancy conditions (anemia, hypertensive disorders in pregnancy, gestational diabetes mellitus, and fetal growth restriction), and untimely ANC attendance, issues predefined by a national expert panel as being of high interest. We performed 18 in-depth interviews with women, and eight with healthcare providers in public primary healthcare clinics in the West Bank and Gaza. Grounding on the results of the in-depth interviews, we used concepts from the Model of Actionable Feedback, social nudging and Enhanced Active Choice to compose the TCC content to be sent as text messages. We assessed the acceptability and understandability of the draft text messages through unstructured interviews with local health promotion experts, healthcare providers, and pregnant women.

Results

We found low awareness of the importance of timely attendance to ANC, and the benefits of ANC for pregnancy outcomes. We identified knowledge gaps and beliefs in the domains of low awareness of susceptibility to, and severity of, anemia, hypertension, and diabetes complications in pregnancy. To increase the utilization of ANC and bridge the identified gaps, we iteratively composed actionable text messages with users, using recommended message framing models. We developed algorithms to trigger tailored text messages with higher intensity for women with a higher risk profile documented in the electronic health registry.

Conclusions

We developed an optimized TCC intervention underpinned by behavior change theory and concepts, and co-designed with users following an iterative process. The electronic maternal and child health registry can serve as a unique platform for TCC interventions using text messages.
Novel prognostication of patients with spinal and pelvic chondrosarcoma using deep survival neural networks
Authors: Ryu Sung Mo , Seo Sung Wook , Lee Sun-Ho
Published: January 2020

Background

We used the Surveillance, Epidemiology, and End Results (SEER) database to develop and validate deep survival neural network machine learning (ML) algorithms to predict survival following a spino-pelvic chondrosarcoma diagnosis.

Methods

The SEER 18 registries were used to apply the Risk Estimate Distance Survival Neural Network (RED_SNN) in the model. Our model was evaluated at each time window with receiver operating characteristic curves and areas under the curves (AUCs), as was the concordance index (c-index).

Results

The subjects (n = 1088) were separated into training (80%, n = 870) and test sets (20%, n = 218). The training data were randomly sorted into training and validation sets using 5-fold cross validation. The median c-index of the five validation sets was 0.84 (95% confidence interval 0.79–0.87). The median AUC of the five validation subsets was 0.84. This model was evaluated with the previously separated test set. The c-index was 0.82 and the mean AUC of the 30 different time windows was 0.85 (standard deviation 0.02). According to the estimated survival probability (by 62 months), we divided the test group into five subgroups. The survival curves of the subgroups showed statistically significant separation (p < 0.001).

Conclusions

This study is the first to analyze population-level data using artificial neural network ML algorithms for the role and outcomes of surgical resection and radiation therapy in spino-pelvic chondrosarcoma.
Can mobile health apps replace GPs? A scoping review of comparisons between mobile apps and GP tasks
Authors: Wattanapisit Apichai , Teo Chin Hai , Wattanapisit Sanhapan , Teoh Emylia , Woo Wing Jun , Ng Chirk Jenn
Published: January 2020

Background

Mobile health applications (mHealth apps) are increasingly being used to perform tasks that are conventionally performed by general practitioners (GPs), such as those involved in promoting health, preventing disease, diagnosis, treatment, monitoring, and support for health services. This raises an important question: can mobile apps replace GPs? This study aimed to systematically search for and identify mobile apps that can perform GP tasks.

Methods

A scoping review was carried out. The Google Play Store and Apple App Store were searched for mobile apps, using search terms derived from the UK Royal College of General Practitioners (RCGP) guideline on GPs’ core capabilities and competencies. A manual search was also performed to identify additional apps.

Results

The final analysis included 17 apps from the Google Play Store and Apple App Store, and 21 apps identified by the manual search. mHealth apps were found to have the potential to replace GPs for tasks such as recording medical history and making diagnoses; performing some physical examinations; supporting clinical decision making and management; assisting in urgent, long-term, and disease-specific care; and health promotion. In contrast, mHealth apps were unable to perform medical procedures, appropriately utilise other professionals, and coordinate a team-based approach.

