bluuebunny/crossref_metadata_2025 huggingface dataset:
Skeletal muscle function and need for long-term care of urban elderly people in Japan (the Bunkyo Health Study): a prospective cohort study
Authors: Someya Yuki , Tamura Yoshifumi , Kaga Hideyoshi , Nojiri Shuko , Shimada Kazunori , Daida Hiroyuki , Ishijima Muneaki , Kaneko Kazuo , Aoki Shigeki , Miida Takashi , Hirayama Satoshi , Konishi Seiki , Hattori Nobutaka , Motoi Yumiko , Naito Hisashi , Kawamori Ryuzo , Watada Hirotaka
Published: September 2019

Purpose

The proportion of elderly individuals (age ≥65 years) in Japan reached 27.7% in 2017, the highest in the world. A serious social problem in a super-aged society is the rise in the number of elderly people who need long-term care (LTC), which is mainly due to cerebrovascular disease, dementia, age-related frailty, falls and fractures, and joint disease. We hypothesised that decreased muscle mass, muscle strength and insulin sensitivity are the common risk factors for these diseases related to needing LTC. We developed a prospective cohort study of elderly subjects in an urban community to test this hypothesis. The primary objective is to prospectively investigate associations between muscle mass, muscle strength, and insulin sensitivity and incidence of main disease and risk factors of needing LTC. The primary outcomes are the incidence of cerebrovascular disease and cognitive decline.

Participants

Participants were 1629 people aged 65–84 years living in 13 communities in an urban area (Bunkyo-ku, Tokyo, Japan). Average age was 73.1±5.4 years.

Findings to date

We obtained baseline data on cognitive function, cerebral small vessel disease (SVD) determined by brain MRI, body composition, bone mineral density, arteriosclerosis, physical function, muscle mass, muscle strength and insulin sensitivity. Mild cognitive impairment and dementia were observed in 18.1% and 3.3% of participants, respectively. The prevalence of cerebral SVD was 24.8%. These characteristics are similar to those previously reported in elderly Japanese subjects.

Future plans

We will ask participants about their health status, including incidence of cerebrovascular disease, falls, fractures and other diseases every year by mail. We plan to re-evaluate cognitive function, brain MRI parameters and other parameters at 5 and 10 years after the baseline evaluation. We will evaluate whether low muscle function (muscle mass, muscle strength or insulin sensitivity) is a risk factor for cognitive decline or cerebrovascular disease.
Using general practice data to monitor influenza vaccination coverage in the medically at risk: a data linkage study
Authors: Badmus Dauda , Menzies Robert
Published: September 2019

Objective

To examine the possibility of using data from a network of Australian General Practices (GPs) to estimate influenza vaccination coverage in Australians medically at risk.

Design

Data electronically extracted from a large national network of Australian GP clinics (MedicineInsight) was analysed for annual influenza vaccination coverage from 2008 to 2014. We compared the results with the 2009 and 2014 Adult Vaccination Survey. We adjusted for differences in the distribution of age, risk groups and provider types.

Setting

All states in Australia.

Participants

GPs participating in MedicineInsight programme.

Interventions

Not applicable.

Main outcome measures

Annual vaccination coverage across risk groups as recorded in Adult Vaccination Survey in 2009 and 2014 were compared with vaccination coverage in MedicineInsight. The impact of National Immunisation Programme expansion of free vaccine in 2010 to cover patients aged <65 years with medical risk factors.

Results

The proportion of MedicineInsight patients aged ≥18 years and diagnosed with medical risk factors was higher in 2014 (33.2%), compared with the AVS in 2009 (25%). In 2009, influenza vaccination coverage estimates for those aged 18–64 years with medical risk factors was lower for MedicineInsight patients compared with the AVS (26% vs 36%). There was no evidence of any change in coverage between 2008 and 2014, despite the vaccine being available free of charge to this group from 2010.

Conclusion

General practice databases have the potential to help fill the gap in vaccination coverage data in patients with medical risk factors.
Complex interaction of obesity, intentional weight loss and heart failure: a systematic review and meta-analysis
Authors: Mahajan Rajiv , Stokes Michael , Elliott Adrian , Munawar Dian A , Khokhar Kashif B , Thiyagarajah Anand , Hendriks Jeroen , Linz Dominik , Gallagher Celine , Kaye David , Lau Dennis , Sanders Prashanthan
Published: September 2019

Objective

The aim of the meta-analysis was to determine the association of obesity and heart failure (HF) and the cardiac impact of intentional weight loss following bariatric surgery on cardiac structure and myocardial function in obese subjects.

Methods

MEDLINE, Embase and Web of Science were searched up to 3 April 2018. Studies reporting association and prognostic impact of obesity in HF and the impact of intentional weight loss following bariatric surgery on cardiac structure and myocardial function in obesity were included in the meta-analysis.

Results

4959 citations were reviewed. After exclusions, 29 studies were analysed. A ‘J curve’ relationship was observed between body mass index (BMI) and risk of HF with maximum risk in the morbidly obese (1.73 (95% CI 1.30 to 2.31), p<0.001, n=11). Although ‘obesity paradox’ was observed for all-cause mortality, the overweight group was associated with lower cardiovascular (CV) mortality (OR=0.86 (95% CI 0.79 to 0.94), n=11) with no significant differences across other BMI groups. Intentional weight loss induced by bariatric surgery in obese patients (n=9) without established HF, atrial fibrillation or known coronary artery disease, was associated with a reduction in left ventricular mass index (p<0.0001), improvement in left ventricular diastolic function (p≤0.0001) and a reduction in left atrial size (p=0.02).

