bluuebunny/crossref_metadata_2025 huggingface dataset:
Concordance of Clinical Alzheimer Diagnosis and Neuropathological Features at Autopsy
Authors: Gauthreaux Kathryn , Bonnett Tyler A , Besser Lilah M , Brenowitz Willa D , Teylan Merilee , Mock Charles , Chen Yen-Chi , Chan Kwun C G , Keene C Dirk , Zhou Xiao-Hua , Kukull Walter A
Published: March 2020

It remains unclear what clinical features inform the accuracy of a clinical diagnosis of Alzheimer disease (AD). Data were obtained from the National Alzheimer’s Coordinating Center to compare clinical and neuropathologic features among participants who did or did not have Alzheimer disease neuropathologic changes (ADNC) at autopsy. Participants (1854) had a clinical Alzheimer dementia diagnosis and ADNC at autopsy (Confirmed-AD), 204 participants had an AD diagnosis and no ADNC (AD-Mimics), and 253 participants had no AD diagnosis and ADNC (Unidentified-AD). Compared to Confirmed-AD participants, AD-Mimics had less severe cognitive impairment, while Unidentified-AD participants displayed more parkinsonian signs, depression, and behavioral problems. This study highlights the importance of developing a complete panel of biomarkers as a tool to inform clinical diagnoses, as clinical phenotypes that are typically associated with diseases other than AD may result in inaccurate diagnoses.
A novel CMB component separation method: hierarchical generalized morphological component analysis
Authors: Wagner-Carena Sebastian , Hopkins Max , Diaz Rivero Ana , Dvorkin Cora
Published: March 2020

We present a novel technique for cosmic microwave background (CMB) foreground subtraction based on the framework of blind source separation. Inspired by previous work incorporating local variation to generalized morphological component analysis (GMCA), we introduce hierarchical GMCA (HGMCA), a Bayesian hierarchical graphical model for source separation. We test our method on Nside = 256 simulated sky maps that include dust, synchrotron, free–free, and anomalous microwave emission, and show that HGMCA reduces foreground contamination by $25{{\ \rm per\ cent}}$ over GMCA in both the regions included and excluded by the Planck UT78 mask, decreases the error in the measurement of the CMB temperature power spectrum to the 0.02–0.03 per cent level at ℓ > 200 (and $\lt 0.26{{\ \rm per\ cent}}$ for all ℓ), and reduces correlation to all the foregrounds. We find equivalent or improved performance when compared to state-of-the-art internal linear combination type algorithms on these simulations, suggesting that HGMCA may be a competitive alternative to foreground separation techniques previously applied to observed CMB data. Additionally, we show that our performance does not suffer when we perturb model parameters or alter the CMB realization, which suggests that our algorithm generalizes well beyond our simplified simulations. Our results open a new avenue for constructing CMB maps through Bayesian hierarchical analysis.
SuperModel predictions in the outskirts of the galaxy cluster Zwicky 3146
Authors: Fusco-Femiano Roberto
Published: March 2020

The relaxed galaxy cluster Zwicky 3146 is analysed via the SuperModel, a tool already tested on many clusters since 2009. In particular, this analysis is focused on the intracluster medium X-ray temperature data measured by XMM–Newton up to r500. A previous analysis was based on the temperature profile derived from the Sunyaev-Zeld′ovich effect pressure data. The gas mass fraction fgas is obtained from the resulting SuperModel temperature profile extrapolated up to the virial radius R, which turns out in agreement with the steep temperature profiles observed by Suzaku, and from the gas density profile observed by XMM–Newton. The comparison between fgas with the universal value indicates a non-thermal pressure component, pnth, in the cluster outskirts. The SuperModel analysis shows a ratio α(R) (${\simeq}50{{\ \rm per\ cent}}$) of pnth to the total pressure greater than the values found by simulations, highlighting the possible presence of accreting substructures and inhomogeneities in the gas density profile. Once that this profile is corrected for clumpiness, the level of pnth is considerably reduced. However, a significant turbulence ($\alpha (R)\simeq 20{{\ \rm per\ cent}}$) and entropy flattening are still present in the outskirts of the galaxy cluster Zwicky 3146.
LARgE survey – III. Environments of ultra-massive passive galaxies at cosmic noon: BCG progenitors growing through mergers
Authors: Sawicki Marcin , Arcila-Osejo Liz , Golob Anneya , Moutard Thibaud , Arnouts Stéphane , Cheema Gurpreet Kaur
Published: March 2020

We study the environments of a sample of 61 extremely rare $z\, \sim$1.6 Ultra-Massive Passively Evolving Galaxies (UMPEGs: stellar masses M⋆ >1011.5 M⊙) which – based on clustering analysis presented in Cheema et al. (2020) – appear to be associated with very massive (Mhalo ∼ 1014.1h−1 M⊙) dark matter haloes that are likely to be the progenitors of $z\, \sim$0 massive (Coma- and Virgo-like) galaxy clusters. We find that UMPEGs on average have fewer than one satellite galaxy with mass ratio $M_{\star }^{\text{sat}}$:$M_{\star }^{{\text{UMPEG}}}$ ≥ 1:5 (i.e. $M_{\star }^{\text{sat}}$$\gtrsim 10^{10.8}$ M⊙) within 0.5 Mpc; the large mass gap that we observe between the typical UMPEG and its most massive satellite implies that the $z\, \sim$1.6 UMPEGs assembled through major mergers. Using observed satellite counts with merger time-scales from the literature, we estimate the growth rate due to mergers with mass ratio of ≥1:4 to be ∼13 per cent Gyr−1 (with a $\sim \, 2 \times$ systematic uncertainty). This relatively low growth rate is unlikely to significantly affect the shape of the massive end of the stellar mass function, whose evolution must instead be driven by the quenching of new cohorts of ultra-massive star-forming galaxies. However, this growth rate is high enough that, if sustained to $z\, \sim$0, the typical $z\, \sim$1.6 $M_{\star }^{{\text{UMPEG}}}$ =1011.6 M⊙ UMPEG can grow into a M⋆ ≈1012 M⊙ brightest cluster galaxy (BCG) of a present-day massive galaxy cluster. Our observations favour a scenario in which our UMPEGs are main-branch progenitors of some of the present-day BCGs that have first assembled through major mergers at high redshifts and grown further through (likely minor) merging at later times.
Human POT1 unfolds G-quadruplexes by conformational selection
Authors: Chaires Jonathan B , Gray Robert D , Dean William L , Monsen Robert , DeLeeuw Lynn W , Stribinskis Vilius , Trent John O
Published: March 2020

