bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of sleep condition and social frailty in community‐dwelling older people
Authors: Nakakubo Sho , Doi Takehiko , Makizako Hyuma , Tsutsumimoto Kota , Kurita Satoshi , Kim Minji , Ishii Hideaki , Suzuki Takao , Shimada Hiroyuki
Published: July 2019

Aim

This cross‐sectional study examined whether sleep duration and excessive daytime sleepiness (EDS) were associated with social frailty in community‐dwelling older people.

Methods

A total of 4427 community‐dwelling older people (51.4% women, mean age 71.9 years) who met the entry criteria were included in this study. Social frailty was assessed by five questions, relating to going out less frequently than last year, not visiting friends sometimes, not feeling helpful to friends or family, living alone and not talking with someone every day. Participants with two or more components were defined as having social frailty. Sleep duration and EDS were assessed by self‐reported questionnaire. Logistic regression analysis estimated odds ratios and 95% confidence intervals of social frailty according to EDS or the three categories of sleep duration (short ≤6.0 h, medium 6.1–8.9 h, long ≥9.0 h), and we used medium‐duration sleepers as the reference group.

Results

Among all participants, the prevalence of social frailty in each sleep duration group was as follows: long 18.3%, short 9.9% and medium 9.7% (P < 0.001). The prevalence of social frailty in participants with EDS was 17.1% (no EDS 10.2%, P < 0.001). Long sleep duration (odds ratio 1.46, 95% confidence interval 1.14–1.84) and presence of EDS (hazard ratio 1.32, 95% confidence interval 1.02–1.71) were associated with higher rates of social frailty after adjustments for several covariates.

Conclusions

Long sleep duration and EDS were associated with social frailty; thus, older people with both sleep patterns would have a higher risk of progression of social frailty. Geriatr Gerontol Int 2019; 19: 885–889.
Evaluating the prognostic potential of the Ki67 proliferation index and tumour‐infiltrating lymphocytes in olfactory neuroblastoma
Authors: Classe Marion , Burgess Alice , El Zein Sophie , Wassef Michel , Herman Philippe , Mortuaire Geoffrey , Leroy Xavier , Malouf Gabriel G , Verillaud Benjamin
Published: July 2019

Aims

Olfactory neuroblastomas (ONBs) are rare malignant tumours that arise in the nasal vault. To date, the Hyams grade remains the only widely used histological grading system. However, it is based only on morphological criteria, and has not been updated since 1988. The objective of this study was to explore the prognostic potential of the Ki67 proliferation index (PI) and tumour‐infiltrating lymphocytes (TILs) in ONB.

Methods and results

A retrospective study was conducted on a bicentric series of 45 cases. The Ki67 PI was determined by counting at least 1000 nuclei on whole slides. TILs were evaluated with CD20, CD4 and CD8 immunohistochemical markers on whole slides. In this series, Hyams grades I, II, III and IV accounted for 13.4%, 44.4%, 20% and 22.2% of all cases, respectively. The Ki67 PI ranged from 1 to 93; the Ki67 PI was significantly higher in Hyams grade III–IV ONBs than in Hyams grade I–II ONBs (P < 0.0001). A Ki67 PI of ≥25 was associated with poorer survival (P = 0.02). TILs were present in both stromal and intratumoral compartments, but were located predominantly in the stromal component of the tumour. The numbers of intratumoral CD8+ cells/mm2 and CD4+ cells/mm2 were greater in high‐grade ONBs than in low‐grade ONBs (P = 0.0015 and P = 0.043, respectively). The numbers of T cells/mm2 and B cells/mm2 were not associated with survival, but a CD4/CD8 ratio of >2 was significantly associated with shorter survival (P = 0.04).

Conclusion

Our findings suggest that the Ki67 PI and TILs could be used as prognostic markers, as a potential alternative to the Hyams grade.
Demographic Data on Syrians in Turkey: What do we know?
Authors: Adalı Tuğba , Türkyılmaz Ahmet Sinan
Published: July 2019

With the outbreak of civil war in Syria, Turkey has become the host of the largest refugee population in the world. In a country where reliable population registration systems are only recently established and where no extensive legal arrangements on migration existed prior to the Syrian crisis, the whole refugee situation was handled rather unsystematically, with ever‐changing institutions and regulations, and various iterations of both. In this paper we present the demographic statistics that have been made public by different sources from the beginning of the crisis up to today because they are hard to reach in one place accompanied by relevant institutional changes; with the aim of assessing the current demographic data and revealing what is missing.
A Unifying Framework and Comparison of Algorithms for Non‐negative Matrix Factorisation
Authors: Hobolth Asger , Guo Qianyun , Kousholt Astrid , Jensen Jens Ledet
Published: July 2019

Non‐negative matrix factorisation (NMF) is an increasingly popular unsupervised learning method. However, parameter estimation in the NMF model is a difficult high‐dimensional optimisation problem. We consider algorithms of the alternating least squares type. Solutions to the least squares problem fall in two categories. The first category is iterative algorithms, which include algorithms such as the majorise–minimise (MM) algorithm, coordinate descent, gradient descent and the Févotte‐Cemgil expectation–maximisation (FC‐EM) algorithm. We introduce a new family of iterative updates based on a generalisation of the FC‐EM algorithm. The coordinate descent, gradient descent and FC‐EM algorithms are special cases of this new EM family of iterative procedures. Curiously, we show that the MM algorithm isnevera member of our general EM algorithm. The second category is based on cone projection. We describe and prove a cone projection algorithm tailored to the non‐negative least square problem. We compare the algorithms on a test case and on the problem of identifying mutational signatures in human cancer. We generally find that cone projection is an attractive choice. Furthermore, in the cancer application, we find that a mix‐and‐match strategy performs better than running each algorithm in isolation.
Long non‐coding RNA NR2F1‐AS1 promoted proliferation and migration yet suppressed apoptosis of thyroid cancer cells through regulating miRNA‐338‐3p/CCND1axis
Authors: Guo Feng , Fu Qingfeng , Wang Yang , Sui Guoqing
Published: July 2019