Conclusions

This scoping review highlights the functions of mHealth apps that can potentially replace GP tasks. Future research should focus on assessing the performance and quality of mHealth apps in comparison with that of real doctors.
The mitochondrial carrier pathway transports non-canonical substrates with an odd number of transmembrane segments
Authors: Rampelt Heike , Sucec Iva , Bersch Beate , Horten Patrick , Perschil Inge , Martinou Jean-Claude , van der Laan Martin , Wiedemann Nils , Schanda Paul , Pfanner Nikolaus
Published: January 2020

Background

The mitochondrial pyruvate carrier (MPC) plays a central role in energy metabolism by transporting pyruvate across the inner mitochondrial membrane. Its heterodimeric composition and homology to SWEET and semiSWEET transporters set the MPC apart from the canonical mitochondrial carrier family (named MCF or SLC25). The import of the canonical carriers is mediated by the carrier translocase of the inner membrane (TIM22) pathway and is dependent on their structure, which features an even number of transmembrane segments and both termini in the intermembrane space. The import pathway of MPC proteins has not been elucidated. The odd number of transmembrane segments and positioning of the N-terminus in the matrix argues against an import via the TIM22 carrier pathway but favors an import via the flexible presequence pathway.

Results

Here, we systematically analyzed the import pathways of Mpc2 and Mpc3 and report that, contrary to an expected import via the flexible presequence pathway, yeast MPC proteins with an odd number of transmembrane segments and matrix-exposed N-terminus are imported by the carrier pathway, using the receptor Tom70, small TIM chaperones, and the TIM22 complex. The TIM9·10 complex chaperones MPC proteins through the mitochondrial intermembrane space using conserved hydrophobic motifs that are also required for the interaction with canonical carrier proteins.

Conclusions

The carrier pathway can import paired and non-paired transmembrane helices and translocate N-termini to either side of the mitochondrial inner membrane, revealing an unexpected versatility of the mitochondrial import pathway for non-cleavable inner membrane proteins.
Methicillin-resistant Staphylococcus aureus in veterinary professionals in 2017 in the Czech Republic
Authors: Neradova Katerina , Jakubu Vladislav , Pomorska Katarina , Zemlickova Helena
Published: January 2020

Background

Cases of colonization or infection caused by Methicillin-resistant Staphylococcus aureus (MRSA) are frequently reported in people who work with animals, including veterinary personnel. The aim of this study was to determine the prevalence of MRSA colonization among veterinary professionals. A total of 134 nasal swabs from healthy attendees of a veterinary conference held in the Czech Republic were tested for presence of MRSA. The stains were further genotypically and phenotypically characterized.

Results

Nine isolated MRSA strains were characterized with sequence type (ST), spa type (t) and Staphylococcal Cassette Chromosome mec type. Five different genotypes were described, including ST398-t011-IV (n = 5), ST398-t2330-IV (n = 1), ST398-t034-V (n = 1), ST225-t003-II (n = 1) and ST4894-t011-IV (n = 1). The carriage of the animal MRSA strain was confirmed in 8 cases, characteristics of one strain corresponded to the possible nosocomial origin. Among animal strains were described three spa types (t011, t034, t2330) belonging into one dominating clonal complex spa-CC11.