Conclusions

Despite the increased risk of HF with obesity, an ‘obesity paradox’ is observed for all-cause mortality. However, the nadir for CV mortality is observed in the overweight group. Importantly, intentional weight loss was associated with improvement in indices of cardiac structure and myocardial function in obese patients.

Trial registration number

APP 74412.
Effect of vitamin D on serum markers of bone turnover in SLE in a randomised controlled trial
Authors: Tedeschi Sara K. , Aranow Cynthia , Kamen Diane L. , LeBoff Meryl , Diamond Betty , Costenbader Karen H.
Published: September 2019

Objective

Bone health in SLE is adversely affected by vitamin D deficiency, inflammatory cytokines and glucocorticoid use. We hypothesised that vitamin D supplementation would increase markers of bone formation and decrease markers of bone resorption in SLE subjects.

Methods

We studied 43 vitamin D-deficient SLE subjects who participated in a 12-week randomised controlled trial of 2000–4000 IU/day vitamin D supplementation versus placebo. Subjects had inactive SLE (SLE Disease Activity Index ≤4) and were taking <20 mg prednisone daily at baseline. We assayed baseline and week 12 serum 25-hydroxyvitamin D, N-terminal propeptide of type 1 collagen (P1NP) and C-telopeptide (CTX). We tested the effect of vitamin D versus placebo on change (Δ) in P1NP and ΔCTX in an intention-to-treat analysis. Secondary analyses evaluated whether vitamin D affected bone turnover among subjects achieving vitamin D repletion (≥30 ng/mL) or currently taking glucocorticoids.

Results

28 subjects were randomised to vitamin D and 15 to placebo. Mean age was 39 years and 40% were using glucocorticoids at enrolment. Repletion was achieved by 46% in the vitamin D group versus none in the placebo group. Changes in bone turnover markers were not significantly different in the vitamin D group versus placebo group (median ΔP1NP −0.2 vitamin D group vs −1.1 placebo group (p=0.83); median ΔCTX +3.5 vitamin D group vs −37.0 placebo group (p=0.50)). The effect of vitamin D did not differ based on achieving vitamin D repletion or baseline glucocorticoid use.

Conclusion

Vitamin D supplementation did not affect the 12-week change in bone turnover markers among SLE subjects in this trial.
Modified theory of gravity and clustering of multi-component system of galaxies
Authors: Hameeda Mir , Pourhassan Behnam , Faizal Mir , Masroor C. P. , Ansari Rizwan Ul Haq , Suresh P. K.
Published: September 2019

In this paper, we analyze the clustering of galaxies using a modified theory of gravity, in which the field content of general relativity has been be increased. This increasing in the field content of general relativity changes the large distance behavior of the theory, and in weak field approximation, it will also modify the large distance behavior of Newtonian potential. So, we will analyzing the clustering of multi-component system of galaxies interacting through this modified Newtonian potential. We will obtain the partition function for this multi-component system, and study the thermodynamics of this system. So, we will analyze the effects of the large distance modification to the Newtonian potential on Helmholtz free energy, internal energy, entropy, pressure and chemical potential of this system. We obtain also the modified distribution function and the modified clustering parameter for this system, and hence observe the effect of large distance modification of Newtonian potential on clustering of galaxies.
Inflation in the Rényi cosmology
Authors: Ghaffari S. , Ziaie A. H. , Bezerra V. B. , Moradpour H.
Published: September 2019

The description of the accelerated phases for the current and primordial cosmos has been obtained in the framework of Rényi cosmology. The results show that corrections to the Friedmann equations, originated from differences between Rényi and Bekenstein entropies, can describe both the current accelerated and inflationary eras. The effects of these corrections can be appointed to a hypothetical fluid which is classically unstable. Although inflation can be obtained in Rényi cosmology as the vacuum solution, the values found for the parameters of the hypothetical fluid which supports the current accelerated and primary inflationary cosmos differ from each other.
Redshift effect implications on revised models of Stephan’s Quintet
Authors: Abdelali Mohamed Lamine , Mebarki Noureddine
Published: September 2019

Recent observations of Stephan’s Quintet (SQ) gave new indications on its formation scenario. Older formation and role of NCG 7317 should be considered in revised numerical models of the compact group. Velocities of group members to recreate are estimated from redshift measurements. Several effects contribute to observed redshifts and a new effect is predicted to be the result of the gravitational interaction between photons and constant magnetic fields creating gravitational waves. The energy carried by these waves is manifested as redshifts of the photons. Cosmological simulation data are used to prove the significant contribution of our effect. The analysis of synthetic observations created from those simulations has shown that redshifts of SQ members could be misinterpreted as caused only from Doppler Effect. The revised models of the group should consider a new method to recreate the formation scenario based on redshift patterns and not mis-estimated velocities.
Testing of model predictions of forward energy flow in pp collisions at s = 7 TeV
Authors: Ajaz M. , Khan R. , Ali Y. , Suleymanov M. K.
Published: September 2019

We simulate proton–proton collisions to calculate the energy flow with four different classes of events: hard scattering, diffractive and non-diffractive enriched interactions and inclusive minimum bias. We use cosmic ray Monte Carlo event generator to determine the energy flow for the above-mentioned classes in pseudorapidity range 1.9[Formula: see text] 4.9 at [Formula: see text] = 7 TeV in pp collisions. A comparison of model predictions to the LHCb data, obtained with the same pseudorapidity and center-of-mass energy, is presented and discussed. While predictions of the models are compatible with the experimental measurements, none of them is able to completely reproduce all the results.
Interaction of manganese corroles with TCNQ and related acceptor molecules
Authors: Wolfram Benedikt , Baş Çağla , Kleeberg Christian , Bröring Martin
Published: September 2019