The reaction mechanism by which the shelterin protein POT1 (Protection of Telomeres 1) unfolds human telomeric G-quadruplex structures is not fully understood. We report here kinetic, thermodynamic, hydrodynamic and computational studies that show that a conformational selection mechanism, in which POT1 binding is coupled to an obligatory unfolding reaction, is the most plausible mechanism. Stopped-flow kinetic and spectroscopic titration studies, along with isothermal calorimetry, were used to show that binding of the single-strand oligonucleotide d[TTAGGGTTAG] to POT1 is both fast (80 ms) and strong (−10.1 ± 0.3 kcal mol−1). In sharp contrast, kinetic studies showed the binding of POT1 to an initially folded 24 nt G-quadruplex structure is four orders of magnitude slower. Fluorescence, circular dichroism and analytical ultracentrifugation studies showed that POT1 binding is coupled to quadruplex unfolding, with a final complex with a stoichiometry of 2 POT1 per 24 nt DNA. The binding isotherm for the POT1-quadruplex interaction was sigmoidal, indicative of a complex reaction. A conformational selection model that includes equilibrium constants for both G-quadruplex unfolding and POT1 binding to the resultant single-strand provided an excellent quantitative fit to the experimental binding data. POT1 unfolded and bound to any conformational form of human telomeric G-quadruplex (antiparallel, hybrid, parallel monomers or a 48 nt sequence with two contiguous quadruplexes), but did not avidly interact with duplex DNA or with other G-quadruplex structures. Finally, molecular dynamics simulations provided a detailed structural model of a 2:1 POT1:DNA complex that is fully consistent with experimental biophysical results.
PHB regulates meiotic recombination via JAK2-mediated histone modifications in spermatogenesis
Authors: Zhang Ling-Fei , Tan-Tai Wen-Jing , Li Xiao-Hui , Liu Mo-Fang , Shi Hui-Juan , Martin-DeLeon Patricia A , O Wai-Sum , Chen Hong
Published: March 2020

Previously, we have shown that human sperm Prohibitin (PHB) expression is significantly negatively correlated with mitochondrial ROS levels but positively correlated with mitochondrial membrane potential and motility. However, the possible role of PHB in mammalian spermatogenesis has not been investigated. Here we document the presence of PHB in spermatocytes and its functional roles in meiosis by generating the first male germ cell-specific Phb-cKO mouse. Loss of PHB in spermatocytes resulted in complete male infertility, associated with not only meiotic pachytene arrest with accompanying apoptosis, but also apoptosis resulting from mitochondrial morphology and function impairment. Our mechanistic studies show that PHB in spermatocytes regulates the expression of STAG3, a key component of the meiotic cohesin complex, via a non-canonical JAK/STAT pathway, and consequently promotes meiotic DSB repair and homologous recombination. Furthermore, the PHB/JAK2 axis was found as a novel mechanism in the maintenance of stabilization of meiotic STAG3 cohesin complex and the modulation of heterochromatin formation in spermatocytes during meiosis. The observed JAK2-mediated epigenetic changes in histone modifications, reflected in a reduction of histone 3 tyrosine 41 phosphorylation (H3Y41ph) and a retention of H3K9me3 at the Stag3 locus, could be responsible for Stag3 dysregulation in spermatocytes with the loss of PHB.
Patient Outcomes With Prevented vs Negative Clostridioides difficile Tests Using a Computerized Clinical Decision Support Tool
Authors: Madden Gregory R , Enfield Kyle B , Sifri Costi D
Published: March 2020

Background

Overtesting and overdiagnosis of Clostridioides difficile infection are suspected to be common. Reducing inappropriate testing through interventions designed to promote evidence-based diagnostic testing (ie, diagnostic stewardship) may improve C. difficile test utilization. However, the safety of these interventions is not well understood despite the potential risk for missed or delayed diagnoses.

Methods

This retrospective case–control study examined the outcomes of patients admitted to the University of Virginia Medical Center following introduction of a computerized clinical decision support tool without hard-stops designed to reduce inappropriate tests. Outcomes were compared between patients with a prevented C. difficile nucleic acid amplification test and those with a negative result. Chart reviews were performed for patients with a subsequent positive within 7 days, as well as those patients who received C. difficile–active antibiotics after implementation of the computerized clinical decision support tool.

Results

Multivariate analysis of 637 cases (490 negative, 147 prevented) showed that a prevented test was not significantly associated with the primary composite outcome (inpatient mortality or intensive care unit transfer) compared with a negative test (adjusted odds ratio, 0.912; P = .747). Fifty-four of 147 (37%) prevented tests were followed by a completed test within 7 days; 11 of these results were positive, resulting in a potential delay in diagnosis. Individual case reviews found that either clinical changes warranted the delay in testing or no adverse events occurred attributable to C. difficile infection. C. difficile treatment without a positive test was not identified.

