bluuebunny/crossref_metadata_2025 huggingface dataset:
Fabrication of Cobaltosic Oxide Nanoparticle‐Doped 3 D MXene/Graphene Hybrid Porous Aerogels for All‐Solid‐State Supercapacitors
Authors: Liu Rui , Zhang Aitang , Tang Jianguo , Tian Jinmi , Huang Weiguo , Cai Jintao , Barrow Colin , Yang Wenrong , Liu Jingquan
Published: February 2019

MXenes are a new family of 2 D transition metal carbides and nitrides, which have attracted enormous attention in electrochemical energy storage, sensing technology, and catalysis owing to their good conductivity, high specific surface area, and excellent electrochemical properties. In this work, a series of Co3O4‐doped 3 D MXene/RGO hybrid porous aerogels is designed and prepared through a facile in situ reduction and thermal annealing process, in which the reduced graphene oxide (RGO) conductive network can electrically link the separated Co3O4‐MXene composite nanosheets, leading to enhanced electronic conductivity. It is found that upon using the Co3O4‐MXene/RGO hybrid porous aerogel prepared with a mass ratio of Co3O4‐MXene/RGO of 3:1 (CMR31) as an electrode for a supercapacitor, a superior specific capacitance of 345 F g−1 at the current density of 1 A g−1 is achieved, which is significantly higher than those of Ti3C2Tx MXene, RGO, and MXene/RGO electrodes. In addition, a high capacitance retention (85 % of the initial capacitance after 10 000 cycles at a high current density of 3 A g−1) and a low internal resistance Rs (0.44 Ω) can be achieved. An all‐solid‐state asymmetric supercapacitor (ASC) device is assembled using CMR31, and it has the ability to light up a blue LED indicator for 5 min if four ASCs are connected in series. Therefore, these novel Co3O4‐MXene/RGO hybrid porous aerogels have potential practical applications in high‐energy storage devices.
Concentric ring topology of mammalian cortical sectors and relevance for patterning studies
Authors: Puelles Luis , Alonso Antonia , García‐Calero Elena , Martínez‐de‐la‐Torre Margaret
Published: February 2019

Models aiming to explain causally the evolutionary or ontogenetic emergence of the pallial isocortex and its regional/areal heterogeneity in mammals use simple or complex assumptions about the pallial structure present in basal mammals and nonmammals. The question arises: how complex is the pattern that needs to be accounted for in causal models? This topic is also paramount for comparative purposes, since some topological relationships may be explained as being ancestral, rather than newly emerged. The mouse pallium is apt to be reexamined in this context, due to the breadth of available molecular markers and correlative experimental patterning results. We center the present essay on a recapitulative glance at the classic theory of concentric mammalian allo‐, meso‐, and neocortex domains. In its simplest terms, this theory postulates a central neocortical island (6 layers) separated by a surrounding mesocortical ring (4–5 layers) from a peripheral allocortical ring (3 layers). These territories show additional partition into regional or areal subdivisions. There are also borderline amygdalar, claustral, and septal areas of the pallium, nuclear in structure. There has been little effort so far to contemplate the full concentric ring model in current “cortex patterning” models. In this essay, we recapitulate the ring idea in mammals (mouse) and consider a potential causal patterning scenario using topologic models. Finally, we briefly explore how far this theory may apply to pallium models proposed recently for sauropsids.
Divergent projections of single pontocerebellar axons to multiple cerebellar lobules in the mouse
Authors: Biswas Mohammad Shahangir , Luo Yuanjun , Sarpong Gideon Anokye , Sugihara Izumi
Published: February 2019

The basilar pontine nucleus (PN) is the key relay point for the cerebrocerebellar link. However, the projection pattern of pontocerebellar mossy fiber axons, which is essential in determining the functional organization of the cerebellar cortex, has not been fully clarified. We reconstructed the entire trajectory of 25 single pontocerebellar mossy fiber axons labeled by localized injection of biotinylated dextran amine into various locations in the PN and mapped all their terminals in an unfolded scheme of the cerebellum in 10 mice. The majority of axons (20/25 axons) entered the cerebellum through the middle cerebellar peduncle contralateral to the origin, while others entered through the ipsilateral pathway. A small number of axons (1/25 axons) had collaterals terminating in the cerebellar nuclei. Axons projected mostly to a combination of lobules, often bilaterally, and terminated in multiple zebrin (aldolase C) stripes, more frequently in zebrin‐positive stripes (83.9%) than in zebrin‐negative stripes, with 66.5 mossy fiber terminals on the average. Axons originating from the rostral (plus medial and lateral), central and caudal PN mainly terminated in the paraflocculus, crus I and lobule VIb–c, in the simplex lobule, crus II and paramedian lobule, and in lobules II–VIa, VIII and copula pyramidis, respectively. The results suggest that the interlobular branching pattern of pontocerebellar axons determines the group of cerebellar lobules that are involved in a related functional localization of the cerebellum. In the hemisphere, crus I may be functionally distinct from neighboring lobules (simple lobule and crus II) in the mouse cerebellum based on the pontocerebellar axonal projection pattern.
The benefits of non‐surgical weight management on weight and glycaemic control in people with complex type 2 diabetes: A primary care service evaluation of clinical outcomes at 12 months
Authors: Avery Amanda , Griffin Jill , Stokes Julie , Coulton Rosie , Pallister Carolyn , Lavin Jacquie
Published: February 2019

