bluuebunny/crossref_metadata_2025 huggingface dataset:
Exosomal miRNAs as novel potential biomarkers for endometriosis
Authors: Zhang Lei , Liu Hao , Zhu Li-tong , Luo Huang-jin , Chen Xiao-Lin , Yu Gui-yuan , Li Qiu-xia , Jin Ping
Published: September 2020

Background: Endometriosis (EMS) is a chronic gynaecological disease. Exosomal miRNAs appear to be associated with the progression of EMS, which suggest potential circulating biomarkers in EMS.Methods: Differential centrifugation, illumina small RNA sequencing, bioinformatics analysis and qRT-PCR are used to compare the pelvic fluid of patients with a clinical diagnosis of EMS and matched controls.Results: Six miRNAs (miR-135a-5p, miR-196a-5p, miR-449b-5p, miR-4454, miR-4286, and miR-5100) showed significant differences in the EMS group in initial screening (log2FC > 2). Receiver-operator curve (ROC) analysis further indicated miR-4454 (area under the curve (AUC) = 0.956, P < 0.05) and miR-5100(area under the curve (AUC) = 0.900, P < 0.05) were highly correlated with the pathogenesis of EMS. Validation on the samples from 10 patients and 10 healthy people.Conclusion: Our miRNA expression data provide altered expression and potential prospects for biomarkers in EMS.
Neferine Enhances Autophagy to Alleviate Cytotoxicity and Apoptosis Induced by CSE in AEC-II through AMPK/mTOR Signaling Pathway
Authors: Wang Mengmeng , Yu Haiyang , Sun Yuqing , Cheng Pengpeng , Wang Qian , Han Fengfeng
Published: September 2020

COPD is a clinical common chronic respiratory disease, its incidence case fatality rate is higher, there is currently no cure drugs and methods. In this study, in order to make clear its role in the development of autophagy in COPD, COPD cell model is established.To further explore whether regulating autophagy could have a protective effect to fight against CSE-induced cytotoxicity and apoptosis, we choose neferine as an autophagy inducer. Neferine activated cell autophagy in an vitro CSE-induced COPD cell model and gradually attenuated CSE-induced cell apoptosis. Furthermore, this process happens largely through the AMPK/mTOR signaling pathway. As a autophagic flux inhibitor, chloroquine abolished the prosurvival autophagy effect, and AMPK inhibitor Compound C blocked neferine-mediated autophagy and then neferine failed to protect COPD cell model from CSE-induced apoptosis. Overall,our findings suggested that neferine possibly has a potentially protective effect in cell damage mechanisms caused by CSE. It hints that neferine has the prospect of turning into a potential therapeutics to cure CSE-induced cytotoxicity and apoptosis and even COPD patients.
Cooperative regulation of PBI1 and MAPKs precisely controls the master transcription factor WRKY45 in rice immunity
Authors: Ichimaru Kota , Harada Kenichi , Shigeta Shusuke , Yamaguchi Koji , Shimada Keita , Ishikawa Kazuya , Inoue Kento , Nishio Yusaku , Yoshimura Satomi , Inoue Haruhiko , Yamashita Eiki , Fujiwara Toshimichi , Nakagawa Atsushi , Kojima Chojiro , Kawasaki Tsutomu
Published: September 2020

The U-box type ubiquitin ligase PUB44 is targeted by the Xanthomonas oryzae XopP effector and positively regulates pattern-triggered immunity in rice. Here we identified PBI1, a protein that interacts with PUB44. Crystal structure analysis indicated that PBI1 forms a four-helix bundle structure. PBI1 also interacts with WRKY45, a key transcriptional activator of rice immunity, and negatively regulates its activity. PBI1 is degraded during the chitin response, and this is suppressed by silencing of PUB44 or expression of XopP, indicating that PBI1 degradation depends on PUB44. These data suggest that PBI1 suppresses WRKY45 activity when cells are in the unelicited state, and during chitin signaling, PUB44-mediated degradation of PBI1 leads to activation of WRKY45. In addition, phosphorylation of WRKY45 by MAP kinases releases WRKY45 from the PBI1-mediated inhibitory effect. These results demonstrate that chitin-induced activation of WRKY45 is regulated by the cooperation between MAP kinase-mediated phosphorylation and PUB44-mediated PBI1 degradation.
Heparin Binding Protein and Endothelial Glycocalyx Markers in Severe COVID-19 – A Prospective Observational Cohort Study
Authors: Mellhammar Lisa , Thelaus Louise , Elén Sixten , Fisher Jane , Linder Adam
Published: September 2020

