bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of Dietary Niacin Intake With Incident Hip Fracture, BMD, and Body Composition: The Cardiovascular Health Study
Authors: Carbone Laura D , Bůžková Petra , Fink Howard A , Raiford Mattie , Le Brian , Isales Carlos M , Shikany James M , Coughlin Steven S , Robbins John A
Published: January 2019

Interest in niacin has increased in the setting of reports suggesting that niacin plays a role in diseases of aging. No study to date has examined the association of dietary niacin intake with multiple skeletal health parameters including bone mineral density (BMD), hip fractures, and body composition, and none have included both African American and white men and women. Participants included 5187 men and women ≥65 years from the Cardiovascular Health Study (CHS). Mean daily dietary niacin intake was 32.6 mg, with quartiles 1 through 4 defined as 3.6 to 21.8 mg/day, 21.9 to 30.2 mg/day, 30.3 to 40.9 mg/day, and 41.0 to 102.4 mg/day, respectively. Risk of incident hip fracture per 10 mg increment of daily dietary niacin intake was estimated using proportional hazards models. During a median follow-up of 13 years, 725 participants had an incident hip fracture. In models adjusted for demographic and clinical characteristics and diet, dietary niacin intake was significantly associated with an increased risk of hip fractures (hazard ratio [HR] 1.12; 95% CI, 1.01 to 1.24) with spline models suggesting a U-shaped association. In post hoc analyses, both the lowest (HR 1.31; 95% CI, 1.04 to 1.66) and highest (HR 1.53; 95% CI, 1.20 to 1.95) quartiles of niacin intake were associated with an increased risk of incident hip fracture versus quartiles 2 and 3. There was a trend for a significant inverse association of dietary niacin intake with hip BMD (p = 0.06), but no significant association with total body BMD or any body composition measures. In this cohort of elderly, community-dwelling African American and white men and women, both high and low dietary niacin intakes were associated with a significantly increased risk of subsequent hip fracture, suggesting a possible U-shaped association. By comparison, dietary niacin may have an inverse linear association with hip BMD. © 2018 American Society for Bone and Mineral Research.
miR‐98 acts as an inhibitor in chronic constriction injury‐induced neuropathic pain via downregulation of high‐mobility group AT‐hook 2
Authors: Zhang Yang , Su Zhen , An Li‐Jun , Li Lin , Wei Meng , Ge Dong‐Jian , Liu Hai‐Lin
Published: January 2019

Neuropathic pain, resulting from somatosensory nervous system dysfunction, remains a serious public health problem worldwide. microRNAs are involved in the physiological processes of neuropathic pain. However, the biological roles of miR‐98 in neuropathic pain development have not been investigated. Therefore, in our current study, we focused on the effects of miR‐98 in neuropathic pain. It was shown that miR‐98 was significantly downregulated in chronic sciatic nerve injury (CCI) rat models. In addition, high mobility group A2 (HMGA2) was obviously upregulated in CCI rats. Overexpression of miR‐98 inhibited neuropathic pain progression, including mechanical and thermal hyperalgesia. By a bioinformatics analysis, HMGA2 was predicted as a direct target of miR‐98. The negative correlation between miR‐98 and HMGA2 was validated in our present study. Furthermore, overexpression of miR‐98 dramatically repressed HMGA2 protein and messenger RNA (mRNA) expression. Neuroinflammation participates in neural‐immune interactions, which can contribute to the neuropathic pain development. Meanwhile, we found that inflammatory cytokine (interleukin [IL]‐6, IL‐1β, and COX‐2) protein expression in rats infected with LV‐miR‐98 was greatly suppressed. Taking these results together, we concluded that miR‐98 might depress neuropathic pain development through modulating HMGA2.
Functional rs6265 polymorphism in the brain‐derived neurotrophic factor gene confers protection against neurocognitive dysfunction in posttraumatic stress disorder among Chinese patients with hepatocellular carcinoma
Authors: Guo Jun‐Cheng , Yang Yi‐Jun , Zheng Jin‐Fang , Guo Min , Wang Xiao‐Dan , Gao Yun‐Suo , Fu Lin‐Qiu , Jiang Xiang‐Ling , Fu Lin‐Mei , Huang Tao
Published: January 2019

Posttraumatic stress disorder (PTSD) is a psychiatric disorder that plagues trauma survivors. Evidence shows that brain‐derived neurotrophic factor (BDNF) may be involved in the occurrence and development of PTSD. Here we tried to demonstrate whether BDNF gene polymorphisms are correlated with neurocognitive function following PTSD in patients with hepatocellular carcinoma (HCC). This study included 102 patients with HCC complicated with PTSD, 146 HCC patients, and 152 healthy volunteers. Initially, we evaluated the neurocognitive function of the study subjects. Next, we measured BDNF G11757C and rs6265 polymorphisms by polymerase chain reaction‐restriction fragment length polymorphism. The correlation of BDNF polymorphisms and BDNF level with HCC complicated with PTSD was evaluated. The results revealed that HCC complicated with PTSD showed decreased serum BDNF level and Mini‐mental state examination (MMSE) score. Serum BDNF level of HCC and HCC complicated with PTSD was positively correlated with MMSE score. GA + AA allele and A allele of rs6265 increased the risk of PTSD among patients with HCC. GA and AA genotypes of rs6265 were correlated with the decreased MMSE score of HCC complicated with PTSD. Haplotype GA of rs6265 and G11757C increased the risk of PTSD for HCC, while haplotype CG decreased this risk. Lastly, the logistic regression analysis suggested that low BDNF level was a contributor to HCC complicated with PTSD, while GG genotype of rs6265 served as a protective factor. Collectively, this study defines the GG genotype of BDNF rs6265 polymorphism as a protector to HCC complicated with PTSD. In addition, these results provided a promising target for PTSD prevention in patients with HCC.
Fearless Me!©: A feasibility case series of cognitive behavioral therapy for adolescents with intellectual disability
Authors: Hronis Anastasia , Roberts Rachel , Roberts Lynette , Kneebone Ian
Published: January 2019

Objective

This study evaluated the feasibility of the Fearless Me! program, an online cognitive behavioral therapy (CBT) program for children with intellectual disability (ID) and anxiety.