Conclusion

According to our results, the prevalence of nasal carriage of MRSA in veterinary personnel is 6.72%. Although we described an increase compared to the results of previous study (year 2008), the prevalence in the Czech Republic is still remaining lower than reported from neighboring countries. Our results also indicate that healthcare - associated MRSA strains are still not spread among animals.
MiR-182-5p and its target HOXA9 in non-small cell lung cancer: a clinical and in-silico exploration with the combination of RT-qPCR, miRNA-seq and miRNA-chip
Authors: Gao Li , Yan Shi-bai , Yang Jie , Kong Jin-liang , Shi Ke , Ma Fu-chao , Huang Lin-zhen , Luo Jie , Yin Shu-ya , He Rong-quan , Hu Xiao-hua , Chen Gang
Published: January 2020

Background

MiR-182-5p, a cancer-related microRNA (miRNA), modulates tumorigenesis and patient outcomes in various human malignances. This study interroted the clinicopathological significance and molecular mechanisms of miR-182-5p in non-small cell lung cancer (NSCLC).

Methods

The clinical significance of miR-182-5p in NSCLC subtypes was determined based on an analysis of 124 samples (lung adenocarcinomas [LUADs], n = 101; lung squamous cell carcinomas [LUSCs], n = 23) obtained from NSCLC patients and paired noncancer tissues and an analysis of data obtained from public miRNA-seq database, miRNA-chip database, and the scientific literature. The NSCLC samples (n = 124) were analyzed using the real-time quantitative polymerase chain reaction (RT-qPCR). Potential targets of miR-182-5p were identified using lists generated by miRWalk v.2.0, a comprehensive atlas of predicted and validated targets of miRNA-target interactions. Molecular events of miR-182-5p in NSCLC were unveiled based on a functional analysis of candidate targets. The association of miR-182-5p with one of the candidate target genes, homeobox A9 (HOXA9), was validated using in-house RT-qPCR and dual-luciferase reporter assays.

Results

The results of the in-house RT-qPCR assays analysis of data obtained from public miRNA-seq databases, miRNA-chip databases, and the scientific literature all supported upregulation of the expression level of miR-182-5p level in NSCLC. Moreover, the in-house RT-qPCR data supported the influence of upregulated miR-182-5p on malignant progression of NSCLC. In total, 774 prospective targets of miR-182-5p were identified. These targets were mainly clustered in pathways associated with biological processes, such as axonogenesis, axonal development, and Ras protein signal transduction, as well as pathways involved in axonal guidance, melanogenesis, and longevity regulation, in multiple species. Correlation analysis of the in-house RT-qPCR data and dual-luciferase reporter assays confirmed that HOXA9 was a direct target of miR-182-5p in NSCLC.

Conclusions

The miR-182-5p expression level was upregulated in NSCLC tissues. MiR-182-5p may exert oncogenic influence on NSCLC through regulating target genes such as HOXA9.
7-oxo-DHEA enhances impaired M. tuberculosis-specific T cell responses during HIV-TB coinfection
Authors: Vecchione María Belén , Laufer Natalia , Sued Omar , Corti Marcelo , Salomon Horacio , Quiroga Maria Florencia
Published: January 2020

Background

Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis (TB), affecting approximately one third of the world’s population. Development of an adequate immune response will determine disease progression or progress to chronic infection. Risk of developing TB among human immunodeficiency virus (HIV)-coinfected patients (HIV-TB) is 20–30 times higher than those without HIV infection, and a synergistic interplay between these two pathogens accelerates the decline in immunological functions. TB treatment in HIV-TB coinfected persons is challenging and it has a prolonged duration, mainly due to the immune system failure to provide an adequate support for the therapy. Therefore, we aimed to study the role of the hormone 7-oxo-dehydroepiandrosterone (7-OD) as a modulator of anti-tuberculosis immune responses in the context of HIV-TB coinfection.

Methods

A cross-sectional study was conducted among HIV-TB patients and healthy donors (HD). We characterized the ex vivo phenotype of CD4 + T cells and also evaluated in vitro antigen-specific responses by Mtb stimulation of peripheral blood mononuclear cells (PBMCs) in the presence or absence of 7-OD. We assessed lymphoproliferative activity, cytokine production and master transcription factor profiles.