Manganese corroles with the Mn atom in the oxidation states +III and +IV have been probed as donor moieties for supramolecular stacked donor–acceptor complexes with the typical acceptor units TCNQ (tetracyanoquinone), TCNP (tetracyanopyrazine), and TCNB (tetracyanobenzene). Four new compounds formed as single crystals from different co-crystallization attempts. In those cases where a Mn(III) corrole was used as the donor component, hydrolyzed and/or oxygenated compounds [(cor)Mn(TCNQ*)] and [(cor*)Mn(TCNP*)] were obtained as the exclusive products. With chloridomanganese(IV) corroles, sandwich-like 2:1 complexes [(cor)MnCl][Formula: see text][TCNQ] and [(cor)MnCl][Formula: see text][TCNB] form, with both components left intact. Crystallographic analyses reveal partial or complete charge transfer to unusual axial ligands and thus prove the high reactivity of Mn(III) corroles in the first two cases. For the sandwich arrangements, almost-unaltered geometric parameters of the Mn(IV) corroles are observed, pointing to negligible structural consequences for metal corroles when engaged in stacking interactions.
BODIPY substituted zinc(II) phthalocyanine and its bulk heterojunction application in solar cells
Authors: Ömeroğlu İpek , Şenocak Ahmet , Yetkin Hazel , Güney H. Yüksel , Demirbaş Erhan , Durmuş Mahmut
Published: September 2019

A novel asymmetrical zinc(II) phthalocyanine-BODIPY conjugate (ZnPc-BODIPY) bearing three iodine groups directly substituted to the macrocycle and one BODIPY connected to the macrocycle with an amide bond was synthesized by the reaction of carboxylic-acid-substituted asymmetrical zinc(II) phthalocyanine (ZnPc) with the BODIPY-derivative-bearing amino group (BODIPY-NH2). This conjugate was fully characterized by spectroscopic methods (FT-IR, UV-vis, 1H NMR, 11B NMR, 19F NMR and mass) and elemental analysis. The fluorescence behavior of ZnPc-BODIPY was studied to determine the energy transfer process. Voltammetry measurements (CV and SWV) were performed to specify the HOMO–LUMO energy levels and band gaps of ZnPc-BODIPY and starting compounds (ZnPc and BODIPY-NH2) for comparison. In addition, the band gaps of these compounds were also determined by UV-vis absorption onset (λonset) and theoretical calculations. Bulk heterojunction solar cells containing ZnPc-BODIPY were fabricated in the structure of ITO/PEDOT:PSS/ZnPc-BODIPY:PCBM/Al. The photovoltaic parameters of the solar cell were obtained and the ZnPc-BODIPY conjugate was found to bring spectral contribution to IPCE at a peak of 510 nm.
Spin-Polarized Currents Induced by Multichannel Magnetic Point Contacts
Authors: Fallahi Vahid , Nazari-Golshan Akbar
Published: September 2019

We consider theoretically the spin blockade effect on the spin polarization of a current passing through a geometrically confined head-to-head 180∘ domain wall at a magnetic point contact in a two-dimensional (2D) metallic nanowire. The analysis is based on coherent scattering of the carriers by spin-dependent potential associated with the wall structure. The transmission properties of coherent states are obtained by introducing an algorithm to solve the coupled spin channels Schrödinger equation with mixed Dirichlet–Neumann boundary conditions applied far from the domain wall. It has been shown that a domain wall separating two media of opposite magnetization direction can act as a spin filter, allowing controllable modification of the spin polarization via the wall width.
Detailed internal structure and along-strike variability of the core of a plate boundary fault: the Highland Boundary fault, Scotland
Authors: McKay Lucy , Shipton Zoe K. , Lunn Rebecca J. , Andrews Billy , Raub Timothy D. , Boyce Adrian J.
Published: September 2019

The Highland Boundary fault near Stonehaven, NE Scotland, provides a rare opportunity to study the internal fault structure of a well-exposed, along-strike section of an ancient plate boundary fault. As in many plate boundaries, serpentinite juxtaposes quartzo-feldspathic crustal rocks of distinct terranes. We report, for the first time, the complex internal structure of the Highland Boundary fault core, comprised of four structurally and chemically distinct clay-rich units that remain unmixed. Despite the evidence for internal strain, relatively intact clasts of wall rock and microfossils are preserved within the clay. The fault core clay minerology is consistent with a shallow, low-temperature authigenesis derived from shear-enhanced chemical reactions between wall rocks of contrasting chemistry during sinistral strike-slip. The observed structure is comparable to those of other major weak-cored plate boundaries (e.g. the San Andreas fault). Through detailed mapping, we demonstrate that the internal structure of a plate boundary fault core can vary in thickness and composition along-strike over centimetre- to metre-length scales.

Earthquake rupture mechanics critically depend on the physical properties of fault rock assemblages. Therefore, models that investigate rupture propagation at active plate boundaries should incorporate, or else assess tolerance and sensitivity to, variable fault core thickness and composition.