Method

Twenty‐one adolescents with mild to moderate ID participated in ten sessions of the therapist‐assisted Fearless Me! program, combining face‐to‐face group sessions and an online component. A case series design was adopted to assess anxiety symptoms at baseline, throughout intervention, and postintervention. Feasibility of the measures, intervention, and trial design were considered.

Results

The measures were appropriate and sensitive to changes in anxiety, whereas the need for attention to factors influencing parent’s completion of them was identified. Reliable Change Index and visual analyses of results indicated reductions in anxiety, particularly for older adolescents with heightened levels of anxiety at baseline.

Conclusions

This is one of the first CBT programs for adolescents with ID, and provides preliminary evidence of adapted CBT as a feasible treatment.
ROS‐ and HIF1α‐dependent IGFBP3 upregulation blocks IGF1 survival signaling and thereby mediates high‐glucose‐induced cardiomyocyte apoptosis
Authors: Huang Yao‐Te , Liu Chung‐Hung , Yang Yao‐Chih , Aneja Ritu , Wen Su‐Ying , Huang Chih‐Yang , Kuo Wei‐Wen
Published: January 2019

The prevalence of chronic hyperglycemia and its complications, imposing a critical burden on the worldwide economy and the global healthcare system, is a pressing issue. Mounting evidence indicates that oxidative stress and hypoxia, two noticeable features of hyperglycemia, play a joint crucial role in mediating cellular apoptosis. However, the underlying detailed molecular mechanism remains elusive. Triggered by the observation that insulin‐like growth factor (IGF1)‐binding protein 3 (IGFBP3) can mediate, in renal cells, high‐glucose‐induced apoptosis by elevating oxidative stress, we wish to, in this study, know whether or not the similar scenario holds in cardiac cells and, if so, to find its relevant molecular key players, thereby dissecting the underlying molecular pathway. Specifically, we used a combination of three different cellular sources (H9c2 cells, diabetic rats, and neonatal rat ventricular cardiomyocytes) as our model systems of study. We made use of Co‐IP assay and western blot analysis in conjunction with loss‐of‐function reasoning, gain‐of‐function logic, and inhibitor treatment as our main analytical tools. As a result, briefly, our main findings are that hyperglycemia can induce cardiac IGFBP3 overexpression and secretion, that high levels of IGFBP3 can sequester IGF1 from IGF1 survival pathway, leading to apoptosis, and that IGFBP3 gene upregulation is hypoxia‐inducible factor (HIF)1α‐dependent and reactive oxygen species dependent. Piecing these findings together allows us to propose the improved molecular regulatory mechanism. In conclusion, we have established the molecular roles of IGFBP3, HIF1, and prolyl hydroxylase domain in connecting oxidative stress with hypoxia and in cellular apoptosis under hyperglycemia.
Circular RNA hsa_circ_0007059 indicates prognosis and influences malignant behavior via AKT/mTOR in oral squamous cell carcinoma
Authors: Su Wen , Wang Yufan , Wang Feng , Zhang Biru , Zhang Hanyu , Shen Yuehong , Yang Hongyu
Published: January 2019

Oral squamous cell carcinoma (OSCC), the most common oral cancer, damages oral epithelial cells after the accumulation of multiple genetic mutations. Although emerging evidence supports the key role of circular RNAs (circRNAs) in various malignancies, the clinical value and function of circRNAs in OSCC remain unclear. In this study, patients with OSCC (n = 8) and controls (
n = 8) were compared using high‐throughput sequencing and microarray circRNA expression profiles. The circRNA hsa_circ_0007059 was downregulated in OSCC. Subsequently, hsa_circ_0007059 levels in OSCC tissues and cell lines were assessed by quantitative reverse‐transcription chain reaction. Loss‐of‐function and gain‐of‐function experiments were performed to determine whether hsa_circ_0007059 affects malignant behavior in SCC15 and CAL27 cells. Importantly, hsa_circ_0007059 upregulation suppressed cell growth, migration, and invasion, facilitating apoptosis of these cells. Furthermore, nude mouse tumor formation was assessed to validate the tumor‐suppressive role of hsa_circ_0007059 in vivo. Finally, hsa_circ_0007059 was determined to alter cell growth via AKT/mTOR signaling, representing a potential prognostic/therapeutic target for OSCC.
Pharmacokinetics, Safety, and Tolerability of Single‐Dose Intravenous Moxifloxacin in Pediatric Patients: Dose Optimization in a Phase 1 Study
Authors: Stass Heino , Lettieri John , Vanevski Konstantina M. , Willmann Stefan , James Laura P. , Sullivan Janice E. , Arrieta Antonio C. , Bradley John S.
Published: January 2019

