Two biomechanical strategies for locomotor adaptation to split-belt treadmill walking in subjects with and without transtibial amputation.

Abstract: Locomotor adaptation is commonly studied using split-belt treadmill walking, in which each foot is placed on a belt moving at a different speed. As subjects adapt to split-belt walking, they reduce metabolic power, but the biomechanical mechanism behind this improved efficiency is unknown. Analyzing mechanical work performed by the legs and joints during split-belt adaptation could reveal this mechanism. Because ankle work in the step-to-step transition is more efficient than hip work, we hypothesized that control subjects would reduce hip work on the fast belt and increase ankle work during the step-to-step transition as they adapted. We further hypothesized that subjects with unilateral, trans-tibial amputation would instead increase propulsive work from their intact leg on the slow belt. Control subjects reduced hip work and shifted more ankle work to the step-to-step transition, supporting our hypothesis. Contrary to our second hypothesis, intact leg work, ankle work and hip work in amputees were unchanged during adaptation. Furthermore, all subjects increased collisional energy loss on the fast belt, but did not increase propulsive work. This was possible because subjects moved further backward during fast leg single support in late adaptation than in early adaptation, compensating by reducing backward movement in slow leg single support. In summary, subjects used two strategies to improve mechanical efficiency in split-belt walking adaptation: a CoM displacement strategy that allows for less forward propulsion on the fast belt; and, an ankle timing strategy that allows efficient ankle work in the step-to-step transition to increase while reducing inefficient hip work.

Selgrade|Brian P|BP|
Toney|Megan E|ME|
Chang|Young-Hui|YH|

Biomechanics Adaptation Split-belt Walking Efficiency Amputee


Acetaminophen use during pregnancy and DNA methylation in the placenta of the extremely low gestational age newborn (ELGAN) cohort.

Abstract: Acetaminophen is considered the safest antipyretic and analgesic medication for pregnant women. However, studies have reported that acetaminophen has endocrine disrupting properties and prenatal exposure has been associated with early life epigenetic changes and later life health outcomes. As the placenta is the central mediator of maternal and fetal interactions, exposure to acetaminophen during pregnancy could manifest as perturbations in the placenta epigenome. Here, we evaluated epigenome-wide cytosine-guanine dinucleotide (CpG) methylation in placental tissue in relation to maternal acetaminophen use during pregnancy in a cohort of 286 newborns born prior to 28 weeks gestation. According to maternal self-report, more than half (166 of 286) of the newborns were exposed to acetaminophen in utero. After adjustment for potential confounders, a total of 42 CpGs were identified to be differentially methylated at a false discovery rate < 0.05, with most displaying increased methylation as it relates to acetaminophen exposure. A notable gene that was significantly associated with acetaminophen is the prostaglandin receptor (PTGDR) which plays an essential role in mediating placental blood flow and fetal growth. Moreover, for 6 of the 42 CpGs, associations of acetaminophen use with methylation were significantly different between male and female placentas; 3 CpG sites were associated with acetaminophen use in the male placenta and 3 different sites were associated with acetaminophen use in the female placenta (P interaction < 0.2). These findings highlight a relationship between maternal acetaminophen use during pregnancy and the placental epigenome and suggest that the responses for some CpG sites are sex dependent.

Addo|Kezia A|KA|
Bulka|Catherine|C|
Dhingra|Radhika|R|
Santos|Hudson P|HP|
Smeester|Lisa|L|
O'Shea|T Michael|TM|
Fry|Rebecca C|RC|

acetaminophen
DNA methylation
placenta
endocrine disruption
prenatal
maternal
sexual dimorphism


Phosphate removal via biological process coupling with hydroxyapatite crystallization in alternating anaerobic/aerobic biofilter reactor.

Abstract: In this work, a laboratory-scale alternating anaerobic/aerobic biofilter (A/O BF) filled with self-made steel slag media was constructed, where the integrated biological and crystalline phosphorus removal process was realized to remove phosphorus and achieve phosphorus recovery from wastewater. Phosphorus accumulating organisms (PAOs) were successfully enriched within 30 days operation, the maximum phosphate removal efficiency was close to 80% under the optimal conditions with the anaerobic time of 34 h, HRT of 4 h and influent COD of 300 mg/L. The analysis of SEM-EDS and XRD indicated that hydroxyapatite (HAP) crystals were formed inside biofilms without addition of chemical reagents. The high phosphate environment created by PAOs and the release of Ca2+ from the steel slag media might be responsible for the generation of HAP. These findings have crucial implications for the application BF technology to remove and recover phosphorus from wastewater.

Sun|Shaofang|S| Gao|Mingchang|M| Wang|Yue|Y| Qiu|Qi|Q| Han|Junli|J| Qiu|Liping|L| Feng|Yan|Y|


Nitrogen and Oxygen Co-doped Graphitized Carbon Fibers with Sodiophilic-Rich Sites Guide Uniform Sodium Nucleation for Ultrahigh-Capacity Sodium-Metal Anodes.

Abstract: Sodium (Na) metal is an ideal anode for high-energy Na batteries due to the low cost and natural abundance of Na metal. Nevertheless, issues regarding dendritic and mossy Na metal deposits have prevented their practical application. Herein, nitrogen and oxygen co-doped graphitized carbon fibers (DGCF) have been developed as the Na plating hosts to direct Na metal homogeneous nucleation and suppress the growth of Na dendrites. We show experimental results as well as first-principles calculations demonstrating that the uniformly doped nitrogen and oxygen function as sodiophilic sites that direct the sodium-metal nucleation to a smooth dendrite-free anode. The resultant DGCF-Na anode can be cycled stably at 1 mA cm-2 for a high areal capacity of 12.7 mA h cm-2 with an average Coulombic efficiency of 99.8%, and a Na|Na symmetrical cell can be cycled with long-term durability for more than 1200 h at 2 mA cm-2. When coupled with P2-Na2/3Ni1/3Mn1/3Ti1/3O2 and Na3V2(PO4)3 cathodes, the DGCF-Na composite demonstrates good feasibility in full cells.

sodium-metal anode
sodiophilic sites
dendrite-free
Na deposition
ultrahigh capacity


Salivary and serum level of CYFRA 21-1 in oral precancer and oral squamous cell carcinoma.

Abstract:
BACKGROUND
CYFRA 21-1, a constituent of the intermediate filament proteins of epithelial cells, is known to be increased in many cancers. This study was designed to estimate the levels of salivary and serum CYFRA 21-1 in patients with oral precancer and oral squamous cell carcinoma (OSCC) and compare them with healthy controls.

MATERIALS AND METHODS
Each group comprised of 100 subjects. Saliva and blood samples were collected from patients with OSCC, premalignant subjects, and normal healthy subjects. Serum and salivary CYFRA 21-1 levels were measured by enzyme-linked immunosorbent assay. Appropriate statistical tests were employed to assess diagnostic potency of CYFRA 21-1.

RESULTS
We found a significant increase in CYFRA 21-1 level in OSCC compared with PML and healthy subjects. Salivary CYFRA 21-1 levels in OSCC was threefold higher when compared to serum levels. PML group showed increased salivary CYFRA 21-1 when compared to control subjects, but it was significantly lower compared with OSCC. Receiver operator characteristic curve analysis showed salivary CYFRA 21-1 to have superior sensitivity in detecting OSCC compared with serum CYFRA 21-1.

CONCLUSIONS
The outcome of this study suggests that salivary CYFRA 21-1 can be utilized as a biomarker in early detection of oral cancer.

Rajkumar|K|K|
Ramya|R|R|
Nandhini|G|G|
Rajashree|P|P|
Ramesh Kumar|A|A|
Nirmala Anandan|S|S|

CYFRA 21-1
squamous cell carcinoma
oral cancer
diagnosis
premalignant lesion


CCT020312 Inhibits Triple-Negative Breast Cancer Through PERK Pathway-Mediated G1 Phase Cell Cycle Arrest and Apoptosis.

Abstract: Triple-negative breast cancer (TNBC) has a poor prognosis due to the lack of specific therapeutic targets. CCT020312, a selective eukaryotic translation initiation factor 2 alpha (eIF2α)/protein kinase RNA-like endoplasmic reticulum kinase (PERK) activator, may have a potent anti-tumor effect. In the present study, we examined the effects of CCT020312 on TNBC and explored the underlying mechanism. We found that CCT020312 inhibited the viability of TNBC cell lines, MDA-MB-453 and CAL-148, by inducing apoptosis and G1 phase cell cycle arrest. CCT020312 decreased the protein levels of cyclin-dependent kinase 4 (CDK4), CDK6, cyclin D1, and B-cell lymphoma 2 (Bcl-2) and increased the levels of Bcl-2-associated X protein (Bax) and cleaved poly (ADP-ribose) polymerase (PARP) compared with those in the control. CCT020312 activated PERK/eIF2α/activating transcription factor 4 (ATF4)/CCAAT-enhancer binding protein (C/EBP) homologous protein transcription factor (CHOP) signaling and inhibited protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling. Furthermore, CCT020312 inhibited tumor growth in an MDA-MB-453 orthotopic xenograft mouse model by activating the PERK/eIF2α/ATF4/CHOP pathway and inhibiting the AKT/mTOR pathway. Thus, our study shows that CCT020312 may be a potential drug candidate for TNBC treatment.

Li|Xiaoli|X| Yu|Xiaoping|X| Zhou|Duanfang|D| Chen|Bo|B| Li|Wenjun|W| Zheng|Xiangru|X| Zeng|Hongfang|H| Long|Liangyuan|L| Zhou|Weiying|W|


Outcome and Treatment of Antenatally Diagnosed Nonimmune Hydrops Fetalis.

Abstract:
INTRODUCTION
The objectives of this study were to evaluate the outcome of nonimmune hydrops fetalis in an attempt to identify independent predictors of perinatal mortality.

MATERIAL AND METHODS
A retrospective cohort study was conducted including all cases of nonimmune hydrops from two tertiary care centers. Perinatal outcome was evaluated after classifying nonimmune hydrops into ten etiological groups. We examined the effect of etiology, site of fluid accumulation, and gestational age at delivery on postnatal survival. Neonatal mortality and hospital discharge survival were compared between the expectant management and fetal intervention groups among those with idiopathic etiology.

RESULTS
A total of 142 subjects were available for analysis. Generally, nonimmune hydrops carried 37% risk of neonatal mortality and 50% chance of survival to discharge, which varies markedly based on the underlying etiology. Ascites was an independent predictor of perinatal mortality (p value = 0.003). There was nonsignificant difference in neonatal mortality and hospital discharge survival among idiopathic cases that were managed expectantly versus those in whom fetal intervention was carried out.

DISCUSSION
The outcome of nonimmune hydrops varies largely according to the underlying etiology and the presence of ascites is an independent risk factor for perinatal mortality. In our series, fetal intervention did not offer survival advantage among fetuses with idiopathic nonimmune hydrops.