Thyroid cancer (TC) is a prevalent endocrine malignant cancer whose pathogenic mechanism remains unclear. The aim of the study was to investigate the roles of long non‐coding RNA (lncRNA) NR2F1‐AS1/miRNA‐338‐3P/CCND1axis in TC progression. Differentially expressed lncRNAs and mRNAs in TC tissues were screened out and visualized by R program. Relative expression of NR2F1‐AS1, miRNA‐338‐3p and cyclin D1 (CCND1) was determined by quantitative real time polymerase chain reaction. In addition, Western blot analysis was adopted for evaluation of protein expression ofCCND1. Targeted relationships between NR2F1‐AS1 and miRNA‐338‐3p, as well as miRNA‐338‐3p andCCND1were predicted using bioinformatics analysis and validated by dual‐luciferase reporter gene assay. Besides, tumour xenograft assay was adopted for verification of the role of NR2F1‐AS1 in TC in vivo. NR2F1‐AS1 andCCND1were overexpressed, whereas miRNA‐338‐3p was down‐regulated in TC tissues and cell lines. Down‐regulation of NR2F1‐AS1 andCCND1suppressed proliferation and migration of TC cells yet greatly enhanced cell apoptotic rate. Silence of NR2F1‐AS1 significantly suppressed TC tumorigenesis in vivo. NR2F1‐AS1 sponged miRNA‐338‐3p to up‐regulateCCND1expression to promote TC progression. Our study demonstrated that up‐regulation of NR2F1‐AS1 accelerated TC progression through regulating miRNA‐338‐3P/CCND1axis.
Virucidal effects of common disinfectants against tilapia lake virus
Authors: Jaemwimol Phitchaya , Sirikanchana Kwanrawee , Tattiyapong Puntanat , Mongkolsuk Skorn , Surachetpong Win
Published: July 2019

Tilapia lake virus (TiLV) is an emerging virus associated with high fish mortality and economic losses. This study investigates the virucidal effects of the following disinfectants (active ingredients) on TiLV: 2.5 ppm iodine, 10 ppm sodium hypochlorite (NaOCl), 300 ppm hydrogen peroxide (H2O2), 80 ppm formalin and 5,000 ppm (0.5%) Virkon®. Factors that affect the disinfectants’ efficacy, including temperature, contact time and soiling (organic matter) interference, were examined under conditions mimicking natural aquaculture practices. TiLV inactivation of higher than 5 log10 TCID50 ml−1 was achieved after 10 min and at 28°C for all disinfectants except formalin; similar inactivation levels were reached by NaOCl and Virkon® at 10 min and 4°C. Extended exposure to formalin from 10 to 60 min at 28°C rendered more than 5 log10 inactivation. Increasing synthetic organic matter in the water to mimic soiling interference reduced the efficacy of NaOCl, iodine and H2O2 when tested at 10 min and 28°C; however, Virkon® still achieved more than 5 log10 inactivation. This study demonstrates that most common disinfectants effectively reduced viral loads to minimum levels. To limit the spread of TiLV in aquaculture farms and related facilities, the appropriate use of such disinfectants should therefore be promoted and implemented.
Usefulness of immunohistochemistry for mismatch repair protein and microsatellite instability examination in adenocarcinoma and background endometrium of sporadic endometrial cancer cases
Authors: Saeki Harumi , Hlaing May T. , Horimoto Yoshiya , Kajino Kazunori , Ohtsuji Naomi , Fujino Kazunari , Terao Yasuhisa , Hino Okio
Published: July 2019

Aim

Microsatellite instability (MSI), which reflects loss of DNA mismatch repair (MMR) activity, and immunohistochemistry (IHC) for MMR proteins are employed as screening examinations for Lynch syndrome (LS). Recent studies revealed that there is a population of MSI‐high tumors in sporadic endometrial cancer (EC). However, MSI data for Japanese EC patients are scarce. Furthermore, sporadic estrogen‐dependent EC (type I) is generally considered to arise from hyperplasia. Because LS is usually associated with type I EC, we hypothesized that MSI might be involved in the oncogenic process in some sporadic EC. We conducted MSI testing to reveal MSI status in sporadic Japanese EC. IHC for MMR proteins was also performed.

Methods

Ninety‐eight tissue samples of sporadic ECs from Japanese patients were used for IHC and MSI examinations. We also evaluated MMR protein expressions in the background normal endometrium.

Results

Microsatellite instability‐high was observed in 10.2% of 98 cases with sporadic EC, a lower percentage than that in Western studies. Loss of some MMR proteins was observed in 23 cases (23.5%) and there was a significant correlation with MSI‐high status (P < 0.001). Concerning the background endometrium, two cases showed partial loss of MLH1 and PMS2, corresponding to adjacent EC lesions, suggesting that MMR deficiency may already be present in the background endometrium.