The pharmacokinetics, safety, and tolerability of a single dose of moxifloxacin were characterized in 31 pediatric patients already receiving antibiotics for a suspected or proven infection in an open‐label phase 1 study. A dosing strategy for each age cohort (Cohort 1: ≥6 years to ≤14 years; Cohort 2: ≥2 years to <6 years; Cohort 3: >3 month to <2 years) was developed using physiology‐based pharmacokinetic modeling combined with a stepwise dosing scheme to obtain a similar exposure to adults receiving 400 mg of moxifloxacin. Doses, adjusted to body weight and age, were gradually escalated from 5 mg/kg in Cohort 1 to 10 mg/kg in Cohort 3 based on interim analysis of the pharmacokinetic and safety data. Plasma and urine samples before and after the 60‐minute infusion were collected for the analysis of moxifloxacin and its metabolites using a validated high‐pressure liquid chromatography assay with tandem mass spectrometry. Moxifloxacin and metabolite concentrations in plasma were within the ranges observed in adults; however, clearance of all analytes was lower in pediatric patients compared with adults. Population pharmacokinetic analyses using the achieved exposure levels in the 3 age cohorts (with known body weight and clearance) predicted similar efficacy and safety profiles to adults. Moxifloxacin was well tolerated in all pediatric age cohorts. Adverse events related to moxifloxacin were mild or moderate in intensity and showed no correlation with increased weight‐adjusted doses. Our findings guided the selection of age‐appropriate clinical doses for a subsequent phase 3 clinical trial in pediatric patients with complicated intra‐abdominal infections.
Contrast‐enhanced MRI for breast cancer screening
Authors: Mann Ritse M. , Kuhl Christiane K. , Moy Linda
Published: January 2019

Multiple studies in the first decade of the 21st century have established contrast‐enhanced breast MRI as a screening modality for women with a hereditary or familial increased risk for the development of breast cancer. In recent studies, in women with various risk profiles, the sensitivity ranges between 81% and 100%, which is approximately twice as high as the sensitivity of mammography. The specificity increases in follow‐up rounds to around 97%, with positive predictive values for biopsy in the same range as for mammography. MRI preferentially detects the more aggressive/invasive types of breast cancer, but has a higher sensitivity than mammography for any type of cancer. This performance implies that in women screened with breast MRI, all other examinations must be regarded as supplemental. Mammography may yield ~5% additional cancers, mostly ductal carcinoma in situ, while slightly decreasing specificity and increasing the costs. Ultrasound has no supplemental value when MRI is used. Evidence is mounting that in other groups of women the performance of MRI is likewise superior to more conventional screening techniques. Particularly in women with a personal history of breast cancer, the gain seems to be high, but also in women with a biopsy history of lobular carcinoma in situ and even women at average risk, similar results are reported. Initial outcome studies show that breast MRI detects cancer earlier, which induces a stage‐shift increasing the survival benefit of screening. Cost‐effectiveness is still an issue, particularly for women at lower risk. Since costs of the MRI scan itself are a driving factor, efforts to reduce these costs are essential. The use of abbreviated MRI protocols may enable more widespread use of breast MRI for screening.

Level of Evidence: 1

Technical Efficacy: Stage 5

J. Magn. Reson. Imaging 2019;50:377–390.
Aortic dilatation associates with flow displacement and increased circumferential wall shear stress in patients without aortic stenosis: A prospective clinical study
Authors: Kauhanen S. Petteri , Hedman Marja , Kariniemi Elina , Jaakkola Pekka , Vanninen Ritva , Saari Petri , Liimatainen Timo
Published: January 2019

Background

The relationship between blood flow characteristics and ascending aortic (AA) dilatation has not been studied in patients with a tricuspid aortic valve (TAV) without aortic stenosis.

Purpose

To evaluate whether 4D flow characteristics determined in MRI are related to AA dilatation by comparing dilated AA and nondilated AA subjects with TAV.

Study Type

Prospective.

Population

Twenty patients with dilated AA and 20 age‐matched patients with nondilated AA.

Field Strength/Sequence

1.5T/4D flow, 2D flow, and anatomic images.

Assessment

Altogether, 16 different 4D flow parameters were assessed in 10 planes in the thoracic aorta. Intra‐ and interobserver reproducibility were analyzed.

Statistical Tests

Independent t‐test for normally distributed and the Mann–Whitney test for skewed distributed parameters were used. A paired‐samples t‐test was used to compare 2D and 4D flow parameters. Intraclass correlation coefficient (ICC) was used in intra‐ and interobserver reproducibility analysis.

Results

Aortic flow was displaced from the centerline of the aorta in the proximal and tubular planes. Flow displacement (FD) was greatest in the proximal plane of AA and was higher in dilated AA (4.5%, range 3.0–5.8%) than in nondilated AA (2.0%, 1.0–3.0%, P < 0.001). Total wall shear stress (WSS) values were 1.3 ± 0.4 times higher on the displaced side than on the opposite side of the aorta (P < 0.01). The circumferential WSS (WSSC) ratio to total WSS was greater in dilated AA, being 0.48 ± 0.11 vs. 0.32 ± 0.09 in the inner curvature of the proximal AA (P < 0.001) and 0.37 ± 0.11 vs. 0.26 ± 0.07 in the whole aortic ring in the distal AA (P < 0.001). Depending on 4D flow parameters, reproducibility varied from excellent (ICC = 0.923) to very low (ICC = 0.204).

Data Conclusion

The present study demonstrates that 4D flow measurements help to visualize the pathological flow patterns related to aortic dilatation. Flow displacement and an increased WSSc/WSS ratio are significantly associated with AA dilatation.