Results

Our results show that HIV-TB patients were not able to generate successful anti-tubercular responses in vitro compared to HD, as reduced IFN-γ/IL-10 and IFN-γ/IL-17A ratios were observed. Interestingly, treatment with 7-OD enhanced Th1 responses by increasing Mtb-induced proliferation and the production of IFN-γ and TNF-α over IL-10 levels. Additionally, in vitro Mtb stimulation augmented the frequency of cells with a regulatory phenotype, while 7-OD reduced the proportion of these subsets and induced an increase in CD4 + T-bet+ (Th1) subpopulation, which is associated with clinical data linked to an improved disease outcome.

Conclusions

We conclude that 7-OD modifies the cytokine balance and the phenotype of CD4 + T cells towards a more favorable profile for mycobacteria control. These results provide new data to delineate novel treatment approaches as co-adjuvant for the treatment of TB.
Biosynthetic engineering of the antifungal, anti-MRSA auroramycin
Authors: Yeo Wan Lin , Heng Elena , Tan Lee Ling , Lim Yi Wee , Ching Kuan Chieh , Tsai De-Juin , Jhang Yi Wun , Lauderdale Tsai-Ling , Shia Kak-Shan , Zhao Huimin , Ang Ee Lui , Zhang Mingzi M. , Lim Yee Hwee , Wong Fong T.
Published: January 2020

Using an established CRISPR-Cas mediated genome editing technique for streptomycetes, we explored the combinatorial biosynthesis potential of the auroramycin biosynthetic gene cluster in Streptomyces roseosporous. Auroramycin is a potent anti-MRSA polyene macrolactam. In addition, auroramycin has antifungal activities, which is unique among structurally similar polyene macrolactams, such as incednine and silvalactam. In this work, we employed different engineering strategies to target glycosylation and acylation biosynthetic machineries within its recently elucidated biosynthetic pathway. Auroramycin analogs with variations in C-, N- methylation, hydroxylation and extender units incorporation were produced and characterized. By comparing the bioactivity profiles of five of these analogs, we determined that unique disaccharide motif of auroramycin is essential for its antimicrobial bioactivity. We further demonstrated that C-methylation of the 3, 5-epi-lemonose unit, which is unique among structurally similar polyene macrolactams, is key to its antifungal activity.
LncRNA BCYRN1/miR-490-3p/POU3F2, served as a ceRNA network, is connected with worse survival rate of hepatocellular carcinoma patients and promotes tumor cell growth and metastasis
Authors: Ding Shichao , Jin Yanfeng , Hao Qingzhi , Kang Yanmeng , Ma Ruiping
Published: January 2020

Abstracts

Backgrounds

LncRNA Brain Cytoplasmic RNA 1 (BCYRN1) has been certified to modulate cancer cells growth and aggressiveness in several tumors. However, research about function of BCYRN1 in hepatocellular carcinoma (HCC) is limited. Therefore, our research intends to explore the function of BCYRN1 in HCC.

Methods

HepG2 and BEL-7402 cell lines were employed for later function experiments. Differently expression levels of BCYRN1, miR-490-3p, and POU class 3 homeobox 2 (POU3F2) were determined on the base of TCGA dataset including 375 HCC patients and 50 normal. 370 cases of patients, which have fairly complete clinical data, were utilized for survival analysis of BCYRN1, miR-490-3p, or POU3F2 by Kaplan–Meier method. Relative expression pattern of BCYRN1 was examined by quantitative real time polymerase chain reaction (qRT-PCR), and relative expression level of POU3F2 was assessed by qRT-PCR and western blot. Cell biological behaviors were analyzed by cell counting kit-8, cloning formation, and transwell assays. Bioinformatics software and dual luciferase assay were applied to predict and confirm the targeted relationship between BCYRN1 and miR-490-3p, as well as miR-490-3p and POU3F2. Further associations among BCYRN1, miR-490-3p, and POU3F2 were analyzed by rescue assays.