Supplementary material
: Further X-ray diffraction (XRD) analytical data are available at
https://doi.org/10.6084/m9.figshare.c.4663640
Role of adipokine zinc-α2-glycoprotein in coronary heart disease
Authors: Huang Dandan , Mao Xiaoxiang , Peng Jiangtong , Cheng Min , Bai Tao , Du Meng , Huang Kun , Liu Bing , Yang Liu , Huang Kai , Zhang Fengxiao
Published: September 2019

Zinc-α2-glycoprotein (AZGP1) is a newly identified adipokine that is associated with lipid metabolism and vascular fibrosis. Although adipokines contribute to lipid dysfunction and its related diseases, including stroke and coronary heart disease (CHD), the role of AZGP1 remains unclear. In this study, the role of AZGP1 in atherosclerosis and CHD was investigated. Serum AZGP1 levels from control ( n = 84) and CHD ( n = 91) patients were examined by ELISA and its relationship with various clinical parameters was analyzed. Immunohistochemistry and immunofluorescence were used to detect the expression of AZGP1 and its receptor in coronary atherosclerotic arteries. THP-1 and human embryonic kidney 293 cells were used to verify its anti-inflammatory role in atherosclerosis. Serum AZGP1 levels in CHD patients were lower than controls ( P < 0.01) and independently associated with CHD prevalence ( P = 0.021). AZGP1 levels also inversely correlated with the Gensini score. Immunohistochemistry and immunofluorescence showed that AZGP1 and its receptor β3-adrenoceptor (β3-AR) colocalized in lipid-rich areas of atherosclerotic plaques, particularly around macrophages. In vitro, AZGP1 had no effect on foam cell formation but showed anti-inflammatory effects through its regulation of JNK/AP-1 signaling. In summary, AZGP1 is an anti-inflammatory agent that can be targeted for CHD treatment.
Chemical and Noble Gas Isotope Compositions of Formation Gases from a 3 km Deep Scientific Borehole in the Koyna Seismogenic Zone, Western India
Authors: Podugu Nagaraju , Mishra Satrughna , Wiersberg Thomas , Roy Sukanta
Published: September 2019

A 3 km deep research borehole KFD1 was drilled in the Koyna reservoir-triggered seismicity region, Western India, between December 2016 and May 2017. The 1967M6.3 Koyna earthquake had generated a NNE-SSW trending surface fissure zone in the Nanel-Donichawadi-Kadoli sector. KFD1 is located ~5 km south of Kadoli along the trend of the Donichawadi fault zone. Online gas monitoring was carried out during drilling of KFD1 from 1315 m to 2831 m depth to sample and study the composition of crustal gases. Formation gases CO2, CH4, H2, and He were only observed during water flushing of ~100 m intervals following coring runs. Laboratory analyses of gas samples collected between 1737 m and 2831 m depth revealed concentrations of up to 1200 ppmv CO2, 186 ppmv CH4, 139 ppmv H2, and 12.8 ppmv He. Zones enriched in gases are mostly below the 2100 m depth with significant He enhancement ranging from 4.6 to 7.6 ppmv above the atmospheric value. The He-rich zones correlate well with the zones of anomalous physical and mechanical properties identified from geophysical logs and are characterized by high fracture density as revealed from borehole images, indicating that the borehole punctured multiple fracture zones. The helium concentrations are consistent with those previously observed over the surface fissures near Kadoli, suggesting a southward extension of the Donichawadi fault zone up to the KFD1 site and confirming that the fault zone is permeable even after 50 years of the 1967 Koyna earthquake.3He/4He ratios of eleven gas samples fall between0.426±0.022and0.912±0.059 Ra, with4He/20Ne values between0.3449±0.0091and0.751±0.020. Air-corrected helium isotope ratios indicate that helium is a mixture of atmospheric and crustal radiogenic components but no mantle contribution within 2σanalytical uncertainties.
Control Design of the Wave Compensation System Based on the Genetic PID Algorithm
Authors: Zhou Mingjian , Wang Yuqin , Wu Haibing
Published: September 2019

The transfer function of the wave compensation system is deduced. The interference signal acting on the system is eliminated by the feed-forward compensation correction method. The pole assignment of the system is carried out after eliminating the interference signal. The genetic PID algorithm is proposed, and the genetic PID controller is designed. The control block diagram of the wave compensation system based on the genetic PID control algorithm is established, and the optimal index and PID parameters are optimized by the crossover and mutation operators of the genetic particle swarm optimization algorithm. The simulations and experiments of the system show that the control performance of the wave compensation system based on the genetic PID algorithm is greatly improved. The higher control precision is obtained. The anti-interference ability and the robustness of the system are increased. The accuracy of the control method is verified.
Psychometric Testing of the CHAMPS Questionnaire in French Canadians with COPD
Authors: Mak Susanne , Bourbeau Jean , Mayo Nancy E. , Wood-Dauphinee Sharon , Soicher Judith E.
Published: September 2019

Physical activity is an important health behaviour in reducing morbidity and mortality in individuals with chronic obstructive pulmonary disease (COPD). Accurate measurement of the characteristics of physical activity is essential to understanding the impact of COPD on physical activity. In a previous article, we reported on the cross-cultural adaptation of the Community Healthy Activities Model Program for Seniors (CHAMPS) questionnaire to produce a Canadian French version. The CHAMPS yields four summary scores: two caloric expenditure scores (moderate-intensity activities and all activities) and two frequency scores (moderate-intensity activities and all activities). The objective of this study was to evaluate test-retest reliability and convergent construct validity, in both English and French versions of the CHAMPS, in individuals with COPD. Test-retest reliability was assessed by administering the CHAMPS at two visits (2-3 weeks apart), to 19 English-speaking and 18 French-speaking participants. Validity was assessed in 56 English-speaking and 74 French-speaking participants, who completed the CHAMPS, Short Form- (SF-) 36, and St. George’s Respiratory Questionnaire (SGRQ) at a single visit. Results from reliability testing indicated that intraclass correlation coefficients (ICCs) generally met the threshold for good reliability (ICC > 0.6), with frequency scores showing greater stability than caloric expenditure scores. Validity testing yielded moderate correlations (r = 0.4-0.5) of the CHAMPS with the SF-36 domains and summary score capturing constructs of physical function, and with the SGRQ activity domain and total score. CHAMPS frequency scores for moderate-intensity activities correlated more strongly than other scores, with physical aspects of the SF-36 and SGRQ. The English and French versions of the CHAMPS did not show any substantial differences in reliability (frequency scores) or validity (frequency and caloric expenditure scores). Findings from this study support the reliability and validity of the CHAMPS. In particular, frequency scores for moderate-intensity activities can provide useful information on physical activity levels in individuals with COPD. This trial is registered with NCT00169897. ISRCTN registration number: IRSCTN32824512.
The Effect of Adipose-Derived Stem Cells on Wound Healing: Comparison of Methods of Application
Authors: Kim Hyeonwoo , Hyun Mi Ri , Kim Sang Wha
Published: September 2019