Conclusions

Diagnostic stewardship of C. difficile testing using computerized clinical decision support may be both safe and effective for reducing inappropriate inpatient testing.
Evolutionary History and Activity of RNase H1-Like Proteins in Arabidopsis thaliana
Authors: Kuciński Jan , Chamera Sebastian , Kmera Aleksandra , Rowley M Jordan , Fujii Sho , Khurana Pragya , Nowotny Marcin , Wierzbicki Andrzej T
Published: March 2020

RNase H1 is an endonuclease specific toward the RNA strand of RNA:DNA hybrids. Members of this protein family are present in most living organisms and are essential for removing RNA that base pairs with DNA. It prevents detrimental effects of RNA:DNA hybrids and is involved in several biological processes. Arabidopsis thaliana has been previously shown to contain three genes encoding RNase H1 proteins that localize to three distinct cellular compartments. We show that these genes originate from two gene duplication events. One occurred in the common ancestor of dicots and produced nuclear and organellar RNase H1 paralogs. Second duplication occurred in the common ancestor of Brassicaceae and produced mitochondrial- and plastid-localized proteins. These proteins have the canonical RNase H1 activity, which requires at least four ribonucleotides for endonucleolytic digestion. Analysis of mutants in the RNase H1 genes revealed that the nuclear RNH1A and mitochondrial RNH1B are dispensable for development under normal growth conditions. However, the presence of at least one organellar RNase H1 (RNH1B or RNH1C) is required for embryonic development. The plastid-localized RNH1C affects plastid DNA copy number and sensitivity to replicative stress. Our results present the evolutionary history of RNH1 proteins in A. thaliana, demonstrate their canonical RNase H1 activity and indicate their role in early embryonic development.
Planktonic stages of the ecologically important sea urchin, Diadema africanum: larval performance under near future ocean conditions
Authors: Hernández José Carlos , Clemente Sabrina , García Eliseba , McAlister Justin S
Published: March 2020

Diadema africanum is a recently described sea urchin from the Eastern Atlantic archipelagos, and adults play a major ecological role mediating the transition between two alternative ecosystem states: macroalgal beds and urchin barrens. The aim of this study was to describe for the first time the egg characteristics, fertilization and larval development. To determine basic life-history characteristics for this species, we reared larvae through to metamorphic competence under an energy shortage experiment and temperature–pH experiments to characterize the morphological plasticity of larval responses to actual and future oceanic conditions. D. africanum produces eggs that are larger both in diameter (82.7 μm) and volume (0.30 nl) than the eggs of both Diadema antillarum (70.0 μm, 0.18 nl) and Diadema mexicanum (68.0 μm, 0.16 nl). Larval development is similar to other species within the Family Diadematidae, with a Echinopluteus transversus larval type morphology. The combined effects of the climate change-related environmental factors resulted in a reduction in fitness of D. africanum at the warmer limit of its thermal range when combined with low pH. Results suggest that the egg and larval life-history characteristics of D. africanum may have evolved to facilitate long-distance oceanic transport; however, near-future oceanic conditions may compromise larval survival.
The assessment of patients with the antiphospholipid antibody syndrome: where are we now?
Authors: Gaspar Pedro , Cohen Hannah , Isenberg David A
Published: March 2020

The antiphospholipid antibody syndrome (APS), a chronic autoimmune thrombophilia with an increased mortality and morbidity, has been recognized for more than three decades. Unlike other autoimmune rheumatic conditions such as systemic lupus erythematosus, myositis and Sjögren’s syndrome, relatively few attempts have been made to develop activity, damage or disease-specific quality of life indices for APS. In this review of the literature, we consider those attempts that have been made to develop assessment tools for patients with APS, but also reflect upon the nature of the condition, to discuss, in particular, whether an activity index is appropriate for this disease.
DOSE ASSESSMENT OF NATURAL TERRESTRIAL RADIONUCLIDES IN COMMONLY CONSUMED FOODS IN NORTH INDIA
Authors: Kaur Sarabjot , Maheshwari Poorvi , Mehra Rohit
Published: March 2020

The present study aimed to record natural radionuclide content in branded food samples representative of a typical North Indian diet. Forty samples of various food items falling into three categories namely, cereal grains, pulses and beverages were collected from the local markets of Punjab. The radiometric analysis was performed using NaI(Tl) scintillator detector. The activity concentrations ranged between 10 ± 1 and 20 ± 5 Bq kg−1 for 226Ra, Below Detectable Limit (BDL) and 10 ± 2 Bq kg−1 for 232Th and 440 ± 56 and 562 ± 70 Bq kg−1 for 40K. The radium equivalent (Raeq) varied from 55 Bq kg−1(corn) to 70 Bq kg−1 (tea) with an average of 62 Bq kg−1. Internal hazard index (HI) was also calculated (0.18–0.24), which was well below the prescribed threshold of one (24). Age-specific annual effective doses were estimated for infants, children and adults. Children were the most sensitive group of population to radionuclide doses from cereal grains. The annual effective doses were further used to calculate the lifetime cancer risk which exceeded the world average of 2.9$\times$10−4 (24). However, the overall results showed that the intake of these dietary products by the general public did not pose any serious health risk.
RNA Sequencing-Associated Study Identifies GmDRR1 as Positively Regulating the Establishment of Symbiosis in Soybean
Authors: Shi Yan , Zhang Zhanguo , Wen Yingnan , Yu Guolong , Zou Jianan , Huang Shiyu , Wang Jinhui , Zhu Jingyi , Wang Jieqi , Chen Lin , Ma Chao , Liu Xueying , Zhu Rongsheng , Li Qingying , Li Jianyi , Guo Miaoxin , Liu Hanxi , Zhu Yongxu , Sun Zhijun , Han Lu , Jiang Hongwei , Wu Xiaoxia , Wang Nannan , Zhang Weiyao , Yin Zhengong , Li Candong , Hu Zhenbang , Qi Zhaoming , Liu Chunyan , Chen Qingshan , Xin Dawei
Published: March 2020

