bluuebunny/crossref_metadata_2025 huggingface dataset:
Initial clinical experience with the GORE® CARDIOFORM ASD occluder for transcatheter atrial septal defect closure
Authors: de Hemptinne Quentin , Horlick Eric M. , Osten Mark D. , Millán Xavier , Tadros Victor‐Xavier , Pighi Michele , Gonzalez Barlatey Francisco , Alnasser Sami M. , Miró Joaquim , Asgar Anita W. , Ibrahim Réda
Published: January 2017

Objectives

To report the initial clinical experience with a novel atrial septal defect (ASD) closure device, the GORE® CARDIOFORM ASD Occluder (GCO).

Background

Transcatheter closure has become the treatment of choice for secundum ASD. A wide range of occluder devices are available, but concern has been raised about the risk of cardiac erosion associated with rigid devices and future access to the left atrium

Methods

Retrospective chart review of patients treated with the GCO at three Canadian centers. Primary outcomes were procedural success and residual shunting at follow‐up, as well as 30‐day major adverse events. Secondary outcomes included new onset atrial arrhythmias, wire frame fractures (WFF), and all cause mortality. Clinical, echocardiographic, procedural data, and follow‐up outcome variables were collected in each participating hospital.

Results

Between February and December 2015, 26 patients (5 children and 21 adults) underwent transcatheter ASD closure with the GCO and were included in the study cohort. Procedural success was achieved in 22 of 26 patients (85%) and no major procedural complications were observed. Two patients (8%) presented new onset atrial tachyarrhythmia during early follow‐up (0–30 days). Follow‐up echocardiography (median of 119 days [IQR: 92–146]) demonstrated no residual shunt in all implanted patients. After a median clinical follow‐up of 174 days (IQR: 135–239), one patient died of an unrelated cause, there were no documented major adverse cardiovascular events. Fluoroscopic imaging of the device was performed in 20 patients (91%), and WFF was noted in five cases. No clinical consequence or device dysfunction was observed in these patients.

Conclusions

In this first‐in‐man multicenter study, the GCO was safe and effective for ASD closure, with no major adverse events or residual shunt at follow‐up. © 2017 Wiley Periodicals, Inc.
Massive perineal defect after radio‐chemotherapy
Authors: Zippi Maddalena , Ramponi Sara , Narduzzi Carla , Alberti Antonio Maria
Published: January 2017

Key Clinical Message

Herein, we present a rare complication of radio‐chemotherapy. A young man presented with loss of urine from the posterior perineum that showed a massive disappearance. He underwent Hartmann procedure for rectal neoplasia, afterwards treated with intensity‐modulated radiotherapy (IMRT) (until 67 Gy) and chemotherapy with FOLFOX protocol (Leucoverin calcium, Fluorouracil, Oxaliplatin).
In Situ Construction of Nickel Phosphosulfide (Ni5P4|S) Active Species on 3D Ni Foam through Chemical Vapor Deposition for Electrochemical Hydrogen Evolution
Authors: Lin Yan , Pan Yuan , Zhang Jun
Published: January 2017

The construction of efficient and robust nickel‐phosphide‐based catalysts for the hydrogen evolution reaction (HER) is still challenging. Previous research demonstrates that surface modification using sulfur atoms is an efficient strategy to improve the hydro‐desulfurization performance, owing to the formation of a phosphosulfide phase. Herein, an in situ construction strategy of nickel phosphosulfide (Ni5P4|S) active species on 3D Ni foam through a chemical vapor deposition reaction is described. The sulfuration and phosphorization temperature, as well as the P/S molar ratio, affect the active‐phase structure and the electrocatalytic performance toward the HER. The as‐synthesized NiPS‐500 (P/S=1:1) catalyst exhibits excellent electrocatalytic activity and stability in both acidic and basic conditions, owing to the formation of a nickel phosphosulfide phase, the high conductivity, and the 3D macroporous structure of the Ni foam substrate. The produced Ni5P4|S active species is not only the most active HDS site, but also the actual active species for efficiently catalyzing the HER. This achievement provides a novel and effective route to design a high‐performance, low‐cost catalyst with a facile synthesis for large‐scale water splitting.
Microfluidic Paper‐Based Analytical Device for Sensitive Detection of Peptides Based on Specific Recognition of Aptamer and Amplification Strategy of Hybridization Chain Reaction
Authors: Ma Chao , Liu Haiyun , Zhang Lina , Li Li , Yan Mei , Yu Jinghua , Song Xianrang
Published: January 2017

In this paper, a microfluidic paper‐based analytical device is presented for sensitively detecting peptides based on the specific recognition of aptamer and the amplification strategy of hybridization chain reaction (HCR). The aptamer/initiation strand (AP/IS) was designed for the specific target recognition, and the presence of the target peptide could release the initiating sequence from the AP/IS. The released IS could trigger the HCR between two hairpin probes, which could complete the detection for the targets indirectly when the electrochemiluminescence (ECL) probe (Ru(phen)32+) is introduced into the double‐strand DNA grooves,which could produce a significantly amplified ECL signal output. Mucin‐1 was employed as a model peptide, and the detection limit of the proposed assay is calculated as 8.33 pMwith a range from 25 pM to 50 nM. The novel sensing platform can be widened for the detection of other kinds of peptides as well as potentials used for sensitively detecting other biomolecules, and even cells.
Chelating P2‐Bis‐phosphazenes with a (R,R)‐1,2‐Diaminocyclohexane Skeleton: Two New Chiral Superbases
Authors: Kögel Julius F. , Kovačević Borislav , Ullrich Sebastian , Xie Xiulan , Sundermeyer Jörg
Published: January 2017