Impaired wound healing is a significant medical problem. Recently, cell-based therapy focused on stem cells has been developed to overcome the challenges of defective wound healing. In this study, we aimed to evaluate the effectiveness of adipose-derived stem cells (ASCs) in promoting wound healing, using different techniques for administering them. Dorsal full-thickness skin defects (1×1 cm) were created in three groups of mice that received intravenous ASCs by intravenous injection, intramuscular injection, and topical application, respectively. Three control groups received saline in the same ways. Wound healing was assessed clinically, wounds were examined histologically, and GFP-labelled ASCs were detected with an IVIS imaging system. The results revealed that ASCs accelerated wound healing independent of their mode of administration. Histological examination showed that the ASCs accelerated reepithelialization, and IVIS analysis indicated that many ASCs were present in the wound area and disappeared after wound healing.
Risk Control Technology for Water Inrush during the Construction of Deep, Long Tunnels
Authors: Liu Yiming , Xia Yuanpu , Lu Hao , Xiong Ziming
Published: September 2019

Water inrush is one of the main disasters occurring during tunnel construction in complex geological areas: once it happens, it can cause economic losses, casualties, and delay. Based on risk analysis and management, a risk control scheme is proposed as an effective means to control the risk of such a disaster; however, there are some deficiencies in existing research because the impacts of human factors on the risk of water inrush, dynamic changes in risk information during construction, and the diversity of types of water inrush are neglected. To enrich the research results of water inrush risk control and improve the effect of water inrush risk control, we first use the advantages of Bayesian network to analyse risk events, construct a Bayesian network structure chart of water inrush risk during construction, and propose a fuzzy probability risk analysis model for water inrush. The model can quickly track changes in risk information and diagnose the cause of water inrush disasters while providing an early warning thereof. In addition, considering that the diversity of water inrush types leads to differences in water inrush mechanisms, we believe that the formulation of any water inrush risk control scheme must be combined with water inrush mechanism analysis; therefore, we take a nondefect generated water inrush in front of the tunnel as a representative case and analyse the possible mechanism of water inrush through the stability analysis of the water‐resisting strata. Then, based on the results of risk analysis and an analysis of the water inrush mechanism, a reasonable risk control scheme for water inrush is derived.
Conceptual Design of Spacesuit Hard Hip Joint
Authors: Zhen-wei Wang , Peng Chen , Dan-lan Lin
Published: September 2019

Spacesuit hip joint plays an important role on astronaut activities, such as planetary walking and surveying. This paper proposes a conceptual design of hard hip joint in consideration of the coupling effect of spacesuit hip joint and astronaut thigh. Firstly, lower extremity activities are introduced to illustrate the mobility of hard hip joint, such as walking, kneeing, and abduction. A conceptual design of hard hip joint is explained in detail, including geometric structure, components, design parameters, and mechanism models. Secondly, a 3-linkage coupling mechanism model is built up by synthesizing that conceptual design of hard hip joint. An equiangular dual-perpendicular representation method is brought out to parameterize that mechanism model of hard hip joint. Particularly, four geometric constraints are, respectively, given out to avoid impact between the hip joint and the thigh and to ensure the continuity of thigh motion. Finally, motion equations of hip joint parts are established by using coordinate transformation and vector representation. A case study is conducted to verify the correctness of the proposed representation method and that coupling mechanism model.
Exploring the Diagnostic Potential of Serum Golgi Protein 73 for Hepatic Necroinflammation and Fibrosis in Chronic HCV Infection with Different Stages of Liver Injuries
Authors: Qian Xiangjun , Zheng Sujun , Wang Leijie , Yao Mingjie , Guan Guiwen , Wen Xiajie , Zhang Ling , Xu Qiang , Chen Xiangmei , Zhao Jingmin , Duan Zhongping , Lu Fengmin
Published: September 2019