Results

Our results exhibited that BCYRN1 was over expressed in HCC samples, which was connected with unfavorable prognosis in HCC patients. In addition, a series of experiments exhibited that overexpression of BCYRN1 significantly expedited HCC cells growth, clone formation, and movement abilities, and vice versa. Moreover, targeted relationships between BCYRN1 and miR-490-3p, as well as miR-490-3p and POU3F2 were affirmed by dual luciferase assay. Furthermore, POU3F2 expression was negatively connected with the expression of miR-490-3p and positively associated with BCYRN1 expression. Whilst, either overexpression of miR-490-3p or knockdown of POU3F2 could remarkably inhibit the increasing trends of proliferation, clone formation, invasion, and migration abilities induced by BCYRN1 in HCC cells.

Conclusions

BCYRN1, served as a competing endogenous RNA, up-regulated the expression of POU3F2 to promote the development of HCC through sponging miR-490-3p, supplying novel molecular targets and underlying prognostic biomarkers for HCC therapy.
CTLA-4 correlates with immune and clinical characteristics of glioma
Authors: Liu Fangkun , Huang Jing , Liu Xuming , Cheng Quan , Luo Chengke , Liu Zhixiong
Published: January 2020

Background

CTLA-4 is a well-studied immune checkpoint protein that negatively regulates T cell-mediated immune responses. However, the expression of CTLA-4 in glioma and the effects of CTLA-4 on prognosis in patients with glioma have not yet been examined.

Methods

We investigated the protein level of CTLA-4 in human glioma samples, extracted genetic and clinical data from 1024 glioma patients to characterize CTLA-4 expression and its relationship with immune functions in gliomas. R language was used for statistical analysis.

Results

Higher CTLA-4 expression was found in patients with higher grade, isocitrate dehydrogenase (IDH)-wild-type, and mesenchymal-molecular subtype gliomas than in patients with lower grade, IDH-mutant, and other molecular subtype gliomas. Further analysis showed that there was a strong positive correlation between CTLA-4 and the specific marker gene expression of immune cells, including CD8+T cells, regulatory T cells, and macrophages in both databases, suggesting that higher CTLA-4 expression in the glioma microenvironment induced greater immune cell infiltration compared with that in gliomas with lower CTLA-4 expression. We further explored the associations between CTLA-4 and other immune-related molecules. Pearson correlation analysis showed that CTLA-4 was associated with PD-1, CD40, ICOS, CXCR3, CXCR6, CXCL12 and TIGIT. Patients with glioma with lower CTLA-4 expression exhibited significantly longer overall survival. Thus, these findings suggested that increased CTLA-4 expression conferred a worse outcome in glioma.

Conclusions

In summary, our findings revealed the expression patterns and clinical characteristics of CTLA-4 in glioma and may be helpful for expanding our understanding of antitumor immunotherapy in gliomas.
The impact of transfluthrin on the spatial repellency of the primary malaria mosquito vectors in Vietnam: Anopheles dirus and Anopheles minimus
Authors: Martin Nicholas J. , Nam Vu S. , Lover Andrew A. , Phong Tran V. , Tu Tran C. , Mendenhall Ian H.
Published: January 2020

Background

The complexity of mosquito-borne diseases poses a major challenge to global health efforts to mitigate their impact on people residing in sub-tropical and tropical regions, to travellers and deployed military personnel. To supplement drug- and vaccine-based disease control programmes, other strategies are urgently needed, including the direct control of disease vectors. Modern vector control research generally focuses on identifying novel active ingredients and/or innovative methods to reduce human-mosquito interactions. These efforts include the evaluation of spatial repellents, which are compounds capable of altering mosquito feeding behaviour without direct contact with the chemical source.

Methods

This project examined the impact of airborne transfluthrin from impregnated textile materials on two important malaria vectors, Anopheles dirus and Anopheles minimus. Repellency was measured by movement within taxis cages within a semi-field environment at the National Institute of Hygiene and Epidemiology in Hanoi, Vietnam. Knockdown and mortality were measured in adult mosquito bioassay cages. Metered-volume air samples were collected at a sub-set of points in the mosquito exposure trial.