Nassr|Ahmed A|AA|
Ness|Amen|A|
Hosseinzadeh|Pardis|P|
Salmanian|Bahram|B|
Espinoza|Jimmy|J|
Berger|Victoria|V|
Werner|Eleonore|E|
Erfani|Hadi|H|
Welty|Stephen|S|
Bateni|Zhoobin H|ZH|
Shamshirsaz|Amir A|AA|
Popek|Edwina|E|
Ruano|Rodrigo|R|
Davis|Alexis S|AS|
Lee|Timothy C|TC|
Keswani|Sundeep|S|
Cass|Darrell L|DL|
Olutoye|Oluyinka O|OO|
Belfort|Michael A|MA|
Shamshirsaz|Alireza A|AA|

D015331:Cohort Studies
D005260:Female
D006801:Humans
D015160:Hydrops Fetalis
D007231:Infant, Newborn
D054238:Perinatal Mortality
D011247:Pregnancy
D012189:Retrospective Studies
D016896:Treatment Outcome
D016216:Ultrasonography, Prenatal

Perinatal mortality
Survival
Neonatal mortality
Fetal intervention
Fetal ascites
Fetal hydrops
Fetal pleural effusion


Acceleration-triggered animal-borne videos show a dominance of fish in the diet of female northern elephant seals.

Abstract: Knowledge of the diet of marine mammals is fundamental to understanding their role in marine ecosystems and response to environmental change. Recently, animal-borne video cameras have revealed the diet of marine mammals that make short foraging trips. However, novel approaches that allocate video time to target prey capture events is required to obtain diet information for species that make long foraging trips over great distances. We combined satellite telemetry and depth recorders with newly developed date-/time-, depth- and acceleration-triggered animal-borne video cameras to examine the diet of female northern elephant seals during their foraging migrations across the eastern North Pacific. We obtained 48.2 h of underwater video, from cameras mounted on the head (n=12) and jaw (n=3) of seals. Fish dominated the diet (78% of 697 prey items recorded) across all foraging locations (range: 37-55°N, 122-152°W), diving depths (range: 238-1167 m) and water temperatures (range: 3.2-7.4°C), while squid comprised only 7% of the diet. Identified prey included fish such as myctophids, Merluccius sp. and Icosteus aenigmaticus, and squid such as Histioteuthis sp., Octopoteuthis sp. and Taningia danae Our results corroborate fatty acid analysis, which also found that fish are more important in the diet, and are in contrast to stomach content analyses that found cephalopods to be the most important component of the diet. Our work shows that in situ video observation is a useful method for studying the at-sea diet of long-ranging marine predators.

Yoshino|Kaori|K|
Takahashi|Akinori|A|0000-0002-9868-0408
Adachi|Taiki|T|
Costa|Daniel P|DP|
Robinson|Patrick W|PW|
Peterson|Sarah H|SH|
Hückstädt|Luis A|LA|
Holser|Rachel R|RR|
Naito|Yasuhiko|Y|

Marine mammal
Foraging
Bio-logging
Diving behavior
Mesopelagic zone


The Senticaudata, a suborder of the Amphipoda - A commentary on d'Udekem d'Acoz and Verheye (2017).

Abstract: A response is given to criticisms in a recent paper of the validity of the amphipod suborder Senticaudata. The tacitly assumed status of truth implied in some molecular higher phylogenies is called in to question.

Senticaudata Amphipoda phylogeny classification


Local Skin Inflammation in Cutaneous Leishmaniasis as a Source of Variable Pharmacokinetics and Therapeutic Efficacy of Liposomal Amphotericin B.

Abstract: Disfiguring skin lesions caused by several species of the Leishmania parasite characterize cutaneous leishmaniasis (CL). Successful treatment of CL with intravenous (i.v.) liposomal amphotericin B (LAmB) relies on the presence of adequate antibiotic concentrations at the dermal site of infection within the inflamed skin. Here, we have investigated the impact of the local skin inflammation on the pharmacokinetics (PK) and efficacy of LAmB in two murine models of localized CL (Leishmania major and Leishmania mexicana) at three different stages of disease (papule, initial nodule, and established nodule). Twenty-four hours after the administration of one 25 mg/kg of body weight LAmB (i.v.) dose to infected BALB/c mice (n = 5), drug accumulation in the skin was found to be dependent on the causative parasite species (L. major > L. mexicana) and the disease stage (papule > initial nodule > established nodule > healthy skin). Elevated tissue drug levels were associated with increased vascular permeability (Evans blue assay) and macrophage infiltration (histomorphometry) in the infected skin, two pathophysiological parameters linked to tissue inflammation. After identical treatment of CL in the two models with 5 × 25 mg/kg LAmB (i.v.), intralesional drug concentrations and reductions in lesion size and parasite load (quantitative PCR [qPCR]) were all ≥2-fold higher for L. major than for L. mexicana In conclusion, drug penetration of LAmB into CL skin lesions could depend on the disease stage and the causative Leishmania species due to the influence of local tissue inflammation.

Wijnant|Gert-Jan|GJ|
Van Bocxlaer|Katrien|K|
Fortes Francisco|Amanda|A|
Yardley|Vanessa|V|
Harris|Andy|A|
Alavijeh|Mo|M|
Murdan|Sudaxshina|S|
Croft|Simon L|SL|

inflammation
cutaneous leishmaniasis
pharmacokinetics
liposomal amphotericin B


Young Adults With Sickle Cell Disease: Challenges With Transition to Adult Health Care.

Abstract: Because life expectancy has increased greatly in the past few decades for individuals living with sickle cell disease (SCD), transition to the adult healthcare setting has become a necessity to continue disease management. Transition for young adults with SCD is associated with declining health outcomes, including increased acute care use and mortality. Nurses can assist young adults with SCD who are at risk after transition by assessing the young adult's ability to carry out disease self-management, facilitating the supportive role of the family, and recognizing young adults who may have difficulty accessing healthcare resources and providers.

D000755:Anemia, Sickle Cell
D003695:Delivery of Health Care
D019468:Disease Management
D006801:Humans
D055815:Young Adult

young adult
self-management
continuity of care
transition to adult care


Endothelial-to-Mesenchymal Transition: Role in Cardiac Fibrosis.

Abstract: Endothelial-to-mesenchymal transition (EndMT) is a complex biological process by which endothelial cells lose their endothelial cell characteristics and acquire mesenchymal cell properties under certain physiological or pathological conditions. Recently, it has been found that EndMT plays an important role in the occurrence and development of fibrotic cardiovascular diseases. In this review, we first summarize the main induction pathways involved in EndMT process. In addition, we discuss the role of EndMT in fibrotic cardiovascular diseases and its potential implication in new therapeutic interventions.

endothelial-to-mesenchymal transition
cardiac fibrosis
cardiovascular diseases
TGF-β signaling
microRNAs
oxidative stress


Real-time kinetics of cadmium transport and transcriptomic analysis in low cadmium accumulator Miscanthus sacchariflorus.

Abstract: The molecular mechanism of low Cd influxes and accumulation in Miscanthus sacchariflorus is revealed by RNA sequencing technique. Soil cadmium (Cd) pollution has posed a serious threat to our soil quality and food security as well as to human health. Some wild plants exhibit high tolerance to heavy metals stress. However, mechanisms of Cd tolerance of wild plants remain to be fully clarified. In this study, we found that two Miscanthus species, Miscanthus (M.) sacchariflorus and M. floridulus, showed different Cd-tolerant mechanisms. M. sacchariflorus accumulated less Cd in both root and leaf by limiting Cd uptake from root and showed superior Cd tolerance, while M. floridulus not only absorbs more Cd from root but also transports more Cd to shoot. To investigate the molecular mechanism of different Cd uptake patterns in the two Miscanthus species, we analyzed the transcriptome of M. sacchariflorus and identified transcriptional changes in response to Cd in roots by high-throughput RNA-sequencing technology. A total of 92,985 unigenes were obtained from M. sacchariflorus root cDNA samples. Based on the assembled de novo transcriptome, 681 DEGs which included 345 upregulated and 336 downregulated genes were detected between two libraries of untreated and Cd-treated roots. Gene ontology (GO) and pathway enrichment analysis revealed that upregulated DEGs under Cd stress are predominately involved in metabolic pathway, starch and sucrose and biosynthesis of secondary metabolites and metal ion transporters. Quantitative RT-PCR was employed to compare the expression levels of some metal transport genes in roots of two Miscanthus species, and the genes involved in Cd uptake from root and transfer from root to shoot were extremely different. The results not only enrich genomic resource but also help to better understand the molecular mechanisms of Cd accumulation and tolerance in wild plants.

Guo|Haipeng|H| Hong|Chuntao|C| Xiao|Mengzhu|M| Chen|Xiaomin|X| Chen|Houming|H| Zheng|Bingsong|B| Jiang|Dean|D|

D018506:Gene Expression Regulation, Plant

D060888:Real-Time Polymerase Chain Reaction

Transcriptomic analysis
Miscanthus sacchariflorus
RT-PCR
Cd fluxes
Metal transport protein
Miscanthus floridulus


Asparagine Synthesis During Tobacco Leaf Curing.

Abstract: Senescence is a genetically controlled mechanism that modifies leaf chemistry. This involves significant changes in the accumulation of carbon- and nitrogen-containing compounds, including asparagine through the activity of asparagine synthetases. These enzymes are required for nitrogen re-assimilation and remobilization in plants; however, their mechanisms are not fully understood. Here, we report how leaf curing-a senescence-induced process that allows tobacco leaves to dry out-modifies the asparagine metabolism. We show that leaf curing strongly alters the concentration of the four main amino acids, asparagine, glutamine, aspartate, and glutamate. We demonstrate that detached tobacco leaf or stalk curing has a different impact on the expression of asparagine synthetase genes and accumulation of asparagine. Additionally, we characterize the main asparagine synthetases involved in the production of asparagine during curing. The expression of ASN1 and ASN5 genes is upregulated during curing. The ASN1-RNAi and ASN5-RNAi tobacco plant lines display significant alterations in the accumulation of asparagine, glutamine, and aspartate relative to wild-type plants. These results support the idea that ASN1 and ASN5 are key regulators of asparagine metabolism during leaf curing.

Bovet|Lucien|L| Cheval|Cecilia|C| Hilfiker|Aurore|A| Battey|James|J| Langlet|Delphine|D| Broye|Herve|H| Schwaar|Joanne|J| Ozelley|Pierrick|P| Lang|Gerhard|G| Bakaher|Nicolas|N| Laparra|Helene|H| Goepfert|Simon|S|

asparagine
tobacco
curing
senescence
asparagine synthetases
nitrogen assimilation


Predictors and outcomes of heart block during surgical stage I palliation of patients with a single ventricle: A report from the NPC-QIC.

Abstract:
BACKGROUND
Mortality in cohorts with a single ventricle remains high with multiple associated factors. The effect of heart block during stage I palliation remains unclear.

OBJECTIVE
The purpose of this study was to study patient and surgical risks of heart block and its effect on 12-month transplant-free survival in patients with a single ventricle.

METHODS
Patient, surgical, outcome data and heart block status (transient and permanent) were obtained from the National Pediatric Cardiology Quality Improvement Collaborative single ventricle database. Bivariate analysis was performed comparing patients with and without heart block, and multivariate modeling was used to identify variables associated with block. One-year outcomes were analyzed to identify variables associated with lower 12-month transplant-free survival.

RESULTS
In total, 1423 patients were identified, of whom 28 (2%) developed heart block (second degree or complete) during their surgical admission. Associated risk factors for block included heterotaxy syndrome (odds ratio [OR] 6.4) and atrial flutter/fibrillation (OR 3.8). Patients with heart block had lower 12-month survival, though only in patients with complete heart block as opposed to second degree block. At 12 months of age, 43% (12/28) of patients with heart block died and were more likely to experience mortality at 12 months than patients without block (OR 4.9; 95% confidence interval 1.4-17.5; P = .01).