Background: The pathophysiology of severe COVID-19 has been implicated to involve neutrophil activation in the blood and in the lungs and endothelial dysfunction. Heparin binding protein (HBP) is a neutrophil protein that plays an important role in bacterial sepsis and is a promising biomarker in severe infections. Syndecans and glypicans are potential markers of sheeding of the glycocalyx and endothelial dysfunction.The primary aims of this study were to assess whether HBP or syndecans and glypicans are involved in the pathophysiology of COVID-19 and if so, whether they can be used to predict severe disease preferably using a point-of-care test (POC) that can substitute more time-consuming analysis with enzyme-linked immunosorbent assay (ELISA).Methods: A prospective convenience sample study of biomarkers. The main cohort consisted of patients admitted to hospital with a confirmed COVID-19 diagnosis. Samples and clinical data were collected at admission, during admission and at discharge and samples were analyzed with ELISA kit (Axis-Shield Diagnostics) for measuring HBP concentration and a novel dry immunofluorescence analyzer (Jet-iStar 800) (Joinstar) for point-of-care testing.Results: Thirty-five COVID-19 patients were prospectively enrolled in the study. HBP was significantly elevated in COVID-19 patients with organ dysfunction (n= 23) compared to those without organ dysfunction (n=6), 24.7 ng/mL (95% CI 17.3-48.4) vs 10.6 ng/mL (95% CI 6.2-17.1 ng/mL), p=0.03. Syndecan-1 and Glypican-4 were not significantly elevated in patients with organ dysfunction. Syndecan-1, 62.1 ng/mL (44.4-102.0) vs 57.5 ng/mL (95% CI 46.0- 63.7), p=0.44 and glypican-4, 3292.4 pg/mL (95% CI 1707.5- 6790.6) vs 3962.7 pg/mL (95% CI 2653.6- 5823.5), p=0.80. The point-of-care (POC) HBP test showed good correlation to the standard ELISA with an R-value of 0.83. HBP measured by the POC device predicted development of COVID-induced organ dysfunction within 72 hours with an AUC of 0.88.Conclusions: The neutrophil-derived HBP is elevated prior to onset of organ dysfunction in patients with severe COVID-19 using a newly developed point-of-care test and hence HBP could be used in a clinical setting as a prognostic marker in COVID-19.
A Method for Experimental Warming of Developing Tree Seeds With A Common Garden Demonstration of Seedling Responses
Authors: Von Moler Ehren Reid , Page Gerald , Flores-Renteria Lluvia , Garms Cory , Hull Julia , Cooper Hillary , Swenson Jared , Perks Sean , Waring Kristen Marie , Whipple Amy Vaughn
Published: September 2020

BackgroundForest dieback driven by rapid climate warming threatens ecosystems worldwide. The health of forested ecosystems depends on how tree species respond to warming during all life history stages. While it is known that seed development is temperature-sensitive, little is known about possible effects of climate warming on seed development and subsequent seedling performance. Exposure of seeds to high air temperatures may influence subsequent seedling performance negatively, though conversely, warming during seed development may aid acclimation of seedlings to subsequent thermal stress. Technical challenges associated with in-situ warming of developing tree seeds limit understanding of how tree species may respond to seed development in a warmer climate. ResultsWe developed and validated a simple method for passively warming seeds as they develop in tree canopies to enable controlled study of climate warming on seedling performance. We quantified thermal effects of the cone-warming method across individual pine trees and stands by measuring the air temperature surrounding seed cones using thermal loggers and the temperature of seed cone tissue using thermocouples. We then investigated seedling phenotypes in relation to the warming method through a common garden study. We assessed plant morphological, physiological, and mycorrhizal nodulation in response to cone-warming for 20 seed source trees on the San Francisco Peaks in northern Arizona, USA. The warming method increased air temperature surrounding developing seed cones by 2.1◦C, a plausible increase in mean air temperature by 2050 under current climate projections. Notable effect sizes of cone-warming were detected for seedling root length, shoot length, and diameter at root collar using Cohen’s Local f 2. Root length was most affected by cone-warming, however, effect sizes of cone-warming on root length and diameter at root collar became negligible after the first year of growth. Cone-warming had small but significant effects on mycorrhizal fungal richness and seedling multispectral near-infrared indices indicative of plant health. ConclusionsThe method was shown to reliably elevate the temperature surrounding seed cones and thereby facilitate experimental in-situ climate change research on forest trees. The method was furthermore shown to influence plant traits that may affect seedling performance under climate warming.
High Performance Temperature Difference Triboelectric Nanogenerator
Authors: Cheng Bolang , Xu Qi , Ding Yaqin , Bai Suo , Jia Xiaofeng , Yu Yangdianchen , Qin Yong
Published: September 2020

Usually, high temperature decreases the output performance of triboelectric nanogenerator (TENG) because of the dissipation of triboelectric charges through the thermionic emission. It would be highly valuable if the high temperature can be used to enhance the output performance of TENG. In this paper, through a simulation combining the electron-cloud-potential-well model for triboelectrification and the thermionic-emission model, we find that there exists an optimum temperature difference ∆T between friction layers under which the output of TENG is maximum. Based on this, a type of contact-separation temperature difference TENG with controllable friction layer temperature (TDNG) is designed and fabricated to enhance the electrical output performance in temperature difference environment. As the temperature difference ∆T increasing from 0 K to 145 K, the output voltage, current, the surface charge density and output power are increased 2.7, 2.2, 3.0 and 2.9 times, respectively (from 315 V, 9.1 μA, 47 nC/m2, 69 μW to 858 V, 20 μA, 0.14 μC/m2, 206.7 μW). Then with the continuous increase of ∆T to 219 K, the surface charge density and output performance gradually decrease. At the optimal temperature difference (145 K), the biggest output current density (396 μA/cm2) has been obtained, which is 13% larger than the reported record value (350 μA/cm2).
Why the energy transition is not enough
Authors: Leiva Benjamin , Schramski John
Published: September 2020