Results

Significant differences in knockdown/mortality were observed along a gradient from the exposure source with higher rates of knockdown/mortality at 2 m and 4 m when compared with the furthest distance (16 m). Knockdown/mortality was also greater at floor level and 1.5 m when compared to 3 m above the floor. Repellency was not significantly different except when comparing 2 m and 16 m taxis cages. Importantly, the two species reacted differently to transfluthrin, with An. minimus being more susceptible to knockdown and mortality. The measured concentrations of airborne transfluthrin ranged from below the limit of detection to 1.32 ng/L, however there were a limited number of evaluable samples complicating interpretation of these results.

Conclusions

This study, measuring repellency, knockdown and mortality in two malaria vectors in Vietnam demonstrates that both species are sensitive to airborne transfluthrin. The differences in magnitude of response between the two species requires further study before use in large-scale vector control programmes to delineate how spatial repellency would impact the development of insecticide resistance and the disruption of biting behaviour.
Childhood malaria case incidence in Malawi between 2004 and 2017: spatio-temporal modelling of climate and non-climate factors
Authors: Chirombo James , Ceccato Pietro , Lowe Rachel , Terlouw Dianne J , Thomson Madeleine C , Gumbo Austin , Diggle Peter J , Read Jonathan M
Published: January 2020

Background

Malaria transmission is influenced by a complex interplay of factors including climate, socio-economic, environmental factors and interventions. Malaria control efforts across Africa have shown a mixed impact. Climate driven factors may play an increasing role with climate change. Efforts to strengthen routine facility-based monthly malaria data collection across Africa create an increasingly valuable data source to interpret burden trends and monitor control programme progress. A better understanding of the association with other climatic and non-climatic drivers of malaria incidence over time and space may help guide and interpret the impact of interventions.

Methods

Routine monthly paediatric outpatient clinical malaria case data were compiled from 27 districts in Malawi between 2004 and 2017, and analysed in combination with data on climatic, environmental, socio-economic and interventional factors and district level population estimates. A spatio-temporal generalized linear mixed model was fitted using Bayesian inference, in order to quantify the strength of association of the various risk factors with district-level variation in clinical malaria rates in Malawi, and visualized using maps.

Results

Between 2004 and 2017 reported childhood clinical malaria case rates showed a slight increase, from 50 to 53 cases per 1000 population, with considerable variation across the country between climatic zones. Climatic and environmental factors, including average monthly air temperature and rainfall anomalies, normalized difference vegetative index (NDVI) and RDT use for diagnosis showed a significant relationship with malaria incidence. Temperature in the current month and in each of the 3 months prior showed a significant relationship with the disease incidence unlike rainfall anomaly which was associated with malaria incidence at only three months prior. Estimated risk maps show relatively high risk along the lake and Shire valley regions of Malawi.

Conclusion

The modelling approach can identify locations likely to have unusually high or low risk of malaria incidence across Malawi, and distinguishes between contributions to risk that can be explained by measured risk-factors and unexplained residual spatial variation. Also, spatial statistical methods applied to readily available routine data provides an alternative information source that can supplement survey data in policy development and implementation to direct surveillance and intervention efforts.
Homeownership status and risk of food insecurity: examining the role of housing debt, housing expenditure and housing asset using a cross-sectional population-based survey of Canadian households
Authors: Fafard St-Germain Andrée-Anne , Tarasuk Valerie
Published: January 2020

Background

Household food insecurity is a potent marker of material deprivation with adverse health consequences. Studies have repeatedly found a strong, independent relationship between owning a home and lower vulnerability to food insecurity in Canada and elsewhere, but the reasons for this relationship are poorly understood. We aimed to examine the influence of housing asset, housing debt and housing expenditure on the relationship between homeownership status and food insecurity in Canada.