Conclusion

The MSI‐high rate was low in our Japanese cohort. Our data confirmed the usefulness of MMR protein assessment for MSI screening in Japanese EC patients. Furthermore, IHC of the background endometrium might reveal the mechanism of MSI‐high tumorigenesis.
White Matter Hyperintensities in Patients with Sporadic Hemiplegic Migraine
Authors: Nagarajan Elanagan , Bollu Pradeep C. , Manjamalai Sivaraman , Yelam Anudeep , Qureshi Adnan I.
Published: July 2019

BACKGROUND AND PURPOSE

To identify the differences in overall occurrence, location, and disease burden of white matter hyperintensities (WMH) in patients with sporadic hemiplegic migraine (SHM) and patients with migraine headaches.

METHODS

We included patients who met diagnostic criteria proposed by the third International Classification of Headache Disorders (ICHD‐3) for SHM and migraine headache. WMHs were identified using T2 fluid‐attenuated inversion recovery axial sequence and classified based upon the location. The disease burden was assessed using Scheltens visual rating scale.

RESULTS

Fifty patients met the diagnostic criteria for SHM and 100 patients for migraine headache. Patients in the study group were similar to the control group in terms of age (47.7 ± 12.2 years vs. 48.17 ± 9.7 years; P = .814) and gender (M: F; 14:36 vs. M: F 25:75; P = .693). WMH were found in 28 (56%) patients with SHM and 44 (44%) in patients with migraine headache. The proportion of patients with WMH was not different between the two groups (P = .166). On univariate analysis, the proportion of patients with WMH in parietal, occipital, and infratentorial regions was higher in patients with SHM. White matter burden determined by visual rating scale and proportion of patients with lesions ≥5 mm in diameter was also significantly higher in patients with SHM. On multivariate analysis, the WMH occurrence in the parietal lobe (P = .043) was found to be significantly higher in SHM.

CONCLUSIONS

The WMH occurrence in patients with SHM is significantly more in the parietal lobe when compared to those with migraine headaches. WMH burden was also higher in patients with SHM, and larger white matter lesions occurred more frequently in these patients with SHM (compared to ordinary migraineurs).
The prognostic role of tumour‐infiltrating lymphocytes in oral squamous cell carcinoma: A meta‐analysis
Authors: Huang Zhengxian , Xie Nan , Liu Haichao , Wan Yuehan , Zhu Yue , Zhang Ming , Tao Yifan , Zhou Han , Liu Xiqiang , Hou Jinsong , Wang Cheng
Published: July 2019

It has been suggested that tumour‐infiltrating lymphocytes (TILs) are associated with the progression of oral squamous cell carcinoma (OSCC). However, the prognostic value of TILs is inconclusive due to the heterogeneity of immune cells within the tumour microenvironment. In this meta‐analysis, we aimed to assess the prognostic value of TILs in OSCC. The PubMed, Cochrane, Embase, Scopus and Web of Science databases were searched up to April 20, 2019, and 33 studies were ultimately included in this meta‐analysis. Our pooled meta‐analysis showed that high infiltration of CD8+ TILs, CD45RO+ TILs and CD57+ TILs favoured better overall survival (OS). However, high infiltration of CD68+ macrophages and CD163+ macrophages was associated with poor prognosis in OSCC. These findings suggest that CD8+ TILs, CD45RO+ TILs, CD57+ TILs, CD68+ macrophages and CD163+ macrophages might serve as novel prognostic factors and therapeutic targets in OSCC.
Optimal consumption and investment with liquid and illiquid assets
Authors: Choi Jin Hyuk
Published: July 2019

I consider an optimal consumption/investment problem to maximize expected utility from consumption. In this market model, the investor is allowed to choose a portfolio that consists of one bond, one liquid risky asset (no transaction costs), and one illiquid risky asset (proportional transaction costs). I fully characterize the optimal consumption and trading strategies in terms of the solution of the free boundary ordinary differential equation (ODE) with an integral constraint. I find an explicit characterization of model parameters for the well‐posedness of the problem, and show that the problem is well posed if and only if there exists a shadow price process. Finally, I describe how the investor's optimal strategy is affected by the additional opportunity of trading the liquid risky asset, compared to the simpler model with one bond and one illiquid risky asset.
The ‘omnivorous badger dilemma’: towards an integration of nutrition with the dietary niche in wild mammals
Authors: Balestrieri Alessandro , Remonti Luigi , Saino Nicola , Raubenheimer David
Published: July 2019

Laboratory studies have demonstrated that, given plenty of food, many animals can achieve a species‐specific macronutrient intake target by selecting nutritionally balanced foods or combining complementary foods.

Wild‐living, broad‐scope omnivorous species often face great heterogeneity in the composition of available resources. Hence they may be precluded, either locally or seasonally, from meeting their nutritional preferences.

With the aim of shedding light on the nutritional niche breadth of a wild‐living omnivore, the European badger Meles meles, we reviewed available scat‐based studies on badger diet and applied right‐angled mixture triangles to examine the relationships between macronutrient availability and composition of diets.

Moreover, to assess the potential of scat analysis to investigate nutritional balancing, we analysed badger diet in two habitats of NW Italy, focusing on identifying the total weight of each food item ‘as ingested’ as accurately as possible.

The average macronutrient content of the European badger's diet comprised 40–45% protein‐energy, 30–35% lipid‐energy, and 20–25% carbohydrate‐energy. Macronutrient intake was not constant throughout the year, suggesting that, in some seasons, badgers may be unable to reach their macronutrient target, and that diet balancing is achieved over longer periods. The macronutrient selection strategy of badgers suggests that their feeding habits are close to those of obligate carnivorous mammals, although badgers were found to be more tolerant towards carbohydrates than obligate carnivores.