In soybean (Glycine max)-rhizobium interactions, the type III secretion system (T3SS) of rhizobium plays a key role in regulating host specificity. However, the lack of information on the role of T3SS in signaling networks limits our understanding of symbiosis. Here, we conducted an RNA sequencing analysis of three soybean chromosome segment substituted lines, one female parent and two derived lines with different chromosome-substituted segments of wild soybean and opposite nodulation patterns. By analyzing chromosome-linked differentially expressed genes in the substituted segments and quantitative trait loci (QTL)-assisted selection in the substituted-segment region, genes that may respond to type III effectors to mediate plant immunity–related signaling were identified. To narrow down the number of candidate genes, QTL assistant was used to identify the candidate region consistent with the substituted segments. Furthermore, one candidate gene, GmDRR1, was identified in the substituted segment. To investigate the role of GmDRR1 in symbiosis establishment, GmDRR1-overexpression and RNA interference soybean lines were constructed. The nodule number increased in the former compared with wild-type soybean. Additionally, the T3SS-regulated effectors appeared to interact with the GmDDR1 signaling pathway. This finding will allow the detection of T3SS-regulated effectors involved in legume-rhizobium interactions.
Mapping Powdery Mildew Resistance Gene pmYBL on Chromosome 7B of Chinese Wheat (Triticum aestivum L.) Landrace Youbailan
Authors: Xu Xiaodan , Liu Wei , Liu Zhiyong , Fan Jieru , Zhou Yilin
Published: March 2020

Chinese wheat landrace Youbailan has excellent resistance to powdery mildew caused by Blumeria graminis f. sp. tritici. In the present study, genetic analysis indicated that a recessive gene, tentatively designated pmYBL, was responsible for the powdery mildew resistance of Youbailan. pmYBL was located in the 695-to-715-Mb genomic region of chromosome 7BL, with 19 gene-linked single-nucleotide polymorphism (SNP) markers. It was flanked by SNP1-12 and SNP1-2 with genetic distances of 0.6 and 1.8 centimorgans, respectively. The disease reaction patterns of Youbailan and four cultivars (lines) carrying the powdery mildew (Pm) genes located on chromosome arm 7BL indicated that pmYBL may be allelic or closely linked to these genes. All of the SNP markers linked to pmYBL were diagnostic, indicating that these markers will be useful for pyramiding pmYBL using marker-assisted selection.
Factors Associated With Cannabis Use Among African American Nondaily Smokers
Authors: Rubenstein Dana , Aston Elizabeth R. , Nollen Nicole L. , Mayo Matthew S. , Brown Alexandra R. , Ahluwalia Jasjit S.
Published: March 2020

Objectives:

Cannabis and tobacco dual use is a growing concern in the United States, especially among African Americans (AAs). Dual use increases nicotine dependence and poses negative health effects. Despite decreasing numbers of people who smoke daily, nondaily smokers (NDS) are increasing. Polytobacco use, including blunt use, is higher in AA NDS than AAs who smoke daily. This study examined factors associated with cannabis use among AA NDS.

Methods:

Adult AA NDS participated in a randomized controlled trial (n = 278) for smoking cessation. A subset of this sample (n = 262; mean age 48.2 years; 50% male) was analyzed to identify correlates of cannabis use. Logistic regression assessed the associations of demographic, smoking-related, and psychosocial variables with cannabis use.

Results:

Participants smoked cigarettes on an average of 18 days of the last 30 and used 4.5 cigarettes on smoking days. Of the participants analyzed, 38% used cannabis, including blunts (ie, cigars hollowed out filled with cannabis) at baseline. Cannabis use was associated with polytobacco product use not including blunts (odds ratio [OR] 2.11, 95% confidence interval [CI] 1.18–3.77, P = 0.012), depressive symptoms (OR 1.22, 95% CI 1.05–1.42, P = 0.011), and younger age (OR 0.97, 95% CI 0.94–0.99, P = 0.004).

Conclusions:

Rates of cannabis and tobacco dual use in our sample exceed national rates. Dual use poses harmful health effects that exceed the risk of either substance alone. Findings will inform future work in tailoring treatments to vulnerable groups of people who use both tobacco and cannabis.
Treatment of thrombotic antiphospholipid syndrome in adults and children
Authors: Madison Jacqueline A. , Duarte-García Alí , Zuo Yu , Knight Jason S.
Published: March 2020

Purpose of review

Antiphospholipid syndrome (APS), more common than once believed, is an autoimmune disease best known for its high risk of incident and recurrent thrombotic events. The approach to treatment potentially differs from treatment of thrombosis in the general population, and this article endeavors to review the latest updates on this topic.

Recent findings

The epidemiology of APS is being increasingly elucidated by large population-based studies, with APS perhaps affecting as many as 1 in 2000 individuals. Vitamin K antagonists, aspirin, and heparinoids continue to have obvious roles in the management of patients with APS. There has recently been intensive study of direct oral anticoagulants in APS, with the most recent randomized studies raising concerns about their inferiority to vitamin K antagonists, at least in some subgroups. Other approaches to treating APS beyond anticoagulants and antiaggregants are also receiving increased attention in mechanistic and preclinical studies with an eye toward future roles in patients with refractory and/or microvascular disease. Pediatric APS is identified as an area in desperate need of additional prospective research.