Optimizing diabetes management in patients with complex type 2 diabetes (T2DM) and obesity presents challenges. This study evaluates weight and HbA1c at 12 months (primary outcomes) and blood pressure, lipids, medication and lifestyle changes (secondary outcomes) in patients referred by a diabetes specialist (DSN) to the weight management intervention (Slimming World). Patients attended up to 12 or 24 funded weekly group sessions. The DSN recorded baseline and 12‐month primary and secondary outcome data. A post‐intervention questionnaire explored the lifestyle changes made. 69 patients achieved a mean weight loss of 5.5 (5.16) %, reduction in BMI [37.7(6.11) to 35.9 (6.30) kg/m2, P < 0.001] and HbA1c levels [62.8 (12.85) to 55.0 (13.02) mmol/mol, P < 0.001] at 12 months. 81.2% reduced their HbA1c levels. Small reductions were observed in SBP, DBP and triglycerides, and six patients reduced their diabetes medications. Twenty patients completed the questionnaire: unhealthy snacking reduced (P < 0.001) and going for walks increased (P < 0.001) with fewer people avoiding moderate activity (P < 0.05). Despite being a chronic, progressive condition, referral to a community‐based programme was successful in supporting patients with established T2DM improve their diet and activity levels, lose weight and improve their glycaemic control 12 months later with a small number able to reduce their medication.
Aquaculture Contributes a Higher Proportion to Children's Daily Intake of Polycyclic Aromatic Hydrocarbons Than to That of Adults in Eastern China
Authors: Li Juan-Ying , He Qing , Li Jiale , Chen Yiqin , Yin Jie , Jin Ling , Wang Qian
Published: February 2019

Asia, especially China, shares a large proportion of global aquaculture production. Consequently, aquaculture food quality and safety with regard to contamination with polycyclic aromatic hydrocarbons (PAHs) were assessed in eastern China, which is a typical area of aquaculture. The concentrations of ∑PAHs ranged from 42 to 600 ng/g dry weight in a variety of dietary species from farm ponds in eastern China. With regard to the total daily intake of PAHs estimated based on the literature data on urinary hydroxy-PAHs in this region, there was a significant difference between children (mean = 130 ng/kg/d) and adults (mean = 600 ng/kg/d for pregnant women, 1700 ng/kg/d for women, and 2300 ng/kg/d for men). Furthermore, we provided a novel estimation on the fractional contribution of aquatic products to the overall human daily intake of PAHs. Specifically, the contribution of aquatic foodstuffs to total daily intake for children and pregnant women reached more than 50 and 10%, respectively, indicating that children and pregnant women were more vulnerable to the PAH-contaminated aquaculture foodstuffs. Meanwhile, no significant region-specific pattern between different provinces was observed. In summary, these results suggested that sensitive subpopulations were vulnerable to exposure to PAH-contaminated aquatic products, and it is necessary to pay attention to the dietary intake pattern of these sensitive subgroups in eastern China. Environ Toxicol Chem 2019;00:1–9. © 2019 SETAC

Abstract

EDI = estimated daily intake.
Outcomes and cost implications of microvascular reconstructions of the head and neck
Authors: Sweeny Larissa , Rosenthal Eben L. , Light Tyler , Grayson Jessica , Petrisor Daniel , Troob Scott H. , Greene Benjamin J. , Carroll William R. , Wax Mark K.
Published: February 2019

Background

Critical review of current head and neck reconstructive practices as related to free flap donor sites and their impact on clinical outcomes and cost.

Methods

Retrospective multicenter review of free tissue transfer reconstruction of head and neck defects (n = 1315). Variables reviewed: defect, indication, T classification, operative duration, and complications. A convenience sample was selected for analysis of overall (operative and inpatient admission) charges per hospitalization (n = 400).

Results

Mean charges of hospitalization by donor tissue: radial forearm free flap (RFFF) $127 636 (n = 183), osteocutaneous RFFF (OCRFFF) $125 456 (n = 70), anterior lateral thigh $133 781 (n = 54), fibula $140 747 (n = 42), latissimus $208 890 (n = 24), rectus $169 637 (n = 18), scapula $128 712 (n = 4), and ulna $110 716 (n = 5; P = .16). Mean operative times for malignant lesions stratified by T classification: 6.9 hours (±25 minutes) for T1, 7.0 hours (±16 minutes) for T2, 7.3 hours (±17 minutes) for T3, and 7.8 hours (±11 minutes) for T4 (P < .0001). Complications correlated with differences in mean charges: minor surgical ($123 720), medical ($216 387), and major surgical ($169 821; P < .001). Operations for advanced malignant lesions had higher mean charges: T1 lesions ($106 506) compared to T2/T3 lesions ($133 080; P = .03) and T4 lesions ($142 183; P = .02). On multivariate analysis, the length of stay, operative duration, and type a postoperative complication were factors affecting overall charges for the hospitalization (P < .018).

Conclusion

Conclusion: The RFFF and OCRFFF had the lowest complication rates, length of hospitalization, duration of operation, and mean charges of hospitalization. Advanced stage malignant disease correlated with increased hospitalization length, operative time, and complication rates resulting in higher hospitalization charges.
The role of age in treatment‐related adverse events in patients with head and neck cancer: A systematic review
Authors: Coca‐Pelaz Andrés , Halmos Gyorgy B. , Strojan Primož , de Bree Remco , Bossi Paolo , Bradford Carol R. , Rinaldo Alessandra , Vander Poorten Vincent , Sanabria Alvaro , Takes Robert P. , Ferlito Alfio
Published: February 2019

Head and neck squamous cell carcinoma (HNSCC) is often diagnosed in advanced stage and therefore requires aggressive, multimodal treatment. Elderly patients are often excluded from standard therapy regimens purely based on age. This clinical review aims to collect all published data in the literature on treatment modality selection in elderly patients and on age‐related adverse events following treatment of HNSCC. We performed a literature search for articles on the treatment of HNSCC in elderly patients. Most of the articles were retrospective studies with the consequent limitations. It can be concluded that age is not an absolute contraindication for intensive treatment and comorbidity is an important predictor of outcome, but not the only one. Despite the existence of multiple tools for pretreatment evaluation, there are not consistent data on their use.
Postoperative radiation performed at the same surgical facility associated with improved overall survival in oral cavity squamous cell carcinoma
Authors: Amini Arya , Stokes William A. , Jones Bernard L. , Sampath Sagus , Kang Robert S. , Gernon Thomas J. , Maghami Ellie G. , Massarelli Erminia , Bradley Cathy J. , Karam Sana D.
Published: February 2019

Background

The purpose of this analysis is to evaluate whether postoperative radiotherapy (PORT) at the same facility as surgery portends to better survival outcomes compared to PORT given at a different facility.