Level of Evidence: 2

Technical Efficacy: Stage 2

J. Magn. Reson. Imaging 2019;50:136–145.
Multiparameter diffusion‐weighted imaging for characterizing pathological patterns in lupus nephritis patients: A preliminary study
Authors: Zhang Shan , Lin Yanwei , Ge Xin , Liu Guiqin , Zhang Jianjian , Xu Shuaishuai , Wu Guangyu , Chen Sheng , Xu Jianrong , Suo Shiteng
Published: January 2019

Background

Microstructural changes of lupus nephritis (LN) kidney such as inflammatory cell infiltration or fibrosis could influence water molecular movement or diffusion, which indicates that diffusion‐weighted imaging (DWI) may become a valuable tool in evaluation of this disease.

Purpose

To explore whether multiparameter diffusion‐weighted imaging (mDWI) could contribute to characterize pathological patterns in LN patients.

Study Type

Retrospective.

Population

Twenty‐two patients with LN.

Field Strength/Sequence

Multi‐b value DWI was performed with a 3.0 T scanner.

Assessment

Apparent diffusion coefficient (ADC)m, perfusion‐related diffusion coefficient (Df), molecular diffusion coefficient (Ds), perfusion fraction (f), ADCs, α, ADCk, and mean kurtosis (MK) were calculated by monoexponential, biexponential, stretched‐exponential, and kurtosis models fits, respectively.

Statistical Tests

Independent sample t‐test, Pearson analysis and receiver operating characteristic (ROC).

Results

In the whole group, the activity index (AI) correlated significantly with alpha values in the medulla (rho = –0.54, P = 0.03). The chronicity index (CI) correlated significantly with Ds values in the medulla (rho = –0.61, P = 0.02). No significant association was found between any other diffusion parameter and histologic grade with all P > 0.05. For differentiating proliferative LN (Class III or IV) from Class V, the area under the ROC curve (AUC) of alpha in the medulla was 0.833 (P = 0.023).

Data Conclusion

mDWI might be used for the characterization of pathological patterns in LN patients.

Level of Evidence: 3

Technical Efficacy Stage: 2

J. Magn. Reson. Imaging 2019;50:1075–1084.
Human metapneumovirus infection: Diagnostic impact of radiologic imaging
Authors: Keske Şiran , Gümüş Terman , Köymen Tamer , Sandıkçı Sunay , Tabak Levet , Ergönül Önder
Published: January 2019

Background

Human metapneumovirus (hMPV) is a recently detected virus, which can cause mild to severe respiratory tract infections. Through this study, we aimed to detail the outcomes of hMPV infections.

Materials/methods

Between January 2012 and November 2017, patients who had hMPV detected in nasopharyngeal or bronchoalveolar lavage by molecular respiratory pathogen tests were evaluated. The Food and Drug Administration cleared multiplexed‐polymerase chain reaction system (Idaho Technology, Salt Lake City, UT) was used for diagnosis. Chest radiography (CR) and computed tomography (CT) were evaluated by an expert radiologist.

Results

In total 100 patients were included, the mean age was 22.9 (0‐87) years, and 50% were male. The hospitalization rate was 52%. Lower respiratory system infection (LRTI) was diagnosed in 44 patients with clinical findings, and in 31 patients out of 44 the radiological findings supported the diagnosis. The LRTI rate was significantly higher in adults than children (66.7%‐32.8%; P = 0.001). In CR, peribronchovascular infiltration (PI) was the most common feature seen in 14 out of 18 patients and was generally bilateral (13 out of 18 patients). In CT imaging, ground‐glass opacity was the most common finding seen in 11 out of 16 patients and nodular consolidation in five patients. Ribavirin was given to four patients, three of whom were severe and required respiratory support. None of the patients died of hMPV infection.

Conclusions

The ground‐glass opacity in CT was similar to other respiratory virus infections, and PI in CR was very common and typical; however, nodular consolidation that may mimic bacterial infection was seen in one‐fourth of CT.
Analysis of genetic and serology of hepatitis A virus infection during and after outbreak in two junior high schools in Surabaya, Indonesia
Authors: Juniastuti  , Wahyuddin Dedy , Nihayatussa'adah  , Amin Mochamad , Yamani Laura Navika , Utsumi Takako , Sustini Florentina , Lusida Maria Inge
Published: January 2019

Outbreaks of hepatitis A have occurred in some cities in Indonesia. In Surabaya, the capital city of East Java province, Indonesia, hepatitis A outbreaks have been reported since2013, with a marked increase in the number of cases in 2015. The aim of the present study was to analyze the genetic and serology of acute symptomatic cases (early infection) during a hepatitis A outbreak and asymptomatic cases after the outbreak in two junior high schools in Surabaya in 2015 to 2016. Students with acute symptomatic hepatitis A during the outbreak and other students who were asymptomatic 3 to 4 months after the outbreak were enrolled. Asymptomatic students had no symptoms from the outbreak until they were enrolled. Sera were collected to identify anti‐hepatitis A virus (HAV) IgM (by enzyme‐linked immunosorbent assay) and HAV genetic variations/genotypes (using polymerase chain reaction [PCR]‐sequencing and phylogenetic analysis). A total of 33 (97.1%) out of 34 sera of students with acute symptoms were positive for anti‐HAV IgM and 18% of them were positive by PCR, identified as HAV subgenotype IA. No prominent amino acid variations were observed from reported HAV sequences from Indonesia. Among 38 sera of asymptomatic students, most (55.3%) were positive for anti‐HAV IgM, while none were positive by PCR. In conclusion, HAV‐IA was the only subgenotype identified in acute symptomatic cases during the outbreak. The percentage of HAV‐specific IgM‐positive cases was very high among acute symptomatic students, but that was also high among asymptomatic students, which might contribute as the important source of infection during the outbreak.
Evaluation of a silver‐amplified immunochromatography kit for adenoviral conjunctivitis
Authors: Fujimoto Tsuguto , Hanaoka Nozomu , Konagaya Masami , Kobayashi Masaaki , Nakagawa Hisashi , Hatano Hiroshi , Tsukahara‐Kawamura Tomoko , Uchio Eiichi , Kaneko Hisatoshi
Published: January 2019

Objective

To compare and evaluate the sensitivity of a newly developed silver‐amplified immunochromatography (SAI) kit with various immunochromatography (IC) kits for adenoviruses based on the detection limit (copies/test).