Progress continues to be made in pursuit of improving the lives of individuals afflicted with APS. The most important future directions would seem to involve leveraging modern molecular technologies in order to improve subphenotyping of antiphospholipid antibody-positive individuals. This will help personalize risk profiles and ideally define the optimal approach to therapy based on future risk, rather than past morbid events.
Segmental Flexibility in Adolescent Idiopathic Scoliosis Assessed Using the Fulcrum-bending Radiography Method
Authors: Kawasaki Sachiko , Shigematsu Hideki , Tanaka Masato , Okuda Akinori , Masuda Keisuke , Yamamoto Yusuke , Tanaka Yasuhito
Published: March 2020

Introduction:

Assessment of segmental flexibility at each disk level of the scoliotic curve in patients with adolescent idiopathic scoliosis (AIS) has rarely been performed, despite its importance for surgical planning of fusion levels. The fulcrum-bending radiography method could be used to assess flexibility at specific spinal segments of the scoliotic curve for preoperative planning. Therefore, our aim was to use the fulcrum-bending method to evaluate the pattern of segmental flexibility in patients with AIS.

Materials and Methods:

Our retrospective analysis was based on preoperative fulcrum-bending radiographs in 21 patients presenting with main thoracic curve scoliosis. The apex vertebra was defined as the “0” level, with the sequential cranial disk levels defined as “+1 to +5” and the sequential caudal levels as “−1 to −5.” The segmental Cobb angle was measured on both, standing and fulcrum-bending radiographs. The segmental flexibility index (FI) was calculated as: [(the segmental Cobb angle in standing position−the segmental Cobb angle in the fulcrum-bending position)/the segmental Cobb angle in standing position]×100. The FI was measured from the upper-most to the lower-most end vertebrae of the main curve.

Results:

There was a significant difference in the FI among segments, with the greatest flexibility detected at the level of the −5 disk (median FI, 50%) and least flexibility at the periapical segments (+1 and −1; FI, 50%–66.7%).

Conclusions:

The curve around the apex and upper thoracic segments in thoracic AIS is relatively rigid. Understanding differences in FI between each disk level is important for optimal corrective surgery.
Human Umbilical Cord-Derived Mesenchymal Stem Cells for Acute Respiratory Distress Syndrome
Authors: Yip Hon-Kan , Fang Wen-Feng , Li Yi-Chen , Lee Fan-Yen , Lee Chen-Hsiang , Pei Sung-Nan , Ma Ming-Chun , Chen Kuan-Hung , Sung Pei-Hsun , Lee Mel S.
Published: March 2020

Objectives:

To investigate the safety, feasibility, and possible adverse events of single-dose human umbilical cord-derived mesenchymal stem cells in patients with moderate-to-severe acute respiratory distress syndrome.

Design:

Prospective phase I clinical trial.

Setting:

Medical center in Kaohsiung, Taiwan.

Patients:

Moderate-to-severe acute respiratory distress syndrome with a Pao
2/Fio
2 ratio less than 200.

Interventions:

Scaling for doses was required by Taiwan Food and Drug Administration as follows: the first three patients received low-dose human umbilical cord-derived mesenchymal stem cells (1.0 × 106 cells/kg), the next three patients with intermediate dose (5.0 × 106 cells/kg), and the final three patients with high dose (1.0 × 107 cells/kg) between December 2017 and August 2019.

Measurements and Main Results:

Nine consecutive patients were enrolled into the study. In-hospital mortality was 33.3% (3/9), including two with recurrent septic shock and one with ventilator-induced severe pneumomediastinum and subcutaneous emphysema. No serious prespecified cell infusion-associated or treatment-related adverse events was identified in any patient. Serial flow-cytometric analyses of circulating inflammatory biomarkers (CD14+CD33+/CD11b+CD16+/CD16+MPO+/CD11b+MPO+/CD14dimCD33+) and mesenchymal stem cell markers (CD26+CD45–/CD29+CD45–/CD34+CD45–/CD44+CD45–/CD73+CD45–/CD90+CD45–/CD105+CD45–/CD26+CD45–) were notably progressively reduced (p for trend < 0.001), whereas the immune cell markers (Helper-T-cellCD3+CD4+/Cytotoxity-T-cellCD3+CD8+/Regulatory-T-cellCD4+CD25+FOXp3+) were notably increased (p for trend < 0.001) after cell infusion.

Conclusions:

The result of this phase I clinical trial showed that a single-dose IV infusion of human umbilical cord-derived mesenchymal stem cells was safe with favorable outcome in nine acute respiratory distress syndrome patients.
Prediction of Symptomatic Venous Thromboembolism in Critically Ill Patients: The ICU-Venous Thromboembolism Score*
Authors: Viarasilpa Tanuwong , Panyavachiraporn Nicha , Marashi Seyed Mani , Van Harn Meredith , Kowalski Robert G. , Mayer Stephan A.
Published: March 2020

Objectives:

To identify risk factors and develop a prediction score for in-hospital symptomatic venous thromboembolism in critically ill patients.

Design:

Retrospective cohort study.

Setting:

Henry Ford Health System, a five-hospital system including 18 ICUs.

Patients:

We obtained data from the electronic medical record of all adult patients admitted to any ICU (total 264 beds) between January 2015 and March 2018.

Interventions:

None.