Methods

Cross-sectional data on food insecurity, housing tenure and expenditures, home value, income and sociodemographic characteristics were derived from the 2010 Survey of Household Spending, a population-based survey. Multivariable logistic regression models were conducted to estimate odds ratios of food insecurity among households of all incomes (n = 10,815) and those with lower incomes (n = 5547).

Results

Food insecurity prevalence was highest among market renters (28.5%), followed by homeowners with a mortgage (11.6%) and mortgage-free homeowners (4.3%). Homeowners with a mortgage (OR: 0.51, 95% CI: 0.39–0.68) and those without a mortgage (OR: 0.23, 95% CI: 0.16–0.35) had substantially lower adjusted odds of food insecurity than market renters, and accounting for the burden of housing cost had minimal impact on the association. Mortgage-free homeowners had lower adjusted odds ratios of food insecurity compared to homeowners with a mortgage, but differences in the burden of housing cost fully accounted for the association. When stratifying homeowners based on presence of mortgage and housing asset level, the adjusted odds ratios of food insecurity for market renters were not significant when compared to mortgage holders with low housing asset. Mortgage-free owners with higher housing asset were least vulnerable to food insecurity (adjusted OR: 0.18, 95% CI: 0.11–0.27).

Conclusions

Substantial disparities in food insecurity exist between households with different homeownership status and housing asset level. Housing policies that support homeownership while ensuring affordable mortgages may be important to mitigate food insecurity, but policy actions are required to address renters’ high vulnerability to food insecurity.
Biological response and cytotoxicity induced by lipid nanocapsules
Authors: Szwed Marzena , Torgersen Maria Lyngaas , Kumari Remya Valsala , Yadava Sunil Kumar , Pust Sascha , Iversen Tore Geir , Skotland Tore , Giri Jyotsnendu , Sandvig Kirsten
Published: January 2020

Background

Lipid nanocapsules (LNCs) are promising vehicles for drug delivery. However, since not much was known about cellular toxicity of these nanoparticles in themselves, we have here investigated the mechanisms involved in LNC-induced intoxication of the three breast cancer cell lines MCF-7, MDA-MD-231 and MDA-MB-468. The LNCs used were made of Labrafac™ Lipophile WL1349, Lipoid®S75 and Solutol®HS15.

Results

High resolution SIM microscopy showed that the DiD-labeled LNCs ended up in lysosomes close to the membrane. Empty LNCs, i.e. without encapsulated drug, induced not only increased lysosomal pH, but also acidification of the cytosol and a rapid inhibition of protein synthesis. The cytotoxicity of the LNCs were measured for up to 72 h of incubation using the MTT assay and ATP measurements in all three cell lines, and revealed that MDA-MB-468 was the most sensitive cell line and MCF-7 the least sensitive cell line to these LNCs. The LNCs induced generation of reactive free oxygen species and lipid peroxidation. Experiments with knock-down of kinases in the near-haploid cell line HAP1 indicated that the kinase HRI is essential for the observed phosphorylation of eIF2α. Nrf2 and ATF4 seem to play a protective role against the LNCs in MDA-MB-231 cells, as knock-down of these factors sensitizes the cells to the LNCs. This is in contrast to MCF-7 cells where the knock-down of these factors had a minor effect on the toxicity of the LNCs. Inhibitors of ferroptosis provided a large protection against LNC toxicity in MDA-MB-231 cells, but not in MCF-7 cells.

Conclusions

High doses of LNCs showed a different degree of toxicity on the three cell lines studied, i.e. MCF-7, MDA-MD-231 and MDA-MB-468 and affected signaling factors and the cell fate differently in these cell lines.
Systematic review of randomized controlled trials for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME)
Authors: Kim Do-Young , Lee Jin-Seok , Park Samuel-Young , Kim Soo-Jin , Son Chang-Gue
Published: January 2020

Background

Although medical requirements are urgent, no effective intervention has been proven for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). To facilitate the development of new therapeutics, we systematically reviewed the randomized controlled trials (RCTs) for CFS/ME to date.