Methods

An SAI kit and four ophthalmic IC kits were evaluated. The detection limits of the five kits were determined using the limiting dilution method for 15 conjunctivitis‐associated adenoviruses (adenoviruses 1, 2, 3, 4, 5, 7, 8, 11, 37, 53, 54, 56, 64, 81, and 85). The detection limits were presented as numerical values as determined by real‐time polymerase chain reaction (PCR).

Results

The detection limit of the SAI kit for the adenovirus types ranged from 1.0 × 103–5.0 × 10
4 copies/test (geometric mean, 4.7 × 10
3). SAI had a 10–250‐fold lower detection limit than the four IC kits for all adenoviruses studied. There were also differences in detection limits among the adenovirus types for each kit.

Discussion

The detection limit of the SAI kit was drastically reduced because the silver‐amplification reaction increased the color development sensitivity. The results revealed the high sensitivity of SAI for detecting adenoviruses and suggested its usefulness for conjunctivitis examination.
Novel capsule phase microextraction in combination with high performance liquid chromatography with diode array detection for rapid monitoring of sulfonamide drugs in milk
Authors: Georgiadis Doukas‐Evangelos , Tsalbouris Athanasios , Kabir Abuzar , Furton Kenneth G. , Samanidou Victoria
Published: January 2019

Capsule phase microextraction is introduced herein for the first time to determine four sulfonamide residues in milk samples (sulfanilamide, sulfadiazine, sulfamethizole, and sulfathiazole). The technique eloquently integrates filtration and stirring mechanism into the extraction device, as such no filtration of the sample is needed prior to introducing the extraction device into the sample, and when placed on a magnetic stirrer, the device spins itself in order to diffuse the sample, resulting in faster extraction equilibrium. Microextraction capsules consist of three main parts; a magnet, a cellulose fiber substrate coated with high performance sol‐gel hybrid organic‐inorganic sorbent, and a porous membrane. Various encapsulated sol‐gel sorbents were tested in standard solutions prepared in deionized water and milk samples under different operational conditions. Analyte extraction time and elution time, type of sol‐gel sorbent, elution solvent, as well as the ratio of the sorbent to the elution solvent were among the optimized conditions. The protocols that yielded the best absolute recovery rates were subsequently tested in various milk samples. Method validation was performed in terms of linearity, accuracy and precision, reusability and ruggedness using the Youden test. The examined sulfonamides were subsequently analysed by reversed phase high performance liquid chromatography with diode array detection.
Pilot Study of the International Parkinson and Movement Disorder Society‐sponsored Non‐motor Rating Scale (MDS‐NMS)
Authors: Martinez‐Martin Pablo , Schrag Anette , Weintraub Daniel , Rizos Alexandra , Rodriguez‐Blazquez Carmen , Chaudhuri Kallol Ray ,   on behalf of the IPMDS Non Motor PD Study Group
Published: January 2019

Background

Non‐motor symptoms (NMS) are integral to Parkinson's disease (PD) and have a detrimental effect on patients and their caregivers. Clinical quantification has been aided by the development of comprehensive assessments such as the Non‐Motor Symptoms Questionnaire (NMSQuest) and Scale (NMSS). The NMSS has been widely used in clinical studies and trials; however, since its validation in 2007, our understanding of NMS has changed substantially. With the support of the International Parkinson and Movement Disorder Society (IPMDS), after a detailed peer review an initiative to develop an updated version of NMSS, the MDS‐NMS was launched in 2015.

Objective

This paper encapsulates the data from the pre‐validation phases carried out under the auspices of the IPMDS Non‐Motor PD Study Group.

Methods

Item selection and wording (formatted as a rater‐based tool) were based on the NMSS, literature review, and expert consensus. Neurologists, PD patients, and healthy controls were included in the cognitive pretesting and administration of the preliminary version of the MDS‐NMS. Primary data on acceptability and reliability were obtained.

Results

The pilot study, carried out in English in the United Kingdom and the United States, demonstrated that the preliminary version of the MDS‐NMS was comprehensive, understandable, and appropriate. Data quality was excellent; moderate floor effect was present in patients for most MDS‐MNS domains, with some components showing weak internal consistency. The results led to additional instrument modifications.

Conclusion

Qualitative and quantitative research results have led to an updated NMSS, the definitive version of the MDS‐NMS, which is currently being validated.
Effects of subthalamic nucleus stimulation and levodopa on decision‐making in Parkinson's disease
Authors: Atkinson‐Clement Cyril , Cavazzini Émilie , Zénon Alexandre , Witjas Tatiana , Fluchère Frédérique , Azulay Jean‐Philippe , Baunez Christelle , Eusebio Alexandre
Published: January 2019

Background

Parkinson's disease (PD) is frequently associated with behavioral disorders, particularly within the spectrum of motivated behaviors such as apathy or impulsivity. Both pharmacological and neurosurgical treatments have an impact on these impairments. However, there still is controversy as to whether subthalamic nucleus deep brain stimulation (STN‐DBS) can cause or reduce impulsive behaviors.

