bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring the feasibility and utility of exome‐scale tumour sequencing in a clinical setting
Authors: Lee Belinda , Tran Ben , Hsu Arthur L. , Taylor Graham R. , Fox Stephen B. , Fellowes Andrew , Marquis Renata , Mooi Jennifer , Desai Jayesh , Doig Ken , Ekert Paul , Gaff Clara , Herath Dishan , Hamilton Anne , James Paul , Roberts Andrew , Snyder Ray , Waring Paul , McArthur Grant
Published: April 2018

Background

Technology has progressed from single gene panel to large‐scale genomic sequencing. This is raising expectations from clinicians and patients alike. The utility and performance of this technology in a clinical setting needs to be evaluated.

Aim

This pilot study investigated the feasibility of using exome‐scale sequencing (ESS) to identify molecular drivers within cancers in real‐time for Precision Oncology in the clinic.

Methods

Between March 2014 and March 2015, the Victorian Comprehensive Cancer Centre Alliance explored the feasibility and utility of ESS in a pilot study. DNA extracted from the tumour specimens underwent both ESS and targeted ‘hotspot’ sequencing (TS). Blood was taken for germline analysis. A multi‐disciplinary molecular tumour board determined the clinical relevance of identified mutations; in particular, whether they were ‘actionable’ and/or ‘druggable’.

Results

Of 23 patients screened, 15 (65%) met the tissue requirements for genomic analysis. TS and ESS were successful in all cases. ESS identified pathogenic somatic variants in 73% (11/15 cases) versus 53% (8/15 cases) using TS. Clinically focused ESS identified 63 variants, consisting of 30 somatic variants (including all 13 identified by TS) and 33 germline variants. Overall, there were 48 unique variants. ESS had a clinical impact in 53% (8/15 cases); 47% (7/15 cases) were referred to the familial cancer clinic, and ‘druggable’ targets were identified in 53% (8/15 cases).

Conclusion

ESS of tumour DNA impacted clinical decision‐making in 53%, with 20% more pathogenic variants identified through ESS than TS. The identification of germline variants in 47% was an unexpected finding.
An exploration of the participation of people with intellectual disabilities in research—a structured interview survey
Authors: Frankena Tessa Kim , Naaldenberg Jenneken , Bekkema Nienke , van Schrojenstein Lantman‐de Valk Henny J. M. , Cardol Mieke , Leusink Geraline
Published: April 2018

Background

Even though participation of people with intellectual disabilities in research is increasingly common, there is little insight into how many people with intellectual disabilities participate, their motivations to participate and their interests regarding study results.

Method

Five questions were added to the Panel Living Together (PLT) survey among 508 people with intellectual disabilities. The questions aimed to gain insight into the (i) frequency of participation; (ii) methods used to participate; (iii) motivations to participate; and (iv) interests regarding study results.

Results

Although 73.5% (n = 347) of the respondents enjoyed their participation and 71.6% (n = 312) found it important to participate, only 11.8% (n = 60) participated in research other than PLT. Of the respondents, 61% (n = 261) indicated they wanted to be informed about study results, 29.1% (n = 148) of this group stated they wanted to compare, learn and share information.

Conclusions

Future research should focus on how motivations of people with intellectual disabilities to participate in inclusive research, such as “empowerment,” can be supported to facilitate their involvement in research.
Efficacy and safety of the G protein‐coupled receptor 119 agonist DS‐8500a in Japanese type 2 diabetes mellitus patients with inadequate glycemic control on sitagliptin: A phase 2 randomized placebo‐controlled study
Authors: Terauchi Yasuo , Yamada Yuichiro , Watada Hirotaka , Nakatsuka Yasuhiko , Shiosakai Kazuhito , Washio Takuo , Taguchi Takashi
Published: April 2018

Introduction

We evaluated the efficacy and safety of DS‐8500a as add‐on therapy to sitagliptin in Japanese type 2 diabetes mellitus patients.

Materials and Methods

This multicenter, randomized, double‐blind, placebo‐controlled, phase 2 trial randomized patients aged ≥20 years with hemoglobin A1c ≥7.0% and <9.0%, and inadequate glycemic control with sitagliptin 50‐mg monotherapy to receive 25 or 75 mg DS‐8500a, or a placebo, orally. The primary end‐point was change from baseline to day 28 in 24‐h weighted mean glucose. Secondary end‐points included change from baseline in fasting plasma glucose, 2‐h postprandial plasma glucose and lipid profiles.