Efforts to accommodate the growth in global energy consumption within a fragile biosphere are primarily focused on managing the transition towards a low-carbon energy mix. We show evidence that a more fundamental problem exists through a scaling relation, akin to Kleiber’s Law, between society’s energy consumption and material stocks. Humanity’s energy consumption scales at 0.78 of its material stocks, which implies predictable environmental pressure regardless of the energy mix. If true, future global energy scenarios imply vast amounts of materials and corresponding environmental degradation, which have not been previously acknowledged. Given this reality, we also show evidence that a worldwide lifestyle limit at 2.0 kW/capita enables a dignified life for all while stabilizing human intervention in the biosphere to current levels, yet the political viability of establishing such limit is very low.
Trends in the use of health services and their relationship with multimorbidity in Brazil, 1998–2013
Authors: de Souza Ana Sara Semeâo , Braga Jose Ueleres
Published: September 2020

Background
Chronic non-communicable diseases (NCDs) are the leading cause of multimorbidity. Access to effective and equitable health services that meet NCDs’ needs is still limited in many countries. This constitutes the main barrier to coping with NCDs, especially in minimising the suffering of those who are already sick. The present study aimed to identify the relationship between multimorbidity and the use of different health services in Brazil from 1998 to 2013.
Methods
This is a panel study using data from the health supplement of the National Household Sample Survey of 1998, 2003 and 2008 and data from the National Health Survey carried out in 2013. Three health service utilization outcomes were considered: 1. search for health services in the last 15 days (excluding dental services), 2. medical consultation in the previous 12 months and 3. hospitalisations over the last 12 months. Multimorbidity was assessed by counting the number of morbidities from a list of 10 morbidities. Poisson regression models stratified by sex were used to estimate the crude and adjusted prevalence ratios and their respective 95% confidence intervals for each outcome of health service use and multimorbidity, per year.
Results
There was an increase in the prevalence of demand for health services and medical consultations in the last 12 months between 1998 and 2013, regardless of the multimorbidity classification. The prevalence of hospitalisations has decreased over the study period and increased twofold in individuals with multimorbidity. Having multimorbidity increased the use of health services for the three outcomes under the study, being more expressive among men.
Conclusions
This study found that individuals with multimorbidity have higher levels of use of health services and better understand the multimorbidity epidemiology. The associated impacts on the use and costs of health services can increase the quality of care provided to these patients and reduce rising health care costs.
How mu-Opioid Receptor Recognizes Fentanyl
Authors: Vo Quynh , Mahinthichaichan Paween , Shen Jana , Ellis Christopher
Published: September 2020

The opioid crisis has escalated during the COVID-19 pandemic. More than half of the overdose-related deaths are related to synthetic opioids represented by fentanyl which is a potent agonist of mu-opioid receptor (mOR). In recent years, crystal structures of mOR complexed with morphine derivatives have been determined; however, structural basis of mOR activation by fentanyl-like synthetic opioids remains lacking. Exploiting the X-ray structure of mOR bound to a morphinan ligand and several state-of-the-art simulation techniques, including weighted ensemble and continuous constant pH molecular dynamics, we elucidated the detailed binding mechanism of fentanyl with mOR. Surprisingly, in addition to the orthosteric site common to morphinan opiates, fentanyl can move deeper and bind mOR through hydrogen bonding with a conserved histidine H297, which has been shown to modulate mOR's ligand affinity and pH dependence in mutagenesis experiments, but its precise role remains unclear. Intriguingly, the secondary binding mode is only accessible when H297 adopts a neutral HID tautomer. Alternative binding modes and involvement of tautomer states may represent general mechanisms in G protein-coupled receptor (GPCR)-ligand recognition. Our work provides a starting point for understanding mOR activation by fentanyl analogs that are emerging at a rapid pace and assisting the design of safer analgesics to combat the opioid crisis. Current protein simulation studies employ standard protonation and tautomer states; our work demonstrates the need to move beyond the practice to advance our understanding of protein-ligand recognition.
Effects of Brief Citrate Interruption on Regional Citrate Anticoagulation During Continuous Renal Replacement Therapy
Authors: Jiang Daishan , Zhou Zhongxia , Yuan Xiaoyu , Shen Yan , Wang Ting , Cai Qi , Li Shanfeng , Jiang Wei , Shen Yanbo , Huang Zhongwei
Published: September 2020

Background: Regional citrate anticoagulation (RCA) has been widely used in continuous renal replacement therapy (CRRT). Having encountered some unexplained and unexpected situations in clinical practice, we speculated if a brief citrate infusion interruption during regular operation would affect anticoagulation. A review of the literature confirmed that no studies to date have explored the effect of short-term citrate interruption on RCA.Method: In ten patients who received continuous veno-venous hemofiltration treatment with RCA, we measured concentrations of ionized calcium (iCa) in the post-filtered and peripheral blood before and after the citrate interruption due to effluent dumping and at 5, 10, 20, and 60 minutes after the return to normal working conditions. Results: The citrate suspension time caused by dumping of the effluent liquid was 5.91 ± 0.89 minutes. The post-filter iCa concentration was significantly increased because of the interruption (0.42 ± 0.04 vs. 0.94 ± 0.06, p<0.001) and positively correlated with the interruption duration (r = 0.69, p = 0.002), whereas the peripheral blood calcium concentration was not significantly affected (1.09 ± 0.05 vs. 1.07 ± 0.04, p=0.47). Conclusion: A brief citrate interruption may affect anticoagulation efficiency, creating a potential hazard. A more reliable RCA protocol or equipment design requires further study.
The Effective Screening Tools for Detecting Hearing Loss in Elderly Population: HHIE-ST Versus TSQ
Authors: CHAYAOPAS NICHTIMA , Kasemsiri Pornthep , Thanawirattananit Panida , Piromchai Patorn , Yimtae Kwanchanok
Published: September 2020