Background and Aim. Serum Golgi protein 73 (GP73) is a promising alternative biomarker of chronic liver diseases, but most data are from patients with HBV infection rather than HCV. Materials and Methods. Two independent cohorts of chronic hepatitis C (CHC) patients from the 5th Medical Centre of the Chinese PLA General Hospital (n=174) and Beijing Youan Hospital (n=120) with different histories of HCV infection were enrolled. The correlations between serum GP73 and other biochemical indices, as well as its correlations with different stages of liver disease progression, were investigated. The receiver operating characteristic (ROC) curve was employed to evaluate the diagnostic potential of serum GP73 for liver necroinflammation and fibrosis, and comparisons of the diagnostic efficiency with traditional indices of hepatic liver injuries were further investigated. Results. Levels of serum GP73 were found significantly elevated in patients with moderate to severe inflammatory grade (G≥2) and/or with advanced fibrotic stages (F≥3) in both cohorts (P<0.05, respectively), as compared to those with a normal or mild liver lesion. Further ROC analysis demonstrated that serum GP73 was comparable to serum ALT and AST in diagnosing the liver necroinflammation grade at G≥2, but its diagnostic values for advanced fibrosis (F≥3) and cirrhosis (F=4) were limited when compared to APRI and FIB-4, and FIB-4 exhibited the best performance. Notably, an obvious elevation of serum GP73 was observed after patients received PEG-IFN and ribavirin treatment. Conclusions. Serum GP73 is an important biomarker in evaluating and monitoring the disease progression including liver necroinflammation and fibrosis in patients with chronic HCV infection, but the value is limited for diagnosing advanced fibrosis and cirrhosis in comparison with APRI and FIB-4.
Network Pharmacology Reveals the Molecular Mechanism of Cuyuxunxi Prescription in Promoting Wound Healing in Patients with Anal Fistula
Authors: Qu Yin , Zhang Zhijun , Lu Yafeng , Zheng De , Wei Yang
Published: September 2019

Background. The healing process of the surgical wound of anal fistulotomy is much slower because of the presence of stool within the wound. Cuyuxunxi (CYXX) prescription is a Chinese herbal fumigant that is being used to wash surgical wound after anal fistulotomy. This study aimed at investigating the molecular mechanism of CYXX prescription using a network pharmacology-based strategy. Materials and Methods. The active compounds in each herbal medicine were retrieved from the traditional Chinese medicine systems pharmacology (TCMSP) database and in Traditional Chinese Medicine Integrated Database (TCMID) analysis platform based on the criteria of oral bioavailability ≥40% and drug-likeness ≥0.2. The disease-related target genes were extracted from the Comparative Toxicogenomics Database. Protein-protein interaction network was built for the overlapped genes as well as functional enrichment analysis. Finally, an ingredient-target genes-pathway network was built by integrating all information. Results. A total of 375 chemical ingredients of the 5 main herbal medicines in CYXX prescription were retrieved from TCMSP database and TCMID. Among the 375 chemical ingredients, 59 were active compounds. Besides, 325 target genes for 16 active compounds in 3 herbal medicines were obtained. Functional enrichment analysis revealed that these overlapped genes were significantly related with immune response, biosynthesis of antibiotics, and complement and coagulation cascades. A comprehensive network which contains 133 nodes (8 disease nodes, 3 drug nodes, 8 ingredients, 103 target gene nodes, 7 GO nodes, and 4 pathway nodes) was built. Conclusion. The network built in this study might aid in understanding the action mechanism of CYXX prescription at molecular level to pathway level.
Early- and Late-Onset Preeclampsia: A Comprehensive Cohort Study of Laboratory and Clinical Findings according to the New ISHHP Criteria
Authors: Wójtowicz Anna , Zembala-Szczerba Małgorzata , Babczyk Dorota , Kołodziejczyk-Pietruszka Monika , Lewaczyńska Olga , Huras Hubert
Published: September 2019

Recently, the diagnostic criteria of preeclampsia have been changed. No studies are available in the literature that analyzed in detail the differences between early-onset preeclampsia (EOP) and late-onset preeclampsia (LOP), taking into account the International Society for the Study of Hypertension in Pregnancy (ISSHP) criteria. Thus, we sought to retrospectively investigate in detail the differences in clinical and laboratory outcomes between EOP and LOP diagnosed according to the ISSHP criteria. A retrospective cohort study was conducted in 214 women with singleton pregnancies and preeclampsia admitted to the Department of Obstetrics and Perinatology of the University Hospital in Kraków, Poland, from 2013 to 2017 (113 (52.8%) women with EOP and 101 (47.2%) women with LOP). Electronic medical records were reviewed for demographics and medical history, laboratory tests, and delivery and neonatal data. Patients with preeclampsia accounted for 1.7% of the women who delivered during the study period. The EOP and LOP groups did not differ in the distribution of risk factors for preeclampsia. The most common risk factor was primiparity, which was observed in 72.0% of cases. Regarding the ISSHP diagnostic criteria, the two groups differed in the incidence of fetal growth restriction (p=0.0009), hemolysis (p=0.0416), and neurological complications (p=00342), which were found more often in the EOP group. In addition, the EOP group had more frequent occurrence of severe cardiorespiratory (p<0.0001) and hematological (p=0.0127) complications, adverse fetoplacental conditions (p<0.0001), and severe fetoplacental complications (p=0.0003). Children born to women with EOP had lower Apgar scores (p<0.001) and higher rates of intraventricular hemorrhage (p<0.0001), respiratory disorders requiring mechanical ventilation (p<0.0001), and early (p=0.0004) and late sepsis (p=0.002). EOP differed from LOP in terms of maternal and perinatal adverse outcomes. The observed higher rates of fetoplacental adverse conditions and severe complications indicate a significant contribution of impaired placentation to the etiopathogenesis of EOP.
Molecular Profiles of Cell-to-Cell Variation in the Regenerative Potential of Mesenchymal Stromal Cells
Authors: O’Connor Kim C.
Published: September 2019