CONCLUSION
Although rare, complete heart block after stage I palliation represents an additional risk of poor outcomes in this high-risk patient population. Heterotaxy syndrome was the most significant risk factor for the development of heart block after stage I palliation. The role of transient block in outcomes and potential rescue with long-term pacing remains unknown and requires additional study.

Czosek|Richard J|RJ|
Anderson|Jeffrey B|JB|
Baskar|Shankar|S|
Khoury|Philip R|PR|
Jayaram|Natalie|N|
Spar|David S|DS|

Heart block
Stage I palliation
Survival
Pediatric cardiology
Hypoplastic left heart syndrome


Fabrication of cellulose acetate/polybenzoxazine cross-linked electrospun nanofibrous membrane for water treatment.

Abstract: Herein, polybenzoxazine based cross-linked cellulose acetate nanofibrous membrane exhibiting enhanced thermal/mechanical properties and improved adsorption efficiency was successfully produced via electrospinning and thermal curing. Initially, suitable solution composition was determined by varying the amount of the benzoxazine (BA-a) resin, cellulose acetate (CA) and citric acid (CTR) to obtain uniform nanofibrous membrane via electrospinning. Subsequently, thermal curing was performed by step-wise at 150, 175, 200 and 225°C to obtain cross-linked composite nanofibrous membranes. SEM images and solubility experiments demonstrated that most favorable result was obtained from the 10% (w/v) CA, 5% (w/v) BA-a and 1% (w/v) CTR composition and cross-linked nanofibrous membrane (CA10/PolyBA-a5/CTR1) was obtained after the thermal curing. Chemical structural changes (ring opening) occurred by thermal curing revealed successful cross-linking of BA-a in the composite nanofibrous membrane. Thermal, mechanical and adsorption performance of pristine CA and CA10/PolyBA-a5/CTR1 nanofibrous membranes were studied. Char yield of the pristine CA nanofibrous membrane has increased notably from 12 to 24.7% for composite CA10/PolyBA-a5/CTR1 membrane. When compared to pristine CA membrane, CA10/PolyBA-a5/CTR1 nanofibrous membrane has shown superior mechanical properties having tensile strength and Young's modulus of 8.64±0.63MPa and 213.87±30.79MPa, respectively. Finally, adsorption performance of pristine CA and CA10/PolyBA-a5/CTR1 nanofibrous membranes was examined by a model polycyclic aromatic hydrocarbon (PAH) compound (i.e. phenanthrene) in aqueous solution, in which CA10/PolyBA-a5/CTR1 nanofibrous membrane has shown better removal efficiency (98.5%) and adsorption capacity (592μg/g).

Cellulose acetate
Polybenzoxazine
Water treatment
Electrospinning
Nanofibers
PAH removal


Mind the gap - Evaluation of the promotion initiatives for implementation of the GLA:D® back clinician courses.

Abstract:
BACKGROUND
Translation of research into practice is a methodological challenge. The GLA:D® Back program was initiated to implement evidence-based care for people with low back pain inspired by GLA:D® (Good Life with osteoArthritis in Denmark) that has succeeded in implementing evidence-based care for knee and hip osteoarthritis. This study evaluates the spread and reach of promotion initiatives for GLA:D® Back clinician courses, and the adoption of the GLA:D® Back intervention in clinical practice.

METHODS
Pre-defined success criteria addressed; i) spread; achievement of intended promotion activities (e.g. social media), ii) reach; recruitment of clinicians with certain profiles (e.g. gender balance). Adoption was defined as patient enrollment in the GLA:D® Back registry by course participants. Univariate and multivariate logistic regression was used to investigate associations between adoption and clinician characteristics.

RESULTS
Most clinicians signed up based on information from colleagues (22%). Pre-defined goals for reach, except one, was obtained. 23% (140) of clinicians initiated the GLA:D® Back program in clinical practice within <90 days of course participation; mainly physiotherapists (p < 0.001). The odds ratio for starting GLA:D® Back patient care in a chiropractic setting was 7.4 [2.5; 21.4], indicating that physiotherapists employed by chiropractors mostly handled the intervention.

CONCLUSION
Future promotion strategies should recognize the influence of colleagues and professional networks. Converting clinician courses into patient care was mostly adopted physiotherapists. Although, evaluation processes were less useful in this study, future evaluation of health care processes has potential to inform the implementation of new models in future studies.

Morsø|Lars|L|
Bogh|Søren Bie|SB|
Ris|Inge|I|
Kongsted|Alice|A|

D006801:Humans
D007719:Knee Joint
D017116:Low Back Pain
D015207:Osteoarthritis, Hip
D059825:Physical Therapists

Spread
Reach
Adaption
Feedback
GLA:D Back®


Clinical Characteristics of Patients with Autoimmune Pancreatitis with or without Mikulicz's Disease and Mikulicz's Disease Alone.

Abstract:
BACKGROUND/AIMS
The objective of this study was to compare the clinical characteristics of patients with autoimmune pancreatitis (AIP) with or without Mikulicz's disease (MD) and with MD alone.

METHODS
We investigated the clinical findings in 15 AIP patients with MD (group A+M), 49 AIP only patients (group A), and 14 MD only patients (group M).

RESULTS
The male-female ratio was significantly higher in group A+M (73%, p<0.05) and group A (78%, p<0.01) than group M (21%). Serum immunoglobulin G (IgG) levels were significantly higher in group A+M than in group A (p<0.01) and group M (p<0.05). Serum IgG4 levels were significantly higher in group A+M than in group A (p<0.01). Other organ involvement was observed in 73% (11/15) of patients in group A+M. The number of patients with diabetes mellitus was significantly higher in group A+M (66%, p<0.01) and group A (51%, p<0.05) than in group M (7%). All of the patients responded well to steroid therapy, but the relapse rate in group A+M (33%) was significantly higher than that in group A (3%, p<0.01). Salivary gland function was impaired in all groups compared with the control group, but the degree of dysfunction was less in group A compared with group A+M and group M.

CONCLUSIONS
The relapse rate of AIP in MD patients was significantly higher than that of AIP in patients without MD.

Kuruma|Sawako|S| Kamisawa|Terumi|T| Tabata|Taku|T| Hara|Seiichi|S| Fujiwara|Takashi|T| Kuwata|Go|G| Egarashira|Hideto|H| Koizumi|Koichi|K| Setoguchi|Keigo|K| Fujiwara|Junko|J| Arakawa|Takeo|T| Momma|Kumiko|K| Mitsuhashi|Toshio|T| Sasaki|Tsuneo|T|

Autoimmune pancreatitis
Immunoglobulin G
Steroid therapy
IgG4-related disease
Mikulicz' disease


The relationships of genetic polymorphisms of the long noncoding RNA growth arrest-specific transcript 5 with uterine cervical cancer.

Abstract: The purposes of the investigation were to examine the implications of long noncoding RNA growth arrest-specific transcript 5 (GAS5) in progression and clinicopathological factors of uterine cervical cancer, and patient survival in Taiwan. Genotypic distributions of two GAS5 genetic variants rs145204276 and rs55829688 were detected in 208 patients including 111 patients with invasive cancer, 97 with precancerous lesions as well as 307 control women using real-time polymerase chain reaction. It explored that patients with cervical precancerous lesion had lower rate of AGGCA deletion (Del) in both alleles (Del/Del) of GAS5 rs145204276 as compared with control women. Patients with invasive cancer did not exhibit higher rate of Del/Del. Meanwhile, there were no different genotypic distributions in rs55829688 among patients with cervical invasive cancer and those with precancerous lesions as well as control women. Moreover, cervical cancer patients with Ins (insertion, AGGCA)/Del and Del/Del (-/-) in GAS5 rs55829688 tended to have poorer hazard ratio (HR) of 5 years survival. In addition, lymph node metastasis status exerted the most significantly predictive of 5 years survival rate. Conclusively, GAS5 polymorphism rs145204276 is probably applicable to predict 5 years survival HR of cervical cancer patients. However, the mechanism elucidating the methylation status and transcription function of rs145204276 in uterine cervical cancer needs to be delineated for its unique implication in uterine cervical cancer.

Weng|Shun-Long|SL| Ng|Soo-Cheen|SC| Lee|Yueh-Chun|YC| Hsiao|Yi-Hsuan|YH| Hsu|Chun-Fang|CF| Yang|Shun-Fa|SF| Wang|Po-Hui|PH|

D020022:Genetic Predisposition to Disease


Constructing covalent interface in rubber/clay nanocomposite by combining structural modification and interlamellar silylation of montmorillonite.

Abstract: Strong interfacial interaction and nanodispersion are necessary for polymer nanocomposites with expectations on mechanical performance. In this work, montmorillonite (MMT) was first structurally modified by acid treatment to produce more silanol groups on the layer surface. This was followed by chemical modification of γ-methacryloxy propyl trimethoxysilane molecule (KH570) through covalent grafting with the silanol groups. (29)Si and (27)Al magic angle spinning (MAS) NMR results revealed the microstructural changes of MMT after acid treatment and confirmed the increase of silanol groups on acid-treated MMT surfaces. Thermogravimetric analysis indicated an increase in the grafted amount of organosilane on the MMT surface. X-ray diffraction (XRD) showed that the functionalization process changed the highly ordered stacking structure of the MMT mineral into a highly disordered structure, indicating successful grafting of organosilane to the interlayer surface of the crystalline sheets. The styrene-butadiene rubber (SBR)/MMT nanocomposites were further prepared by co-coagulating with SBR latex and grafted-MMT aqueous suspension. During vulcanization, a covalent interface between modified MMT and rubber was established through peroxide-radical-initiated reactions, and layer aggregation was effectively prevented. The SBR/MMT nanocomposites had highly and uniformly dispersed MMT layers, and the covalent interfacial interaction was finally achieved and exhibited high performance.

Zha|Chao|C| Wang|Wencai|W| Lu|Yonglai|Y| Zhang|Liqun|L|

rubber
montmorillonite
acid treatment
latex compounding method
silane


Evaluating Identity Disclosure Risk in Fully Synthetic Health Data: Model Development and Validation.

Abstract:
BACKGROUND
There has been growing interest in data synthesis for enabling the sharing of data for secondary analysis; however, there is a need for a comprehensive privacy risk model for fully synthetic data: If the generative models have been overfit, then it is possible to identify individuals from synthetic data and learn something new about them.

OBJECTIVE
The purpose of this study is to develop and apply a methodology for evaluating the identity disclosure risks of fully synthetic data.

METHODS
A full risk model is presented, which evaluates both identity disclosure and the ability of an adversary to learn something new if there is a match between a synthetic record and a real person. We term this "meaningful identity disclosure risk." The model is applied on samples from the Washington State Hospital discharge database (2007) and the Canadian COVID-19 cases database. Both of these datasets were synthesized using a sequential decision tree process commonly used to synthesize health and social science data.

RESULTS
The meaningful identity disclosure risk for both of these synthesized samples was below the commonly used 0.09 risk threshold (0.0198 and 0.0086, respectively), and 4 times and 5 times lower than the risk values for the original datasets, respectively.