Objectives

We aimed to identify the influence of functional surgery on decision‐making processes in PD.

Methods

We studied 13 PD patients and 13 healthy controls. The experimental task involved squeezing a dynamometer with variable force to obtain rewards of various values under four conditions: without treatment, with l‐dopa or subthalamic stimulation alone, and with both l‐dopa and subthalamic stimulation. Statistical analyses consisted of generalized linear mixed models including treatment condition, reward value, level of effort, and their interactions. We analyzed acceptance rate (the percentage of accepted trials), decision time, and force applied.

Results

Comparatively to controls, patients without treatment exhibited lower acceptance rate and force applied. Patients under l‐dopa alone did not exhibit increased acceptance rate. With subthalamic stimulation, either with or without added l‐dopa, all measures were improved so that patients’ behaviors were undistinguishable from healthy controls’.

Conclusions

Our study shows that l‐dopa administration does not fully restore cost‐benefit decision‐making processes, whereas STN‐DBS fully normalizes patients’ behaviors. These findings suggest that dopamine is partly involved in cost‐benefit valuation, and that STN‐DBS can have a beneficial effect on motivated behaviors in PD and may improve certain forms of impulsive behaviors. © 2019 International Parkinson and Movement Disorder Society
Helix aspersa as sentinel of development damage for biomonitoring purpose: A validation study
Authors: Carbone Donatella , Faggio Caterina
Published: January 2019

Environmental health has always been threatened by the bioaccumulation of heavy metals in the terrestrial ecosystem, affecting its quality and safety. The aim of this review is to investigate the effects of heavy metal soil contamination, using the land snail Helix aspersa as a bioindicator.
H. aspersa, a common species of land snail present in the area, has been used as a bioindicator of metal contamination and represents a promising ecological indicator. Various land snails species have become popular in microcosm studies because they accumulate high concentrations of certain trace metals. They express contamination as a whole through ingestion of polluted foods, such as live plants, microorganisms, soil, and water and also through cutaneous contact and from the polluted air they breathe. Land snails are considered appropriate sentinel species because trace metals tend to accumulate in their digestive gland to allow biomonitoring of metal pollution. Different experiments demonstrate that exposure in areas chronically polluted with metals, especially with lead, often causes changes in reproduction, with a variation in the mineral composition in the snail's eggs and also in its development, due to increased energy expenses associated with detoxiﬁcation and the excretion process.
Dependence of the MR signal on the magnetic susceptibility of blood studied with models based on real microvascular networks
Authors: Cheng Xiaojun , Berman Avery J.L. , Polimeni Jonathan R. , Buxton Richard B. , Gagnon Louis , Devor Anna , Sakadžić Sava , Boas David A.
Published: January 2019

Purpose

The primary goal of this study was to estimate the value of , the exponent in the power law relating changes of the transverse relaxation rate and intra‐extravascular local magnetic susceptibility differences as . The secondary objective was to evaluate any differences that might exist in the value of obtained using a deoxyhemoglobin‐weighted distribution versus a constant distribution assumed in earlier computations. The third objective was to estimate the value of β that is relevant for methods based on susceptibility contrast agents with a concentration of higher than that used for BOLD fMRI calculations.

Methods

Our recently developed model of real microvascular anatomical networks is used to extend the original simplified Monte‐Carlo simulations to compute from the first principles.

Results

Our results show that for most BOLD fMRI measurements of real vascular networks, as opposed to earlier predictions of .5 using uniform distributions. For perfusion or fMRI methods based on contrast agents, which generate larger values for , for 9.4 T, whereas at 14 T can drop below 1 and the variation across subjects is large, indicating that a lower concentration of contrast agent with a lower value of is desired for experiments at high B0.

Conclusion

These results improve our understanding of the relationship between R2* and the underlying microvascular properties. The findings will help to infer the cerebral metabolic rate of oxygen and cerebral blood volume from BOLD and perfusion MRI, respectively.
Performance of a computable phenotype for identification of patients with diabetes within PCORnet: The Patient‐Centered Clinical Research Network
Authors: Wiese Andrew D. , Roumie Christianne L. , Buse John B. , Guzman Herodes , Bradford Robert , Zalimeni Emily , Knoepp Patricia , Morris Heather L. , Donahoo William T. , Fanous Nada , Epstein Britany F. , Katalenich Bonnie L. , Ayala Sujata G. , Cook Megan M. , Worley Katherine J. , Bachmann Katherine N. , Grijalva Carlos G. , Rothman Russell L. , Chakkalakal Rosette J.
Published: January 2019

Purpose

PCORnet, the National Patient‐Centered Clinical Research Network, represents an innovative system for the conduct of observational and pragmatic studies. We describe the identification and validation of a retrospective cohort of patients with type 2 diabetes (T2DM) from four PCORnet sites.

Methods

We adapted existing computable phenotypes (CP) for the identification of patients with T2DM and evaluated their performance across four PCORnet sites (2012‐2016). Patients entered the cohort on the earliest date they met one of three CP categories: (CP1) coded T2DM diagnosis (ICD‐9/ICD‐10) and an antidiabetic prescription, (CP2) diagnosis and glycosylated hemoglobin (HbA1c) ≥6.5%, or (CP3) an antidiabetic prescription and HbA1c ≥6.5%. We required evidence of health care utilization in each of the 2 prior years for each patient, as we also developed an incident T2DM CP to identify the subset of patients without documentation of T2DM in the 365 days before t0. Among a systematic sample of patients, we calculated the positive predictive value (PPV) for the T2DM CP and incident‐T2DM CP using electronic health record (EHR) review as reference.