Macronutrient ratios as assessed by scat analysis matched well with those obtained by reviewing available data, confirming that meta‐analyses of diet studies can provide useful information on the macronutrient requirements of elusive wild mammals.
Clinical Applications of 3‐Dimensional Printing Technology in Hip Joint
Authors: Xia Run‐zhi , Zhai Zan‐jing , Chang Yong‐yun , Li Hui‐wu
Published: July 2019

Three‐dimensional (3D) printing is a digital rapid prototyping technology based on a discrete and heap‐forming principle. We identified 53 articles from PubMed by searching “Hip” and “Printing, Three‐Dimensional”; 52 of the articles were published from 2015 onwards and were, therefore, initially considered and discussed. Clinical application of the 3D printing technique in the hip joint mainly includes three aspects: a 3D‐printed bony 1:1 scale model, a custom prosthesis, and patient‐specific instruments (PSI). Compared with 2‐dimensional image, the shape of bone can be obtained more directly from a 1:1 scale model, which may be beneficial for preoperative evaluation and surgical planning. Custom prostheses can be devised on the basis of radiological images, to not only eliminate the fissure between the prosthesis and the patient's bone but also potentially resulting in the 3D‐printed prosthesis functioning better. As an alternative support to intraoperative computer navigation, PSI can anchor to a specially appointed position on the patient's bone to make accurate bone cuts during surgery following a precise design preoperatively. The 3D printing technique could improve the surgeon's efficiency in the operating room, shorten operative times, and reduce exposure to radiation. Well known for its customization, 3D printing technology presents new potential for treating complex hip joint disease.
Retrotransposon promoter of Ruby1 controls both light‐ and cold‐induced accumulation of anthocyanins in blood orange
Authors: Huang Ding , Yuan Yue , Tang Zhouzhou , Huang Yue , Kang Chunying , Deng Xiuxin , Xu Qiang
Published: July 2019

Blood orange is generally recognized to accumulate anthocyanins in its fruit pulp in a cold‐inducible manner. We observed that the fruit peel of blood orange can also accumulate anthocyanins under ample light conditions. Interestingly, purple pummelo can accumulate anthocyanins only in its fruit peel but not in its pulp. The mechanism underlying the tissue specificity of anthocyanin accumulation in citrus is unknown. Here, we show that the active promoter of Ruby1, a key activator of anthocyanin biosynthesis, is also light inducible in addition to its already known cold inducibility in blood orange. Electrophoretic mobility shift assays and transient expression assays showed that HY5 positively regulated the transcription of Ruby1 by binding to the G‐box motif (CACGTC). The tissue specificity of anthocyanin accumulation in the peel of purple pummelo may be due to the lack of a low temperature responsive element and a MYC binding site, which were shown to be involved in cold inducibility of CsRuby1 in blood orange by insertion of a long terminal repeat type retrotransposon in the promoter. These results bring new insights into the regulatory mechanism of anthocyanin biosynthesis in response to environmental stimuli and provide cis‐elements for genetic improvement of anthocyanin‐stable fruits rich in antioxidant metabolites.
Present knowledge and controversies, deficiencies, and misconceptions on nitric oxide synthesis, sensing, and signaling in plants
Authors: León José , Costa‐Broseta Álvaro
Published: July 2019

After 30 years of intensive work, nitric oxide (NO) has just started to be characterized as a relevant regulatory molecule on plant development and responses to stress. Its reactivity as a free radical determines its mode of action as an inducer of posttranslational modifications of key target proteins through cysteine S‐nitrosylation and tyrosine nitration. Many of the NO‐triggered regulatory actions are exerted in tight coordination with phytohormone signaling. This review not only summarizes and updates the information accumulated on how NO is synthesized, sensed, and transduced in plants but also makes emphasis on controversies, deficiencies, and misconceptions that are hampering our present knowledge on the biology of NO in plants. The development of noninvasive accurate tools for the endogenous NO quantitation as well as the implementation of genetic approaches that overcome misleading pharmacological experiments will be critical for getting significant advances in better knowledge of NO homeostasis and regulatory actions in plants.
Doppler sonography of uterine blood flow at mid‐oestrus during different degree of clinical endometritis in dairy cows
Authors: Sharma Akshay , Singh Madhumeet , Abrol Ankur , Soni Tania
Published: July 2019

The present study was aimed at analysing the mid‐oestrous uterine blood flow parameters during varying degree of endometritis in dairy cows. Degree of clinical endometritis was adjudged on the basis of visual examination of uterine discharge collected from cows at mid‐oestrus, that is mild (slightly turbid; n = 13), moderate (turbid with pus flakes; n = 14) and severe (milky; n = 13). Pulsatility and resistance indices (PI and RI), time average mean velocity (TAMEAN), time average maximum velocity (TAMAX), diameter of the artery, volume of blood flow, Doppler pulse duration (DPD) and systolic upstroke/acceleration time (AT) were measured to study the spectral waveforms at mid‐oestrus. Significantly higher (p < .01) PI and RI were found in cows diagnosed with mild degree in comparison with cows diagnosed with moderate and severe degrees of clinical endometritis. There was significantly higher (p < .01) velocity (TAMEAN and TAMAX), volume of blood flow (BFV‐TAMEAN, BFV‐TAMAX) and DPD in both the middle uterine arteries during moderate and severe degrees of clinical endometritis as compared to mild endometritis. However, significantly higher (p < .01) AT was recorded in cows diagnosed with mild degree as compared to moderate and severe degrees of clinical endometritis. Pearson's correlation analysis has shown that RI was positively correlated with PI and AT in all the groups under study (mild degree, r = .72 and .49; moderate degree, r = .54 and .38; severe degree, r = .90 and .42; p < .05). However, there found significantly negative correlation (p < .05) with other parameters in all the cows irrespective of degree of inflammation. Therefore, it may be deducted that assessment of uterine inflammation can be done with a non‐invasive technique known as Doppler sonography which can be useful in adjudging the hemodynamic changes inside uterus and future fertility of dairy cows.
Structural insights into the interaction between phytoplasmal effector causing phyllody 1 and MADS transcription factors
Authors: Liao Yi‐Ting , Lin Shih‐Shun , Lin Shin‐Jen , Sun Wan‐Ting , Shen Bing‐Nan , Cheng Han‐Pin , Lin Chan‐Pin , Ko Tzu‐Ping , Chen Yi‐Fan , Wang Hao‐Ching
Published: July 2019