CONCLUSIONS
We have presented a comprehensive identity disclosure risk model for fully synthetic data. The results for this synthesis method on 2 datasets demonstrate that synthesis can reduce meaningful identity disclosure risks considerably. The risk model can be applied in the future to evaluate the privacy of fully synthetic data.

privacy
synthetic data
data access
data sharing
de-identification
open data


The c-Ski family member and transcriptional regulator Corl2/Skor2 promotes early differentiation of cerebellar Purkinje cells.

Abstract: Purkinje cells (PCs) provide the primary output from the cerebellar cortex, which controls movement and posture, and loss of PCs causes severe cerebellar dysfunction. The mechanisms underlying cell fate determination and early differentiation of PC remain largely unknown. Here we show that the c-Ski family member and transcriptional regulator Corl2 is required for correct differentiation of PCs. In Corl2 knock-out embryos, initial PC specification appeared largely normal, but in a subset of presumptive PCs generated near the ventral border of the PC domain, cell fate choice was compromised and cells showed a mixed identity expressing the interneuron marker Pax2 as well. Additionally, selection and maintenance of the transmitter phenotype was compromised in most developing PCs in the mutants. During later differentiation steps, induction of PC marker genes was significantly suppressed, suggesting that maturation was delayed in the absence of Corl2. Consistently, defects in migration, cell polarization and dendrite formation were observed in mutant PCs, although their axonal trajectories appeared normal. These phenotypes closely resembled those of mutants for Rora, an essential regulator of PC differentiation. However, Rora expression was not significantly changed in the Corl2 mutants, indicating that Corl2 does not simply act upstream of Rora to promote PC differentiation. ChIP experiments revealed that Corl2 bound to the promoter regions of several PC-selective genes, which are also known to be direct downstream targets of RORα. Altogether, our results identified a novel regulatory program of PC differentiation involving Corl2, which might cooperate with the RORα pathway.

Nakatani|Tomoya|T| Minaki|Yasuko|Y| Kumai|Minoru|M| Nitta|Chiemi|C| Ono|Yuichi|Y|

D018507:Gene Expression Regulation, Developmental

D057094:Nuclear Receptor Subfamily 1, Group F, Member 1

Corl2/Skor2
Differentiation
Purkinje cell
Migration
RORα
Cerebellum


Dataset on part replacement of dipalmitoylphophatidylcholine with locust bean on stimulated tracheobronchial fluid, in vitro bioaccessibility test and modeling of lung deposition of trace elements bound to airborne particulates.

Abstract: The data presented in this article are related to our work on development of tracheobronchial fluid, in vitro bioaccessibility test and modeling of lung deposition of trace elements bound to airborne particulates [1]. In this article, a neutral modeled tracheobronchial fluid was formulated by partial replacement of some constituents in recipes of previously used lung epithelium fluids with local materials and was used in in vitro bioaccessibility extraction of elements-bound to airborne particulates. Dataset of particulate matters-bound trace elements collected in selected locations Ado - Ekiti is presented and the deposition of elements in different regions of respiratory tracts is estimated using Multiple-path particle deposition (MPPD) mathematic model. The data reveals that the formulated fluid has physical characteristics with superior properties to the existing fluids. The data also shows that bioaccessibility of elements were generally low (<30%) except for Cd and As with relatively moderate values (between 45 and 50%). Additionally, the lung deposition modeling shows that greater percentage of Cd (about 40% of inhaled dose) deposition in the lower alveolar part of the respiratory tract while tracheobronchial and extra-thoracic had 33% and 27% respectively. The data sets can be used as references to analyze data obtained using other formulation.

Olumayede|Emmanuel Gbenga|EG|
Oguntimehin|Ilemobayo|I|
Ojiodu|Chekwube C|CC|
Babalola|Bolanle M|BM|
Ojo|Ayomipo|A|
Adeoye|Olagboye S|OS|
Sodipe|Olubunmi G|OG|

Tracheobronchial fluid
Bioaccessibility test
Lung deposition
Trace elements
Particulates


New method of preoperative immobilization for the proximal femoral fractures.

Abstract:
OBJECTIVE
To evaluate the efficacy of a new method of provisional preoperative imobilization for patientes with transtrochanteric femoral fractures.

METHODS
Over a three-month period, 33 patients were treated at the Orthopaedic Trauma Service for transtrochanteric femoral fracture. We selected 22 patients and they were divided into groups with and without the use of the developed imobilization. The patients were evaluated according to the Visual Analogue Scale for Pain (VAS) during the preoperative and postoperative period in order to verify the analgesic consume and clinical complications.

RESULTS
The group that used the imobilization had lower pain, reduced analgesic consume and had less clinical complications.

CONCLUSION
The new imobilization therefore presents good results, however not statistical significant. Level of Evidence II, Prospective Comparative Study.

Lopes|João Ivan|JI|
Rotoly|André Luís|AL|
Dos Santos|Carlos Alberto Azevedo|CA|
Cardoso|Francisco José Nunes|FJ|

Immobilization
Femoral fractures
Hip fractures


Renal function in relation to sodium intake: a quantitative review of the literature.

Abstract: We undertook a quantitative literature review to search for evidence underpinning current guidelines proposing a reduction of sodium intake to less than 2.4 g/d for the management of chronic kidney disease. We searched PubMed for peer-reviewed articles published from January 1980 through May 2016. Two investigators screened 5072 publications and extracted data from 36, including 11 cross-sectional and 5 longitudinal observational studies and 20 intervention trials. Within-study effect sizes were pooled and standardized to a sodium gradient of 100 mmol/d by using inverse-variance weighted random effects models. Among cross-sectional studies, the pooled odds ratio for albuminuria was 1.23 (95% confidence interval [CI], 0.92-1.64, P = 0.16), and the pooled mean difference in glomerular filtration rate amounted to 8.5 ml/min (CI, -2.3 to 19.2 ml/min; P = 0.12). In the cohort studies, the pooled relative risk of a renal endpoint was 1.08 (CI, 0.92-1.29; P = 0.35). In the intervention trials (median duration, 14 days [range, 4-186 days]), the mean differences in estimated glomerular filtration rate and albuminuria (high vs. low sodium intake) averaged 4.6 ml/min (CI, 3.4-5.8 ml/min; P < 0.0001) and 53% (CI, 21-84; P = 0.001), respectively. Cochran's Q statistic indicated significant heterogeneity among cross-sectional studies for both estimated glomerular filtration rate and albuminuria (P < 0.0001) and among intervention trials for albuminuria (P = 0.04). In conclusion, there is no robust evidence suggesting that long-term reduction of salt intake would prevent chronic kidney disease or delay its progression. However, our current findings, which were mainly obtained in people with slight renal impairment, cannot be extrapolated to patients with moderate or severe chronic kidney disease.

Nomura|Kyoko|K|
Asayama|Kei|K|
Jacobs|Lotte|L|
Thijs|Lutgarde|L|
Staessen|Jan A|JA|

sodium
albuminuria
glomerular filtration rate
salt
CKD
meta-analysis


The relation between systemic inflammation and incident cancer in patients with stable cardiovascular disease: a cohort study.

Abstract:
AIMS
Low-grade inflammation, measured by elevated plasma concentrations of high-sensitive C-reactive protein (CRP), is a risk factor for cardiovascular disease (CVD). There is evidence that low-grade inflammation is also related to a higher risk of cancer. The present prospective cohort study evaluates the relation between low-grade systemic inflammation and risk of cancer in patients with stable CVD.

METHODS AND RESULTS
In total, 7178 patients with stable CVD and plasma CRP levels ≤10 mg/L were included. Data were linked to the Dutch national cancer registry. Cox regression models were fitted to study the relation between CRP and incident CVD and cancer. After a median follow-up time of 8.3 years (interquartile range 4.6-12.3) 1072 incident cancer diagnoses were observed. C-reactive protein concentration was related to total cancer [hazard ratio (HR) 1.35; 95% confidence interval (CI) 1.10-1.65] comparing last quintile to first quintile of CRP. Especially lung cancer, independent of histopathological subtype, was related to CRP (HR 3.39; 95% CI 2.02-5.69 comparing last to first quintile of CRP). Incidence of epithelial neoplasms and especially squamous cell neoplasms were related to CRP concentration, irrespective of anatomical location. Sensitivity analyses after excluding patients with a cancer diagnosis within 1, 2, and 5 years of follow-up showed similar results. No effect modification was observed by smoking status or time since smoking cessation (P-values for interaction > 0.05).

CONCLUSION
Chronic systemic low-grade inflammation, measured by CRP levels ≤10 mg/L, is a risk factor for incident cancer, markedly lung cancer, in patients with stable CVD. The relation between inflammation and incident cancer is seen in former and current smokers and is uncertain in never smokers.

Van't Klooster|Cilie C|CC|
Ridker|Paul M|PM|
Hjortnaes|Jesper|J|
van der Graaf|Yolanda|Y|
Asselbergs|Folkert W|FW|
Westerink|Jan|J|
Aerts|Joachim G J V|JGJV|
Visseren|Frank L J|FLJ|

D009375:Neoplasms, Glandular and Epithelial

Incident cancer
High-sensitive C-reactive protein
Risk factor
Chronic systemic low-grade inflammation
Patients with vascular disease


Anti-N-methyl-D-aspartate Receptor Encephalitis.

Abstract: Anti-N-methyl-D-aspartate receptor (NMDA) encephalitis is an underrecognized encephalitis that may be mistaken for a wide variety of mental illnesses and causes of delirium. This syndrome is predominantly present in young females presenting with acute psychotic episodes, autonomic instability, and neurologic abnormalities. It is commonly associated with ovarian teratoma. Our case illustrates anti-NMDA encephalitis presenting in a young female with progressive mental status changes and neurologic abnormalities throughout her emergency department course. We review the investigative approach, diagnostic modalities, and treatment options in patient management. This case emphasizes the need for a high index of suspicion of anti-NMDA receptor encephalitis when approaching a patient with unexplained changes in mentation.

Tanquary|Gregory|G|
Fraser|William|W|
Bowers|Kaitlin M|KM|

encephalitis
ovarian teratoma
altered mental status
autoimmune encephalitis
immunotherapy
lumbar puncture
nmda receptor encephalitis


Posterior Shoulder Instability: Surgical Outcomes and Risk of Failure in Adolescence.

Abstract:
BACKGROUND
Arthroscopic capsulolabral reconstruction has proven to be effective in treating posterior shoulder instability. Few studies have examined the risk factors that may contribute to poor outcomes in the adolescent population.

PURPOSE
To identify risk factors for surgical failure by comparing anatomic and subjective variations in children who underwent surgical intervention for posterior shoulder instability.

STUDY DESIGN
Case series; Level of evidence, 4.

METHODS
All patients undergoing arthroscopic shoulder surgery at one institution between 2011 and 2018 were reviewed. Patients >18 years old at presentation and those with Ehlers-Danlos syndrome were excluded. Posterior instability was defined as unidirectional subluxation on posterior drawer testing while under anesthesia. Two-year minimum follow-up was required, but those whose treatment failed earlier were included for calculation purposes. Demographics and intraoperative findings were recorded, as were Single Assessment Numeric Evaluation (SANE) scoring, Pediatric and Adolescent Shoulder Survey (PASS), and the short version of the Disabilities of the Arm, Shoulder and Hand (QuickDASH) results. Major complication was defined as revision arthroscopy or redislocation, and minor complications included self-reporting a poor outcome score (eg, SANE score <65).