Results

Overall, 29, 28 and 27 patients in the placebo, 25‐ and 75‐mg groups, respectively, were analyzed. A significant dose‐dependent reduction was observed in 24‐h weighted mean glucose (linear: P = 0.0006, saturated at 25 mg: P = 0.0003, responded from 75 mg: P = 0.0176) when compared with the placebo (25 mg: −13.19 mg/dL [−0.73 mmol/L], P = 0.0044 vs placebo and 75 mg: −16.12 mg/dL [−0.89 mmol/L], P = 0.0006 vs placebo). A significant reduction in fasting plasma glucose at 75 mg vs placebo was observed (P < 0.001). At 25 and 75 mg, significant reductions of 2‐h postprandial plasma glucose (after breakfast), total cholesterol, low‐cholesterol and triglycerides were observed (all P < 0.05), with a (non‐significant) trend towards increased high‐density lipoprotein cholesterol. Both doses of DS‐8500a were well tolerated. There were no significant treatment‐emergent adverse events leading to discontinuation during the study.

Conclusions

DS‐8500a was well tolerated, and showed significant glycemic benefits and favorable changes in lipid profile in Japanese type 2 diabetes mellitus patients with inadequate glycemic control with sitagliptin therapy.
One‐Year Effect of the Medicare Annual Wellness Visit on Detection of Cognitive Impairment: A Cohort Study
Authors: Fowler Nicole R. , Campbell Noll L. , Pohl Gerhardt M. , Munsie Leanne M. , Kirson Noam Y , Desai Urvi , Trieschman Erich J. , Meiselbach Mark K. , Andrews J. Scott , Boustani Malaz A.
Published: April 2018

Objectives

To examine the effect of the Medicare Annual Wellness Visit (AWV) on the detection of cognitive impairment and on follow‐up cognitive care for older adults.

Design

Retrospective matched‐cohort study.

Setting

United States.

Participants

A 5% random sample of fee‐for‐service Medicare beneficiaries continuously enrolled for 12 months before and after an index ambulatory visit occurring from 2011 to 2013 with no claims evidence of cognitive impairment before index.

Measurements

Outcomes include 12‐month post‐index visit claims‐based measurements of cognitive impairment, including new Alzheimer's disease and related dementia (ADRD) diagnoses; medications for ADRD; and cognitive care‐related diagnostic examination such as neurobehavioral testing, brain imaging, and blood tests for thyroid‐stimulating hormone (TSH), serum B12, folate, and syphilis. We also measured changes in burden of anticholinergic medication.

Results

There were no clinically relevant differences between the AWV and control groups in the rates of incident ADRD diagnoses (6.16% vs 6.86%, p<.001) and initiation of ADRD medications (1.00% vs 1.08%, p=.15), although there were differences favoring the AWV group in rates of TSH (39.80% vs 28.36%, p<.001), B12 (9.41% vs 6.97%, p<.001), folate (4.76% vs 3.72%, p<.001), and neurobehavioral (0.75% vs 0.55%, p<.001) testing.

Conclusions

Although the AWV is correlated with an increase in some measures of cognitive care, such as laboratory testing for reversible causes of cognitive impairment, it does not appear to substantially increase recognition of undetected ADRD.
Gait Speed and Mobility Disability: Revisiting Meaningful Levels in Diverse Clinical Populations
Authors: Miller Michael E. , Magaziner Jay , Marsh Anthony P. , Fielding Roger A. , Gill Thomas M. , King Abby C. , Kritchevsky Stephen , Manini Todd , McDermott Mary M. , Neiberg Rebecca , Orwig Denise , Santanasto Adam J. , Pahor Marco , Guralnik Jack , Rejeski W. Jack ,   for the LIFE Investigators
Published: April 2018

Objectives

To investigate the heterogeneity of clinically meaningful levels of gait speed relative to self‐reported mobility disability (SR‐MD).

Design

Five longitudinal studies with older adults in different health states (onset of acute event, presence of chronic condition, sedentary, community living) were used to explore the relationship between gait speed and SR‐MD.

Setting

Lifestyle Interventions and Independence for Elders Pilot (LIFE‐P), LIFE, Trial of Angiotensin‐Converting Enzyme Inhibition and Novel Cardiovascular Risk Factors (TRAIN), Baltimore Hip Fracture Study (BHS2), Invecchiare in Chianti (InCHIANTI).