Methods

RCTs targeting CFS/ME were surveyed using two electronic databases, PubMed and the Cochrane library, through April 2019. We included only RCTs that targeted fatigue-related symptoms, and we analyzed the data in terms of the characteristics of the participants, case definitions, primary measurements, and interventions with overall outcomes.

Results

Among 513 potentially relevant articles, 56 RCTs met our inclusion criteria; these included 25 RCTs of 22 different pharmacological interventions, 29 RCTs of 19 non-pharmacological interventions and 2 RCTs of combined interventions. These studies accounted for a total of 6956 participants (1713 males and 5243 females, 6499 adults and 457 adolescents). CDC 1994 (Fukuda) criteria were mostly used for case definitions (42 RCTs, 75.0%), and the primary measurement tools included the Checklist Individual Strength (CIS, 35.7%) and the 36-item Short Form health survey (SF-36, 32.1%). Eight interventions showed statistical significance: 3 pharmacological (Staphypan Berna, Poly(I):poly(C12U) and CoQ10 + NADH) and 5 non-pharmacological therapies (cognitive-behavior-therapy-related treatments, graded-exercise-related therapies, rehabilitation, acupuncture and abdominal tuina). However, there was no definitely effective intervention with coherence and reproducibility.

Conclusions

This systematic review integrates the comprehensive features of previous RCTs for CFS/ME and reflects on their limitations and perspectives in the process of developing new interventions.
Toll-like receptor 4 agonist and antagonist lipopolysaccharides modify innate immune response in rat brain circumventricular organs
Authors: Vargas-Caraveo Alejandra , Sayd Aline , Robledo-Montaña Javier , Caso Javier R. , Madrigal José L. M. , García-Bueno Borja , Leza Juan C.
Published: January 2020

Background

The circumventricular organs (CVOs) are blood-brain-barrier missing structures whose activation through lipopolysaccharide (LPS) is a starting point for TLR-driven (Toll-like receptors) neuroinflammation. The aim of this study was to evaluate in the CVO area postrema (AP), subfornical organ (SFO), and median eminence (ME), the inflammatory response to two TLR4 agonists: LPS fromEscherichia coli(EC-LPS), the strongest endotoxin molecule described, and LPS fromPorphyromonas gingivalis(PG-LPS), a pathogenic bacteria present in the periodontium related to neuroinflammation in neurodegenerative/psychiatric diseases. The response to LPS from the cyanobacteriaRhodobacter sphaeroides(RS-LPS), a TLR4 antagonist with an interesting anti-inflammatory potential, was also assessed.

Methods

LPSs were intraperitoneally administered to Wistar rats and, as indicatives of neuroinflammation in CVOs, the cellular localization of the nuclear factor NF-κB was studied by immunofluorescence, and microglia morphology was quantified by fractal and skeleton analysis.

Results

Data showed that EC-LPS increased NF-κB nuclear translocation in the three CVOs studied and PG-LPS only induced NF-κB nuclear translocation in the ME. RS-LPS showed no difference in NF-κB nuclear translocation compared to control. Microglia in the three CVOs showed an ameboid-shape after EC-LPS exposure, whereas PG-LPS only elicited a mild tendency to induce an ameboid shape. On the other hand, RS-LPS produced a markedly elongated morphology described as “rod” microglia in the three CVOs.

Conclusions

In conclusion, at the doses tested, EC-LPS induces a stronger neuroinflammatory response than PG-LPS in CVOs, which might be related to their different potency as TLR4 agonists. The non-reduction of basal NF-κB activation and induction of rod microglia by RS-LPS, a cell morphology only present in severe brain injury and infections, suggests that this molecule must be carefully studied before being proposed as an anti-inflammatory treatment for neuroinflammation related to neurodegenerative/psychiatric diseases.