RESULTS
A total of 48 children (23 girls and 25 boys) met criteria, with a mean age of 16.5 years (range, 12.4-17.9 years) and a mean follow-up of 3.75 years. Fifteen (31.3%) patients had a complication by our criteria, including 12.5% with surgical failures; regarding major complications, boys were treated successfully 96% of the time and girls 78% of the time (P = .049). Of the anatomic and subjective variables tested, only younger age (P≤ .001) and presentation type (P < .05) were correlated with complications. SANE scores differed significantly (P < .002) by presentation type, with mean scores of 52 (trauma), 94 (recurrent instability), and 81 (pain). QuickDASH scores demonstrated patients with a history of trauma (mean, 37), instability (mean, 9), and pain (mean, 11).

CONCLUSION
Adolescents treated surgically for posterior shoulder instability are at risk of treatment failure (when including outcome scores), and it appears that patients of female sex, younger age, and traumatic presentation are at the highest risk to require revision surgery or experience continued limitations secondary to their shoulder.

Asturias|Alicia M|AM|
Bastrom|Tracey P|TP|
Pennock|Andrew T|AT|
Edmonds|Eric W|EW|

posterior shoulder
instability
pediatric
glenoid labrum


Computer-assisted reading intervention for children with hearing impairment using cochlear implants: Effects on auditory event-related potentials and mismatch negativity.

Abstract:
OBJECTIVES
The primary aim was to find out whether a computer-assisted reading intervention program with a phonic approach can affect event-related (ERPs) and mismatch negativity (MMN) in hearing impaired (HI) children using cochlear implants (CIs).

METHODS
This study involved a test group of 15 HI children with CIs and a control group of 14 normal hearing (NH) children. The children were 4 years and 10 months to 8 years and 1 month old. ERPs were recorded immediately before and after 4 weeks of training with a computer-assisted reading intervention, GraphoGame. A multi-feature paradigm, Optimum-1, was used, i.e. a standard stimulus alternated with five different deviants: gap intensity, pitch, location and duration. MMN was calculated from the mean amplitude ERP of each deviant minus the standard stimulus response in a specific time interval, 80 - 224 ms. Repeated measures ANOVA was used for the statistical analysis.

RESULTS
The results did not show any significant changes with the computerassisted training in the ERPs and MMNs among the HI children with CIs. The presence of both MMN and a positive mismatch response (pMMR), which might reflect an immaturity, complicates interpreting the results in this age group. Individually, there was a mix of MMNs and pMMRs among all participants, pre and post training, and the change of each deviant after intervention was not predictable.

CONCLUSIONS
There are no significant changes in ERP or MMN after intervention, however lack of significances must be interpreted with caution. Besides the presence of both MMNs and pMMRs, only modest changes are to be expected on an individual basis and small samples hinder making statistical conclusions regarding the training's effects. The study contributes to some more descriptive pieces of ERPs and MMNs among the HI children with CIs. The issues of MMN and pMMR are highlighted.

Engström|Elisabet|E|
Kallioinen|Petter|P|
Lindgren|Magnus|M|
Nakeva von Mentzer|Cecilia|C|
Sahlén|Birgitta|B|
Lyxell|Björn|B|
Uhlén|Inger|I|

Reading intervention
Children
Cochlear implant
ERP
MMN
GraphoGame
pMMR
Sensorineural hearing loss


Risk score model for the development of hepatocellular carcinoma in treatment-naïve patients receiving oral antiviral treatment for chronic hepatitis B.

Abstract:
BACKGROUND/AIMS
This study aimed to develop and validate a risk prediction model for the development of hepatocellular carcinoma (HCC) in treatment-naïve patients receiving oral antiviral treatment for chronic hepatitis B (CHB).

METHODS
We investigated 2,061 Korean treatment-naïve patients with CHB treated with entecavir as an initial therapy. A risk score model for HCC development was developed based on multivariable Cox regression model in a single center (n=990) and was validated using the time-dependent area under the receiver operating characteristic curve (AUROC) in three other centers (n=1,071). The difference of HCC development among risk groups (low, intermediate, and high) categorized by risk score was also investigated.

RESULTS
The cumulative incidence rates of HCC at 5 years were 11.2% and 8.9% in the testing and validation cohorts, respectively. HCC-Risk Estimating Score in CHB patients Under Entecavir (HCC-RESCUE) is formulated as (age+15×gender [female=0 / male=1]+23×cirrhosis [absence=0 / presence=1]). The AUROCs at 1 year, 3 years, and 5 years were 0.82, 0.81, and 0.81, respectively, in the validation cohort. A significant difference of HCC development in each risk group was determined by the 5-year HCC risk score in the validation cohort (low risk group, 2.1%; intermediate risk group, 9.3%; high risk group, 41.2%, p<0.001).

CONCLUSIONS
The study presents a new risk score model with a good ability to predict HCC development and determine high risk patients for HCC development consisting of readily available clinical factors in treatment-naïve CHB patients receiving entecavir.

Sohn|Won|W|
Cho|Ju-Yeon|JY|
Kim|Ji Hoon|JH|
Lee|Jung Il|JI|
Kim|Hyung Joon|HJ|
Woo|Min-Ah|MA|
Jung|Sin-Ho|SH|
Paik|Yong-Han|YH|0000-0002-3076-2327

D000284:Administration, Oral
D000328:Adult
D000998:Antiviral Agents
D019540:Area Under Curve
D006528:Carcinoma, Hepatocellular
D004279:DNA, Viral
D005260:Female
D006147:Guanine
D006513:Hepatitis B e Antigens
D006515:Hepatitis B virus
D019694:Hepatitis B, Chronic
D006801:Humans
D015994:Incidence
D008113:Liver Neoplasms
D008297:Male
D008875:Middle Aged
D016016:Proportional Hazards Models
D012372:ROC Curve
D012189:Retrospective Studies
D012307:Risk Factors

Hepatocellular carcinoma
Chronic hepatitis B
Antiviral drugs
Assessment, Risk


Production of D-allose from D-fructose using immobilized L-rhamnose isomerase and D-psicose 3-epimerase.

Abstract: D-Allose is a rare sugar, can be used as an ingredient in a range of foods and dietary supplements, has alimentary activities, especially excellent anti-cancer effects and used in assisting cancer chemotherapy and radiotherapy, etc. To develop a simple and low-cost process for D-allose production, a one-pot enzymatic process using the substrate of D-fructose, and the recombinant enzymes of D-psicose 3-epimerase (DPE) and L-rhamnose isomerase (L-RhI) was developed. These enzymes were cloned from Ruminococcus sp. and B. subtilis, respectively, successfully expressed in E. coli, extracted and immobilized using anion exchange resin and amino resin, respectively. The mass ratio of D-fructose, D-psicose and D-allose was 6.6:2.4:1.0 when the reaction reached equilibrium after 5 h of reaction. Using the low-cost substrate of D-fructose, the reusable immobilized enzymes and the one-pot reaction, the production process is simplified and the production cost is decreased. In addition, to simplify the enzyme extraction and immobilization processes, new methods for enzyme capture and immobilization were developed especially for DPE immobilization. This is the first report for one-pot D-allose production using immobilized L-RhI and DPE.

Li|Can|C| Gao|Ling|L| Du|Kai|K| Lin|Huibin|H| Ren|Yilin|Y| Lin|Jianqun|J| Lin|Jianqiang|J|

D-allose
L-rhamnose isomerase
D-psicose
D-psicose 3-epimerase
Enzyme immobilization


Culturally Grounded Stress Reduction and Suicide Prevention for African American Adolescents.

Abstract: Suicide is an often-overlooked manifestation of violence among African American youth that has become more prevalent in the last two decades. This article reports on the process used to culturally adapt a cognitive-behavioral coping with stress prevention intervention for African American adolescents. We implemented this adapted school-based suicide prevention intervention with 758 African American 9th, 10th and 11th grade students at four high schools in a large Midwestern city. The findings presented are preliminary. The adolescents in this sample endorsed high levels of suicide risk, with females endorsing significantly more suicide risk than males. Those receiving the prevention intervention evidenced an 86% relative suicide risk reduction, compared to the standard care control participants. The presented model of adaptation and resulting culturally-grounded suicide prevention intervention significantly reduced suicide risk among African American adolescents. Clinical, research and policy implications are discussed.

Robinson|W LaVome|WL|
Case|Mary H|MH|
Whipple|Christopher R|CR|
Gooden|Adia S|AS|
Lopez-Tamayo|Roberto|R|
Lambert|Sharon F|SF|
Jason|Leonard A|LA|

Suicide prevention
African American adolescents
culturally-grounded intervention


Selection against recombinant hybrids maintains reproductive isolation in hybridizing Populus species despite F1 fertility and recurrent gene flow.

Abstract: Natural hybrid zones have proven to be precious tools for understanding the origin and maintenance of reproductive isolation (RI) and therefore species. Most available genomic studies of hybrid zones using whole- or partial-genome resequencing approaches have focused on comparisons of the parental source populations involved in genome admixture, rather than exploring fine-scale patterns of chromosomal ancestry across the full admixture gradient present between hybridizing species. We have studied three well-known European 'replicate' hybrid zones of Populus alba and P. tremula, two widespread, ecologically divergent forest trees, using up to 432 505 single-nucleotide polymorphisms (SNPs) from restriction site-associated DNA (RAD) sequencing. Estimates of fine-scale chromosomal ancestry, genomic divergence and differentiation across all 19 poplar chromosomes revealed strikingly contrasting results, including an unexpected preponderance of F1 hybrids in the centre of genomic clines on the one hand, and genomically localized, spatially variable shared variants consistent with ancient introgression between the parental species on the other. Genetic ancestry had a significant effect on survivorship of hybrid seedlings in a common garden trial, pointing to selection against early-generation recombinants. Our results indicate a role for selection against recombinant genotypes in maintaining RI in the face of apparent F1 fertility, consistent with the intragenomic 'coadaptation' model of barriers to introgression upon secondary contact. Whole-genome resequencing of hybridizing populations will clarify the roles of specific genetic pathways in RI between these model forest trees and may reveal which loci are affected most strongly by its cyclic breakdown.

Christe|Camille|C|
Stölting|Kai N|KN|
Bresadola|Luisa|L|
Fussi|Barbara|B|
Heinze|Berthold|B|
Wegmann|Daniel|D|0000-0003-2866-6739
Lexer|Christian|C|

D018742:DNA, Chloroplast
D018744:DNA, Plant
D005298:Fertility
D051456:Gene Flow
D005828:Genetics, Population
D018745:Genome, Plant
D005838:Genotype
D006239:Haplotypes
D006824:Hybridization, Genetic
D015810:Linkage Disequilibrium
D020641:Polymorphism, Single Nucleotide
D032107:Populus
D060047:Reproductive Isolation
D012641:Selection, Genetic
D017422:Sequence Analysis, DNA

Populus
Hybrid zones
admixture
divergence
RAD
differentiation
common garden
genotyping by sequencing
local genetic ancestry
speciation


Precaution, governance and the failure of medical implants: the ASR((TM)) hip in the UK.