The linkage of two P2‐phosphazenyl groups through a C2‐symmetric (R,R)‐1,2‐diaminocyclohexane (DACH) backbone yielded the new chiral superbases DACH‐P2NMe2 and DACH‐P2Pyr (Pyr=pyrrolidinyl). These bases were prepared by a Kirsanov reaction and studied with respect to their spectroscopic and structural characteristics. Theoretical calculations concerning their basicity properties revealed remarkable pKBH+ values of 38.1 and 39.9 on the acetonitrile scale; this makes them the strongest nonionic chiral superbases known to date.
Effective treatment of high phosphorus pharmaceutical wastewater by chemical precipitation
Authors: Sun Wenquan , Ma Genchao , Sun Yongjun , Liu Yang , Song Ninghui , Xu Yanhua , Zheng Huaili
Published: January 2017

The conditions for the treatment of high phosphorus pharmaceutical wastewater using chemical precipitation were determined to achieve high efficiency on the removal of total phosphorus (TP). The key factors affecting the TP removal efficiencies of four metal salts (FeCl3, AlCl3, MgCl2, and CaCl2), such as molar ratio, initial wastewater pH, and reaction time, were investigated. The optimal metal mole ratios of FeCl3, AlCl3P, MgCl2, and CaCl2 for the TP removal were 1.8:1, 1.8:1, 1.6:1, and 1.6:1 in the initial pH range, respectively. The TP removal efficiencies obtained by FeCl3, AlCl3, MgCl2, and CaCl2 were 99.8 %, 98.3 %, 96.9 %, and 99.2 % at the optimal mole ratio and pH conditions with 30 min reaction time, respectively. FeCl3 and AlCl3 had better removal performance on COD, wherein the removal rates of COD by FeCl3 and AlCl3 were 38.6 % and 27.6 %, respectively. FeCl3 and CaCl2 were selected for the combined process of removing TP and overcoming the aforementioned problem. The final effluent quality was better than the one only used on one of the four metal salts, in which the removal rates of TP and COD were as high as 99.8 % and 46.9 %, respectively. The combined process with FeCl3 and CaCl2 was an effective method for the pretreatment of high phosphorus pharmaceutical wastewater to reduce the processing cost and to decrease the chemical oxygen demand (COD) and TP.
Bioequivalence Studies of a Reformulated Dutasteride and Tamsulosin Hydrochloride Combination Capsule and a Commercially Available Formulation
Authors: Kurczewski Renee , Bowen Chet , Collins David , Zhu John , Serbest Gulyeter , Manyak Michael
Published: January 2017

A dutasteride 0.5 mg and tamsulosin hydrochloride 0.4 mg combination (DTC) capsule (Duodart®) was reformulated to reduce the capsule size and enhance product stability. Bioequivalence of the reformulated DTC capsule with the commercial formulation was evaluated in 2 single‐dose, open‐label, randomized, 2‐way crossover studies in healthy adult male volunteers. Subjects in a fasted or fed state received a single oral dose of either the reformulated DTC or the commercial formulation followed by a 28‐day washout period between treatments. Blood samples were taken predose and up to 72 hours postdose for pharmacokinetic (PK) analysis of dutasteride and tamsulosin serum concentrations. From the serum concentration‐vs‐time data, a noncompartmental method was used to calculate the maximum observed serum concentration (Cmax) and area under the serum concentration‐time curve (AUC0‐t) for dutasteride and tamsulosin, and AUC0‐∞ for tamsulosin. The 90% confidence intervals for the ratios of the Cmax and AUC0‐t (for dutasteride and tamsulosin) and for AUC0‐∞ (for tamsulosin) were all completely contained within the range of 80% to 125%; therefore, the reformulated DTC capsule is bioequivalent to the commercial formulation under both fed and fasted states.
An Open‐Label, Randomized Bioavailability Study of Alternative Methods of Oral Administration of Naloxegol in Healthy Subjects
Authors: Bui Khanh , Birmingham Bruce , Diva Ulysses , Berger Bruce
Published: January 2017

Naloxegol is a peripherally acting μ‐opioid receptor antagonist approved as an orally administered tablet for the treatment of opioid‐induced constipation. Patients with swallowing difficulties may benefit from alternative approaches to the oral administration of the whole‐tablet formulation of naloxegol. This open‐label, randomized, 4‐period, 4‐treatment, crossover, single‐dose study (NCT02446171) evaluated the pharmacokinetic (PK) characteristics of crushed naloxegol 25‐mg tablets (suspended in water) administered orally or by nasogastric tube and a naloxegol solution compared with the commercially available 25‐mg tablet formulation in healthy volunteers. The PK profiles for the crushed tablet, whether administered orally or by nasogastric tube, and the 25‐mg oral solution were similar to that of the 25‐mg tablet administered orally. Compared with naloxegol commercial tablets, the relative bioavailability of naloxegol using 3 alternative methods of administration was approximately 100%. For each pairwise treatment comparison of the 3 alternative methods with the approved whole tablet, the geometric least‐squares mean ratio ranges were 94.37%–100.04%, 94.83%–100.44%, and 97.05%–102.05% for area under the curve (AUC), AUC0–t, and maximum plasma concentration, respectively, and their 90% confidence intervals were entirely within the predefined 80% to 125% bioequivalence limits. Naloxegol was well tolerated when administered in both liquid and solid form.
Improving Medicine Use for Children: A Global Imperative
Authors: MacLeod SM
Published: January 2017

Professionals committed to optimal medical care of children recognize the need to increase future availability of thoroughly validated medicinal treatments. This will only be achieved through expanded efforts of pediatric clinical pharmacologists and clinical pharmacists equipped with the necessary skills in relevant research and educational methods. Recent research has demonstrated a shortfall in the human resource pool, particularly in low‐ and lower‐middle‐income countries where a majority of children under 14 years of age reside.
Do the hydrological responses to forest disturbances in large watersheds vary along climatic gradients in the interior of British Columbia, Canada?
Authors: Zhang Mingfang , Wei Xiaohua , Li Qiang
Published: January 2017