Participants

Individuals aged 65 and older (N=3,540): sedentary, community dwelling (LIFE‐P/LIFE), with hip fracture (BHS2), random population‐based sample (InCHIANTI), high cardiovascular risk (TRAIN).

Measurements

Usual‐pace gait speed across 3 to 4 m and SR‐MD, defined as inability to walk approximately 1 block or climb 1 flight of stairs.

Results

The mean gait speed of participants without SR‐MD was greater than 1.0 m/s in InCHIANTI and TRAIN, 0.79 m/s in LIFE‐P/LIFE, and 0.46 m/sec in BHS2. Of individuals with SR‐MD, mean gait speed was 0.08 m/s slower in LIFE‐P/LIFE, 0.19 m/s slower in TRAIN, 0.22 m/s slower in BHS2, and 0.36 m/s slower in InCHIANTI. The optimal gait speed cutpoint for minimizing SR‐MD misclassification rates ranged from 0.3 m/s in BHS2 to 1.0 m/s in TRAIN. In longitudinal analyses, development of SR‐MD was dependent on initial gait speed and change in gait speed (p<.001).

Conclusion

The relationship between absolute levels of gait speed and SR‐MD may be context specific, and there may be variations between populations. Across diverse clinical populations, clinical interpretations of how change in usual pace gait speed relates to development of SR‐MD depend on where on the gait speed continuum change occurs.
Treatment of gingival recession using a coronally‐advanced flap procedure with or without placental membrane
Authors: George Sarah Grace , Kanakamedala Anil Kumar , Mahendra Jaideep , Kareem Nashra , Mahendra Little , Jerry Jeethu John
Published: April 2018

Aim

The aim of the present study was to compare the treatment of gingival recession defects using a coronally‐advanced flap procedure with or without placental membrane.

Methods

Sixty teeth in 15 patients with single and multiple Miller's class I and II gingival recession defects bilaterally in the anterior and premolar region of the maxilla and mandible were divided into two groups. In group I (control), 30 recession defects were treated with coronally‐advanced flap alone using Zucchelli's technique. In group II (test), 30 recession defects were treated with coronally‐advanced flap along with placental membrane. Probing depth, height of the gingival recession (HGR), clinical attachment level (CAL), width of the gingival recession, and width of the keratinized tissue (WKT) were recorded at baseline and 3 and 6 months after the surgical procedures.

Results

There was a statistically‐significant reduction in the HGR, gain in the CAL, and WKT in group II compared to group I.

Conclusion

Coronally‐advanced flap with placental allograft provides a reliable technique for root coverage when compared to coronally‐advanced flap alone.
Ultrahigh‐temperature osumilite gneisses in southern Madagascar record combined heat advection and high rates of radiogenic heat production in a long‐lived high‐T orogen
Authors: Holder Robert M. , Hacker Bradley R. , Horton Forrest , Rakotondrazafy A. F. Michel
Published: April 2018

We report the discovery of osumilite in ultrahigh‐temperature (UHT) metapelites of the Anosyen domain, southern Madagascar. The gneisses equilibrated at ~930°C/0.6 GPa. Monazite and zircon U–Pb dates record 80 Ma of metamorphism. Monazite compositional trends reflect the transition from prograde to retrograde metamorphism at 550 Ma. Eu anomalies in monazite reflect changes in fO2 relative to quartz–fayalite–magnetite related to the growth and breakdown of spinel. The ratio Gd/Yb in monazite records the growth and breakdown of garnet. High rates of radiogenic heat production were the primary control on metamorphic grade at the regional scale. The short duration of prograde metamorphism in the osumilite gneisses (<29 ± 8 Ma) suggests that a thin mantle lithosphere (<80 km) or advective heating may have also been important in the formation of this high‐T, low‐P terrane.
Safety and complications of absorbable threads made of poly‐L‐lactic acid and poly lactide/glycolide: Experience with 148 consecutive patients
Authors: Sarigul Guduk Sukran , Karaca Nezih
Published: April 2018

Background

Thread lifting is a minimally invasive procedure for lifting and repositioning tissues. Few articles with absorbable sutures exist in the literature. Furthermore there is no study focusing on complications of absorbable sutures.