Phytoplasmas are bacterial plant pathogens which can induce severe symptoms including dwarfism, phyllody and virescence in an infected plant. Because phytoplasmas infect many important crops such as peanut and papaya they have caused serious agricultural losses. The phytoplasmal effector causing phyllody 1 (PHYL1) is an important phytoplasmal pathogenic factor which affects the biological function of MADS transcription factors by interacting with their K (keratin‐like) domain, thus resulting in abnormal plant developments such as phyllody. Until now, lack of information on the structure of PHYL1 has prevented a detailed understanding of the binding mechanism between PHYL1 and the MADS transcription factors. Here, we present the crystal structure of PHYL1 from peanut witches’‐broom phytoplasma (PHYL1PnWB). This protein was found to fold into a unique α‐helical hairpin with exposed hydrophobic residues on its surface that may play an important role in its biological function. Using proteomics approaches, we propose a binding mode of PHYL1PnWB with the K domain of the MADS transcription factor SEPALLATA3 (SEP3_K) and identify the residues of PHYL1PnWB that are important for this interaction. Furthermore, using surface plasmon resonance we measure the binding strength of PHYL1PnWB proteins to SEP3_K. Lastly, based on confocal images, we found that α‐helix 2 of PHYL1PnWB plays an important role in PHYL1‐mediated degradation of SEP3. Taken together, these results provide a structural understanding of the specific binding mechanism between PHYL1PnWB and SEP3_K.
Practical, Non-Invasive Measurement of Urinary Catheter Insertion Forces and Motions
Authors: Safdari Amer , Ling Xiaoyin , Tradewell Michael B. , Kowalewski Timothy M. , Sweet Robert M.
Published: July 2019

Catheter associated urinary tract infections (CAUTI) are among the most common nonpayment hospital acquired conditions. Inexperienced health care providers placing indwelling urinary catheters are associated with an increased risk of CAUTI. The creation of high-fidelity simulators may reduce CAUTI risk during critical early learning. As a first step toward the creation of accurate simulators our group set out to characterize the mechanical aspects of urethral catheterization. This work presents an inexpensive, yet practical means of acquiring motion and force data from urethral catheter insertion procedures using OpenCV ArUco markers. Evaluation of the video system’s accuracy was done to understand the performance characteristics within the boundaries of the procedure’s target workspace. The tracking accuracy was validated to be roughly ± 3 mm in the plane of the camera, and ± 10–25 mm along its axis depending on the distance. Feasibility of using this platform in a clinically relevant setting was demonstrated by capturing the force and motion data when performing urinary catheterization on cadaveric donors (N=2).
Iron-Sulfur Cluster Repair Contributes to Yersinia pseudotuberculosis Survival within Deep Tissues
Authors: Davis Kimberly M. , Krupp Joanna , Clark Stacie , Isberg Ralph R.
Published: July 2019

To successfully colonize host tissues, bacteria must respond to and detoxify many different host-derived antimicrobial compounds, such as nitric oxide (NO). NO has direct antimicrobial activity through attack on iron-sulfur (Fe-S) cluster-containing proteins. NO detoxification plays an important role in promoting bacterial survival, but it remains unclear if repair of Fe-S clusters is also important for bacterial survival within host tissues.
Lithological and structural controls on river profiles and networks in the northern Sierra Nevada (California, USA)
Authors: Gabet Emmanuel J.
Published: July 2019

In this study, the strong lithological heterogeneity of the northern Sierra Nevada (California, USA) is exploited to elucidate the role of lithology on river profiles and patterns at the mountain-range scale. The analyses indicate that plutonic, metavolcanic, and quartzite bedrock generally host the steepest river reaches, whereas gentle reaches flow across non-quartzite metasedimentary rocks and fault zones. In addition, the largest immobile boulders are often in the steepest reaches, suggesting that wide joint spacing plays a role in creating steep channels, and a positive relationship between boulder size and hillslope angle highlights the coupling of the hillslope and fluvial systems. With respect to river network configurations, dendritic patterns dominate in the plutonic bedrock, with channels aligned down the slope of the range; in contrast, river reaches in the metamorphic belts are mainly longitudinal and parallel to the structural grain. River profiles and patterns in the northern Sierra Nevada, therefore, bear a strong lithological imprint related to differential erosion. These observations indicate that attempts to infer uplift and tilting of the range based on the gradients and orientations of paleochannel remnants should first account for the effect of bedrock erodibility. Indeed, the differences in gradients of Tertiary paleochannel remnants used to argue for late Cenozoic uplift of the range can be wholly explained by differences in lithology.
Proximal tibiofibular joint dislocation treated using flexible and permanent syndesmosis fixation
Authors: Moscon Antonio Carlos , Martimbianco Ana Luiza Cabrera , Duarte Junior Aires , Gracitelli Guilherme Conforto
Published: July 2019