Measurements and Main Results:

Symptomatic venous thromboembolism was defined as deep vein thrombosis, pulmonary embolism, or both, diagnosed greater than 24 hours after ICU admission and confirmed by ultrasound, CT, or nuclear medicine imaging. A prediction score (the ICU-Venous Thromboembolism score) was derived from independent risk factors identified using multivariable logistic regression. Of 37,050 patients who met the eligibility criteria, 529 patients (1.4%) developed symptomatic venous thromboembolism. The ICU-Venous Thromboembolism score consists of six independent predictors: central venous catheterization (5 points), immobilization greater than or equal to 4 days (4 points), prior history of venous thromboembolism (4 points), mechanical ventilation (2 points), lowest hemoglobin during hospitalization greater than or equal to 9 g/dL (2 points), and platelet count at admission greater than 250,000/μL (1 point). Patients with a score of 0–8 (76% of the sample) had a low (0.3%) risk of venous thromboembolism; those with a score of 9–14 (22%) had an intermediate (3.6%) risk of venous thromboembolism (hazard ratio, 6.7; 95% CI, 5.3–8.4); and those with a score of 15–18 (2%) had a high (17.7%) risk of venous thromboembolism (hazard ratio, 28.1; 95% CI, 21.7–36.5). The overall C-statistic of the model was 0.87 (95% CI, 0.85–0.88).

Conclusions:

Clinically diagnosed symptomatic venous thromboembolism occurred in 1.4% of this large population of ICU patients with high adherence to chemoprophylaxis. Central venous catheterization and immobilization are potentially modifiable risk factors for venous thromboembolism. The ICU-Venous Thromboembolism score can identify patients at increased risk for venous thromboembolism.
Advancements in medical and surgical treatments of Takayasu arteritis-induced renal arteritis: a systematic review
Authors: Dai Xiao-Min , Yin Meng-Meng , Liu Yun , Ma Li-Li , Ying Jun , Jiang Lin-Di
Published: March 2020

Background

Takayasu arteritis-induced renal arteritis (TARA), commonly seen in Takayasu arteritis (TA), has become one of the main causes of poor prognosis and early mortality in patients with TA. TARA progressing into Takayasu arteritis-induced renal artery stenosis (TARAS), could lead to severe complications including malignant hypertension, cardiac-cerebral vascular disease, and ischemic nephropathy. Since there existed no guidelines on treatments, this study aimed to review the comprehensive treatments for TARA.

Methods

We searched systematically in databases including PubMed, Ovid-Medline, EMBASE, Web of Science, China National Knowledge Infrastructure, Wanfang, and SinoMed, from inception to May 2018. Literature selection, data extraction, and statistical analysis were performed.

Results

Eighty-two literatures were recruited focusing on medical treatments (n = 34) and surgical treatments (n = 48). We found that combined medical treatments of glucocorticoids and conventional synthetic disease-modifying anti-rheumatic drugs could reach high rates of remission in patients with TARA, and biological disease-modifying anti-rheumatic drugs were preferred for refractory patients. After remission induction, surgical treatment could help reconstruct renal artery and recover renal function partly. Percutaneous transluminal angioplasty was the first choice for patients with TARAS, while open surgery showed a good long-term survival.

Conclusions

Patients with TARA should benefit both from medical treatments and from surgical treatments comprehensively and sequentially. Multidisciplinary team coordination is recommended especially in patients with severe complications.
Effect of KIF22 on promoting proliferation and migration of gastric cancer cells via MAPK-ERK pathways
Authors: Yu Ze-Yuan , Jiang Xiang-Yan , Zhao Rong-Rong , Qin Jun-Jie , Luo Chang-Jiang , Ren Yan-Xian , Ren Wen , Ma Zhi-Jian , Jiao Zuo-Yi
Published: March 2020

Background

Gastric cancer (GC) is one of the most globally prevalent cancers in the world. The pathogenesis of GC has not been fully elucidated, and there still lacks effective targeted therapeutics. The influence of altered kinesin superfamily protein 22 (KIF22) expression in GC progression is still unclearly. The aim of this study was to investigate the KIF22 effects on GC and related mechanisms.

Methods

Gastric carcinoma tissues and matching non-cancerous tissues were collected from patients with GC who have accepted a radical gastrectomy in Lanzhou University Second Hospital from May 2013 to December 2014. The expression of KIF22 was examined in GC of 67 patients and 20 para-carcinoma tissues by immunochemical staining. The relationship between the expression of KIF22 and clinicopathologic characteristics was next investigated in the remaining 52 patients except for 15 patients who did not complete follow-up for 5 years. Cell viability was performed via 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) test and colony formation assay in the MGC-803 and BGC-823 GC cells. Cell scratch and trans-well invasion assay was performed to assess migration ability in the MGC-803 and BGC-823 GC cells. Gene set enrichment analysis (GSEA) pathway enrichment analysis was performed to explore the potential functions. Cell cycle was detected by flow cytometry. In addition, the two GC cell lines were used to elucidate the underlying mechanism of KIF22 in GC in vitro via assessing the effects on mitogen-activated protein kinase and extracellular regulated protein kinases (MAPK/ERK) signal transduction pathway-related expressions by Western blotting assays. The differences were compared by t tests, one-way analysis of variance, and Chi-squared tests.

Results

The study showed that KIF22 was up-regulated in GC, and KIF22 high expression was significantly related to differentiation degree (χ
2 = 12.842, P = 0.002) and poorly overall survivals. GSEA pathway enrichment analysis showed that KIF22 was correlated with the cell cycle. Silence of KIF22 decreased the ability of the proliferation and migration in gastric cells, induced G1/S phase cell cycle arrest via regulating the MAPK-ERK pathways.