Abstract: Hip implants have provided life-changing treatment, reducing pain and improving the mobility and independence of patients. Success has encouraged manufacturers to innovate and amend designs, engendering patient hopes in these devices. However, failures of medical implants do occur. The failure rate of the Articular Surface Replacement metal-on-metal hip system, implanted almost 100,000 times world-wide, has re-opened debate about appropriate and timely implant governance. As commercial interests, patient hopes, and devices' governance converge in a socio-technical crisis, we analyse the responses of relevant governance stakeholders in the United Kingdom between 2007 and 2014. We argue that there has been a systemic failure of the governance system entrusted with the safety of patients fitted with medical implants. Commercial considerations of medical implants and the status quo of medical implant governance have been given priority over patient safety despite the availability of significant failure data in an example of uncertainty about what constitutes appropriate precautionary action.

Wienroth|Matthias|M|
McCormack|Pauline|P|
Joyce|Thomas J|TJ|

Governance
Metal-on-metal hips
DePuy ASR
Medical device
Medical implant failure
Precautionary principle


Design and Biological Evaluation of Manganese- and Ruthenium-Based Hybrid CO-RMs (HYCOs).

Abstract: Interest in the therapeutic effects of carbon monoxide (CO), a product of heme degradation catalyzed by the enzyme heme oxygenase-1 (HO-1), has led to the development of CO-releasing molecules (CO-RMs) for the controlled delivery of this gas in vivo. We recently proposed conjugating a cobalt-based CO-RM with various activators of nuclear factor erythroid 2-related factor 2 (Nrf2), the transcription factor that regulates HO-1 expression, in order to exploit the beneficial effects of exogenous and endogenous CO. In this study, we describe the preparation of hybrid molecules (termed HYCOs) conjugating a fumaric acid derivative as an Nrf2 activator to a Mn- or a Ru-based CO-RM known to be pharmacologically active. With the exception of an acyl-manganese complex, these hybrids were obtained by associating the two bioactive entities by means of a linker of variable structure. X-ray diffraction analyses and preliminary biological investigations are also presented.

biological activity
drug design
manganese
medicinal chemistry
ruthenium


Diagnostic Performance of (1→3)-β-D-Glucan Alone and in Combination with Aspergillus PCR and Galactomannan in Serum of Pediatric Patients after Allogeneic Hematopoietic Stem Cell Transplantation.

Abstract: Data on biomarker-assisted diagnosis of invasive aspergillosis (IA) in pediatric patients is scarce. Therefore, we conducted a cohort study over two years including 404 serum specimens of 26 pediatric patients after allogeneic hematopoietic stem cell transplantation (alloSCT). Sera were tested prospectively twice weekly for Aspergillus-specific DNA, galactomannan (GM), and retrospectively for (1→3)-β-D-glucan (BDG). Three probable IA and two possible invasive fungal disease (IFD) cases were identified using the European Organization for Research and Treatment of Cancer and the Mycoses Study Group (EORTC/MSGERC) 2019 consensus definitions. Sensitivity and specificity for diagnosis of probable IA and possible IFD was 80% (95% confidential interval (CI): 28-99%) and 55% (95% CI: 32-77%) for BDG, 40% (95% CI: 5-85%) and 100% (95% CI: 83-100%) for GM, and 60% (95% CI: 15-95%) and 95% (95% CI: 75-100%) for Aspergillus-specific real-time PCR. However, sensitivities have to be interpreted with great caution due to the limited number of IA cases. Interestingly, the low specificity of BDG was largely caused by false-positive BDG results that clustered around the date of alloSCT. The following strategies were able to increase BDG specificity: two consecutive positive BDG tests for diagnosis (specificity 80% (95% CI: 56-94%)); using an optimized cutoff value of 306 pg/mL (specificity 90% (95% CI: 68-99%)) and testing BDG only after the acute posttransplant phase. In summary, BDG can help to diagnose IA in pediatric alloSCT recipients. However, due to the poor specificity either an increased cutoff value should be utilized or BDG results should be confirmed by an alternative Aspergillus assay.

Springer|Jan|J|
Held|Jürgen|J|
Mengoli|Carlo|C|
Schlegel|Paul Gerhardt|PG|
Gamon|Florian|F|
Träger|Johannes|J|
Kurzai|Oliver|O|
Einsele|Hermann|H|0000-0002-7680-0819
Loeffler|Juergen|J|
Eyrich|Matthias|M|0000-0002-8099-5903

Aspergillus
galactomannan
pediatric
real-time PCR
beta-D-glucan


A high-throughput microfluidic dental plaque biofilm system to visualize and quantify the effect of antimicrobials.

Abstract:
OBJECTIVES
Few model systems are amenable to developing multi-species biofilms in parallel under environmentally germane conditions. This is a problem when evaluating the potential real-world effectiveness of antimicrobials in the laboratory. One such antimicrobial is cetylpyridinium chloride (CPC), which is used in numerous over-the-counter oral healthcare products. The aim of this work was to develop a high-throughput microfluidic system that is combined with a confocal laser scanning microscope (CLSM) to quantitatively evaluate the effectiveness of CPC against oral multi-species biofilms grown in human saliva.

METHODS
Twenty-four-channel BioFlux microfluidic plates were inoculated with pooled human saliva and fed filter-sterilized saliva for 20 h at 37°C. The bacterial diversity of the biofilms was evaluated by bacterial tag-encoded FLX amplicon pyrosequencing (bTEFAP). The antimicrobial/anti-biofilm effect of CPC (0.5%-0.001% w/v) was examined using Live/Dead stain, CLSM and 3D imaging software.

RESULTS
The analysis of biofilms by bTEFAP demonstrated that they contained genera typically found in human dental plaque. These included Aggregatibacter, Fusobacterium, Neisseria, Porphyromonas, Streptococcus and Veillonella. Using Live/Dead stain, clear gradations in killing were observed when the biofilms were treated with CPC between 0.5% and 0.001% w/v. At 0.5% (w/v) CPC, 90% of the total signal was from dead/damaged cells. Below this concentration range, less killing was observed. In the 0.5%-0.05% (w/v) range CPC penetration/killing was greatest and biofilm thickness was significantly reduced.

CONCLUSIONS
This work demonstrates the utility of a high-throughput microfluidic-CLSM system to grow multi-species oral biofilms, which are compositionally similar to naturally occurring biofilms, to assess the effectiveness of antimicrobials.

Nance|William C|WC|
Dowd|Scot E|SE|
Samarian|Derek|D|
Chludzinski|Jeffrey|J|
Delli|Joseph|J|
Battista|John|J|
Rickard|Alexander H|AH|

microfluidics
multi-species biofilm
pyrosequencing
Live/Dead staining
confocal scanning laser microscopy


A Bayesian model for estimating multi-state disease progression.

Abstract: A growing number of individuals who are considered at high risk of cancer are now routinely undergoing population screening. However, noted harms such as radiation exposure, overdiagnosis, and overtreatment underscore the need for better temporal models that predict who should be screened and at what frequency. The mean sojourn time (MST), an average duration period when a tumor can be detected by imaging but with no observable clinical symptoms, is a critical variable for formulating screening policy. Estimation of MST has been long studied using continuous Markov model (CMM) with Maximum likelihood estimation (MLE). However, a lot of traditional methods assume no observation error of the imaging data, which is unlikely and can bias the estimation of the MST. In addition, the MLE may not be stably estimated when data is sparse. Addressing these shortcomings, we present a probabilistic modeling approach for periodic cancer screening data. We first model the cancer state transition using a three state CMM model, while simultaneously considering observation error. We then jointly estimate the MST and observation error within a Bayesian framework. We also consider the inclusion of covariates to estimate individualized rates of disease progression. Our approach is demonstrated on participants who underwent chest x-ray screening in the National Lung Screening Trial (NLST) and validated using posterior predictive p-values and Pearson's chi-square test. Our model demonstrates more accurate and sensible estimates of MST in comparison to MLE.

Shen|Shiwen|S|
Han|Simon X|SX|
Petousis|Panayiotis|P|
Weiss|Robert E|RE|
Meng|Frank|F|
Bui|Alex A T|AA|
Hsu|William|W|

D011857:Radiographic Image Interpretation, Computer-Assisted

Mean sojourn time
Markov model
Observation error
Chest x-ray
Posterior predictive p-value
Bayesian analysis
Lung cancer
Markov chain Monte Carlo
Transition probability


Fast and safe fabrication of a free-standing chitosan/alginate nanomembrane to promote stem cell delivery and wound healing.

Abstract: Polymeric ultrathin membranes that are compatible with cells offer tremendous advantages for tissue engineering. In this article, we report a free-standing nanomembrane that was developed using a layer-by-layer self-assembly technique with a safe and sacrificial substrate method. After ionization, two oppositely charged polyelectrolytes, alginate and chitosan, were alternately deposited on a substrate of a solidified gelatin block to form an ultrathin nanomembrane. The space between the two adjacent layers was ∼200 nm. The thickness of the nanomembrane was proportional to the number of layers. The temperature-sensitive gelatin gel served as a sacrificial template at 37°C. The free-standing nanomembrane promoted bone marrow stem cell adhesion and proliferation. Fluorescence-activated cell sorting was used to analyze green-fluorescent-protein-positive mesenchymal stem cells from the wounds, which showed a significantly high survival and proliferation from the nanomembrane when cells were transplanted to mouse dorsal skin that had a full-thickness burn. The bone-marrow-stem-cell-loaded nanomembrane also accelerated wound contraction and epidermalization. Therefore, this methodology provides a fast and facile approach to construct free-standing ultrathin scaffolds for tissue engineering. The biocompatibility and free-standing nature of the fabricated nanomembrane may be particularly useful for stem cell delivery and wound healing.

Kong|Yi|Y|
Xu|Rui|R|
Darabi|Mohammad Ali|MA|
Zhong|Wen|W|
Luo|Gaoxing|G|
Xing|Malcolm Mq|MM|
Wu|Jun|J|

nanomembrane
cell delivery
wound healing
layer-by-layer


Lyophilization of Small-Molecule Injectables: an Industry Perspective on Formulation Development, Process Optimization, Scale-Up Challenges, and Drug Product Quality Attributes.

Abstract: Lyophilization is a pivotal manufacturing process to obtain a stable drug product that is unstable as a ready-to-use formulation. Some formulations may require the addition of drug-specific excipients such as stabilizers, buffers, and bulking agents to support the cake appearance and ensure long-term stability of the drug product. Optimization of the lyophilization process parameters at each stage including freezing and primary and secondary drying is important because these parameters can have a direct impact on the process efficiency (shortened cycle time) and product performance (cake appearance and homogeneous moisture content). Several parameters of the formulation, including properties of the active pharmaceutical ingredient, excipients, solvent system, and container closure, determine the success of lyophilization. Development, scale-up, and transfer of the lyophilization cycle are challenging; hence, a comprehensive understanding of the critical parameters related to the formulation, lyophilization process, and lyophilizer design allows designing a quality drug product. One approach for a successful transfer of the lyophilization cycle between the laboratory and commercial-scale lyophilizer is using vial heat transfer coefficient and ice slab test to establish a maximum sublimation rate. This review provides a general overview of the lyophilization process and discusses several key considerations and product development aspects of formulation, process optimization, container closure system, scale-up principles, and drug product quality attributes from the industrial viewpoint. Grapical abstract.