Methods

Patients underwent upfront surgery at the National Cancer Database reporting facility followed by PORT. PORT was coded as performed at either the same facility or at a different facility as surgery.

Results

A total of 10 832 patients were selected. Five‐year overall survival (OS) was higher in patients undergoing PORT at the same facility: 52.5% vs 48.4% (P < 0.001). PORT performed at the same facility was associated with improved OS under multivariate (HR, 0.92; P = 0.01) and propensity score matched (hazard ratio, 0.90; P = 0.004) analyses.

Conclusions

OS was better among patients with head and neck cancer who received PORT at the same facility as surgery.
Dynamic changes in chemosensitivity immune predictors in patients with hypopharyngeal cancer treated with induction chemotherapy
Authors: Sun Wei , Chen Lin , Huang Jin‐Qiang , Li Jian , Zhu Xiao‐Lin , Wen Yi‐Hui , Wen Wei‐Ping
Published: February 2019

Background

There are currently no data predicting chemosensitivity of induction chemotherapy (ICT) for hypopharyngeal squamous cell carcinomas (SCC).

Methods

Associations between immune cells and overall response (OR) to ICT and changes in immune cells during ICT were observed in 40 patients with hypopharyngeal SCC undergoing ICT.

Results

CD4+ and CD8+ T‐cell and regulatory T‐cell (Treg) frequencies reached diagnostic accuracy for OR to ICT. OR rate was significantly higher in CD4+‐high T cell, CD8+‐high T cell, and low Treg groups. A transient reduction in Tregs and increases in Tregs in the non‐OR and OR groups were observed during the course of ICT. Conversely, increases in CD8+ T cells and reductions in CD8+ T cells in the non‐OR and OR groups were observed.

Conclusion

High CD4+ T‐cell, high CD8+ T‐cell, and low Treg frequencies can be predictors for high efficacy of ICT in patients with hypopharyngeal SCC.
Bezafibrate Improves GLOBE and UK‐PBC Scores and Long‐Term Outcomes in Patients With Primary Biliary Cholangitis
Authors: Honda Akira , Tanaka Atsushi , Kaneko Tetsuji , Komori Atsumasa , Abe Masanori , Inao Mie , Namisaki Tadashi , Hashimoto Naoaki , Kawata Kazuhito , Takahashi Atsushi , Ninomiya Masashi , Kang Jong‐Hon , Arakawa Mie , Yamagiwa Satoshi , Joshita Satoru , Umemura Takeji , Sato Ken , Kaneko Akira , Kikuchi Kentaro , Itakura Jun , Nomura Takako , Kakisaka Keisuke , Fujii Hideki , Kawada Norifumi , Takikawa Yasuhiro , Masaki Tsutomu , Ohira Hiromasa , Mochida Satoshi , Yoshiji Hitoshi , Iimuro Satoshi , Matsuzaki Yasushi , Takikawa Hajime ,   Japan PBC Study Group
Published: February 2019

In Japan, bezafibrate (BF) is a second‐line agent for primary biliary cholangitis (PBC) that is refractory to ursodeoxycholic acid (UDCA) treatment. From a retrospective cohort (n = 873) from the Japan PBC Study Group, we enrolled 118 patients who had received UDCA monotherapy for at least 1 year followed by combination therapy with UDCA+BF for at least 1 year. GLOBE and UK‐PBC scores after UDCA monotherapy (i.e., immediately before UDCA+BF combination therapy) were compared with those after 1 year of UDCA+BF combination therapy. The real outcomes of enrolled patients estimated by Kaplan–Meier analysis were compared with the predicted outcomes calculated using GLOBE and UK‐PBC scores. In addition, the hazard ratio of BF treatment was calculated using propensity score analysis. The mean GLOBE score before the combination therapy was 0.504 ± 0.080, which improved significantly to 0.115 ± 0.085 (P < 0.0001) after 1 year of combination therapy. The real liver transplant‐free survival of enrolled patients was significantly better than that predicted by GLOBE score before introducing BF. Combination therapy did not significantly improve the real rates of liver transplantation or liver‐related death compared with those predicted by UK‐PBC risk score before introducing BF, but the predicted risk was significantly reduced by the addition of BF (P < 0.0001). Cox regression analysis with inverse probability of treatment weighting showed that the addition of BF significantly reduced the hazard of liver transplant or liver‐related death in patients who, after 1 year of UDCA monotherapy, had normal serum bilirubin (adjusted hazard ratio 0.09, 95% confidence interval 0.01‐0.60, P = 0.013). Conclusion: Addition of BF to UDCA monotherapy improves not only GLOBE and UK‐PBC scores but also the long‐term prognosis of PBC patients, especially those with early‐stage PBC.
Axis inhibition protein 1 (Axin1) Deletion–Induced Hepatocarcinogenesis Requires Intact β‐Catenin but Not Notch Cascade in Mice
Authors: Qiao Yu , Wang Jingxiao , Karagoz Eylul , Liang Binyong , Song Xinhua , Shang Runze , Evert Katja , Xu Meng , Che Li , Evert Matthias , Calvisi Diego F. , Tao Junyan , Wang Bruce , Monga Satdarshan P. , Chen Xin
Published: February 2019