Hydrological responses to forest disturbances are highly variable among watersheds. Climatic factors including water and energy are major drivers that determine the hydrological responses to forest disturbances. Although there are a number of large watershed studies on identifying the role of climate in the hydrological response to forest disturbances (e.g., logging, insect infestation, and fire), they are mainly concentrated on the precipitation effect. Given that climatic factors including both water and energy interact dynamically with hydrology and forest, and accordingly with forest–water relationships, there is a need for understanding the joint controls of water and energy on hydrological responses to forest changes by use of an integrated climatic index. In this study, 6 large watersheds along climatic gradients (Willow, Cottonwood, Baker, Moffat, Tulameen, and Ashnola) in the interior of British Columbia (BC), Canada, were selected for investigating the effect of climate on hydrological responses to forest disturbances at a large watershed scale by using modified double mass curves and statistical analysis (time series cross‐correlation, linear regression, and Mann–Whitney U test). Key results include the following: (a) in watersheds with a cumulative equivalent clear‐cut area of over 30% (Willow, Baker, Moffat, and Tulameen), mean annual flows were significantly increased by about 21–60 mm due to cumulated forest disturbances and (b) mean annual flow response to forest disturbances varied along climatic gradient. The amount of mean annual flow increase due to forest disturbances in energy‐limited watersheds Willow and Tulameen was as 3 times as that in water‐limited watersheds Baker and Moffat. Similarly, mean annual flow changes due to forest disturbances in wetter years were greater than those in drier years as suggested by results from the study watersheds. These findings highlight the need to develop different strategies for forests management in water‐limited and energy‐limited watersheds to minimize or adapt hydrological changes due to forest disturbances.
Donor bone marrow cells are essential for iNKT cell‐mediated Foxp3+ Treg cell expansion in a murine model of transplantation tolerance
Authors: Miyairi Satoshi , Hirai Toshihito , Ishii Rumi , Okumi Masayoshi , Nunoda Shinichi , Yamazaki Kenji , Ishii Yasuyuki , Tanabe Kazunari
Published: January 2017

Mixed chimerism induction is the most reliable method for establishing transplantation tolerance. We previously described a novel treatment using a suboptimal dose of anti‐CD40 ligand (anti‐CD40L) and liposomal formulation of a ligand for invariant natural killer T cells administered to sub‐lethally irradiated recipient mice after donor bone marrow cell (BMC) transfer. Recipient mice treated with this regimen showed expansion of a Foxp3‐positive regulatory T(Treg) cell phenotype, and formation of mixed chimera. However, the mechanism of expansion and bioactivity of Treg cells remains unclear. Here, we examine the role of donor BMCs in the expansion of bioactive Treg cells. The mouse model was transplanted with a heart allograft the day after treatment. The results showed that transfer of spleen cells in place of BMCs failed to deplete host interferon (IFN)‐γ‐producing CD8+T cells, expand host Ki67+CD4+CD25+Foxp3+ Treg cells, and prolong graft survival. Severe combined immunodeficiency mice who received Treg cells obtained from BMC‐recipients accepted skin grafts in an allo‐specific manner. Myeloid‐derived suppressor cells, which were a copious cell subset in BMCs, enhanced the Ki67 expression of Treg cells. This suggests that donor BMCs are indispensable for the expansion of host bioactive Treg cells in our novel treatment for transplant tolerance induction.
Towards the Iodine‐Catalyzed Regioselective Sulfenylation of Unsymmetrical Ketones
Authors: Devi Namita , Rahaman Rajjakfur , Sarma Kuladip , Khan Tuhina , Barman Pranjit
Published: January 2017

An efficient method for the synthesis of β‐keto sulfides was developed. A thermodynamically stable enolate was generated from unsymmetrical ketones and was found to react with sulfenyl iodides generated in situ from various disulfides to give α‐sulfenylation products. Potassium tert‐butoxide was used in a solvent mixture of tBuOH/1,3‐dimethyl‐2‐imidazolidinone (DMI, 7:3) at a mild reaction temperature of 40 °C. This iodine‐catalyzed method led to products in excellent yields up to 92 % within 2 h. The method is economical and no hazardous waste products are recovered throughout the process. The protocol is important, as unmodified ketones (linear and cyclic) are easily sulfenylated, which is otherwise not trivial. The Lewis acid FeCl3 could be used as an alternative reagent to avoid the use of base and DMI. However, treatment with this Lewis acid lowered the yields and the maximum yield obtained was 85 %.
Nanomaterial Based Biosensors for Detection of Biomarkers of Exposure to OP Pesticides and Nerve Agents: A Review
Authors: Zhang Weiying , Guo Zhenzhong , Chen Yong , Cao Yiping
Published: January 2017

Organophosphorus (OP) pesticides are primarily used as insecticides and chemical warfare agents worldwide. Due to their impact on the environment and health, it is important to develop prompt and accurate pesticide analysis method. This review addresses recent advances and new trends in nanotechnology‐based biosensors for biological monitoring of exposures to OP pesticides and nerve agents. In order to determine them, we have to find the corresponding biomarkers. In 1989, the national academy of sciences (NAS)divided biomarkers into the following three categories: biomarker of exposure, biomarker of effect and biomarker of susceptibility (Figure 1A). The unique chemical and physical properties of nanomaterial have paved the way to new and improved sensing devices, in general, and electrochemical/optical biosensors, in particular. In this paper, background information and a general overview of electrochemical/immunoassay detection techniques are provided. Various nanomaterial labels are discussed. Usually nanomaterials can be roughly divided into nanometer powder, nanometer fiber, nanometer film, nanometer block and so on four classes, such as colloidal gold, semiconductor nanoparticles and carbon nanomaterial (Figure 1B). In addition, we discuss some future considerations and opportunities for advancing the use of biosensors for environmental and health studies.
Complex observation of scalp fast (40–150 Hz) oscillations in West syndrome and related disorders with structural brain pathology
Authors: Kobayashi Katsuhiro , Endoh Fumika , Agari Takashi , Akiyama Tomoyuki , Akiyama Mari , Hayashi Yumiko , Shibata Takashi , Hanaoka Yoshiyuki , Oka Makio , Yoshinaga Harumi , Date Isao
Published: January 2017