We present the case of a 40-year-old man who suffered an isolated proximal tibiofibular dislocation of the left knee after a trauma during a soccer game. Physical examination and radiographic imaging revealed an anterolateral dislocation of the proximal fibula. The diagnosis was confirmed by MRI. The treatment choice was open reduction and internal fixation under direct visualisation using flexible and permanent internal fixation. Postoperative treatment includes knee immobilisation during the first week, and partial weight was allowed for 2 weeks progressing to full weight bearing over 4 weeks. The patient started a gradual and progressive physical therapy programme with range of motion exercises, muscle strengthening and gait training. Full knee range of motion was achieved after 4 weeks. No complaint of pain or hardware discomfort was reported, and the patient is back to daily life and sports activities after 6 months of surgical treatment.
Association of sirolimus with pericardial effusion in renal transplant patient and discussion of potential mechanism
Authors: Meng Lingbin , Deng Bo , Liu Baoqiong , Gordon Dwayne
Published: July 2019

Sirolimus is an important immunosuppressive drug in renal transplantation but contains numerous side effects. In this study, we describe a case of renal transplant recipient treated with sirolimus who developed pericardial effusion associated with interstitial pneumonia. An extensive search for alternative causes were all negative, and all symptoms disappeared after sirolimus interruption. Therefore, this case demonstrates that sirolimus can cause pericardial effusion possibly through a proinflammatory mechanism.
Blastic plasmacytoid dendritic cell neoplasm in the background of myeloproliferative disorder and chronic lymphocytic leukaemia
Authors: Khan Abdul Moiz , Munir Ayesha , Raval Mihir , Mehdi Syed
Published: July 2019

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an extremely rare haematological malignancy defined by concurrent expression of CD4, CD56, BCL-2 and CD123. The disease has a very poor prognosis and there are no well-established treatment guidelines. We describe a case of BPDCN in a 65-year-old female patient with myeloproliferative disorder (essential thrombocythemia) and chronic lymphocytic leukaemia. She presented with rapidly progressive facial and scalp lesions. Skin biopsy confirmed BPDCN and the imaging revealed widespread disease. Patient was started on hyper-CVAD (cyclophosphamide, vincristine, doxorubicin, dexamethasone) and intrathecal methotrexate. Due to progression on initial treatment, she was treated with decitabine and venetoclax (BCL-2 inhibitor). However, patient continued to deteriorate and died after 4 months from initial diagnosis. We emphasise on the clinical features, emerging treatment modalities and prognosis of BPDCN.
Perinatal palliative care: a dedicated care pathway
Authors: Rusalen Francesca , Cavicchiolo Maria Elena , Lago Paola , Salvadori Sabrina , Benini Franca
Published: July 2019

Objective

Ensure access to perinatal palliative care (PnPC) to all eligible fetuses/infants/parents.

Design

During 12 meetings in 2016, a multidisciplinary work-group (WG) performed literature review (Grading of Recommendations, Assessment, Development and Evaluation (GRADE) method was applied), including the ethical and legal references, in order to propose shared care pathway.

Setting

Maternal-Infant Department of Padua’s University Hospital.

Patients

PnPC eligible population has been divided into three main groups: extremely preterm newborns (first group), newborns with prenatal/postnatal diagnosis of life-limiting and/or life-threatening disease and poor prognosis (second group) and newborns for whom a shift to PnPC is appropriate after the initial intensive care (third group).

Interventions

The multidisciplinary WG has shared care pathway for these three groups and defined roles and responsibilities.

Main outcome measures

Prenatal and postnatal management, symptom’s treatment, end-of-life care.

Results

The best care setting and the best practice for PnPC have been defined, as well as the indications for family support, corpse management and postmortem counselling, as well suggestion for conflicts’ mediation.

Conclusions

PnPC represents an emerging field within the paediatric palliative care and calls for the development of dedicated shared pathways, in order to ensure accessibility and quality of care to this specific population of newborns.
Man versus machine: comparison of naked-eye estimation and quantified capillary refill
Authors: Toll John Rani , Henricson Joakim , Anderson Chris D , Björk Wilhelms Daniel
Published: July 2019

Background

Capillary refill (CR) time is traditionally assessed by ‘naked-eye’ inspection of the return to original colour of a tissue after blanching pressure. Few studies have addressed intra-observer reliability or used objective quantification techniques to assess time to original colour. This study compares naked-eye assessment with quantified CR (qCR) time using polarisation spectroscopy and examines intra-observer and interobserver agreements in using the naked eye.

Method

A film of 18 CR tests (shown in a random fixed order) performed in healthy adults was assessed by a convenience sample of 14 doctors, 15 nurses and 19 secretaries (Department of Emergency Medicine, Linköping University, September to November 2017), who were asked to estimate the time to return to colour and characterise it as ‘fast’, ‘normal’ or ‘slow’. The qCR times and corresponding naked-eye time assessments were compared using the Kruskal-Wallis test. Three videos were shown twice without observers’ knowledge to measure intra-observer repeatability. Intra-observer categorical assessments were compared using Cohen’s Kappa analysis. Interobserver repeatability was measured and depicted with multiple-observer Bland-Altman plotting. Differences in naked-eye estimation between professions were analysed using ANOVA.