BackgroundGlobally increasing number of elders is concerned. Hearing loss process in elderly cannot be avoided. An effective screening tool for hearing loss is essential for proper diagnosis and rehabilitation, which can improve QOL in elderly individuals.MethodsThis prospective-diagnostic test study evaluates the diagnostic value of Thai version of the Hearing Handicap Inventory for Elderly Screening (HHIE-ST) and the Thai Single Question (TSQ) surveys in screening hearing disability in 1109 Thai elderly participants aged 60 years and older in communities in four provinces in Thailand. The HHIE-ST consisted of 10 selected questions from the validated HHIE-Thai version. A TSQ survey was developed to have the same meaning as an English Single Question survey. The participants answered both questionnaires, and a standard audiometry test assessed with air conduction from 250 to 8000 Hz was included as a gold standard.ResultsThe prevalence of hearing disability was 38.34%. The HHIE-ST achieved a sensitivity of 88.96% (95% CI 85.77–91.64) and specificity of 52.19% (95% CI 48.24–56.13) for diagnosis hearing disability in Thai elderly subjects, whereas the TSQ yielded a sensitivity of 88.73% and a specificity of 55.93%. A combined test including the HHIE-ST and TSQ achieved better performance with sensitivity of 85.29% and specificity of 60.13%.ConclusionsEither the HHIE-ST or the TSQ is a sensitive and useful tool for screening hearing disability in Thai elderly subjects. Using the HHIE-ST together with the TSQ resulted in a better screening tool for detecting moderate hearing loss elderly individuals who will be benefit and recommended for hearing rehabilitation.Trial RegistrationThe study is registered with the following number in the Thai Clinical Trials Registry: TCTR20151015003. URL: http://www.clinicaltrials.in.th/index.php?tp=regtrials&menu=trialsearch&smenu=fulltext&task=search&task2=view1&id=1562
Unilateral Lateral Rectus Recession is an Effective Surgery for Intermittent Exotropia in Young Children
Authors: Spierer Oriel , Spierer Abraham
Published: September 2020

Background: Different surgical methods have been suggested for the correction of intermittent exotropia. Unilateral lateral rectus recession has been described as a surgical alternative for small and moderate-angle exotropia. In general, previous studies did not focus on the outcomes of unilateral lateral rectus recession in young children with intermittent exotropia. The purpose of this study is to evaluate the surgical outcomes of unilateral lateral rectus recession in the treatment of moderate-angle exotropia (≤25 PD (prism diopters)) in children.Methods: The charts of all patients younger than 12 years of age with moderate-angle exotropia (up to 25 PD) who were operated during the years 2006-2018 were retrospectively reviewed. Fifty-eight patients underwent unilateral lateral rectus recession and had a minimum follow up of 6 months. The angle of exotropia (PD) before and after surgery and the success rate were documented.Results: Mean age at surgery was 6.4 ± 1.9 (range 3.5–11.0) years. Exotropia improved from a preoperative angle of 21.4 ± 4.0 PD to 3.5 ± 5.9 PD postoperatively (p < 0.001). Success rate, defined as deviation of ≤ 10 PD, was achieved in 86.2%. There were 2 (3.4%) cases of overcorrection (consecutive esotropia). There were no intra- or postoperative complications. The mean follow-up duration after surgery was 2.3 ± 1.7 years. Conclusion: In children with moderate angle exotropia, good postoperative success rate was achieved by performing unilateral lateral rectus recession.
An ethnobotanical study of wild edible plants in Yilmana Densa and Quarit Districts, West Gojjam, Western Ethiopia
Authors: Alemneh Derebe
Published: September 2020

Backgrounds: Globally, wild edible plants are one of the main non-timber forest products and possess up to 96% of the value of forests. They are an essential source of supplementary foods in many parts of Ethiopia. However, they have been highly degraded and lost due to anthropogenic factors. Thus, current study aims at recording and documenting wild edible plants in Yilmana Densa and Quarit Districts, West Gojjam, Western Ethiopia to pave a way for further research and conservation. Methods: Semi-structured interviews, focus group discussions, participant observation and market survey were the data collection tools. Preference and direct matrix ranking were used to analyze the data. Results: Thirty two wild edible plant species were reported in the two Districts. Most of the species were herbs while the major (53.1%) edible parts were fruits. Most of the collectors of the wild food were young males. Ficus sur was the most preferred wild edible plant. Conclusion: The districts are still rich sources of wild edible plants. However, there was low potential of conservation. Therefore, there should be extensive awareness rising for wild edible plant conservation.
Non-invasive, opsin-free mid-infrared modulation activates cortical neurons and accelerates associative learning
Authors: Chen Xiaowei , Zhang Jianxiong , He Yong , Liang Shanshan , Liao Xiang , Li Tong , Qiao Zhi , Chang Chao , Jia Hongbo
Published: September 2020