We investigated the relationship between the scalp distribution of fast (40–150 Hz) oscillations (FOs) and epileptogenic lesions in West syndrome (WS) and related disorders. Subjects were 9 pediatric patients with surgically confirmed structural epileptogenic pathology (age at initial electroencephalogram [EEG] recording: mean 7.1 months, range 1–22 months). The diagnosis was WS in 7 patients, Ohtahara syndrome in 1, and a transitional state from Ohtahara syndrome to WS in the other. In the scalp EEG data of these patients, we conservatively detected FOs, and then examined the distribution of FOs. In five patients, the scalp distribution of FOs was consistent and concordant with the lateralization of cerebral pathology. In another patient, FOs were consistently dominant over the healthy cerebral hemisphere, and the EEG was relatively low in amplitude over the pathological atrophic hemisphere. In the remaining 3 patients, the dominance of FOs was inconsistent and, in 2 of these patients, the epileptogenic hemisphere was reduced in volume, which may result from atrophy or hypoplasia. The correspondence between the scalp distribution of FOs and the epileptogenic lesion should be studied, taking the type of lesion into account. The factors affecting scalp FOs remain to be elucidated.
Assessment of early life stage mahi-mahi windows of sensitivity during acute exposures to Deepwater Horizon crude oil
Authors: Mager Edward M. , Pasparakis Christina , Schlenker Lela S. , Yao Zongli , Bodinier Charlotte , Stieglitz John D. , Hoenig Ronald , Morris Jeffrey M. , Benetti Daniel D. , Grosell Martin
Published: January 2017

Windows of exposure to a weathered Deepwater Horizon oil sample (slick A) were examined for early life stage mahi-mahi (Coryphaena hippurus) to determine whether there are developmental periods of enhanced sensitivity during the course of a standard 96-h bioassay. Survival was assessed at 96 h following oil exposures ranging from 2 h to 96 h and targeting 3 general periods of development, namely the prehatch phase, the period surrounding hatch, and the posthatch phase. In addition, 3 different oil preparations were used: high- and low-energy water accommodated fractions of oil and very thin surface slicks of oil (∼1 μm). The latter 2 were used to distinguish between effects due to direct contact with the slick itself and the water underlying the slick. Considering the data from all 3 exposure regimes, it was determined that the period near or including hatch was likely the most sensitive. Furthermore, toxicity was not enhanced by direct contact with slick oil. These findings are environmentally relevant given that the concentrations of polycyclic aromatic hydrocarbons eliciting mortality from exposures during the sensitive periods of development were below or near concentrations measured during the active spill phase. Environ Toxicol Chem 2017;36:1887–1895. © 2016 SETAC
The Impact of Regression to the Mean on Economic Evaluation in Quasi‐Experimental Pre–Post Studies: The Example of Total Knee Replacement Using Data from the Osteoarthritis Initiative
Authors: Schilling Chris , Petrie Dennis , Dowsey Michelle M. , Choong Peter F. , Clarke Philip
Published: January 2017

Many treatments are evaluated using quasi‐experimental pre–post studies susceptible to regression to the mean (RTM). Ignoring RTM could bias the economic evaluation. We investigated this issue using the contemporary example of total knee replacement (TKR), a common treatment for end‐stage osteoarthritis of the knee.

Data (n = 4796) were obtained from the Osteoarthritis Initiative database, a longitudinal observational study of osteoarthritis. TKR patients (n = 184) were matched to non‐TKR patients, using propensity score matching on the predicted hazard of TKR and exact matching on osteoarthritis severity and health‐related quality of life (HrQoL). The economic evaluation using the matched control group was compared to the standard method of using the pre‐surgery score as the control.

Matched controls were identified for 56% of the primary TKRs. The matched control HrQoL trajectory showed evidence of RTM accounting for a third of the estimated QALY gains from surgery using the pre‐surgery HrQoL as the control. Incorporating RTM into the economic evaluation significantly reduced the estimated cost effectiveness of TKR and increased the uncertainty. A generalized ICER bias correction factor was derived to account for RTM in cost‐effectiveness analysis.

RTM should be considered in economic evaluations based on quasi‐experimental pre–post studies. Copyright © 2017 John Wiley & Sons, Ltd.
Glecaprevir and pibrentasvir for 12 weeks for hepatitis C virus genotype 1 infection and prior direct‐acting antiviral treatment
Authors: Poordad Fred , Felizarta Franco , Asatryan Armen , Sulkowski Mark S. , Reindollar Robert W. , Landis Charles S. , Gordon Stuart C. , Flamm Steven L. , Fried Michael W. , Bernstein David E. , Lin Chih‐Wei , Liu Ran , Lovell Sandra S. , Ng Teresa I. , Kort Jens , Mensa Federico J.
Published: January 2017