Conclusions

KIF22 protein level was negatively correlated with prognosis. KIF22 knockdown might inhibit proliferation and metastasis of GC cells via the MAPK-ERK signaling pathway.
Chemokine-like factor-like MARVEL transmembrane domain-containing family in autoimmune diseases
Authors: Duan Hong-Ji , Li Xin-Yi , Liu Chang , Deng Xiao-Li
Published: March 2020

The chemokine-like factor (CKLF)-like MARVEL transmembrane domain-containing family (CMTM) is widely expressed in the immune system. Abnormal expression of CMTM is associated with the development of various diseases. This article summarizes the relevant research on the role of the CMTM family in immune disorders. This information will increase our understanding of pathogenesis and identify promising targets for the diagnosis and treatment of autoimmune diseases. The CMTM family is highly expressed in peripheral blood mononuclear cells. CKLF1 may be involved in the development of arthritis through its interaction with C-C chemokine receptor 4. CKLF1 is associated with the pathogenesis of lupus nephritis and psoriasis. Both CMTM4 and CMTM5 are associated with the pathogenesis of systemic lupus erythematosus. CMTM1, CMTM2, CMTM3, and CMTM6 play a role in rheumatoid arthritis, systemic sclerosis, Sjögren syndrome, and anti-phospholipid syndrome, respectively. The CMTM family has been implicated in various autoimmune diseases. Further research on the mechanism of the action of CMTM family members may lead to the development of new treatment strategies for autoimmune diseases.
Correction of the Tear Trough Deformity and Concomitant Infraorbital Hollows With Extracellular Matrix/Stromal Vascular Fraction Gel
Authors: Luo Sai , Zhang Xi , Dong Huishuang , Wen Changlong , Hao Lijun
Published: March 2020

BACKGROUND

The tear trough deformity is a sign of eye aging. Filling is an ideal choice for the tear trough accompanied by infraorbital hollows.

OBJECTIVE

To evaluate the efficacy and safety of stromal vascular fraction gel (SVF-gel) as a filler for the tear trough deformity which is combined with infraorbital hollows.

MATERIALS AND METHODS

From July 2017 to June 2018, 33 patients underwent autologous fat aspiration and were followed up successfully. Stromal vascular fraction gel was used to correct patients with bilateral Barton Ⅰ/Ⅱ tear trough deformity and infraorbital hollows. Improvement was evaluated by measuring skin-periosteal depth, 3D volume, global aesthetic improvement scale (GAIS), and patient self-assessment.

RESULTS

Skin-periosteal depth improved significantly (p < .001). The volumetric increment of the tear trough and infraorbital regions increased 2.132 ± 0.671 mL, and the retention rate was excellent (72.87 ± 10.23%). The GAIS showed a high score (2.5 ± 0.5 points), with patient self-assessment showing satisfactory results for all 7 questions on the questionnaire.

CONCLUSION

The high retention rate of SVF-gel suggests that it can provide an effective solution to tear trough deformity accompanied by infraorbital hollows.
Are There Differences Between Intradermal and Intramuscular Injections of Botulinum Toxin on the Forehead?
Authors: Kim Yu Jin , Lim Oh Kyung , Choi Won Jun
Published: March 2020

BACKGROUND

The intradermal technique to inject botulinum toxin is a popular procedure in upper facial rejuvenation to minimize side effects, such as brow ptosis, and can sometimes result in a lifting effect.

OBJECTIVE

The present study investigated differences in effects according to injection modality.

METHODS AND MATERIALS

Fifteen women received intradermal injections of botulinum toxin (total dose, 8U) into the forehead, and 14 women received intramuscular injections.

RESULTS

The maximal antiwrinkle effect was recorded at Week 2, and the duration of the effect was the same in both groups. The brow position was lowered at Weeks 2 and 4 in the intramuscular injection group and was preserved in the intradermal injection group throughout the follow-up period. The amount of maximal voluntary eyebrow movement was decreased at Weeks 2 and 4 and recovered at Week 16 in both groups. The change in the electromyographic amplitude of the frontalis muscle was prolonged until Week 16 in both groups. Subjective satisfaction with wrinkles was similar in both groups. However, the intradermal injection was more painful.

CONCLUSION

Intradermal injection of botulinum toxin is a safe and effective method to improve forehead rhytides.
Factors Affecting Depth of Penetration in Microneedling- and Laser-Assisted Drug Delivery: The Importance of Timing of Topical Application
Authors: Chung Hye Jin , Cheng Judy , Gonzalez Manuel , Al-Janahi Sara
Published: March 2020

BACKGROUND

Microneedling- and laser-assisted drug delivery are emerging techniques used to treat various conditions. However, key parameters affecting drug penetration remain unknown.

OBJECTIVE

This study aims to investigate the importance of timing of topical application, needle length, and device type for drug delivery.

MATERIALS AND METHODS

Skin harvested from cosmetic surgeries was treated with black ink applied before or after treatment with a microneedling pen (MP), roller, or fractional ablative CO2 laser, and incubated for different time intervals. Ink penetration was additionally tested using different needle lengths. Sandwich estimator was used for statistical analysis.

RESULTS

Ink applied before MP penetrated deeper compared to ink applied afterward at 1 and 3 hours, and roller microneedling in both the ink-before and -after scenarios at 1, 3, and 6 hours (p < .05). Microneedling demonstrated lateral extension of ink beyond microchannels with increased ink penetration over time. CO2 laser demonstrated ink localization within microthermal zones without time-dependent increases in depth after 30 minutes. Ink penetration increases by 0.06 mm per 1 mm increase in needle length.