Boosting learning capability represents a long-sought dream of mankind. Neurostimulant drugs or magnetic/electrical stimulation techniques can overcome attention deficits, but these drugs or techniques are weakly beneficial in boosting the learning capabilities of healthy subjects. Here, we report a stimulation technique, mid-infrared modulation (MIM), that delivers mid-infrared light energy through opened skull or even non-invasively through thinned intact skull and can activate brain neurons in vivo without introducing any exogeneous gene. Using c-Fos immunohistochemistry, in vivo single-cell electrophysiology and two-photon Ca2+ imaging in mice, we demonstrate that MIM significantly induces firing activities of neurons in the targeted cortical area. Moreover, mice that receive MIM targeting to the auditory cortex during an auditory associative learning task exhibit a strikingly faster learning speed (~ 50% faster) than control mice. Together, this non-invasive, opsin-free MIM technique is demonstrated with a great translational potential for activating brain neurons and boosting brain learning capability.
Evidence of Neuroplasticity Due to Acupuncture: An fNIRS Study
Authors: Khan M. N. Afzal , Ghafoor Usman , Yoo Ho-Ryong , Hong Keum-Shik
Published: September 2020

Background: Mild cognitive impairment (MCI) is a precursor to the critical disease known as Alzheimer’s. It is imperative to develop a proper treatment for this neurological disease in the aging society. This study investigates the effects of acupuncture therapy (AT) on MCI patients.Methods: Eleven healthy individuals and eleven MCI patients were recruited for this study. Oxy- and deoxy-hemoglobin signals in the prefrontal cortex during working-memory tasks were monitored using functional near-infrared spectroscopy. Before the AT, working-memory experiments were conducted for healthy control (HC) and MCI groups (MCI-0), followed by 24 sessions of AT for the MCI group. The AT sessions were initially carried out for six weeks (two sessions per week), after which experiments were performed again on the MCI group (MCI-1). This was followed by another set of AT sessions that also lasted for six weeks, after which the experiments were repeated again on the MCI group (MCI-2). Statistical analyses of the signals and classifications based on activation maps as well as temporal features were performed.Results: The highest classification accuracies obtained using binary connectivity maps were 85.7% HC vs. MCI-0, 69.5% HC vs. MCI-1, and 61.69% HC vs. MCI-2. The classification accuracies using the temporal features mean (i.e., mean(5:28 s)) and maximum (i.e., max(5:28 s)) values were 60.6% HC vs. MCI-0, 56.9% HC vs. MCI-1, and 56.4% HC vs. MCI-2. Conclusions: The results reveal that there was a change in the temporal characteristics of the hemodynamic response of MCI patients due to acupuncture. This was reflected by a reduction in the classification accuracy after the therapy, indicating that the patients’ brain response improved and became comparable to those of healthy subjects. Similar trend was reflected in the classification using image feature. These results indicate that acupuncture can be used for the treatment of MCI patients.Trial registration: Clinical research and information service (CRIS), KCT 0002451, Registered 05 September 2017, https://cris.nih.go.kr/cris/en/
Accelerated failure time modelling of Tuberculosis predictors in HIV/AIDS patients in Albert Luthuli Municipality of South Africa
Authors: Bengura Pepukai , Ndlovu Principal , Managa Mulalo Annah
Published: September 2020

Background: Tuberculosis (TB) is one of the most common opportunistic diseases and leading cause of death among Human immunodeficiency virus and acquired immune deficiency syndrome (HIV/AIDS) patients. There has been a drastic rise of TB infection associated with the pandemic occurrence of HIV/AIDS infection in South Africa and other resource-limited countries world-wide. South Africa faces an immense burden on health care systems posed by diagnostic and therapeutic challenges resulting from the concomitant HIV and TB epidemics. This study aimed to determine the prevalence and the factors associated with TB and HIV co-infection for patients attending clinical care at rural public health facilities in Albert Luthuli municipality of South Africa. Methods: A cohort of HIV/AIDS patients was retrospectively followed from inception in 2010 to 2017 until TB was diagnosed or until the end of the study. Accelerated Failure Time (AFT) model was used to analyse survival data on HIV/AIDS patients. Factors associated to TB were modelled using log-logistic AFT model and further analysis of the significant factors was done using Kaplan-Meier, log-rank and hazard ratios. Results: From 357 HIV/AIDS patients, 65 patients (18.2%) had TB. Out of the 65 HIV/AIDS patients with TB, 15 (23.1%) of them died. Thus, of the 41 HIV/AIDS patients who died during the follow-up period, 15 of them (36.6%) had TB. Log-logistic AFT model determined factors associated with TB at significance level of 0.05 as: hospital, WHO stage, treatment (regimen 1), ART adherence, follow-up CD4 count, baseline haemoglobin, follow-up white blood cell count, baseline viral load, baseline sodium and follow-up alanine transaminase. Discussion: Although antiretroviral therapy is effective in reducing the risk of developing TB, the overall burden of TB in HIV/AIDS community may not substantially diminish.Conclusion: TB/HIV co-infection is one of the serious public health problems in Albert Luthuli municipality. Collaborative TB/HIV activities in form of early diagnosis of both TB and HIV need a holistic approach in order to reduce drug resistance, drug toxicity, co-morbidities and mortalities which are associated with TB/HIV co-infection.
The Efficacy of Moxibustion and Acupuncture Therapy for Ankylosing Spondylitis: A Protocol for an Overview of Systematic Reviews and Meta-analyses
Authors: Chen Jun , Xiong Jun , Lu Lunbin , Zhu Siyuan , Zhong Zhiying , Tang Genhua , Zhou Xingchen , Guo Han
Published: September 2020