Although direct‐acting antiviral (DAA) therapies for chronic hepatitis C virus (HCV) infection have demonstrated high rates of sustained virologic response, virologic failure may still occur, potentially leading to the emergence of viral resistance, which can decrease the effectiveness of subsequent treatment. Treatment options for patients who failed previous DAA‐containing regimens, particularly those with nonstructural protein 5A inhibitors, are limited and remain an area of unmet medical need. This phase 2, open‐label study (MAGELLAN‐1) evaluated the efficacy and safety of glecaprevir (GLE) + pibrentasvir (PIB) ± ribavirin (RBV) in HCV genotype 1–infected patients with prior virologic failure to HCV DAA‐containing therapy. A total of 50 patients without cirrhosis were randomized to three arms: 200 mg GLE + 80 mg PIB (arm A), 300 mg GLE + 120 mg PIB with 800 mg once‐daily RBV (arm B), or 300 mg GLE + 120 mg PIB without RBV (arm C). By intent‐to‐treat analysis, sustained virologic response at posttreatment week 12 was achieved in 100% (6/6, 95% confidence interval 61‐100), 95% (21/22, 95% confidence interval 78‐99), and 86% (19/22, 95% confidence interval 67‐95) of patients in arms A, B, and C, respectively. Virologic failure occurred in no patients in arm A and in 1 patient each in arms B and C (two patients were lost to follow‐up in arm C). The majority of adverse events were mild in severity; no serious adverse events related to study drug and no relevant laboratory abnormalities in alanine aminotransferase, total bilirubin, or hemoglobin were observed. Conclusion: The combination of GLE and PIB was highly efficacious and well tolerated in patients with HCV genotype 1 infection and prior failure of DAA‐containing therapy; RBV coadministration did not improve efficacy. (Hepatology 2017;66:389–397).
Role of surface antibody in hepatitis B reactivation in patients with resolved infection and hematologic malignancy: A meta‐analysis
Authors: Paul Sonali , Dickstein Aaron , Saxena Akriti , Terrin Norma , Viveiros Kathleen , Balk Ethan M. , Wong John B.
Published: January 2017

Patients with resolved hepatitis B virus (HBV) infection who are treated for hematological malignancies remain at risk for HBV reactivation. Because of conflicting studies about whether the antibody to hepatitis B surface antigen (anti‐HBs) protects against reactivation in patients with resolved infection (hepatitis B surface antigen negative) receiving chemotherapy for hematological malignancies, we conducted a meta‐analysis to determine if anti‐HBs reduces HBV reactivation risk. We sought English‐language studies through March 1, 2016, in Medline and other sources that examined reactivation in patients with resolved HBV infection receiving chemotherapy for hematologic malignancies. The absolute risks and odds ratio (OR) of reactivation with versus without anti‐HBs were estimated in random‐effects model meta‐analyses. In 20 studies involving 1,672 patients not receiving antiviral prophylaxis, the reactivation risk was 14% (95% confidence interval [CI] 9.4%‐19%) in 388 patients who had antibodies to hepatitis B core antigen only versus 5.0% (95% CI 3.0%‐7.0%) in 1,284 patients who also had anti‐HBs. Anti‐HBs reduced reactivation risk with a pooled OR of 0.21 (95% CI 0.14‐0.32) versus patients with antibody to hepatitis B core antigen only. Similar results were found when limiting the analysis to rituximab chemotherapy (OR = 0.19, 95% CI 0.11‐0.32) and lymphoma (OR = 0.18, 95% CI 0.11‐0.28). Conclusion: In patients with resolved HBV receiving chemotherapy for hematological malignancies without antiviral prophylaxis, anti‐HBs positivity is associated with a decreased risk of reactivation; HBV screening in this patient population should include the routine use of anti‐HBs, and those who are anti‐HBs‐negative should receive antiviral prophylaxis. Future studies should examine the effect of anti‐HBs serum titers, the potential role for booster vaccinations, and antiviral prophylaxis prior to chemotherapy in this patient population. (Hepatology 2017;66:379–388).
Synthesis and Biochemical Evaluation of Biotinylated Conjugates of Largazole Analogues: Selective Class I Histone Deacetylase Inhibitors
Authors: Zhao Le , Dunne Christine E. , Clausen Dane J. , Roberts Justin M. , Paulk Joshiawa , Liu Haining , Wiest Olaf G. , Bradner James E. , Williams Robert M.
Published: January 2017

The synthesis of biotinylated conjugates of synthetic analogues of the potent and selective histone deacetylase (HDAC) inhibitor largazole is reported. The thiazole moiety of the parent compound's cap group was derivatized to allow the chemical conjugation to biotin. The derivatized largazole analogues were assayed across a panel of HDACs 1–9 and retained potent and selective inhibitory activity towards the class I HDAC isoforms. The biotinylated conjugate was further shown to pull down HDACs 1, 2, and 3.
Age‐related changes in pre‐ and post‐conization HPV genotype distribution among women with high‐grade cervical intraepithelial neoplasia
Authors: Giannella Luca , Fodero Cristina , Boselli Fausto , Rubino Teresa , Mfuta Kabala , Prandi Sonia
Published: January 2017

Objective

To assess the effect of age on pre‐ and post‐conization HPV genotype distribution.

Methods

The present retrospective observational study included consecutive women with high‐grade cervical intraepithelial neoplasia who underwent conization at the Cervical Cancer Screening Centre of Reggio Emilia, Italy, and University Hospital of Modena, Italy, between February 1, 2012, and October 31, 2014. Pre‐conization and 6‐month post‐conization HPV genotyping results were compared between four age groups (<30, 30–39, 40–49, and ≥50 years) and age‐related changes in the HPV genotypes present were evaluated.

Results

There were 162 patients included. The lowest occurrence of pre‐conization high‐risk and probable high‐risk HPV genotypes was observed among patients aged at least 50 years when compared with younger patients (P=0.017). Conversely, women aged at least 50 years exhibited the highest level of post‐conization high‐risk and probable high‐risk HPV genotypes (P=0.043). Additionally, an increasing incidence of recording identical pre‐ and post‐conization HPV genotypes was associated with increasing age (P=0.024), as was increasing post‐treatment recurrence of cervical intraepithelial neoplasia grade 2+ (P=0.030).