Objective

To describe complications of thread lifting using a totally absorbable suture composed of poly‐L‐lactic acid affixed with poly lactide/glycolide cones.

Methods

Data regarding complications were analyzed retrospectively for 148 patients underwent thread lifting between June 2014 and February 2017.

Results

A total of 321 pairs of sutures used in the 148 patients studied. Overall 40 (27%) patients had complications regarded as minimal or moderate without permanent sequela. The most common complication was skin dimpling and irregularity (n = 17, 11.4%) followed by ecchymosis (n = 12, 8.1%), suture extrusion (n = 4, 2.7%), and pain (n = 4, 2.7%) Except one patient, dimpling, and irregularity resolved in all patients after 3–7 days spontaneously. Suture migration was observed in 2 (1.35%) patients. Hematoma and infection were seen in 2 patients one for each.

Conclusions

The procedure using sutures made of absorbable poly‐L‐lactic acid and poly lactide/glycolide is a relatively safe procedure without major complications.
A novel heterozygous missense mutation of DSP in a Chinese Han pedigree with palmoplantar keratoderma
Authors: Xue Ke , Zheng Yajie , Cui Yong
Published: April 2018

Background

Mutations in the desmoplakin (DSP) gene have been demonstrated to be associated with lethal acantholytic epidermolysis bullosa, cardiomyopathy, and palmoplantar keratoderma (PPK).

Aims

To better understand the relationship between PPK and the gene mutations in DSP.

Methods

A pedigree of PPK was subjected to heterozygous missense mutation analysis in the DSP gene. Dermoscopy, reflectance confocal microscopy, and histopathological examination were performed from each epidermis layer in this study. Samples were derived from the blood of patients and normal healthy controls. DSP gene sequence analysis and Q‐PCR analysis was performed for evaluating DSP gene mutation and expression.

Results

A novel heterozygous missense mutation c.3550 C>T in the coding region of the DSP gene, predicting substitution of arginine (Arg,R) by tryptophan (Trp,W) in the desmoplakin polypeptide, was discovered in a Chinese pedigree of PPK. In the meanwhile, this mutation was not found in 100 healthy individuals.

Conclusions

The novel missense mutation c.3550 C>T(p.Arg1184Trp) of DSP gene expanded the mutation spectrum in palmoplantar keratoderma.
Effectiveness of antenatal perineal massage in reducing perineal trauma and post‐partum morbidities: A randomized controlled trial
Authors: Ugwu Emmanuel Onyebuchi , Iferikigwe Eric Sunday , Obi Samuel Nnamdi , Eleje George Uchenna , Ozumba Benjamin Chukwuma
Published: April 2018

Aim

The study aimed to evaluate the effectiveness of antenatal perineal massage (APM) in reducing perineal trauma and post‐partum morbidities.

Methods

A randomized controlled trial of 108 primigravidae at the University of Nigeria Teaching Hospital, Enugu, Nigeria, was conducted from January 2013 to May 2014. The intervention group received APM, while the control group did not receive APM.

Results

Women who received APM were significantly more likely to have an intact perineum after childbirth [27/53 (50.9%) vs 16/55 (29.1%); RR: 1.75; 95% CI: 1.07–2.86; P = 0.02]. The incidence of episiotomy was lower in the intervention group [20/53 (37.7%) vs 32/55 (58.2%); RR: 0.65; 95% CI: 0.43–0.98; P = 0.03; NNT = 5]. Women who received APM were significantly less likely to develop flatus incontinence [4/53 (8.3%) vs 13/55 (26.0%); RR: 0.32; 95% CI: 0.11–0.91; P = 0.03]. However, the incidences of premature rupture of membranes, preterm labor and birth asphyxia were similar between the two groups (P > 0.05).

Conclusion

APM reduces the incidence of episiotomy and increases the incidence of women with an intact perineum after vaginal delivery. It also reduces the risk of flatus incontinence after childbirth without increased maternal or neonatal complications. Women should therefore be counseled on the likely benefits of APM and the information provided during antenatal care. Obstetricians should consider the technique as routine prenatal care for nulliparous women so as to reduce the incidence of perineal trauma during vaginal birth.
Melatonin improves insulin resistance and hepatic steatosis through attenuation of alpha‐2‐HS‐glycoprotein
Authors: Heo Jee‐In , Yoon Dae Wui , Yu Ji Hee , Kim Nam Hoon , Yoo Hye Jin , Seo Ji A. , Kim Sin Gon , Choi Kyung Mook , Baik Sei Hyun , Choi Dong Seop , Kim Nan Hee
Published: April 2018