CONCLUSION

Ink applied before MP results in the deepest penetration of ink. Microneedling offers unique advantages in transdermal delivery as its channels exhibit increasing penetration over time and lateral extension of product.
Direct Oral Anticoagulants for the Treatment of Left Ventricular Thrombus—A New Indication? A Meta-summary of Case Reports
Authors: Tomasoni Daniela , Sciatti Edoardo , Bonelli Andrea , Vizzardi Enrico , Metra Marco
Published: March 2020

Left ventricular thrombus (LVT) can be a consequence of cardiac diseases such as heart failure with reduced ejection fraction and acute myocardial infarction. Currently, the guidelines recommend the use of warfarin for the treatment of this condition. However, there are increasing reports of patients with LVTs being treated with direct oral anticoagulants (DOACs), for several reasons. We set out to review the available literature to assess the safety and the efficacy of this approach. We analyzed 52 cases, extrapolated by 34 papers contained in literature, focusing on the characteristics of patients, treatment, outcome, and follow-up. Rivaroxaban was the most commonly used DOAC, followed by apixaban. The diagnosis of LVT and the follow-up were mainly performed by transthoracic echocardiography. The thrombus resolved in 45 patients (92%) of 49 (there are no data available regarding the outcome of 3 patients) and failed to resolve in 4 patients treated with DOACs. The resolution occurred in a median of 32 days. DOACs are shown to be a reasonable and valid option for the treatment of LVT. Our study provides a rationale for a prospective randomized controlled trial.
Association between osteoporosis and menopause in relation to SOX6 rs297325 variant in Taiwanese women
Authors: Hsu Tzu-Liang , Tantoh Disline Manli , Chou Ying-Hsiang , Hsu Shu-Yi , Ho Chien-Chang , Lung Chia-Chi , Jan Cheng-Feng , Wang Lee , Liaw Yung-Po
Published: March 2020

Objective:

Osteoporosis, the most prevalent bone disorder in humans, is a global public health issue and its relationship with menopause is well-established. The interaction between menopause and genes on osteoporosis risk is, however, yet to be fully elucidated. We assessed the association between menopause and osteoporosis in relation to the SOX6 rs297325 variant in Taiwanese women.

Methods:

There were 7,581 female participants, aged 30 to 70 years old. Information on SOX6 rs297325 and menopause were obtained from the Taiwan Biobank Database while that on osteoporosis was obtained from the National Health Insurance Research Database.

Results:

Menopause but not SOX6 rs297325 was significantly associated with a higher risk of osteoporosis (odds ratio [OR] = 1.48; 95% confidence interval [CI] = 1.04-2.10). The interaction between menopause and rs297325 on osteoporosis was significant (P = 0.0216). After stratification by rs297325 genotypes, the risk of osteoporosis was significantly higher in menopausal women having the TT + CC genotype (OR = 2.02; 95% CI = 1.21-3.38). After stratification by menopausal status and rs297325 genotypes, the OR; 95% CI was 0.62; 0.38 to 0.99 in premenopausal women with the TC + CC genotype and 1.24; 0.82 to 1.88 in menopausal women with the TC + CC genotype.

Conclusion:

SOX6 rs297325 was not significantly associated with osteoporosis but might have modulated the association between menopause and osteoporosis. The risk of osteoporosis was higher in menopausal women with the TC + CC genotype but lower in premenopausal women with the TC + CC genotype.
Minimally Invasive Surgery in Pregnancy
Authors: CHOHAN LUBNA , NIJJAR J. BIBA
Published: March 2020

If it is medically necessary to perform nonobstetrical abdominal surgery in pregnancy, a minimally invasive approach should be considered. The benefits of laparoscopy are well known and current studies promote the safety of laparoscopy in pregnancy, when certain guidelines are followed. This article will review the safety of surgery in pregnancy, maternal physiology, fetal considerations, maternal obesity, laparoscopic cerclage, large adnexal mass, and complications. Guidelines for surgery will be reviewed as well.
Molecular and Epidemiologic Analysis of Diarrheal Pathogens in Children With Acute Gastroenteritis in Bangladesh During 2014–2019
Authors: Sharif Nadim , Nobel Nasir Uddin , Sakib Najmuj , Liza Syeda Moriam , Khan Shafia Tasnim , Billah Baki , Parvez Anowar Khasru , Haque Aynul , Talukder Ali Azam , Dey Shuvra Kanti
Published: March 2020

Background:

Diarrheal disease is one of the leading causes of childhood morbidity and mortality in the 21st century in developing countries. Mainly infants and young children develop diarrheal diseases. This study aims to determine the incidence of diarrheal pathogens in children in Bangladesh.

Methods:

During 2014 to 2019, 387 fecal specimens were collected from children with diarrhea in Bangladesh. Bacterial pathogens were detected by conventional bacteriologic, biochemical and molecular sequence analysis methods. DNA virus and RNA virus (diarrheal viruses) were detected using polymerase chain reaction and reverse transcriptase polymerase chain reaction, respectively and confirmed by molecular sequence analysis.

Results:

Bacterial infections were detected in 39.27% (152 of 387) of the stool samples. Escherichia coli was the most prevalent (17.3%) followed by Vibrio cholerae (13.5%), Salmonella spp. (4.9%) and Shigella spp. (3.6%). From 387 fecal specimens tested, 42.4% (164 of 387) were positive for viral infections. Rotavirus was the most prevalent (26.3%), followed by adenovirus (5.7%), norovirus (5.4%) and human bocavirus (4.9%). Dual infection between rotavirus and E. coli accounted for the largest portion of coinfection (48%). Diarrhea (77%) and abdominal pain (65%) were most common followed by vomiting (63%), fever (43%) and dehydration (39%). E. coli and V. cholerae were most resistant against ciprofloxacin (62.7%) and tetracycline (88.5%). qnrA and sul4 resistance genes were isolated from these pathogens.

Conclusions:

Data from this study underline the high incidence of diarrheal pathogens and presence of antibiotics resistance genes in a pediatric population in Bangladesh.