Results

Naked-eye assessed CR time and qCR time differ substantially, and agreement for the categorical assessments (naked-eye assessment vs qCR classification) was poor (Cohen’s kappa 0.27). Bland-Altman intra-observer repeatability ranged from 6% to 60%. Interobserver agreement was low as shown by the Bland-Altman plotting with a 95% limit of agreement with the mean of ±1.98 s for doctors, ±1.6 s for nurses and ±1.75 s for secretaries. The difference in CR time estimation (in seconds) between professions was not significant.

Conclusions

Our study suggests that naked-eye-assessed CR time shows poor reproducibility, even by the same observers, and differs from an objective measure of CR time.
Current status of use of big data and artificial intelligence in RMDs: a systematic literature review informing EULAR recommendations
Authors: Kedra Joanna , Radstake Timothy , Pandit Aridaman , Baraliakos Xenofon , Berenbaum Francis , Finckh Axel , Fautrel Bruno , Stamm Tanja A , Gomez-Cabrero David , Pristipino Christian , Choquet Remy , Servy Hervé , Stones Simon , Burmester Gerd , Gossec Laure
Published: July 2019

Objective

To assess the current use of big data and artificial intelligence (AI) in the field of rheumatic and musculoskeletal diseases (RMDs).

Methods

A systematic literature review was performed in PubMed MEDLINE in November 2018, with key words referring to big data, AI and RMDs. All original reports published in English were analysed. A mirror literature review was also performed outside of RMDs on the same number of articles. The number of data analysed, data sources and statistical methods used (traditional statistics, AI or both) were collected. The analysis compared findings within and beyond the field of RMDs.

Results

Of 567 articles relating to RMDs, 55 met the inclusion criteria and were analysed, as well as 55 articles in other medical fields. The mean number of data points was 746 million (range 2000–5 billion) in RMDs, and 9.1 billion (range 100 000–200 billion) outside of RMDs. Data sources were varied: in RMDs, 26 (47%) were clinical, 8 (15%) biological and 16 (29%) radiological. Both traditional and AI methods were used to analyse big data (respectively, 10 (18%) and 45 (82%) in RMDs and 8 (15%) and 47 (85%) out of RMDs). Machine learning represented 97% of AI methods in RMDs and among these methods, the most represented was artificial neural network (20/44 articles in RMDs).

Conclusions

Big data sources and types are varied within the field of RMDs, and methods used to analyse big data were heterogeneous. These findings will inform a European League Against Rheumatism taskforce on big data in RMDs.
Relaxation times obtained from the rate equations using path probability method for the spin-1 Ising model
Authors: Erdem Rıza , Özüm Songül
Published: July 2019

We have presented the time-dependent behaviors of a spin-1 Ising model (with both bilinear and biquadratic interactions) in the neighborhood of the equilibrium states via the path probability method. The rate equations as introduced by Keskin and co-workers (1989) have been linearized to obtain the characteristic relaxation times. The temperature variations of these times were produced in accordance with the Tanaka and Mannari’s work (1976) on the equilibrium properties. Results are compared to one using Onsager’s phenomenological theory and a good agreement is achieved.
Nested Closed Invariant Curves in Piecewise Smooth Maps
Authors: Avrutin Viktor , Zhusubaliyev Zhanybai T.
Published: July 2019

The paper describes how several coexisting stable closed invariant curves embedded into each other can arise in a two-dimensional piecewise-linear normal form map. Phenomena of this type have been recently reported for a piecewise smooth map, modeling the behavior of a power electronic DC–DC converter. In the present work, we demonstrate that this type of multistability exists in a more general class of models and show how it may result from the well-known period adding bifurcation structure due to its deformation so that the phase-locking regions start to overlap. We explain how this overlapping structure is related to the appearance of coexisting stable closed invariant curves nested into each other.

By means of detailed, numerically calculated phase portraits we hereafter present an example of this type of multistability. We also demonstrate that the basins of attraction of the nested stable invariant curves may be separated from each other not only by repelling closed invariant curves, as previously reported, but also by a chaotic saddle. It is suggested that the considered kind of multistability is a generic phenomenon in piecewise smooth dynamical systems.
Bifurcation of Multiple Limit Cycles in an Epidemic Model on Adaptive Networks
Authors: Zhang Xiaoguang , Jin Zhen , Yu Pei
Published: July 2019

Very recently, Zhang et al. considered an epidemic model on adaptive networks [Zhang et al., 2019], in which Hopf bifurcation, homoclinic bifurcation and Bogdanov–Takens bifurcation are studied. Degenerate Hopf bifurcation is investigated via simulation and a numerical example is given to show the existence of two limit cycles. However, whether the codimension of the Hopf bifurcation is two is still open. In this paper, we will rigorously prove that the codimension of the Hopf bifurcation is two. That is, the maximal two limit cycles can bifurcate from the Hopf critical point. Moreover, the conditions for the existence of two limit cycles are derived.
Stable isotopes of nonsulphide Zn–Pb ores in Britain and Ireland: fluid characteristics and palaeoclimatic variability
Authors: Boni Maria , Gilg H. Albert , Balassone Giuseppina , Mondillo Nicola , Menschik Florian , Rumsey Mike , Struck Ulrich
Published: July 2019