Conclusion

The presence of high‐risk and probable high‐risk HPV genotypes was lowest among older patients before conization and was highest among these patients post‐conization; post‐treatment HPV clearance decreased with age and increasing age could be a risk factor for post‐conization recurrence.
Inverted multiscale optical resolution photoacoustic microscopy
Authors: Qi Weizhi , Jin Tian , Rong Jian , Jiang Huabei , Xi Lei
Published: January 2017

Optical resolution photoacoustic microscopy (ORPAM) is one of the fastest evolving photoacoustic imaging modalities. It not only has a comparable spatial resolution to pure optical microscopies such as epifluorescence microscopy, confocal microscopy, and two‐photon microscopy, but also owns a higher penetration depth. In this study, we report an inverted multiscale (IM)‐ORPAM that utilizes a two‐dimensional galvanometric scanner integrated with two microscopic imaging lenses to achieve rotary‐scanning‐based multiscale imaging. A 15 MHz cylindrically focused ultrasonic transducer is mounted on a motorized rotator to synchronously follow the optical scanning paths. To minimize the loss of signal‐to‐noise ratio, the acoustic focal line is precisely adjusted confocal with the optical focal plane. Black tapes, carbon fibers, and sharp blades are imaged to evaluate the performance of the system, and in vivo multiscale imaging of vasculatures inside the ears and brains of mice is demonstrated using this system.

magnified image
Cyclin-Dependent Kinase Inhibitor-1-Deficient Mice are Susceptible to Osteoarthritis Associated with Enhanced Inflammation
Authors: Kihara Shinsuke , Hayashi Shinya , Hashimoto Shingo , Kanzaki Noriyuki , Takayama Koji , Matsumoto Tomoyuki , Chinzei Nobuaki , Iwasa Kenjiro , Haneda Masahiko , Takeuchi Kazuhiro , Nishida Kotaro , Kuroda Ryosuke
Published: January 2017

Osteoarthritis (OA) is a multifactorial disease, and recent data suggested that cell cycle–related proteins play a role in OA pathology. Cyclin-dependent kinase (CDK) inhibitor 1 (p21) regulates activation of other CDKs, and recently, we reported that p21 deficiency induced susceptibility to OA induced by destabilization of the medial meniscus (DMM) surgery through STAT3-signaling activation. However, the mechanisms associated with why p21 deficiency led to susceptibility to OA by the STAT3 pathway remain unknown. Therefore, we focused on joint inflammation to determine the mechanisms associated with p21 function during in vitro and in vivo OA progression. p21-knockout (p21−/−) mice were used to develop an in vivo OA model, and C57BL/6 (p21+/+) mice with the same background as the p21−/− mice were used as controls. Morphogenic changes were measured using micro-CT, IL-1β serum levels were detected by ELISA, and histological or immunohistological analyses were performed. Our results indicated that p21-deficient DMM-model mice exhibited significant subchondral bone destruction and cartilage degradation compared with wild-type mice. Immunohistochemistry results revealed p21−/− mice susceptibility to OA changes accompanied by macrophage infiltration and enhanced MMP-3 and MMP-13 expression through IL-1β-induced NF-κB signaling. p21−/− mice also showed subchondral bone destruction according to micro-CT analysis, and cathepsin K staining revealed increased numbers of osteoclasts. Furthermore, p21−/− mice displayed increased serum IL-1β levels, and isolated chondrocytes from p21−/− mice indicated elevated MMP-3 and MMP-13 expression with phosphorylation of IκB kinase complex in response to IL-1β stimulation, whereas treatment with a specific p-IκB kinase inhibitor attenuated MMP-3 and MMP-13 expression. Our results indicated that p21-deficient DMM mice were susceptible to alterations in OA phenotype, including enhanced osteoclast expression, macrophage infiltration, and MMP expression through IL-1β-induced NF-κB signaling, suggesting that p21 regulation may constitute a possible therapeutic strategy for OA treatment. © 2017 American Society for Bone and Mineral Research.
Matrix metalloproteinase‐1 promoter ‐1607 bp 1G/2G polymorphism associated with increased risk of spinal tuberculosis in Southern Chinese Han population
Authors: Zhou Ying , Gao Qile , He Dan , Deng Ang , Huang Rongfu , Li Yanbing , Tan Chunyan , Guo Chaofeng , Guo Qiang , Wang Longjie , Yang Guanteng , Zhang Hongqi
Published: January 2017

Background

Spinal tuberculosis is the most common form of musculoskeletal tuberculosis. The expression of matrix metalloproteinase‐1 (MMP‐1) is increased in cells with Mycobacterium tuberculosis infection. MMP‐1 plays a curial role in extracellular matrix degradation during the progression of tuberculosis. Although the 1G/2G polymorphism in MMP‐1‐1607 influences its transcription, its role in spinal tuberculosis remains unknown.

Methods

Healthy controls and patients with spinal tuberculosis of Han ethnicity were recruited between January 2010 and May 2016. The MMP‐1‐1607 1G/2G polymorphism was genotyped using the Sequenom mass Array polymorphism analysis system.

Results

The genotypes of 1G/1G, 1G/2G, and 2G/2G were found in 13.7%, 53.6%, and 32.8% of patients, and 12.2%, 37.4%, and 50.4% of controls, respectively. The 1G/2G genotype were more common in cases than in controls (P=2.05E‐04). The 1G allele showed an association with an increased risk for spinal tuberculosis when compared to 2G allele (P=.004). 1G genotypes, having at least one 1G allele, were associated with the risk of developing spinal tuberculosis (1G/1G+1G/2G vs 2G/2G: OR=2.084, 95%CI=1.401‐3.100, P=2.65E‐04).