Inactivating mutations of axis inhibition protein 1 (AXIN1), a negative regulator of the Wnt/β‐Catenin cascade, are among the common genetic events in human hepatocellular carcinoma (HCC), affecting approximately 10% of cases. In the present manuscript, we sought to define the genetic crosstalk between Axin1 mutants and Wnt/β‐catenin as well as Notch signaling cascades along hepatocarcinogenesis. We discovered that c‐MET activation and AXIN1 mutations occur concomitantly in ~3%‐5% of human HCC samples. Subsequently, we generated a murine HCC model by means of CRISPR/Cas9‐based gene deletion of Axin1 (sgAxin1) in combination with transposon‐based expression of c‐Met in the mouse liver (c‐Met/sgAxin1). Global gene expression analysis of mouse normal liver, HCCs induced by c‐Met/sgAxin1, and HCCs induced by c‐Met/∆N90‐β‐Catenin revealed activation of the Wnt/β‐Catenin and Notch signaling in c‐Met/sgAxin1 HCCs. However, only a few of the canonical Wnt/β‐Catenin target genes were induced in c‐Met/sgAxin1 HCC when compared with corresponding lesions from c‐Met/∆N90‐β‐Catenin mice. To study whether endogenous β‐Catenin is required for c‐Met/sgAxin1‐driven HCC development, we expressed c‐Met/sgAxin1 in liver‐specific Ctnnb1 null mice, which completely prevented HCC development. Consistently, in AXIN1 mutant or null human HCC cell lines, silencing of β‐Catenin strongly inhibited cell proliferation. In striking contrast, blocking the Notch cascade through expression of either the dominant negative form of the recombinant signal‐binding protein for immunoglobulin kappa J region (RBP‐J) or the ablation of Notch2 did not significantly affect c‐Met/sgAxin1‐driven hepatocarcinogenesis. Conclusion: We demonstrated here that loss of Axin1 cooperates with c‐Met to induce HCC in mice, in a β‐Catenin signaling–dependent but Notch cascade–independent way.
Differential expression of estrogen receptor–α on follicular dendritic cells from patients with grade 1‐2 and grade 3 follicular lymphoma
Authors: Ohe Rintaro , Meng Hong‐Xue , Ye Aung Naing , Yamada Akane , Kabasawa Takanobu , Utsunomiya Aya , Tamazawa Nobuyuki , Tamura Yuka , Kitaoka Takumi , Hashimoto Toshio , Shibata Kenichi , Toubai Tomomi , Kimura Wataru , Ishizawa Kenichi , Yamakawa Mitsunori
Published: February 2019

Hormone therapy has been used for patients with estrogen receptor alpha (ERα)–positive breast cancers. Recently, some studies reported the expression of ERα on neoplastic cells from B‐cell lymphomas. However, there has been only one report of ERα expression on the follicular dendritic cells (FDCs) that structurally and functionally support the microenvironment of follicular lymphomas (FLs). The objective of this study was to investigate the frequency of ERα expression on FDCs in nonneoplastic reactive lymphoid tissues and to compare the frequency of ERα expression on FDCs in the axillary lymph nodes between patients with and without antiestrogen therapy and among patients with grades 1‐3 of FL. Reverse transcription–polymerase chain reaction was performed to detect ERα mRNA in FL. In nonneoplastic germinal centers (GCs) from patients with tonsillitis or reactive lymphadenitis, ERα was expressed in the light zone. ERα‐positive cells strongly correlated with the width of GCs (rs = 0.81, P < 0.01) and the CD21‐positive (rs = 0.69, P < 0.01) and CD23‐positive (rs = 0.83, P < 0.01) FDC meshwork. The axillary lymph nodes had fewer ERα‐positive cells, smaller GCs, and a looser CD21‐ and CD23‐positive FDC meshwork with hormone therapy than without hormone therapy (P < 0.01). Neoplastic follicles of G1‐2 FL had more ERα‐positive cells and a larger CD23+ FDC meshwork than those of G3 FL (P < 0.01). ERα mRNA was detected in both G1‐2 FL and G3 FL by reverse transcription–polymerase chain reaction. In conclusion, these results suggested that antiestrogen hormone therapy may decrease the number of ERα‐positive FDCs and that the responses mediated by the estrogen‐ERα interaction on FDCs may differ between G1‐2 FL and G3 FL.
The expression of brown fat‐associated proteins in colorectal cancer and the relationship of uncoupling protein 1 with prognosis
Authors: Alnabulsi Abdo , Cash Beatriz , Hu Yehfang , Silina Linda , Alnabulsi Ayham , Murray Graeme I.
Published: February 2019

Colorectal carcinoma is one of the most common types of malignancy and a leading cause of cancer related death. The aberrant expression of a brown fat‐like phenotype in cancer cells has been previously implicated in tumour growth. Therefore, the expression of brown fat‐associated proteins in colorectal cancer could be associated with tumour prognosis. Monoclonal antibodies to brown fat‐associated proteins CIDEA, ELOVL3, ELOVL5, and UCP1 were developed. The antibodies were used to profile the expression of protein targets by immunohistochemistry in a discovery cohort comprising 50 normal colonic mucosa samples and 274 primary colorectal cancers and a validation cohort comprising 549 colorectal cancers. Immunostaining for UCP1 was observed in the majority of colorectal tumours while no immunostaining was observed in normal colonic mucosa (p < 0.001). The expression of UCP1 was significantly associated with better overall survival in both the discovery cohort (HR = 0.615, 95%CI = 0.416–0.909, χ2 = 6.119, p = 0.013) and the validation cohort (HR = 0.629, 95%CI = 0.480–0.825, χ2 = 11.558, p = 0.001). Furthermore, UCP1 was independently prognostic in multivariate analysis (p = 0.004). This study has identified the brown fat‐like phenotype as a novel pathway associated with survival in colorectal cancer. The expression of UCP1 was identified as a significant prognostic biomarker for colorectal cancer.
Idelalisib for optimized CD19‐specific chimeric antigen receptor T cells in chronic lymphocytic leukemia patients
Authors: Stock Sophia , Übelhart Rudolf , Schubert Maria‐Luisa , Fan Fuli , He Bailin , Hoffmann Jean‐Marc , Wang Lei , Wang Sanmei , Gong Wenjie , Neuber Brigitte , Hückelhoven‐Krauss Angela , Gern Ulrike , Christ Christiane , Hexel Monika , Schmitt Anita , Schmidt Patrick , Krauss Jürgen , Jäger Dirk , Müller‐Tidow Carsten , Dreger Peter , Schmitt Michael , Sellner Leopold
Published: February 2019