Background:Ankylosing Spondylitis (AS) is a complex and progressive autoimmune inflammatory disease with a worldwide prevalence ranging up to 0.9%. Several systematic reviews and meta-analyses of traditional Chinese medicine alternative therapies, such as acupuncture or moxibustion, have demonstrated the effectiveness of moxibustion and acupuncture in the treatment of ankylosing spondylitis. However, there is no relevant literature to comprehensively evaluate the evidence.The purpose of this overview is to synthesize and evaluate the reliability of evidence generated in the systematic review (SR) and meta-analysis of moxibustion and acupuncture as a primary or complementary therapy for patients with ankylosing spondylitis.Methods:PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, Chinese National Knowledge Infrastructure[CNKI], Chinese VIP Information, Wanfang Database, and Chinese Biomedical Literature Database[CBM] were searched for systematic reviews and Meta-analysis that review the efficacy of acupuncture or moxibustion as the primary treatment for patients with Ankylosing Spondylitis. The literature published before August 2020 will be selected. Additionally, the relevant SRs and Meta-analyses that unpublished or ongoing will be searched in PROSPERO and INPLASY. The methodological guidelines for overviews will be used to reviews and extract data by two reviewers, and their will do it independently.Methodology quality will be analyzed by the AMSTAR-2 and the risk of bias by POBIS. For the included studies, we will adopt the following results as primary evaluation indicators: effective rate, Visual Analogue Scale (VAS) and Bath AS Disease Activity Index (BASDAI). Reviewers will assess the certainty of evidence by Grading of Recommendations Assessment, Development and Evaluation(GRADE).Results: The results will be published in a peer-reviewed journal. Conclusion: This overview will provide comprehensive evidence of moxibustion and acupuncture for patients with Ankylosing Spondylitis. Registration number: INPLASY202080035
Multiorgan failure with fatal outcome after stem cell tourism
Authors: Večerić-Haler Željka , Borštnar Špela , Luzar Boštjan , Kojc Nika
Published: September 2020

Background: unproven stem cell treatments may involve serious health, personal and financial considerations. Due to worldwide spread, illegal stem cell therapies have become a major public health problem. We have already witnessed numerous reports in the mass media of severe and occasionally even fatal outcomes after such therapies. However, there are only few scientifically documented cases in which the causality between stem cell therapy and side effects cannot be refuted.Case presentation: here we present a case report of a 48-years old patient with serious side effects including disseminated skin ulcers, hepatitis and cardiomyopathy with eventual fatal outcome following unproven stem cell treatment.Conclusions: the case of the patient presented here draws attention to the worst possible outcome of stem cell tourism. To effectively combat this issue, professionals and patients should be empowered with the right knowledge on possible side effects.
Development of Individual Tree Growth and Yield Model Across Multiple Contrasting Species Using Non-parametric and Parametric Methods in the Hyrcanian Forests of Northern Iran
Authors: Hamidi Seyedeh Kosar , Weiskittel Aaron , Bayat Mahmoud , Fallah Asghar
Published: September 2020

BackgroundThe Hyrcanian forests of Iran contain many species-rich communities that can only be maintained through an understanding of the renewal and development of these forests. Located in the Jojadeh section of the Farim forest in northern Iran, individual tree growth of five distinct species [(Oriental beech (Fagus orientalis Lipsky), chestnut-leaved oak (Quercus castaneifolia Coss. ex J.Gay), Persian maple (Acer velutinum Boiss.), common hornbeam (Carpinus betulus L.) and Caucasian alder (Alnus subcordata C.A.Mey.)] were measured on 313 permanent sample plots (0.1 ha) over a 10-year period (2003-2013). MethodsIn this analysis, various tree-level predictions were investigated using the available data with application of parametric models and two artificial neural networks (i.e., the multilayer perceptron (MLP) and radial basis function (RBF) networks). ResultsIndividual tree diameter growth models showed a robust negative relationship with basal area in larger trees (BAL), which was relatively consistent across species. A total height model indicated that the examined species did not differ for a given set of covariates. In the survival model, the survival probability of Oriental beech was lower than the other species, while the ingrowth model revealed sapling density of all species increased with the greater basal area. The artificial neural network based on the MLP was superior for all models and predicted more accurately than the RBF. Furthermore, the models based on the MLP were also superior to the parametric individual tree models developed using mixed-effect regression. ConclusionThe use of these developed models in forest planning and management is imperative, but assessment of long-term projection behavior across the contrasting statistical approaches used is warranted despite the general superiority of the non-parametric models.
Usefulness of β-lactam and Macrolide Combination Therapy for Treating Community-acquired Pneumonia Patients Hospitalized in the Intensive Care Unit: Propensity Score Analysis of a Prospective Cohort Study
Authors: Ito Akihiro , Ishida Tadashi , Tachibana Hiromasa , Nakanishi Yosuke , Tokioka Fumiaki , Yamazaki Akio , Washio Yasuyoshi , Irie Hiromasa , Otake Takanao
Published: September 2020