Results

The CP identified 50 657 patients with T2DM. The PPV of patients randomly selected for validation was 96.2% (n = 1572; CI:95.1‐97.0) and was consistently high across sites. The PPV for the incident‐T2DM CP was 5.8% (CI:4.5‐7.5).

Conclusions

The T2DM CP accurately and efficiently identified patients with T2DM across multiple sites that participate in PCORnet, although the incident T2DM CP requires further study. PCORnet is a valuable data source for future epidemiological and comparative effectiveness research among patients with T2DM.
Depression predicts longitudinal declines in social support among women with newly diagnosed breast cancer
Authors: Chang Howard A. , Barreto Nicolas , Davtyan Arpine , Beier Ellis , Cangin Marissa A. , Salman Jaroslava , Patel Sunita K.
Published: January 2019

Objective

Among breast cancer survivors, low social support is associated with adverse clinical and psychosocial outcomes. This study prospectively examined longitudinal trends in perceived social support in women with newly diagnosed breast cancer as a function of depression status prior to initiation of cancer treatment.

Methods

One hundred ten patients with newly diagnosed breast cancer and 59 age‐matched noncancer controls completed behavioral measures at four assessments: prior to treatment and at 1 month, 1 year, and 2 years post‐treatment. Participants reported their perceived tangible and emotional/informational support using the Medical Outcomes Study Social Support Survey and were categorized as “depressed” or “non‐depressed” based on the Brief Symptom Inventory‐18 (BSI‐18). Analyses first compared longitudinal trends in support between patients and controls and then examined differences in longitudinal trends as a function of depression status in patients only, controlling for key covariates.

Results

Both tangible and emotional/informational support decreased among breast cancer patients but increased or remained unchanged among noncancer controls across the assessments. Among patients, depressed individuals experienced a significant decline in both tangible (P = 0.004) and emotional/informational support (P = 0.013) between 1 month and 1 year post‐treatment, which remained unchanged between 1 year and 2 years post‐treatment. In contrast, nondepressed individuals had stable levels across all assessments. Depressed patients also had lower levels of both support types compared with nondepressed patients across all assessments.

Conclusions

Breast cancer patients with depressive symptomatology have an elevated risk for declines in perceived social support over time.
Study of a pulsed post‐discharge plasma deposition process of APTES: synthesis of highly organic pp‐APTES thin films with NH2 functionalized polysilsesquioxane evidences
Authors: Bulou Simon , Lecoq Elodie , Loyer François , Frache Gilles , Fouquet Thierry , Gueye Magamou , Belmonte Thierry , Choquet Patrick
Published: January 2019

This article reports the use of pulsed remote Ar‐O2 microwave plasma assisted chemical vapor deposition with an −NH2 containing organosilicon precursor ((3‐Aminopropyl)triethoxysilane: APTES). It is shown that modifying the plasma pulses duration (ton) and the plasma off duration (toff) allows to finely tune the deposited layer composition. In addition, the results of this work demonstrate that an important film growth occurs during toff, which results in an increased −NH2 density. Besides, high resolution MALDI‐ORBITRAP Mass spectrometry analysis clearly points out that APTES oligomers up to eight base units, including silsesquioxanes (cages), and cyclosiloxanes (rings) molecules with intact −NH2 groups are embedded into the as grown pp‐APTES thin film.
Magnetic resonance imaging of the larynx in the pediatric population: A systematic review
Authors: Elders Bernadette B. L. J. , Hermelijn Sergei M. , Tiddens Harm A. W. M. , Pullens Bas , Wielopolski Pjotr A. , Ciet Pierluigi
Published: January 2019

Background

Magnetic Resonance Imaging (MRI) techniques to image the larynx have evolved rapidly into a promising and safe imaging modality, without need for sedation or ionizing radiation. MRI is therefore of great interest to image pediatric laryngeal diseases. Our aim was to review MRI developments relevant for the pediatric larynx and to discuss future imaging options.

Methods

A systematic search was conducted to identify all morphological and diagnostic studies in which MRI was used to image the pediatric larynx, laryngeal disease, or vocal cords.

Results

Fourteen articles were included: three studies on anatomical imaging of the larynx, two studies on Diffusion Weighted Imaging, four studies on vocal cord imaging and five studies on the effect of anaesthesiology on the pediatric larynx. MRI has been used for pediatric laryngeal imaging since 1991. MRI provides excellent soft tissue contrast and good visualization of vascular diseases such as haemangiomas. However, visualization of cartilaginous structures, with varying ossification during childhood, and tissue differentiation remain challenging. The latter has been partly overcome with diffusion weighted imaging (DWI), differentiating between benign and malignant masses with excellent sensitivity (94‐94.4%) and specificity (91.2‐100%). Vocal cord imaging evolved from static images focused on vocal tract growth to dynamic images able to detect abnormal vocal cord movement.