Despite encouraging results with chimeric antigen receptor T (CART) cells, outcome can still be improved by optimization of the CART cell generation process. The proportion of less‐differentiated T cells within the transfused product is linked to enhanced in vivo CART cell expansion and long‐term persistence. The clinically approved PI3Kδ inhibitor idelalisib is well established in the treatment of B cell malignancies. Besides B cell receptor pathway inhibition, idelalisib can modulate T cell differentiation and function. Here, detailed longitudinal analysis of idelalisib‐induced effects on T cell phenotype and function was performed during CART cell production. A third generation CD19.CAR.CD28.CD137zeta CAR vector system was used. CART cells were generated from peripheral blood mononuclear cells of healthy donors (HDs) and chronic lymphocytic leukemia (CLL) patients. Idelalisib‐based CART cell generation resulted in an enrichment of less‐differentiated naïve‐like T cells (CD45RA+CCR7+), decreased expression of the exhaustion markers PD‐1 and Tim‐3, as well as upregulation of the lymph node homing marker CD62L. Idelalisib increased transduction efficiency, but did not impair viability and cell expansion. Strikingly, CD4:CD8 ratios that were altered in CART cells from CLL patients were approximated to ratios in HDs by idelalisib. Furthermore, in vivo efficacy of idelalisib‐treated CART cells was validated in a xenograft mouse model. Intracellular TNF‐α and IFN‐γ production decreased in presence of idelalisib. This effect was reversible after resting CART cells without idelalisib. In summary, PI3Kδ inhibition with idelalisib can improve CART cell products, particularly when derived from CLL patients. Further studies with idelalisib‐based CART cell generation protocols are warranted.
Zinc‐oxide nanoparticles act catalytically and synergistically with nitric oxide donors to enhance antimicrobial efficacy
Authors: Singha Priyadarshini , Workman Christina D. , Pant Jitendra , Hopkins Sean P. , Handa Hitesh
Published: February 2019

The development of infection‐resistant materials is of substantial importance as seen with an increase in antibiotic resistance. In this project, the nitric oxide (NO)‐releasing polymer has an added topcoat of zinc oxide nanoparticle (ZnO‐NP) to improve NO‐release and match the endogenous NO flux (0.5–4 × 10−10 mol cm−2 min−1). The ZnO‐NP is incorporated to act as a catalyst and provide the additional benefit of acting synergistically with NO as an antimicrobial agent. The ZnO‐NP topcoat is applied on a polycarbonate‐based polyurethane (CarboSil) that contains blended NO donor, S‐nitroso‐N‐acetylpenicillamine (SNAP). This sample, SNAP‐ZnO, continuously sustained NO release above 0.5 × 10−10 mol cm−2 min−1 for 14 days while samples containing only SNAP dropped below physiological levels within 24 h. The ZnO‐NP topcoat improved NO release and reduced the amount of SNAP leached by 55% over a 7‐day period. ICP‐MS data observed negligible Zn ion release into the environment, suggesting longevity of the catalyst within the material. Compared to samples with no NO‐release, the SNAP‐ZnO films had a 99.03% killing efficacy against Staphylococcus aureus and 87.62% killing efficacy against Pseudomonas aeruginosa. A cell cytotoxicity study using mouse fibroblast 3T3 cells also noted no significant difference in viability between the controls and the SNAP‐ZnO material, indicating no toxicity toward mammalian cells. The studies indicate that the synergy of combining a metal ion catalyst with a NO‐releasing polymer significantly improved NO‐release kinetics and antimicrobial activity for device coating applications. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 00A: 000–000, 2019.
Clinical significance of cancer‐associated fibroblasts and their correlation with microvessel and lymphatic vessel density in lung adenocarcinoma
Authors: Chen Ling , Qin Yue , Zhang Tenglong , Ding Ning , Chen Yi , Zhang Zhe , Guo Chengye
Published: February 2019

Background

To determine whether cancer‐associated fibroblasts (CAFs) are associated with microvessel density (MVD) and lymphatic vessel density (LVD) in lung adenocarcinoma (ADC) or are not prognostic.

Methods

Ninety‐three lung adenocarcinoma patients without adjuvant therapy between January 2010 and June 2011 were enrolled. CAFs, MVD, and LVD were identified by α‐smooth muscle actin (α‐SMA), CD34 and D2‐40 staining via immunohistochemistry. Staining intensities were assessed and quantified. For statistics, Pearson's chi‐square test, logistic regression, Kaplan‐Meier, and log‐rank tests were applied. In addition, the Cox proportional hazards model was used for multifactor analysis to predict survival.

Results

CAFs abundance in lung adenocarcinoma is associated with higher MVD and LVD. In addition, a correlation was demonstrated between MVD and LVD (P < 0.05). CAFs, MVD, and LVD are significantly correlating with age, tumor size, differentiation grade, clinical stage, and lymph node metastasis (P < 0.05), but not influenced by gender, tumor location, and smoking history. Three‐year overall survival in the CAFs‐poor group is 64.5%, which is significant higher than that in the CAFs‐rich cohort (41.9%). Further, we found that age, clinical stage, α‐SMA, CD34, D2‐40 positivity, tumor size, differentiation grade, and lymph node metastasis significantly correlate with overall survival of patients with lung adenocarcinoma. However, sex, smoking history, and tumor location have no association with 3‐year survival. The clinical stage is an independent prognostic factor in overall survival (P < 0.05).