Conclusion

1G genotypes of the MMP‐1‐1607 may be associated with susceptibility to spinal tuberculosis in Southern Chinese Han population.
Synthesis, Reactions, and Spectral Characterization of New Fused Pyrazolothienopyridine and Pyrazolopyrrolopyridine Systems
Authors: Geies A. A. , Abdel Moneam M. I. , Kamal El‐Dean A. M. , Zaki R. M. , Abd El‐Naeem E. E.
Published: January 2017

4‐Oxo‐1‐phenyl‐4,7‐dihydropyrazolo[3,4‐b]pyridine‐5‐carbonitrile compound (4) was prepared by the reaction of 5‐amino‐3‐methyl‐1‐phenyl pyrazole (1) with ethyl 2‐cyano‐3‐ethoxyacrylate followed by cyclization using diphenyl ether. The pyrazolopyridinone compound 4 was converted to the chloropyrazolopyridine 5 by the reaction with phosphorus oxychloride. Compound 5 was used as a starting material to synthesize 3‐amino‐4‐substituted pyrazolothienopyridine derivatives 10a–f and ethyl‐3‐aminopyrazolopyrrolopyridine‐2‐carboxylate 21, which were used as a versatile precursors for synthesis of poly‐fused heterocyclic compounds.
Sea and land surface temperatures, ocean heat content, Earth's energy imbalance and net radiative forcing over the recent years
Authors: Dieng H. B. , Cazenave A. , Meyssignac B. , von Schuckmann K. , Palanisamy H.
Published: January 2017

We investigate the global mean and regional change of sea surface and land surface temperature over 2003–2013, using a large number of different data sets, and compare with changes observed over the past few decades (starting in 1950). We find that over 2003–2013, both global land surface temperature and global sea surface temperature have increased at a rate significantly lower than over the previous decades. While confirming cooling of eastern tropical Pacific during the last decade as reported in several recent studies, our results show that the reduced rate of change of the 2003–2013 time span is a global phenomenon. GMST short‐term trends since 1950 computed over successive 11‐year windows with 1‐year overlap show important decadal variability that highly correlates with 11‐year trends of the Atlantic Multidecadal Oscillation index. The GMST 11‐year trend distribution is well fitted by a Gaussian function, confirming an unforced origin related to internal climate variability. We evaluate the time derivative of full‐depth ocean heat content to determine the planetary energy imbalance with different approaches: in situ measurements, ocean reanalysis and global sea level budget. For 2003–2013, it amounts to 0.5 +/− 0.1 W m−2, 0.68 +/− 0.1 W m−2 and 0.65 +/− 0.1 W m−2, respectively for the three approaches. Comparing with the Energy Balanced and Filled (EBAF) data of the Clouds and Earth's Radiant Energy Systems (CERES) project, we find significant agreement at interannual scales. Finally, using 15‐year averages of GMST and total ocean heat content rate, we compute the net radiative forcing since 1970 (this start date being constrained by availability of ocean temperature data). Although the uncertainty is quite large because of considerable errors in the climate sensitivity parameter, we find no evidence of decrease in net radiative forcing in the recent years, but rather an increase compared to the previous decades.
Soil residual nitrogen under various crop rotations and cultural practices
Authors: Sainju Upendra M. , Lenssen Andrew W. , Allen Brett L. , Stevens William B. , Jabro Jalal D.
Published: January 2017

Crop rotation and cultural practice may influence soil residual N available for environmental loss due to crop N uptake and N immobilization. We evaluated the effects of stacked vs. alternate‐year crop rotations and cultural practices on soil residual N (NH4‐N and NO3‐N contents) at the 0–125 cm depth, annualized crop N uptake, and N balance from 2005 to 2011 in the northern Great Plains, USA. Stacked rotations were durum (Triticum turgidum L.)–durum–canola (Brassica napus L.)–pea (Pisum sativum L.) (DDCP) and durum–durum–flax (Linum usitatissimum L.)–pea (DDFP). Alternate‐year rotations were durum–canola–durum–pea (DCDP) and durum–flax–durum–pea (DFDP). Both of these are legume‐based rotations because they contain legume (pea) in the crop rotation. A continuous durum (CD) was also included for comparison. Cultural practices were traditional (conventional tillage, recommended seeding rate, broadcast N fertilization, and reduced stubble height) and improved (no‐tillage, increased seeding rate, banded N fertilization, and increased stubble height) systems. The amount of N fertilizer applied to each crop in the rotation was adjusted to soil NO3‐N content to a depth of 60 cm observed in the autumn of the previous year. Compared with other crop rotations, annualized crop biomass N was greater with DCDP and DDCP in 2007 and 2009, but was greater with DDFP than DCDP in 2011. Annualized grain N was greater with DCDP than CD, DFDP, and DDFP and greater in the improved than the traditional practice in 2010 and 2011. Soil NH4‐N content was greater with CD than other crop rotations in the traditional practice at 0–5 cm, but was greater with DDCP than CD and DDFP in the improved practice at 50–88 cm. Soil NO3‐N content was greater with CD than other crop rotations at 5–10 cm, but was greater with CD and DFDP than DCDP and DDCP at 10–20, 88–125, and 0–125 cm. Nitrate‐N content at 88–125 and 0–125 cm was also greater in the traditional than the improved practice. Nitrogen balance based on the difference between N inputs and outputs was greater with crop rotations than CD. Increased N fertilization rate increased soil residual N with CD, but legume N fixation increased N balance with crop rotations. Legume‐based crop rotations (all rotations except CD) reduced N input and soil residual N available for environmental loss, especially in the improved practice, by increasing crop N uptake and N immobilization compared with non‐legume monocrop.
In‐situ isothermal micro‐Raman spectroscopy reveals the activation energy of dehydration in α‐FeOOH
Authors: Sendova Mariana , Hosterman Brian D. , Grebe Anthony
Published: January 2017

A real‐time, isothermal micro‐Raman spectroscopy was developed as a single technique for monitoring the solid state kinetics of dehydration and measuring its activation energy. The technique comprises of acquisition and numerical analysis of a set of isothermal time‐dependent Raman spectra. α‐FeOOH transformation to Fe2O3 in N2 atmosphere was continuously monitored for up to 16 h at three temperatures. Dehydration activation energy of 1.4(1) eV was estimated. The Raman band evolution of two modes with different symmetries (B1g ~ 240 cm−1 and Ag ~ 400 cm−1) and the intensity decay of B1g mode at ~540 cm−1 are analyzed independently utilizing kinetic model‐free approach. The study opens new possibilities for developing versatile solid state chemical and bio‐chemical Raman sensors and advances the field of analytical micro‐Raman spectroscopy. Copyright © 2017 John Wiley & Sons, Ltd.
Lymphocyte to monocyte ratio and neutrophil to lymphocyte ratio are superior inflammation‐based predictors of recurrence in patients with hepatocellular carcinoma after hepatic resection
Authors: Yang Tianbo , Zhu Jiye , Zhao Lei , Mai Kangye , Ye Jiazhou , Huang Shan , Zhao Yinnong
Published: January 2017

Aim

The purpose of this study was to investigate which inflammation‐based marker more accurately predict recurrence in patients receiving hepatectomy for hepatocellular carcinoma (HCC).