Cell-to-cell variation in the regenerative potential of mesenchymal stromal cells (MSCs) impedes the translation of MSC therapies into clinical practice. Cellular heterogeneity is ubiquitous across MSC cultures from different species and tissues. This review highlights advances to elucidate molecular profiles that identify cell subsets with specific regenerative properties in heterogeneous MSC cultures. Cell surface markers and global signatures are presented for proliferation and differentiation potential, as well as immunomodulation and trophic properties. Key knowledge gaps are discussed as potential areas of future research. Molecular profiles of MSC heterogeneity have the potential to enable unprecedented control over the regenerative potential of MSC therapies through the discovery of new molecular targets and as quality attributes to develop robust and reproducible biomanufacturing processes. These advances would have a positive impact on the nascent field of MSC therapeutics by accelerating the development of therapies with more consistent and effective treatment outcomes.
Effects of Rainfall Intensity and Vegetation Cover on Erosion Characteristics of a Soil Containing Rock Fragments Slope
Authors: Zhao Bingqin , Zhang Lun , Xia Zhenyao , Xu Wennian , Xia Lu , Liang Yongzhe , Xia Dong
Published: September 2019

Rainfall events coupled with shallow and gravelly sloping farmland have led to serious soil erosion and associated problems in the Three Gorges reservoir. Previous studies have shown that the use of vegetation is an effective way to control soil erosion. Therefore, an artificial, simulated rainfall experiment study is conducted to determine the effect of rainfall intensity and vegetation cover on runoff volume, sediment load, and runoff hydraulics characteristics. The experiment consists of seven vegetation treatments subjected to three rainfall intensities on a soil that contains rock fragments on a slope of 30°. The results indicate that the runoff volume and sediment load of the bare plot were greater than those of vegetation‐covered plots under three different rainfall intensities. When Cynodon dactylon and Indigofera amblyantha were applied together, the plot displayed the best performance for soil loss control, with a reduction of 87.88%–99.11%. According to a redundancy analysis, the change in rainfall intensity had the least impact on the Reynolds number and the runoff volume of the herb‐shrub mixed plot in this study. These findings suggest that the effect of combining Cynodon dactylon and Indigofera amblyantha and increasing the vegetation coverage is an effective solution for soil and water loss conservation. The application of this method can alleviate environmental stress on the Three Gorges reservoir.
CRISPR/Cas9 Knockout of Bak Mediates Bax Translocation to Mitochondria in response to TNFα/CHX-induced Apoptosis
Authors: Zhang Jingtian , Niu Han , Zhao Zhizhuang Joe , Fu Xueqi , Wang Yuxiang , Zhang Xu , Zhang Fuqiang , Zeng Linlin
Published: September 2019

TNFα/CHX-induced apoptosis is dependent on caspase-8 activation and regulated by Bcl-2. However, the specific participants and precise mechanisms underlying this apoptotic pathway are poorly understood. The proapoptotic proteins Bak and Bax—members of the Bcl-2 family—are essential for the functioning of the mitochondrial apoptotic pathway. In this study, we used the CRISPR/Cas9 system to knockout Bak in the human SH-SY5Y cell line and determined the effects of this knockout on TNFα/CHX-induced apoptosis. Our data showed that overexpression of Bcl-2 dramatically prevented TNFα/CHX-induced apoptosis, and then pro-apoptotic protein Bak was downregulated and became more resistant to TNFα/CHX-induced apoptosis, because both TNFα/CHX-induced PARP cleavage and caspase activation were blocked in BAK−/− cells or using specific siRNA, whereas Bax was dispensable in TNFα/CHX-induced apoptosis, as evidenced using specific siRNA. Bax translocated from the cytosol into the mitochondria in response to TNFα/CHX, and CRISPR/Cas9 knockout of Bak significantly decreased this translocation. These results indicate that TNFα/CHX-induced apoptosis does not occur in Bak−/− cells, suggesting that TNFα/CHX-induced apoptosis is Bak-dependent but Bax-independent.
Lysosomal Destabilizing Drug Siramesine and the Dual Tyrosine Kinase Inhibitor Lapatinib Induce a Synergistic Ferroptosis through Reduced Heme Oxygenase-1 (HO-1) Levels
Authors: Villalpando-Rodriguez Gloria E. , Blankstein Anna R. , Konzelman Carmen , Gibson Spencer B.
Published: September 2019

Ferroptosis is an iron-dependent type of cell death distinct from apoptosis or necrosis characterized by accumulation of reactive oxygen species. The combination of siramesine, a lysosomotropic agent, and lapatinib, a dual tyrosine kinase inhibitor (TKI), synergistically induced cell death in breast cancer cells mediated by ferroptosis. In this study, we showed that this combination of siramesine and lapatinib induces synergistic cell death in glioma cell line U87 and lung adenocarcinoma cell line A549. This cell death was characterized by the increase in iron content, reactive oxygen species (ROS) production, and lipid peroxidation accumulation after 24 hours of treatment. Moreover, iron chelator DFO and ferrostatin-1, a ferroptosis inhibitor, significantly reduced cell death. The mechanism underlying the activation of the ferroptotic pathway involves lysosomal permeabilization and increase in reactive iron levels in these cells. In addition, the downregulation of heme oxygenase-1 (HO-1) protein occurred. Overexpression of HO-1 resulted in reduction of ROS and lipid peroxidation production and cell death. Furthermore, knocking down of HO-1 combined with siramesine treatment resulted in increased cell death. Finally, we found that the inhibition of the proteasome system rescued HO-1 expression levels. Our results suggest that the induction of ferroptosis by combining a lysosomotropic agent and a tyrosine kinase inhibitor is mediated by iron release from lysosomes and HO-1 degradation by the proteasome system.
Therapeutic Targeting of TGFβ Ligands in Glioblastoma Using Novel Antisense Oligonucleotides Reduces the Growth of Experimental Gliomas
Authors: Papachristodoulou Alexandros , Silginer Manuela , Weller Michael , Schneider Hannah , Hasenbach Kathy , Janicot Michel , Roth Patrick
Published: September 2019

Purpose:

Transforming growth factor (TGF)-β is expressed at high levels by glioma cells and contributes to the malignant phenotype of glioblastoma. However, its therapeutic targeting remains challenging. Here, we examined an alternative therapeutic approach of TGFβ inhibition using two novel phosphorothioate-locked nucleic acid (LNA)-modified antisense oligonucleotide gapmers, ISTH1047 and ISTH0047, which specifically target TGFβ1 and TGFβ2.