Conclusions

The density of CAFs identified by α‐SMA staining is associated with progression and metastasis of lung adenocarcinoma and affects the patient's disease outcome.
Iodine status of euthyroid adults: A cross‐sectional, multicenter study
Authors: Wang Danchen , Yu Songlin , Yin Yicong , Xie Shaowei , Cheng Qian , Li Honglei , Cheng Xinqi , Qiu Ling
Published: February 2019

Background

Iodine, an essential nutrient, is the most important trace element in thyroid hormone synthesis and maintenance of thyroid function. This study investigated the iodine nutrition status in healthy Chinese adults and assessed the relationship between urinary iodine concentration (UIC) and thyroid hormone levels.

Methods

A cross‐sectional, multicenter study was conducted between October 2017 and January 2018, with 1017 adults recruited from five cities in China. All subjects underwent thyroid ultrasonography, and only those with normal results were included in the study. UICs were measured by inductively coupled plasma mass spectroscopy and adjusted using urine creatinine levels. Thyroid hormone levels were measured using an automated immunoassay analyzer.

Results

The median UIC and adjusted UIC were 134.0 µg/L and 114.2 µg/g, respectively. UIC was not significantly different between males and females (P = 0.737). However, the adjusted UIC was significantly different between sexes (P < 0.001). The median UIC was higher than 100 µg/L. According to the World Health Organization criterion (100 µg/L), the total prevalence of iodine deficiency is 33.1% (n = 271). The prevalence rates of iodine deficiency in our study were 33.2% and 32.9% in males and females, respectively, and had no difference between sexes and among cities (P > 0.05). Serum thyroid‐stimulating hormone (TSH) levels increased when UIC increased. The Kruskal‐Wallis test showed no significant differences in free triiodothyronine, free thyroxine, and TSH, with different levels of UIC (all P > 0.05).

Conclusions

Chinese adults with normal thyroid structure have relatively sufficient iodine levels.
The association between CRP / Albumin ratio and in‐stent restenosis development in patients with ST‐segment elevation myocardial infarction
Authors: Aksu Uğur , Gulcu Oktay , Aksakal Emrah , Kalkan Kamuran , Öztürk Mustafa , Korkmaz Ali Fuat , Uslu Abdulkadir , Demirelli Selami
Published: February 2019

Background

Although interventional methods are the first‐line treatment options in ST‐segment elevation myocardial infarction (STEMI), the incidence of stent restenosis (SR) is frequent. We investigated the relationship between CRP/albumin ratio (CAR), a novel indicator of inflammatory response, and SR in this study.

Method

This study was carried out on the patients who underwent coronary angiography in our clinic between January 2017 and September 2017. Two groups were generated according to restenosis status (group 1: restenosis (−), group 2: restenosis (+)), and clinical biochemical and angiographical features were compared. As baseline demographic and angiographic characteristics are slightly different in two groups, propensity score matching analysis was performed to reduce bias. 45 SR patients were matched on a 1:1 basis were enrolled final cohort.

Results

The mean age of the patients was 55 ± 5.1 and 80% were male; Cox regression model was performed to demonstrate independent predictor of restenosis development; and during the one‐year follow‐up period, CAR (P < 0.001) was found an independent predictor of SR

Conclusion

In this study, we demonstrate that there may be a strong relationship between SR development and CAR. We implied that inflammatory reaction may be an important diagnostic tool for prediction of SR development in STEMI patients.
Factors complicating the informed consent process for whole exome sequencing in neonatal and pediatic intensive care units
Authors: Diamonstein Callie J.
Published: February 2019

Whole exome and whole genome sequencing (WES/WGS) is increasingly utilized in inpatient settings such as neonatal and pediatric intensive care units (ICU), but no research has explored the process of informed consent in this setting. My experience as an inpatient genetic counselor has illuminated factors unique to the ICU that may threaten elements of informed consent such as voluntariness, disclosure, understanding, and capacity. I present three cases that exemplify elements complicating consent counseling for WES/WGS in the ICU, including the emotional state of the parents, involvements of other healthcare providers, environmental distractions and competing clinical priorities. I offer strategies to navigate these factors based on my experience.
Risk of esophageal cancer in achalasia cardia: A meta‐analysis
Authors: Gillies Clare L , Farrukh Affifa , Abrams Keith R , Mayberry John F
Published: February 2019

Introduction

The association between cancer of the esophagus and achalasia has long been recognized. However, it has also been recognized that cancers themselves can give rise to achalasia‐like syndromes. The risk of developing cancer is also a factor in assessing whether there is a potential role for surveillance in this disease. This paper uses published work to form the basis for a meta‐analysis of the risk of developing esophageal cancer among patients with pre‐existing achalasia.

Methods

This paper considered cancer risk reported in a range of studies of achalasia published over a 50‐year period. Twenty‐seven potential studies were identified. In 16 reports, it was possible to extract information on both length of follow‐up and duration of achalasia so that person‐years duration (PYD) could be calculated. The analysis was stratified between cancers identified in the first year after diagnosis of achalasia and cancers identified in subsequent years.

Results

From pooling the results of 16 studies, the incidence rate of esophageal cancer in achalasia patients was estimated to be 1.36 (95% CI: 0.56, 2.51) per 1000 person years. This is over 10 times higher than the general population incidence rates as reported by the lARC.