Background: Previous studies reported that β-lactam and macrolide combination therapy significantly improved outcomes for patients with severe community-acquired pneumonia hospitalized in the intensive care unit (ICU) compared with a non-macrolide regimen. However, whether β-lactam and macrolide therapy truly reduces mortality is controversial, because no randomized, controlled trials have been conducted. The aim of the present study was to evaluate the usefulness of β-lactam and macrolide combination therapy for severe community-acquired pneumonia patients hospitalized in the ICU compared with a non-macrolide β-lactam-containing regimen.Methods: A prospective, observational, cohort study of hospitalized pneumonia patients was performed. Hospitalized severe community-acquired pneumonia patients admitted to the ICU within 24 hours between October 2010 and October 2017 were included for analysis. The primary outcome was 30-day mortality, and secondary outcomes were 14-day mortality and ICU mortality. Inverse probability of treatment weighting analysis as a propensity score analysis was used to reduce biases, including six covariates: age, sex, C-reactive protein, albumin, Pneumonia Severity Index score, and APACHE II score.Results: A total of 78 patients were included. There were 48 patients in the non-macrolide-containing β-lactam therapy group, including β-lactam monotherapy and β-lactam and non-macrolide-containing combination therapy, and 30 patients in the macrolide combination therapy group. β-lactam and macrolide combination therapy significantly decreased 30-day mortality (16.7% vs. 43.8%; P=0.015) and 14-day mortality (6.7% vs. 31.3%; P=0.020), but not ICU mortality (10% vs 27.1%, P=0.08) compared with non-macrolide-containing β-lactam therapy. After adjusting by inverse probability of treatment weighting, macrolide combination therapy also decreased 30-day mortality (odds ratio, 0.29; 95%CI, 0.09-0.96; P=0.04) and 14-day mortality (odds ratio, 0.19; 95%CI, 0.04-0.92; P=0.04), but not ICU mortality (odds ratio, 0.34; 95%CI, 0.08-1.36; P=0.13).Conclusions: Combination therapy with β-lactam and macrolides significantly improved the prognosis of severe community-acquired pneumonia patients hospitalized in the ICU compared with a non-macrolide-containing β-lactam regimen on propensity score analysis.Trial registration: UMIN Clinical Trials Registry, UMIN000004353. Registered on 7 October 2010,
Entropic evidence for a Pomeranchuk effect in Magic Angle graphene
Authors: Ilani Shahal , Rozen Asaf , Park Jeong Min , Zondiner Uri , Cao Yuan , Rodan-Legrain Daniel , Taniguchi Takashi , Watanabe Kenji , Oreg Yuval , Stern Ady , Berg Erez , Jarillo-Herrero Pablo
Published: September 2020

In the 1950's, Pomeranchuk predicted that, counterintuitively, liquid 3He may solidify upon heating, due to a high excess spin entropy in the solid phase. Here, using both local and global electronic entropy and compressibility measurements, we show that an analogous effect occurs in magic angle twisted bilayer graphene. Near a filling of one electron per moiré unit cell, we observe a dramatic increase in the electronic entropy to about 1kB per unit cell. This large excess entropy is quenched by an in-plane magnetic field, pointing to its magnetic origin. A sharp jump in the compressibility as a function of the electron density, associated with a reset of the Fermi level back to near the Dirac point, marks a clear boundary between two phases. We map this jump as a function of electron density, temperature, and magnetic field. This reveals a phase diagram that is consistent with a Pomeranchuk-like temperature- and field-driven transition from a rather conventional metal to a correlated state with nearly-free magnetic moments. The correlated state features an unusual dichotomy between properties associated with itinerant electrons, such as the absence of a thermodynamic gap, metallicity, and a Dirac-like compressibility, and properties usually associated with localized moments, such as a large entropy and its disappearance with magnetic field. Moreover, the energy scales characterizing these two sets of properties are vastly different: whereas the compressibility jump onsets at T∼30K, the bandwidth of magnetic excitations is ∼3K or smaller. This dichotomy and the large separation of energy scales have key implications for the physics of correlated states in twisted bilayer graphene.
Surgical masks decontamination for reuse by members of the public: feasibility study and development of home-based methods
Authors: Hong Mun Cheok , Lan Tan Sook , Fiona Phua Soo Zeng , Qi Lim Wei , Wei Pang Shyue , Vidhya Novem , Geraldine Chee , Shermin Soh Yi Hui
Published: September 2020

This study aims to propose decontamination methods that are suitable for use by members of the public to cope with the shortage of surgical masks during the current COVID-19 pandemic. 3-ply surgical masks were subjected to different decontamination protocols (heat, chemical, ultraviolet irradiation) to assess their abilities to achieve at least 4-log reduction of two common respiratory pathogens, H1N1 Influenza A virus, a single-stranded RNA enveloped virus similar to SARS-CoV-2 and Staphylococcus aureus, a Gram-positive bacterium that is more resistant to decontamination than single stranded RNA enveloped virus. Decontaminated surgical masks were assessed for differences in breathability, particle filtration efficiency and bacteria filtration efficiency as compared with non-decontaminated masks. The number of decontamination cycles that the 3-ply surgical masks could undergo without significant changes in breathability and filtration efficiencies were also determined. It was found that surgical masks decontaminated by either soaking for 60 min in 0.5% (v/v) aqueous hydrogen peroxide solution, or 30 min of soaking in 0.05% - 0.5% (v/v) aqueous sodium hypochlorite diluted from household bleach or ultraviolet irradiation by a surface dose of 13.5 kJ/m2 were able to achieve at least a 4-log reduction of both Staphylococcus aureus and H1N1 Influenza A virus spiked on surgical mask test swatches. No significant changes in breathability and filtration efficiencies of the surgical masks were observed after ten decontamination cycles of hydrogen peroxide or diluted bleach treatment or 30 cycles of ultraviolet irradiation.
Effectiveness and Safety of Plum - Blossom Needle in the Treatment of Myopia：A Protocol for Systematic Review and Meta-analysis
Authors: Zhu Siyuan , Xiong Jun , Chen Jun , Tang Genhua , Lu Lunbin , Zhong Zhiying , Zhou Xingchen , Guo Han , Fan Hao
Published: September 2020