Butreddy|Arun|A|
Dudhipala|Narendar|N|
Janga|Karthik Yadav|KY|
Gaddam|Rajendra Prasad|RP|

lyophilization
scale-up
product quality attributes
excipients
container closure
critical temperatures


TRA2A Binds With LncRNA MALAT1 To Promote Esophageal Cancer Progression By Regulating EZH2/β-catenin Pathway.

Abstract: The RNA binding protein TRA2A, a member of the transformer 2 homolog family, plays a crucial role in the alternative splicing of pre-mRNA. However, it remains unclear whether TRA2A is involved in non-coding RNA regulation and, if so, what are the functional consequences. By analyzing expression profiling data, we found that TRA2A is highly expressed in esophageal cancer and is associated with disease-free survival and overall survival time. Subsequent gain- and loss-of-function studies demonstrated that TRA2A promotes proliferation and migration of esophageal squamous cell carcinoma and adenocarcinoma cells. RNA immunoprecipitation and RNA pull-down assay indicated that TRA2A can directly bind specific sites on MALAT1 in cells. In addition, ectopic expression or depletion of TRA2A leads to MALAT expression changes accordingly, thus modulates EZH2/β-catenin pathway. Together, these findings elucidated that TRA2A triggers carcinogenesis via MALAT1 mediated EZH2/β-catenin axis in esophageal cancer cells.

Zhao|Xing|X| Chen|Qiuyang|Q| Cai|Yujie|Y| Chen|Danze|D| Bei|Mingrong|M| Dong|Hongyan|H| Xu|Jianzhen|J|


Diethylcarbamazine citrate ameliorates insulin resistance in high-fat diet-induced obese mice via modulation of adipose tissue inflammation.

Abstract: Diethylcarbamazine citrate (DEC) had been known as anti-inflammatory drug but its effect on obesity-induced insulin resistance as a result of released inflammatory mediators from adipose tissue (AT) was not known. White male albino mice were fed with high fat diet (HFD) for 18weeks to induce obesity. DEC at different three doses (12, 50 and 200mg/kg) was orally administered twice a week starting at week 6. Body, liver and adipose tissue weights were taken, while glucose tolerance, insulin resistance, blood triglycerides and levels of adipokines (leptin, TNF-α, IL-6 and MCP-1) were tested. The activity of cyclooxygenase (COX) in the liver tissue homogenate was also tested. In addition, NF-κBp65 localization in liver cell cytoplasmic and nuclear fractions was detected using Western blotting. The only effective anti-inflammatory dose was 50mg/kg to reduce (p<0.05) the high levels of glucose, insulin and triglycerides in serum. DEC was not anti-obesity drug because the weights of body, liver and adipose tissues were not changed. Hyperleptinemia was decreased (p<0.001) and associated with a reduction in serum levels of TNF-α, IL-6 and MCP-1 (p<0.001). In addition, the activity of COX in DEC treatment decreased significantly (p<0.01), while NF-κBp65 localization in nuclear extracts was obviously inhibited in 50mg/kg treated group. It could be concluded that DEC was the only effective dose against mouse insulin resistance but not lipid accumulation.

Diethylcarbamazine citrate
Insulin
Adipose tissue
Inflammation


Efficacy and safety of fosphenytoin for benign convulsions with mild gastroenteritis.

Abstract:
OBJECTIVE
To clarify the efficacy and safety of fosphenytoin for seizures in children with benign convulsions and mild gastroenteritis.

METHODS
Using the mailing list of the Annual Zao Conference on Pediatric Neurology, we recruited patients who met the following criteria: (1) clinical diagnosis of benign convulsions with mild gastroenteritis and (2) treatment with intravenous fosphenytoin. Benign convulsions with mild gastroenteritis were defined as a condition of (a) seizures associated with gastroenteritis without electrolyte imbalance, hypoglycemia, or dehydration in patients (b) between 6 months and 3 years of age with (c) no preexisting neurological disorders, (d) no impaired consciousness, and (e) a body temperature less than 38.0 °C before and after the seizures. The efficacy of fosphenytoin was categorized as effective when cessation of seizures was achieved.

RESULTS
Data from 16 child patients were obtained (median age, 20 months). Seizures were completely controlled after the initial dose of fosphenytoin in 14 of 16 patients. The median loading dose of fosphenytoin was 22.5 mg/kg. In 10 patients, fosphenytoin was administered after other antiepileptic drugs such as diazepam and midazolam were used. Adverse effects of fosphenytoin, excessive sedation, or intravenous fluid incompatibility were not observed in any patients.

CONCLUSION
Fosphenytoin is effective and well tolerated among children with benign convulsions with mild gastroenteritis.

Nakazawa|Mika|M| Toda|Soichiro|S| Abe|Shinpei|S| Ikeno|Mitsuru|M| Igarashi|Ayuko|A| Nakahara|Eri|E| Yamashita|Shintaro|S| Niijima|Shinichi|S| Shimizu|Toshiaki|T| Okumura|Akihisa|A|


Remarkable problem-solving ability of unicellular amoeboid organism and its mechanism.

Abstract: Choosing a better move correctly and quickly is a fundamental skill of living organisms that corresponds to solving a computationally demanding problem. A unicellular plasmodium of Physarum polycephalum searches for a solution to the travelling salesman problem (TSP) by changing its shape to minimize the risk of being exposed to aversive light stimuli. In our previous studies, we reported the results on the eight-city TSP solution. In this study, we show that the time taken by plasmodium to find a reasonably high-quality TSP solution grows linearly as the problem size increases from four to eight. Interestingly, the quality of the solution does not degrade despite the explosive expansion of the search space. Formulating a computational model, we show that the linear-time solution can be achieved if the intrinsic dynamics could allocate intracellular resources to grow the plasmodium terminals with a constant rate, even while responding to the stimuli. These results may lead to the development of novel analogue computers enabling approximate solutions of complex optimization problems in linear time.

Physarum
travelling salesman problem
amoeba computing
bioinspired computing
natural computing


Optimization of mass spectrometry acquisition parameters for determination of polycarbonate additives, degradation products, and colorants migrating from food contact materials to chocolate.

Abstract: The interest towards "substances of emerging concerns" referred to objects intended to come into contact with food is recently growing. Such substances can be found in traces in simulants and in food products put in contact with plastic materials. In this context, it is important to set up analytical systems characterized by high sensitivity and to improve detection parameters to enhance signals. This work was aimed at optimizing a method based on UHPLC coupled to high resolution mass spectrometry to quantify the most common plastic additives, and able to detect the presence of polymers degradation products and coloring agents migrating from plastic re-usable containers. The optimization of mass spectrometric parameter settings for quantitative analysis of additives has been achieved by a chemometric approach, using a full factorial and d-optimal experimental designs, allowing to evaluate possible interactions between the investigated parameters. Results showed that the optimized method was characterized by improved features in terms of sensitivity respect to existing methods and was successfully applied to the analysis of a complex model food system such as chocolate put in contact with 14 polycarbonate tableware samples. A new procedure for sample pre-treatment was carried out and validated, showing high reliability. Results reported, for the first time, the presence of several molecules migrating to chocolate, in particular belonging to plastic additives, such Cyasorb UV5411, Tinuvin 234, Uvitex OB, and oligomers, whose amount was found to be correlated to age and degree of damage of the containers.

D002851:Chromatography, High Pressure Liquid

polycarbonate
additives
degradation products
migration
chocolate


C-reactive protein/albumin ratio as prognostic score in oral squamous cell carcinoma.

Abstract:
OBJECTIVES
Many studies have examined histopathological factors and various prognostic scores related to inflammation to predict outcomes. Here, we examined the prognostic value of the C-reactive protein/albumin (CRP/alb) ratio in oral squamous cell carcinoma (OSCC).

MATERIALS AND METHODS
This retrospective study included 40 patients with OSCC. Using univariate and multivariate analyses, we focused on the correlation of the CRP/alb ratio with clinicopathological characteristics and with overall survival. We then compared five inflammation-based prognostic scores, CRP/alb ratio, modified Glasgow Prognostic Score (mGPS), neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and prognostic nutritional index (PNI), based on receiver operating characteristic (ROC) curves.

RESULTS
The optimal cut-off value for the CRP/alb ratio was 0.085. The group with a high CRP/alb ratio had a high TNM clinical stage (P=0.002) and larger primary tumors (P=0.029), with statistically significant differences in lymph node metastasis and distant metastasis. In addition, when the CRP/alb ratio was high, multivariate analysis showed a lower survival rate (P=0.002; hazard ratio=6.078), and the ROC curve showed more outstanding discriminatory ability regarding overall survival compared to other inflammation-based prognostic scores.

CONCLUSION
The CRP/alb ratio can be an independent prognostic factor when predicting prognosis in OSCC and has good prognostic ability.

C-reactive protein
Albumin
Squamous cell carcinoma


Generating human intestinal tissues from pluripotent stem cells to study development and disease.

Abstract: As one of the largest and most functionally complex organs of the human body, the intestines are primarily responsible for the breakdown and uptake of macromolecules from the lumen and the subsequent excretion of waste from the body. However, the intestine is also an endocrine organ, regulating digestion, metabolism, and feeding behavior. Intricate neuronal, lymphatic, immune, and vascular systems are integrated into the intestine and are required for its digestive and endocrine functions. In addition, the gut houses an extensive population of microbes that play roles in digestion, global metabolism, barrier function, and host-parasite interactions. With such an extensive array of cell types working and performing in one essential organ, derivation of functional intestinal tissues from human pluripotent stem cells (PSCs) represents a significant challenge. Here we will discuss the intricate developmental processes and cell types that are required for assembly of this highly complex organ and how embryonic processes, particularly morphogenesis, have been harnessed to direct differentiation of PSCs into 3-dimensional human intestinal organoids (HIOs) in vitro. We will further describe current uses of HIOs in development and disease research and how additional tissue complexity might be engineered into HIOs for better functionality and disease modeling.

stem cells
organoids
endoderm
intestinal development
tissue engineering


Vehicle safety characteristics in vulnerable driver populations.

Abstract:
OBJECTIVE
National data suggest drivers who are younger, older, and have lower socioeconomic status (SES) have heightened crash-related injury rates. Ensuring vulnerable drivers are in the safest vehicles they can afford is a promising approach to reducing crash injuries in these groups. However, we do not know the extent to which these drivers are disproportionately driving less safe vehicles. Our objective was to obtain population-based estimates of the prevalence of important vehicle safety criteria among a statewide population of drivers.

METHODS
We analyzed data from the NJ Safety and Health Outcomes warehouse, which includes all licensing and crash data from 2010-2017. We borrowed the quasi-induced exposure method's fundamental assumption-that non-responsible drivers in clean (i.e., only one responsible driver) multi-vehicle crashes are reasonably representative of drivers on the road-to estimate statewide prevalence of drivers' vehicle characteristics across four driver age groups (17-20; 21-24; 25-64, and ≥65) and quintiles of census tract median household income (n = 983,372). We used NHTSA's Product Information Catalog and Vehicle Listing platform (vPIC) to decode the VIN of each crash-involved vehicle to obtain model year, presence of electronic stability control (ESC), vehicle type, engine horsepower, and presence of front, side, and curtain air bags.

RESULTS
The youngest and oldest drivers were more likely than middle-aged drivers to drive vehicles that were older, did not have ESC, and were not equipped with side airbags. Additionally, across all age groups drivers of higher SES were in newer and safer vehicles compared with those of lower SES. For example, young drivers living in lowest-income census tracts drove vehicles that were on average almost twice as old as young drivers living in highest-income tracts (median [IQR]: 11 years [6-14] vs. 6 years [3-11]).