Melatonin plays an important role in regulating circadian rhythms. It also acts as a potent antioxidant and regulates glucose and lipid metabolism, although the exact action mechanism is not clear. The α2‐HS‐glycoprotein gene (AHSG) and its protein, fetuin‐A (FETUA), are one of the hepatokines and are known to be associated with insulin resistance and type 2 diabetes. The aim of this study was to determine whether melatonin improves hepatic insulin resistance and hepatic steatosis in a FETUA‐dependent manner. In HepG2 cells treated with 300 μmol/L of palmitic acid, phosphorylated AKT expression decreased, and FETUA expression increased, but this effect was inhibited by treatment with 10 μmol/L of melatonin. However, melatonin did not improve insulin resistance in FETUA‐overexpressing cells, indicating that improvement in insulin resistance by melatonin was dependent on downregulation of FETUA. Moreover, melatonin decreased palmitic acid‐induced ER stress markers, CHOP, Bip, ATF‐6, XBP‐1, ATF‐4, and PERK. In addition, in the high‐fat diet (HFD) mice, oral treatment with 100 mg/kg/day melatonin for 10 weeks reduced body weight gain to one‐third of that of the HFD group and hepatic steatosis. Insulin sensitivity and glucose intolerance improved with the upregulation of muscle p‐AKT protein expression. FETUA expression and ER stress markers in the liver and serum of HFD mice were decreased by melatonin treatment. In conclusion, melatonin can improve hepatic insulin resistance and hepatic steatosis through reduction in ER stress and the resultant AHSG expression.
Immunohistochemical differentiation of reactive from malignant mesothelium as a diagnostic aid in canine pericardial disease
Authors: Milne E. , Martinez Pereira Y. , Muir C. , Scase T. , Shaw D. J. , McGregor G. , Oldroyd L. , Scurrell E. , Martin M. , Devine C. , Hodgkiss‐Geere H.
Published: April 2018

Objectives

To develop a provisional immunohistochemistry panel for distinguishing reactive pericardium, atypical mesothelial proliferation and mesothelioma in dogs.

Materials and Methods

Archived pericardial biopsies were subject to haematoxylin and eosin staining, immunohistochemistry for cytokeratin, vimentin, insulin‐like growth factor II mRNA‐binding protein 3, glucose transporter 1 and desmin. Samples were scored for intensity and number of cells stained.

Results

Ten biopsies of reactive mesothelium, 17 of atypical mesothelial proliferation, 26 of mesothelioma and five of normal pericardium were identified on the basis of haematoxylin and eosin staining. Cytokeratin and vimentin were expressed in all biopsies, confirming mesothelial origin. Normal pericardial samples had the lowest scores for insulin‐like growth factor II mRNA‐binding protein 3, glucose transporter 1 and desmin. Mesothelioma and atypical proliferative samples were similar to each other, with higher scores for insulin‐like growth factor II mRNA‐binding protein 3 and glucose transporter 1 than the reactive samples. Desmin staining was variable. Insulin‐like growth factor II mRNA‐binding protein 3 was the best to distinguish between disease groups.

Clinical Significance

An immunohistochemistry panel of cytokeratin, vimentin, insulin‐like growth factor II mRNA‐binding protein 3 and glucose transporter 1 could provide superior information compared with haematoxylin and eosin staining alone in the diagnosis of cases of mesothelial proliferation in canine pericardium, but further validation is warranted.
Prevalence of proteinuria in a canine oncology population
Authors: Prudic R. A. , Saba C. F. , Lourenço B. N. , Bugbee A. C.
Published: April 2018

Objective

To evaluate the point prevalence of proteinuria in dogs presenting to the University of Georgia Oncology Service for the first time.

Materials and Methods

In this prospective study, 60 client‐owned dogs with a confirmed cancer diagnosis were included but those with lower urinary tract neoplasia were excluded. Each dog's signalment, cancer diagnosis, previous cancer treatments, current medications and travel history were recorded. Renal values, electrolytes, packed cell volume, total solids, systolic blood pressure, urinalysis, urine protein:urine creatinine and retinal examinations were recorded. Non‐proteinuric, borderline proteinuria and overt proteinuria were defined as urine protein:urine creatinine <0·2, ≥0·2 but <0·5, and ≥0·5, respectively. Urine culture was performed in dogs with active urine sediments or overt proteinuria.