Conclusions

Therefore, our meta‐analysis shows that achalasia is a major risk factor for the development of esophageal cancer. This is supported by the results from the time‐stratified analysis. Incidence of esophageal cancer per 1000 person years was lower in the first year after diagnosis of achalasia than in subsequent years. This is strong evidence against the idea that achalasia may be induced by esophageal cancer instead of vice versa.
Pleural metastasis detected by transesophageal endoscopic ultrasonography
Authors: Rana Surinder S , Gupta Parikshaa , Sharma Ravi K , Gupta Rajesh
Published: February 2019

Patients with pleural effusion and inconclusive repeated pleural fluid biochemical and cytological analysis are a diagnostic dilemma that is usually solved by invasive procedures such as diagnostic thoracoscopy. We report a 62‐year‐old male with malignant pleural effusion as well as ascites who was diagnosed using endoscopic ultrasound‐guided fine‐needle aspiration of pleural deposit. We also report contrast enhanced endoscopic ultrasound findings of pleural deposits.
Brain imaging in classic nonketotic hyperglycinemia: Quantitative analysis and relation to phenotype
Authors: Stence Nicholas V. , Fenton Laura Z. , Levek Claire , Tong Suhong , Coughlin Curtis R. , Hennermann Julia B. , Wortmann Saskia B. , Van Hove Johan L.K.
Published: February 2019

Patients with severe nonketotic hyperglycinemia (NKH) have absent psychomotor development and intractable epilepsy, whereas attenuated patients have variable psychomotor development and absent or treatable epilepsy; differences in brain magnetic resonance imaging (MRI) between phenotypes have not been reported. In a retrospective cross‐sectional study, we reviewed 38 MRI studies from 24 molecularly proven NKH patients, and 2 transient NKH patients. Quantitative analyses included corpus callosum size, apparent diffusion coefficient, automated brain volumetric analysis, and glycine/creatine ratio by spectroscopy. All patients age <3 months had restricted diffusion in the posterior limb of the internal capsule, anterior brainstem, posterior tegmental tracts, and cerebellum, not present in transient NKH. In older infants, the pattern evolved and included generalized diffusion restriction in the supratentorial white matter, which quantitatively peaked between 3 and 12 months. No patient had absent corpus callosum or gyral malformation. The corpus callosum was relatively short in severe compared to attenuated phenotypes, and thin in severe cases only. The corpus callosum growth rate differed by severity; age‐matched Z‐scores of thickness worsened in severe cases only. Cerebral volume was decreased in the hippocampus, globus pallidus, cerebral cortex, thalamus, and cerebellum. Severe patients had greatest glycine/creatine ratios. In this study, no brain malformations were identified. The growth failure of the corpus callosum is worse in severe NKH, whereas the diffusion restriction pattern, reflecting microspongiosis, does not discriminate by phenotypic severity. NKH is therefore a disorder of brain growth best recognized in the corpus callosum, whereas spongiosis is not prognostic.
Prostatic volume determination by transabdominal ultrasonography: Does accuracy vary significantly with urinary bladder volumes between 50 to 400 mL?
Authors: Brakohiapa Edmund K. , Botwe Benard O. , Sarkodie Benjamin D.
Published: February 2019

Introduction

In Ghana, trans‐abdominal ultrasonography is the main sonographic method of prostatic volume evaluation. The examinations are done when the patient's bladder is full. However, the delay and the discomforting experiences associated with a full bladder have been well documented. In an attempt to investigate other less discomforting options, this study was undertaken to determine if sonographic transabdominal prostatic evaluations performed at urinary bladder volumes of 50–99 mL differ significantly to evaluations done at volumes of 100–199, 200–299 and 300–399 mL.

Methods

A prostatic study of adult patients was undertaken in Accra, from 2014 to 2015. Using an ultrasound machine, 79 sets of prostatic measurements were recorded at a urinary bladder volume of 50–99 mL (V1 as our reference volume), and at least one of three other urinary bladder volumes (V2 = 100–199 mL, V3 = 200–299 mL and V4 = 300–399 mL), in 66 males. Twelve of the participants had multiple sets of prostate volume measurements.SPSSwas used to analyse the data.T‐test, Bland‐Altman plots and linear regression were used to compare and test for the existence of proportional biases in measurements.

Results

There was a statistically significant difference in prostatic volumes recorded at V1 and V2 (P = 0.017). However, the prostatic volume differences recorded for V1/V3, and V1/V4 groups of data were all not statistically significant (P > 0.05). The limits of agreement for the set of measurements spread from approximately −29 to +18 mL for V1/V2, −48 to +36 mL for V1/V3 and −12 to +12 mL for V1/V4 variables. There was no proportional bias in the V1/V2 (P = 0.55) and V1/V4 (P = 0.463) measurements.

Conclusion

Urinary bladder volume of 50–99 mL produces prostatic volume measurements comparable to volumes measured in patients with a full (300–399 mL), or nearly full urinary bladder (200–299 mL). A urinary bladder volume of 50–99 mL may therefore be adequate for scanning the prostate gland, and is likely to be tolerated much better by patients.
Assessment of seven CMIP5 model precipitation extremes over Iran based on a satellite‐based climate data set
Authors: Katiraie‐Boroujerdy Pari‐Sima , Akbari Asanjan Ata , Chavoshian Ali , Hsu Kuo‐lin , Sorooshian Soroosh
Published: February 2019