CONCLUSIONS
Vehicle safety is an important component of seminal road safety philosophies that aim to reduce crash fatalities. However, driver groups that are overrepresented in fatal crashes-young drivers, older drivers, and those of lower SES-are also driving the less safe vehicles. Ensuring drivers are in the safest car they can afford should be further explored as an approach to reduce crash-related injuries among vulnerable populations.

Metzger|Kristina B|KB|
Sartin|Emma|E|
Foss|Robert D|RD|
Joyce|Nina|N|
Curry|Allison E|AE|

vehicle safety
young drivers
older drivers
Automobile driving
teen drivers
traffic accidents


Social-ecological correlates of fundamental movement skills in young children.

Abstract:
Purpose
To identify the social-ecological correlates associated with fundamental movement skills at the child, family, and environment levels in young children.

Methods
Preschool children from 4 Colorado Head Start/preschool centers were recruited from 2010 to 2012. Two hundred twenty-eight children (128 girls; age = 56.08 ± 4.09 months; body mass index (BMI) z-score = 0.53 ± 1.12 (mean ± SD); 42.1% Hispanic/Latino) and 159 families were included in the final analysis. Children's perceived competence and fundamental movement skills were assessed via the Pictorial Scale of Perceived Competence and Social Acceptance and the Bruininks-Oseretsky Test of Motor Proficiency, 2nd edition. Data on the number of children in the family, parent age, BMI, education, employment status, family income, perception of child coordination, and home physical activity environment were collected via a questionnaire. Linear regressions adjusted for child BMI, age, sex, and school site were performed at each level.

Results
Child perceived cognitive competence was positively associated with locomotor skills (p = 0.04; adjusted R 2 = 0.035) and object-control skills (p = 0.003; adjusted R 2 = 0.083) at the child level. Parent education, BMI, and perception of child coordination were positively associated with locomotor skills and explained 8.8% of variance, but only parent education was significant (p = 0.04) at the family level. In addition, physical environment was positively associated with locomotor skills (p = 0.02) and explained 5.5% of variance at the environment level.

Conclusion
Social-ecological correlates associated with young children's fundamental movement skills are multidimensional and differ according to skill category at the child, family, and environment levels.

Zeng|Nan|N|
Johnson|Susan L|SL|
Boles|Richard E|RE|
Bellows|Laura L|LL|

Fundamental movement skills
Preschool children
Activity environment
Perceived cognitive competence
Parent education


Suicide reporting within British newspapers' arts coverage.

Abstract:
BACKGROUND
Many suicide prevention strategies promote media guidelines on suicide reporting, given evidence that irresponsible reporting of suicide can influence imitative suicidal behavior. Due to limited resources, monitoring of guideline adherence has tended to focus on news outputs, with a risk of neglecting other journalistic content.

AIMS
To determine whether British newspapers' arts coverage adheres to media guidelines on suicide reporting.

METHOD
Purposive sampling was used to capture current national practice on suicide reporting within newspapers' arts coverage of exhibitions. Recent major UK exhibitions by artists who had died by suicide were identified: Kirchner, Rothko, Gorky, and Van Gogh. Content analysis of all UK national newspaper coverage of these exhibitions was performed to measure the articles' adherence to widely accepted media guidelines.

RESULTS
In all, 68 newspaper reviews satisfied inclusion criteria, with 100% failing to show full adherence to media guidelines: 21% used inappropriate language; 38% provided explicit descriptions of the suicide; 7% employed simplistic explanations for suicide triggers; 27% romanticized the suicide; and 100% omitted information on sources of support.

CONCLUSION
British newspapers' arts coverage of exhibitions deviates considerably from media guidelines on the reporting of suicide. The findings suggest scope to improve journalists' awareness of the importance of this component of suicide prevention strategies.

suicide reporting
suicide prevention
media guidelines
content analysis
imitative behavior


Computer-aided diagnosis: detection and localization of prostate cancer within the peripheral zone.

Abstract: We propose a methodology for prostate cancer detection and localization within the peripheral zone based on combining multiple segmentation techniques. We extract four image features using Gaussian and median filters. Subsequently, we use each image feature separately to generate binary segmentations. Finally, we take the intersection of all four binary segmentations, incorporating a model of the peripheral zone, and perform erosion to remove small false-positive regions. The initial evaluation of this method is based on 275 MRI images from 37 patients, and 86% of the slices were classified correctly with 87% and 86% sensitivity and specificity achieved, respectively. This paper makes two contributions: firstly, a novel computer-aided diagnosis approach, which is based on combining multiple segmentation techniques using only a small number of simple image features, and secondly, the development of the proposed method and its application in prostate cancer detection and localization using a single MRI modality with the results comparable with the state-of-the-art multimodality and advanced computer vision methods in the literature. Copyright © 2015 John Wiley & Sons, Ltd.

Rampun|Andrik|A| Chen|Zhili|Z| Malcolm|Paul|P| Tiddeman|Bernie|B| Zwiggelaar|Reyer|R|

prostate cancer detection
MRI
prostate cancer localization


Shift rotation and age - interactions with sleep-wakefulness and inflammation.

Abstract: The interaction of age with shift rotation in relation to sleep-wakefulness and inflammation were studied among male employees (n = 772). Cross-sectional analyses in day, two-shift and three-shift work with different shift rotations, as well as changes in leukocytes and hsCRP among three shift workers who changed their shift system during the 2.5- yr follow-up were completed. Shift work was associated with problems to fall asleep (p < 0.001) and feeling of the current working time being harmful to sleep and wakefulness (p < 0.001). Quickly forward-rotation shift workers considered their working time less harmful compared with slower backward-rotation shift workers. Age did not influence sleep in general, but older workers in the quickly forward-rotating three-shift system had less sleep complaints than their younger colleagues. The age differences in the inflammatory markers partly depended on the shift system. The results give some support that rapidly forward-rotating shift systems are more 'age-friendly' than backward-rotating shift systems.

Viitasalo|Katriina|K| Puttonen|Sampsa|S| Kuosma|Eeva|E| Lindström|Jaana|J| Härmä|Mikko|M|

D020178:Sleep Disorders, Circadian Rhythm

age
inflammation
shift work
sleep
shift schedule


GITRL on dendritic cells aggravates house dust mite-induced airway inflammation and airway hyperresponsiveness by modulating CD4+ T cell differentiation.

Abstract:
BACKGROUND
Glucocorticoid-induced tumor necrosis factor receptor family-related protein ligand (GITRL) plays an important role in tumors, autoimmunity and inflammation. However, GITRL is not known to modulate the pathogenesis of allergic asthma. In this study, we investigated whether regulating GITRL expressed on dendritic cells (DCs) can prevent asthma and to elucidate its mechanism of action.

METHODS
In vivo, the role of GITRL in modulating house dust mite (HDM)-induced asthma was assessed in adeno-associated virus (AAV)-shGITRL mice. In vitro, the role of GITRL expression by DCs was evaluated in LV-shGITRL bone marrow dendritic cells (BMDCs) under HDM stimulation. And the direct effect of GITRL was observed by stimulating splenocytes with GITRL protein. The effect of regulating GITRL on CD4+ T cell differentiation was detected. Further, GITRL mRNA in the peripheral blood of asthmatic children was tested.

RESULTS
GITRL was significantly increased in HDM-challenged mice. In GITRL knockdown mice, allergen-induced airway inflammation, serum total IgE levels and airway hyperresponsiveness (AHR) were reduced. In vitro, GITRL expression on BMDCs was increased after HDM stimulation. Further, knocking down GITRL on DCs partially restored the balance of Th1/Th2 and Th17/Treg cells. Moreover, GITRL stimulation in vitro inhibited Treg cell differentiation and promoted Th2 and Th17 cell differentiation. Similarly, GITRL mRNA expression was increased in the peripheral blood from asthmatic children.

CONCLUSIONS
This study identified a novel role for GITRL expressed by DCs as a positive regulator of CD4+ T cells responses in asthma, which implicates that GITRL inhibitors may be a potential immunotherapy for asthma.

Wang|Yaping|Y| Liao|Kou|K| Liu|Bo|B| Niu|Chao|C| Zou|Wenjing|W| Yang|Lili|L| Wang|Ting|T| Tian|Daiyin|D| Luo|Zhengxiu|Z| Dai|Jihong|J| Li|Qubei|Q| Liu|Enmei|E| Gong|Caihui|C| Fu|Zhou|Z| Li|Ying|Y| Ding|Fengxia|F|


An Ultra-Low Power Surface EMG Sensor for Wearable Biometric and Medical Applications.

Abstract: In recent years, the surface electromyography (EMG) signal has received a lot of attention. EMG signals are used to analyze muscle activity or to evaluate a patient's muscle status. However, commercial surface EMG systems are expensive and have high power consumption. Therefore, the purpose of this paper is to implement a surface EMG acquisition system that supports high sampling and ultra-low power consumption measurement. This work analyzes and optimizes each part of the EMG acquisition circuit and combines an MCU with BLE. Regarding the MCU power saving method, the system uses two different frequency MCU clock sources and we proposed a ping-pong buffer as the memory architecture to achieve the best power saving effect. The measured surface EMG signal samples can be forwarded immediately to the host for further processing and additional application. The results show that the average current of the proposed architecture can be reduced by 92.72% compared with commercial devices, and the battery life is 9.057 times longer. In addition, the correlation coefficients were up to 99.5%, which represents a high relative agreement between the commercial and the proposed system.

power consumption
EMG acquisition system
biosensor devices and interface circuit
wireless transmission


Operational Barriers in Providing Comprehensive Emergency Obstetric Care by Task Shifting of Medical Officers in Selected States of India.

Abstract:
Background
A network of first referral unit (FRU) is set up to improve the availability and accessibility of comprehensive emergency obstetric care (CEmOC) services. To fill the gap of the scarcity of obstetricians and anesthetists at FRU, two short-term trainings in CEmOC and anesthesia were started for in-service medical officers.

Objective
This study aimed to assess the operational status of FRU in providing CEmOC services by task shifting of trained medical officers in selected states of India.

Materials and Methods
The study was done in seven states of India. A team of experts assessed conveniently selected health facilities designated as FRU by using a semi-structured, predesigned, and pretested checklist for CEmOC functionality status. A total of 50 designated FRUs were assessed and data were systematically analyzed.

Results
We documented the availability of five key elements for the operationalization of CEmOC services at FRU. Out of 50 facilities, 9 (18%) reported conducting operative delivery and 11 (22%) of the facilities were fully operational with all elements available. At 9 (18%) facilities, one element and, at 17 (34%) facilities, two elements were missing. The blood storage unit was the most important missing element (68%) followed by operative facilities (36%). The challenges of FRUs remained uniform across states. Barriers identified to operationalize FRU were the availability of trained doctors in cesarean section and anesthesia together, lack of operative facilities, and blood storage units.

Conclusions
To operationalize the network of FRU for CEmOC services by task shifting of medical officer, it is important to ensure the availability of all five key elements together at all facilities.

Keshri|Vikash Ranjan|VR|
Garg|Bishan Swarup|BS|

Comprehensive emergency obstetrics care
task shifting
medical officer
first referral unit
life-saving anesthetic skills