Methods

A total of 1020 patients was included. The impacts of clinical variables and inflammation‐based markers on disease‐free survival (DFS) were measured by Kaplan‐Meier method. Selected potential prognostic factors were further analyzed in multivariate model. To reduce influences of selection bias and possible confounders, clinical characteristics of patients were balanced by propensity score matching (PSM).

Results

Of the 1020 patients, 881 (86.4%) were male and 323 (31.7%) received major hepatectomy. In multivariate analysis, cirrhosis (HR: 1.49), tumor size (HR: 1.32), tumor number (HR: 1.57), portal vein tumor thrombus (HR: 1.66), microvascular invasion (HR: 1.60), histological grade (HR: 1.82), operation time (HR: 1.50), alpha foetal protein (HR: 1.29), neutrophil to lymphocyte ratio (NLR) (HR: 1.38), and lymphocyte to monocyte ratio (LMR) (HR: 1.51) were independently predictive of DFS. After PSM, 258 and 213 pairs of patients were generated for LMR and NLR, respectively. LMR and NLR were still independent predictors of recurrence for HCC patients receiving hepatectomy.

Conclusion

Both LMR and NLR might be preferable independent prognostic factors for DFS in HCC patients undergoing hepatectomy.
Improved local control with an aggressive strategy of preoperative (with or without intraoperative) radiation therapy combined with radical surgical resection for retroperitoneal sarcoma
Authors: Hull Melissa A. , Molina George , Niemierko Andrzej , Haynes Alex B. , Jacobson Alex , Bernstein Karen De Amorim , Chen Yen‐Lin , DeLaney Thomas F. , Mullen John T.
Published: January 2017

Background and Objectives

We sought to examine our outcomes with advanced preoperative and intraoperative radiation therapy (XRT) combined with aggressive en bloc surgical resection of retroperitoneal sarcoma (RPS) as a strategy to minimize the risk of local recurrence (LR).

Methods

From 2003 to 2013, 46 patients with RPS received preoperative XRT followed by radical en bloc surgical resection, with or without intraoperative electron radiation therapy (IOERT). Clinical and pathologic variables predictive of LR and distant recurrence (DR) were evaluated.

Results

Thirty‐seven patients had primary tumors and 80% were intermediate grade or higher. All patients received preoperative XRT to a median dose of 50.4 Gy and underwent complete (R0/R1) tumor resection, and 16 patients received IOERT. After a median follow‐up of 53 months, 33 (72%) patients were disease‐free, and there were 8 (17%) DRs, 2 (4%) abdominal recurrences outside of the XRT field, and 5 (10.9%) LRs. High tumor grade and recurrent disease at presentation were the only factors associated with higher rates of recurrence.

Conclusions

Excellent local control can be achieved with a coordinated strategy of preoperative (±intraoperative) XRT combined with aggressive en bloc surgical resection of RPS, but systemic failure remains a problem for higher‐grade tumors.
Two Rate Constant Kinetic Model for the Chromium(III)–EDTA Complexation Reaction by Numerical Simulations
Authors: Perez‐Benito Joaquin F.
Published: January 2017

The complexation reaction of Cr(III) ion in the presence of a large excess of ethylenediaminetetraacetic acid (EDTA) does not follow a pseudo–first‐order kinetics as sometimes suggested. There are two causes for the deviation from this simple behavior: the involvement of a long‐lived intermediate, precluding the application of the steady‐state approximation, and the autoinhibition provoked by the release of hydrogen ions from the organic ligand to the medium as the final Cr(III)–EDTA violet complex is formed. Numerical simulations have allowed obtaining for each kinetic experiment the values of two rate constants, k1 (corresponding to the formation of the long‐lived intermediate from the reactants) and k2 (corresponding to the formation of the final complex product from the long‐lived intermediate), as well as the number of hydrogens liberated per molecule of final complex product formed (Hkin). The results indicate that k1 is associated with a fast step (Ea = 87 ± 4 kJ mol−1) and k2 to a slow step (Ea = 120 ± 2 kJ mol−1), whereas the number of hydrogen ions lies within the range 0 < Hkin < 2 in all the kinetic runs. A mechanism in accordance with the experimental data has been proposed.
Design of a Bioabsorbable Multilayered Patch for Esophagus Tissue Engineering
Authors: Dorati Rossella , De Trizio Antonella , Marconi Stefania , Ferrara Anna , Auricchio Ferdinando , Genta Ida , Modena Tiziana , Benazzo Marco , Benazzo Alberto , Volpato Gino , Conti Bice
Published: January 2017

A gold standard for esophagus reconstruction is not still available. The present work aims to design a polymer patch combining synthetic polylactide‐co‐polycaprolacton and chitosan biopolymers, tailoring patch properties to esophageal tissue characteristics by a temperature‐induced precipitation method, to get multilayered patches (1L, 2L, and 3L). Characterization shows stable multilayered patches (1L and 2L) by selection of copolymer type, and their M
w. In vitro investigation of the functional patch properties in simulated physiologic and pathologic conditions demonstrates that the chitosan layer (patch 3L) decreases patch stability and cell adhesion, while improves cell proliferation. Patches 2L and 3L comply with physiological esophageal pressure (3–5 kPa) and elongation (20%).

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