Stable isotope (C–O) analysis was applied to smithsonites and cerussites from Zn(Pb) nonsulphide ores from Britain and Ireland, to determine the nature of the fluids responsible for the precipitation of secondary carbonates, and any relationship with palaeoclimatic conditions. The carbon isotope compositions of the Irish smithsonites show a major contribution of organic carbon whereas those of both Zn- and Pb-carbonates in the UK deposits indicate contribution of organic carbon and host-rock carbonates. δ
18
O
VSMOW
values for cerussite from both areas are about 13‰ lower than those of smithsonites, UK smithsonite δ
18
O
VSMOW
values are more variable than those for cerussites and the Irish smithsonites have unusually high values. Isoscape maps indicate that δ
18
O values for both carbonates are higher in the west and decrease toward the east. This trend correlates with a general decrease in the oxygen isotope compositions of rainwater moving eastward, and suggests that oxidation of sulphides occurred at temperatures of about 15–20°C, under climatic conditions warmer than today.

Supplementary material:
A comprehensive overview of the investigated sites, detailed data for the samples and SEM images are available at
https://doi.org/10.6084/m9.figshare.c.4579535
MH Cache
Authors: Park Jungwoo , Lee Myoungjun , Kim Soontae , Ju Minho , Hong Jeongkyu
Published: July 2019

Mobile devices have become the most important devices in our life. However, they are limited in battery capacity. Therefore, low-power computing is crucial for their long lifetime. A spin-transfer torque RAM (STT-RAM) has become emerging memory technology because of its low leakage power consumption. We herein propose MH cache, a multi-retention STT-RAM-based cache management scheme for last-level caches (LLC) to reduce their power consumption for mobile hardware rendering systems. We analyzed the memory access patterns of processes and observed how rendering methods affect process behaviors. We propose a cache management scheme that measures write-intensity of each process dynamically and exploits it to manage a power-efficient multi-retention STT-RAM-based cache. Our proposed scheme uses variable threshold for a process’ write-intensity to determine cache line placement. We explain how to deal with the following issue to implement our proposed scheme. Our experimental results show that our techniques significantly reduce the LLC power consumption by 32% and 32.2% in single- and quad-core systems, respectively, compared to a full STT-RAM LLC.
Metabolomics of anoxia tolerance inDrosophila melanogaster: evidence against substrate limitation and for roles of protective metabolites and paralytic hypometabolism
Authors: Campbell Jacob B. , Werkhoven Simon , Harrison Jon F.
Published: July 2019

Animals vary tremendously in their capacities to survive anoxia, and the mechanisms responsible are poorly understood. Adult Drosophila melanogaster are rapidly paralyzed and survive up to 12 h of anoxia, whereas larvae vigorously attempt escape but then die if anoxia exceeds 2 h. Here we use nuclear magnetic resonance methods to compare the metabolome of larvae and adult D. melanogaster under normoxic conditions and after various anoxic durations up to 1 h. Glucose increased during anoxia in both larvae and adults, so anoxic death by carbohydrate limitation is unlikely for either stage. Lactate and alanine were the primary anaerobic end products in both adults and larvae. During the first 30 min of anoxia, larvae accumulated anaerobic end products (predominately lactate) at a higher rate, suggesting that larvae may experience greater initial acid-base disruption during anoxic exposures. Adult Drosophila did not possess higher levels of putative protective metabolites; however, these increased during anoxia in adults and decreased in larvae. Metabolites that decreased during anoxia in larvae included mannitol, xylitol, glycerol, betaine, serine, and tyrosine, perhaps due to use as fuels, antioxidants, or binding to denatured proteins. Adults showed significant increases in glycine, taurine, and the polyols glycerol, mannitol, and xylitol, suggesting that adults upregulate protective metabolites to prevent damage. Our results suggest that lower initial metabolic demand due to paralytic hypometabolism and capacities to upregulate protective metabolites may assist the better anoxia tolerance of adult Drosophila.
PIM1, CYP1B1, and HSPA2 Targeted by Quercetin Play Important Roles in Osteoarthritis Treatment by Achyranthes bidentata
Authors: Ma Dujun , Yu Tian , Peng Liping , Wang Lixin , Liao Zhouwei , Xu Wenming
Published: July 2019

Aim. Achyranthes bidentata is one of the most commonly used Chinese herbal medicines (CHM) that is currently considered for the treatment of osteoarthritis. The purpose of this study was to reveal the mechanism of Achyranthes bidentata in osteoarthritis treatment based on the network pharmacology. Methods. The effective components of Achyranthes bidentata were firstly screened out from the TCMSP database with ADME property parameters. Then, osteoarthritis-related proteins targeted by the effective components were predicted based on the DrugBank and CTD databases. Subsequently, enrichment analysis and interaction network between targets of effective components and pathways were also studied. In addition, the differentially expressed genes (DEGs) of GSE55457 were used for validation of the osteoarthritis-related target proteins. Finally, the effective components–target molecular docking models were predicted. Results. A total of 10 effective components were identified, of which kaempferol and quercetin had 1 and 29 targets, respectively. There were 26 target proteins of quercetin related to the osteoarthritis. These targets were mainly enriched in mitochondrial ATP synthesis coupled proton transport, cellular response to estradiol stimulus, and nitric oxide biosynthetic process. In addition, there were three common proteins, PIM1, CYP1B1, and HSPA2 based on the DEGs of GSE55457, which were considered as the key targeted proteins of the quercetin. Conclusion. The docking of PIM1-quercetin, CYP1B1-quercetin, and HSPA2-quercetin may play important roles during the treatment of osteoarthritis by Achyranthes bidentata.