The ability of the seven CMIP5 models to simulate extreme precipitation events over Iran was evaluated using the Precipitation Estimation from Remotely Sensed Information using Artificial Neural Networks–Climate Data Record (PERSIANN‐CDR) data set. The criterion used to select the CMIP5 models was the availability of historical daily precipitation data (PERSIANN‐CDR) for the retrospective period 1983–2005, as well as future projections for the three representative concentration pathways emission scenarios (RCP2.6, RCP4.5, and RCP8.5) and spatial resolution higher than 2 × 2°. This is the first study to focus on extreme precipitation climate model simulations over Iran that includes high topography and different climates. The results show that CCSM4 has the highest correlation coefficients (CC = 0.85) and lowest root‐mean‐square error (RMSE = 73.6 mm) compared to PERSIANN‐CDR for the mean annual precipitation. However, HadGEM2‐ES shows the best (highest CCs between 0.67–0.79 and almost the lowest root‐mean‐square errors [RMSEs] compared to PERSIANN‐CDR) performance for intensity indices; MIROC5 ranked seventh (least CCs and almost the highest RMSEs) among the selected models. The results show that BCC‐CSM1‐1‐M captures maximum consecutive dry days (CDD) better than the other models. The probability matching method (PMM) is used to bias‐correct daily precipitation events from CMIP5 models with respect to the PERSIANN‐CDR estimations. All the model performances designed to capture the mean annual precipitation, as well as extreme intensity indices, improved after correction. The ensemble, constructed from the bias‐corrected model simulations using multiple linear regression (MLR), has the best performance for simulating the mean annual precipitation and extreme indices (CCs between 0.82 for consecutive wet days [CWD] and 0.93 for the mean annual precipitation) compared to the PERSIANN‐CDR estimations. Among the seven selected models, CCSM4 has the highest ranking (CCs between 0.70 for CWD to 0.91 for mean annual precipitation) after bias correction.
Antimicrobial effect of anesthetic‐eluting ultra‐high molecular weight polyethylene for post‐arthroplasty antibacterial prophylaxis
Authors: Gil Dmitry , Grindy Scott , Muratoglu Orhun , Bedair Hany , Oral Ebru
Published: February 2019

Despite being a relatively safe surgery, total joint replacement is often associated with two major complications—severe post‐operative pain and periprosthetic joint infection. Local sustained delivery of therapeutics to the surgical site has a potential to address these complications more effectively than current clinical approaches. Given that several analgesics were shown to possess antibacterial activity, we propose here to use analgesic‐loaded ultra‐high molecular weight polyethylene (UHMWPE) as a delivery vehicle to provide antimicrobial effect after an arthroplasty. Three commonly used anesthetics, lidocaine, bupivacaine, and ropivacaine, were analyzed in order to reveal the drug with the highest antibacterial activity against methicillin‐sensitive Staphylococcus aureus. Having shown highest antibacterial activity in the bacterial susceptibility tests, bupivacaine was chosen to be incorporated into UHMWPE to provide antibacterial properties. Bupivacaine‐loaded UHMWPE possessed moderate dose‐dependent antimicrobial properties, decreasing the S. aureus proliferation rate by up to 70%. Biofilm formation was also substanitally inhibited during the first 9 h of culture as quantified by bacterial counts and SEM. This proof‐of‐concept study is first of its kind to demonstrate that analgesic‐loaded UHMWPE can be used as part of a multimodal antimicrobial therapy. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res
Depletion of cytotoxic (CD8+) T cells impairs implant fixation in rat cancellous bone
Authors: Bernhardsson Magnus , Dietrich‐Zagonel Franciele , Tätting Love , Eliasson Pernilla , Aspenberg Per
Published: February 2019

As cytotoxic (CD8+) T cells seem to impair shaft fracture healing, we hypothesized that depletion of CD8+ cells would instead improve healing of cancellous bone. Additionally, we also tested if CD8‐depletion would influence the healing of ruptured Achilles tendons. Rats received a single injection of either anti‐CD8 antibodies or saline and put through surgery 24 h later. Three different surgical interventions were performed as follows: (1) a drill hole in the proximal tibia with microCT (BV/TV) to assess bone formation; (2) a screw in the proximal tibia with mechanical evaluation (pull‐out force) to assess fracture healing; (3) Achilles tendon transection with mechanical evaluation (force‐at‐failure) to assess tendon healing. Furthermore, CD8‐depletion was confirmed with flow cytometry on peripheral blood. Flow cytometric analysis confirmed depletion of CD8+ cells (p < 0.001). Contrary to our hypothesis, depletion of CD8+ cells reduced the implant pull‐out force by 19% (p < 0.05) and stiffness by 34% (p < 0.01), although the bone formation in the drill holes was the same as in the controls. Tendon healing was unaffected by CD8‐depletion. Our results suggest that CD8+ cells have an important part in cancellous bone healing. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res
Surgeon perception versus reality: Opioid use after breast cancer surgery
Authors: Park Ko Un , Kyrish Kristin , Terrell John , Yi Min , Caudle Abigail S. , Hunt Kelly K. , Kuerer Henry M. , Bedrosian Isabelle , Thompson Alastair , DeSnyder Sarah M. ,   other members of Department of Breast Surgical Oncology Study Group
Published: February 2019

Background

Few guidelines exist for an opioid prescription after breast surgical oncology (BSO) procedures. We sought to characterize opioid prescribing and use patterns by surgery type.

Methods

Patients (n = 332) undergoing BSO procedure were surveyed one week postoperatively for opioid use. The surgeons were surveyed about pain management preferences surgery type. CPT codes were collected for 2017 to calculate the amount of opioids used by surgery type relative to surgeon preference.

Results

Mean oral morphine equivalent (OME) preferred prescription for surgeons who did not tailor prescriptions by surgery type (n = 7, group A) was 177, whereas for those who did tailor (n = 10, group B) varied from 137 to 257 OME. There was a significant difference in opioid use by surgery type: 32 OME for segmental mastectomy (SM) ± sentinel lymph node dissection (SLND), 63 for SM + axillary lymph node dissection (ALND), 76 for total mastectomy (TM) ± SLND, 115 for TM + ALND (P < 0.001). Considering the type of surgeries performed group A prescribers would have 229190 unused OME and group B would have 230826 in 1 year.

Conclusion

Wide variation in opioid use by BSO procedure type was noted with substantial unused OME regardless ofprescribing preference. Evidence‐based guidelines are needed to tailor analgesic prescriptions according to the need.