Background: In recent years, the prevalence of myopia has increased significantly, and it has become one of the major eye diseases that cause visual impairment in the world,which is particularly prominent among young people. And uncorrected myopia is the leading cause of blindness.The purpose of this study is to evaluate the efficacy and safety of plum-blossom needle in delaying adolescent myopia progression through systematic evaluation.Methods and analysis:The following electronic databases will be searched from inception to July 2020 regardless of publication status and language: Medline, EMBASE, Web of Science, the Cochrane Library, PubMed, China National Knowledge Infrastructure (CNKI), China Biology Medicine (CBM), Chinese Scientific Journal Database (VIP), Wanfang Database, Chinese Biomedical Literature Database (CBLD), Chinese Science and Technology Periodical Database (CSTPD). RCT registration websites, including http://www.ClinicalTrials.gov and http://www.chictr.org.cn, will also be searched. Review Manager V.5.4 will be used to analysis the statistic. Two reviewers will independently select studies, extract and code the data, assess risk of bias of the included studies, evaluate the quality of evidence for outcomes.Discussion:So far, many studies have been conducted on the treatment of adolescent myopia with plum-blossom needles. However, there is still no clear conclusion on the effectiveness and safety of plum-blossom needles in the treatment of juvenile myopia.In this systematic review and meta-analysis, available data will be pooled together to further inform research and clinical practice.Systematic review registration: Inplasy protocol 202080026
Biomarkers in Juvenile Systemic Sarcoidosis: A Case Report and Literature Review
Authors: Alsarhan Ali , Habeeb Shameer Mohamed , Popatia Rizwana , Fathalla Basil
Published: September 2020

Background: Juvenile sarcoidosis represents a spectrum of rare granulomatous inflammatory conditions characterized by non-caseating granulomas that can affect multiple systems. Nonetheless, no laboratory markers can conclusively indicate a diagnosis of sarcoidosis. In this report, we discuss the role of serum soluble interleukin-2 receptor (sIL-2r) levels in supporting the diagnosis of sarcoidosis in a child with ocular, renal, and pulmonary involvement. We further discuss trends in this marker, as well as serum angiotensin converting enzyme (ACE) and 1,25(OH)2D levels, in relation to disease activity and response to treatment. Case Presentation: A previously healthy 14-year-old Arabic girl presented with fever, anorexia, and dyspnea upon exertion. She exhibited elevated levels of acute-phase reactants, anemia, elevated serum creatinine, and proteinuria. An eye exam revealed bilateral uveitis. High-resolution computed tomography (CT) of the chest revealed subpleural interlobar septal thickening with reticular changes and subtle ground glass opacities. The results of an extensive work-up to rule out infectious etiology, immune deficiency, malignancy, and other rheumatic diseases were unremarkable. Serum levels of sIL-2r were extraordinarily high at 18,589 U/L (normal range: 223–710 U/L), and the trend of subsequent measurements correlated with disease response and disease reactivation. Although ferritin levels were elevated at 1,136 ng/mL (normal: 13–68 ng/mL), bone marrow biopsy was negative for hemophagocytosis. Kidney biopsy revealed granulomatous interstitial nephritis with tubular atrophy. Serum ACE and 1,25(OH)2D levels were also elevated at diagnosis. The patient was treated with glucocorticosteroids, mycophenolate mofetil, and anti-tumor necrosis factor (anti-TNF). Clinical responses to such treatment were correlated with trends in serum sIL-2r and 1,25 (OH)2D levels, but not with trends in serum levels of ACE. Conclusions: Our findings highlight the promise of sIL-2r as a marker of diagnosis and disease activity during the treatment period in patients with juvenile sarcoidosis. Further prospective studies involving large cohorts of patients with childhood sarcoidosis are required to elucidate the diagnostic and prognostic roles of serum sIL-2r levels.
Cell non-autonomy amplifies disruption of neurulation by mosaic Vangl2 deletion
Authors: Galea Gabriel , Maniou Eirini , Marshall Abigail R , DE Greene Nicholas , Copp Andrew J
Published: September 2020

Post-zygotic mutations that generate tissue mosaicism are increasingly associated with severe congenital defects, including those arising from failed neural tube closure. We observed that elevation of the neural folds during mouse spinal neurulation is vulnerable to deletion of the planar cell polarity core component Van Gogh-like (Vangl)2 in as few as 16% of neuroepithelial cells. Vangl2-deleted cells are typically dispersed throughout the neuroepithelium, and each non-autonomously prevents apical constriction by an average of five Vangl2-replete neighbours. This inhibition of apical constriction involves reduced myosin-II recruitment to neighbour cell borders and shortening of basally-extending microtubule tails, which are known to facilitate apical constriction. Vangl2-deleted cells themselves continue to apically constrict and preferentially recruit myosin-II to their apical cell cortex rather than to apical cap sarcomere-like organisations. Such non-autonomous effects can explain how post-zygotic mutations affecting a minority of cells can cause catastrophic failure of morphogenesis leading to clinically important birth defects.