Experimental Design:

We characterized the effects of ISTH1047 and ISTH0047 on TGFβ1/2 expression, downstream signaling and growth of human LN-308, LN-229, and ZH-161 cells as well as murine SMA-560 glioma cells in vitro. Furthermore, we assessed their target inhibition and effects on survival in orthotopic xenogeneic and syngeneic rodent glioma models in vivo.

Results:

Both antisense oligonucleotides specifically silenced their corresponding target and abrogated SMAD2 phosphorylation in several glioma cell lines. Moreover, inhibition of TGFβ1 or TGFβ2 expression by ISTH1047 or ISTH0047 reduced the migration and invasiveness of LN-308 and SMA-560 glioma cells. Systemic antisense oligonucleotide administration to glioma-bearing mice suppressed TGFβ1 or TGFβ2 mRNA expression as well as the expression of the downstream target PAI-1 in orthotopic gliomas. Glioma-bearing mice had significantly prolonged survival upon systemic treatment with ISTH1047 or ISTH0047, which was associated with a reduction of intratumoral SMAD2 phosphorylation and, in a fully immunocompetent model, with increased immune cell infiltration.

Conclusions:

Targeting TGFβ expression with the novel LNA antisense oligonucleotides ISTH1047 or ISTH0047 results in strong antiglioma activity in vitro and in vivo, which may represent a promising approach to be examined in human patients with glioma.
Trabectedin Reveals a Strategy of Immunomodulation in Chronic Lymphocytic Leukemia
Authors: Banerjee Priyanka , Zhang Ronghua , Ivan Cristina , Galletti Giovanni , Clise-Dwyer Karen , Barbaglio Federica , Scarfò Lydia , Aracil Miguel , Klein Christian , Wierda William , Plunkett William , Caligaris-Cappio Federico , Gandhi Varsha , Keating Michael J. , Bertilaccio Maria Teresa S.
Published: September 2019

Chronic lymphocytic leukemia (CLL) is a B-cell neoplasia characterized by protumor immune dysregulation involving nonmalignant cells of the microenvironment, including T lymphocytes and tumor-associated myeloid cells. Although therapeutic agents have improved treatment options for CLL, many patients still fail to respond. Some patients also show immunosuppression. We have investigated trabectedin, a marine-derived compound with cytotoxic activity on macrophages in solid tumors. Here, we demonstrate that trabectedin induces apoptosis of human primary leukemic cells and also selected myeloid and lymphoid immunosuppressive cells, mainly through the TRAIL/TNF pathway. Trabectedin modulates transcription and translation of IL6, CCL2, and IFNα in myeloid cells and FOXP3 in regulatory T cells. Human memory CD8+ T cells downregulate PD-1 and, along with monocytes, exert in vivo antitumor function. In xenograft and immunocompetent CLL mouse models, trabectedin has antileukemic effects and antitumor impact on the myeloid and lymphoid cells compartment. It depletes myeloid-derived suppressor cells and tumor-associated macrophages and increases memory T cells. Trabectedin also blocks the PD-1/PD-L1 axis by targeting PD-L1+ CLL cells, PD-L1+ monocytes/macrophages, and PD-1+ T cells. Thus, trabectedin behaves as an immunomodulatory drug with potentially attractive therapeutic value in the subversion of the protumor microenvironment and in overcoming chemoimmune resistance.
Complete Clinical Response in Locally Advanced Metastatic de novo Breast Cancer after Front-Line Treatment with Ribociclib/Letrozole within the RIBANNA Study
Authors: Rudlowski Christian , Beermann Nina , Leitzen Lena , Nuding Benno
Published: September 2019

Introduction: Ribociclib is an orally bioavailable cyclin-dependent kinase 4/6 inhibitor. In combination with aromatase inhibitor letrozole, it has approval for treatment of hormone receptor positive (HR+) and human epidermal growth factor receptor 2-negative (HER2−) advanced breast cancer. First-line therapy with ribociclib + letrozole significantly improves progression-free survival compared to placebo + letrozole in patients with HR+/HER2− advanced breast cancer. In patients with de novo advanced or metastatic breast cancer, ribociclib was able to provide substantial clinical benefit according to data from the MONALEESA-2 study. Case Presentation: Here, we report the complete clinical response in a postmenopausal patient with de novo, locally advanced, pulmonary metastatic breast cancer treated with ribociclib + letrozole. Our patient presented an ulcerated breast-consuming tumor with multiple pulmonary metastases. HR+/HER2– breast cancer was confirmed by tumor biopsy. Ki67 expression was 90%. After three months of initial treatment, the tumor-associated ulcerations disappeared, and no measurable pulmonary disease was detectable on CT scan. Treatment was well tolerated, and after dosage reduction due to neutropenia, no further side effects have been documented. At present, complete clinical response remains after 15 months of ongoing treatment. Conclusion: This case report documents an exceptional tumor response of a fast growing, locally advanced, pulmonary metastatic HR+/HER2– de novo breast cancer treated by ribociclib/letrozole combination therapy. Treatment success was long lasting with few side effects. The patient was very satisfied with the treatment and had no specific restrictions in her daily life.