Conclusion

MRI is promising to evaluate the pediatric larynx, but studies using MRI as diagnostic imaging modality are scarce. New static and dynamic MR imaging techniques could be implemented in the pediatric population. Further research on imaging of pediatric laryngeal diseases should be conducted.
Oxidase or peptidase? A computational insight into a putative aflatoxin oxidase from Armillariella tabescens
Authors: Tomin Marko , Tomić Sanja
Published: January 2019

Aflatoxin oxidase (AFO), an enzyme isolated from Armillariella tabescens, has been reported to degrade aflatoxin B1 (AFB1). However, recent studies reported sequence and structure similarities with the dipeptidyl peptidase III (DPP III) family of enzymes and confirmed peptidase activity toward DPP III substrates. In light of these investigations, an extensive computational study was performed in order to improve understanding of the AFO functions. Steered MD simulations revealed long‐range domain motions described as protein opening, characteristic for DPPs III and necessary for substrate binding. Newly identified open and partially open forms of the enzyme closely resemble those of the human DPP III orthologue. Docking of a synthetic DPP III substrate Arg2‐2‐naphthylamide revealed a binding mode similar to the one found in crystal structures of human DPP III complexes with peptides with the S1 and S2 subsites’ amino acid residues conserved. On the other hand, no energetically favorable AFB1 binding mode was detected, suggesting that aflatoxins are not good substrates of AFO. High plasticity of the zinc ion coordination sphere within the active site, consistent with that of up to date studied DPPs III, was observed as well. A detailed electrostatic analysis of the active site revealed a predominance of negatively charged regions, unsuitable for the binding of the neutral AFB1. The present study is in line with the most recent experimental study on this enzyme, both suggesting that AFO is a typical member of the DPP III family.
A General Framework for Assessing In vitro/In vivo Correlation as a Tool for Maximizing the Benefit‐Risk Ratio of a Treatment Using a Convolution‐Based Modeling Approach
Authors: Gomeni Roberto , Fang Lanyan (Lucy) , Bressolle‐Gomeni Françoise , Spencer Thomas J. , Faraone Stephen V. , Babiskin Andrew
Published: January 2019

The net benefit of a treatment can be defined by the relationship between clinical improvement and risk of adverse events: the benefit‐risk ratio. The optimization of the benefit‐risk ratio can be achieved by identifying the most adequate dose (and/or dosage regimen) jointly with the best‐performing in vivo release properties of a drug. A general in silico tool is presented for identifying the dose, the in vitro and the in vivo release properties that maximize the benefit‐risk ratio using convolution‐based modeling, an exposure‐response model, and a surface response analysis. A case study is presented to illustrate how the benefit‐risk ratio of methylphenidate for the treatment of attention deficit hyperactivity disorder can be maximized using the proposed strategy. The results of the analysis identified the characteristics of an optimized dose and in vitro/in vivo release suitable to provide a sustained clinical response with respect to the conventional dosage regimen and formulations.
Power Determination During Drug Development: Is Optimizing the Sample Size Based on Exposure‐Response Analyses Underutilized?
Authors: Jones Aksana K. , Salem Ahmed Hamed , Freise Kevin J.
Published: January 2019

The use of model‐based drug development (MBDD) has been demonstrated to improve the efficiency of clinical trial design. However, MBDD complexity can limit its use, particularly early in clinical development. In this tutorial, a simple and generalizable exposure‐response analysis approach to determine the power for dose‐ranging studies is presented and described. We identified situations in which higher power and sample size reduction is achieved by utilizing the exposure‐response powering methodology compared with conventional power calculations.
Toward a fully robotic surgery: Performing robotic major liver resection with no table‐side surgeon
Authors: Chen Po‐Da , Hu Rey‐Heng , Liang Jin‐Tung , Huang Chiun‐Sheng , Wu Yao‐Ming
Published: January 2019

Background

Evidence has suggested that robotic system helps perform more major liver resections. However, the required table‐side surgeon has remained a concern because of the uncertain performance and the incomplete control of console surgeon.

Methods

Data were reviewed for consecutive 333 robotic liver resections, of which 56 patients underwent left liver resection with the usual setting, and 35 with no table‐side surgeon.

Results

No conversion was required in the setting with no table‐side surgeon. The group without the table‐side surgeon had similar complication rates, blood loss, and operative time compared with that of the normal settings, as well as focused analysis on major left hemihepatectomy.

Conclusion

Our data suggest that performing robotic major liver resection without the presence of the table‐side surgeon is safe and feasible. The concise performance of robotic platforms might accelerate the machine learning process along with the ability to predict patterns of future autonomous surgery.
Citations of Norms and Lines of Flight in One Immigrant Boy's Performances of Masculinities and Reading Identities
Authors: Qin Kongji
Published: January 2019

In this ethnographic case study, the author examined one immigrant adolescent's performances of masculinities through reading practices. The author analyzed how Omar (pseudonym), a Muslim boy from Libya, used reading practices to produce himself as a boy in one U.S. multilingual classroom. Extending the anti‐essentialist scholarship on gender and reading, the author brought together Butler's queer feminism and Deleuze and Guattari's philosophy of becoming to further trouble gender and analyze the instability of Omar's masculinity performances in relation to reading practice. Through analyses of field notes, classroom interactions, and artifacts, this study showed that Omar discursively performed and negotiated multiple and seemingly conflicting reading identities across time and space. Although he was discursively positioned as a nonreader in classroom interactions, he also performed disengagement with reading to display a cool, nonschoolish masculinity aligned to the normative discourses of Arab masculinity to which he was subject. However, he also enacted reader identity and behaviors not traditionally associated with masculinity. Omar's identity negotiation, interactionally and socially situated, demonstrated the instability of masculinity performances, featuring repeated citation of gender norms fissured with lines of flight breaking away from normative ways of being. This analysis contributes to the anti‐essentialist research on boys and literacies by shedding light on the regulations and ruptures in masculinity performances of a gendered subject. The study highlights the importance of situating analysis of gender and reading practices within the social and power relations in the discursive and interactional space. Addressing space allows a close reading of how gender hegemonies operate and fracture in micro movements of identity performance and how space can be shaped to open up opportunities for becoming‐other.