Results

Twenty‐nine dogs were non‐proteinuric (48·3%), 22 (36·7%) borderline proteinuric and nine (15%) overtly proteinuric. None were azotaemic. Hypertension (systolic blood pressure ≥160 mmHg) was detected in 18 (30%) dogs. Of these, six were non‐proteinuric, nine borderline proteinuric, and three overtly proteinuric. Proteinuria was detected in 51% of dogs presented to our oncology service, the majority of which were classified as borderline.

Clinical Significance

The high proportion of proteinuria in dogs in this study suggests that screening for proteinuria in dogs with cancer may be prudent. Larger studies are required to correlate specific cancer types and the impact of treatment with the development, magnitude and persistence of proteinuria.
Twenty‐five‐year trajectories of insulin resistance and pancreatic β‐cell response and diabetes risk in nonalcoholic fatty liver disease
Authors: VanWagner Lisa B. , Ning Hongyan , Allen Norrina B. , Siddique Juned , Carson April P. , Bancks Michael P. , Lewis Cora E. , Carr John Jeffrey , Speliotes Elizabeth , Terrault Norah A. , Rinella Mary E. , Vos Miriam B. , Lloyd‐Jones Donald M.
Published: April 2018

Background & Aims

Insulin resistance is a risk marker for non‐alcoholic fatty liver disease, and a risk factor for liver disease progression. We assessed temporal trajectories of insulin resistance and β‐cell response to serum glucose concentration throughout adulthood and their association with diabetes risk in non‐alcoholic fatty liver disease.

Methods

Three thousand and sixty participants from Coronary Artery Risk Development in Young Adults, a prospective bi‐racial cohort of adults age 18‐30 years at baseline (1985‐1986; Y0) who completed up to 5 exams over 25 years and had fasting insulin and glucose measurement were included. At Y25 (2010‐2011), non‐alcoholic fatty liver disease was assessed by noncontrast computed tomography after exclusion of other liver fat causes. Latent mixture modelling identified 25‐year trajectories in homeostatic model assessment insulin resistance and β‐cell response homeostatic model assessment‐β.

Results

Three distinct trajectories were identified, separately, for homeostatic model assessment insulin resistance (low‐stable [47%]; moderate‐increasing [42%]; and high‐increasing [12%]) and homeostatic model assessment‐β (low‐decreasing [16%]; moderate‐decreasing [63%]; and high‐decreasing [21%]). Y25 non‐alcoholic fatty liver disease prevalence was 24.5%. Among non‐alcoholic fatty liver disease, high‐increasing homeostatic model assessment insulin resistance (referent: low‐stable) was associated with greater prevalent (OR 95% CI = 8.0, 2.0‐31.9) and incident (OR = 10.5, 2.6‐32.8) diabetes after multivariable adjustment including Y0 or Y25 homeostatic model assessment insulin resistance. In contrast, non‐alcoholic fatty liver disease participants with low‐decreasing homeostatic model assessment‐β (referent: high‐decreasing) had the highest odds of prevalent (OR = 14.1, 3.9‐50.9) and incident (OR = 10.3, 2.7‐39.3) diabetes.

Conclusion

Trajectories of insulin resistance and β‐cell response during young and middle adulthood are robustly associated with diabetes risk in non‐alcoholic fatty liver disease. Thus, how persons with non‐alcoholic fatty liver disease develop resistance to insulin provides important information about risk of diabetes in midlife above and beyond degree of insulin resistance at the time of non‐alcoholic fatty liver disease assessment.
Metastasis in patients with hepatocellular carcinoma: Prevalence, determinants, prognostic impact and ability to improve the Barcelona Clinic Liver Cancer system
Authors: Hsu Chia‐Yang , Liu Po‐Hong , Ho Shu‐Yein , Huang Yi‐Hsiang , Lee Yun‐Hsuan , Lee Rheun‐Chuan , Nagaria Teddy S. , Hou Ming‐Chih , Huo Teh‐Ia
Published: April 2018

Background & Aim

Patients with hepatocellular carcinoma and metastasis are classified as advanced or terminal stage by the Barcelona Clinic Liver Cancer system. This study investigates the prevalence, determinants, and prognostic effect of metastasis and its ability to improve the Barcelona Clinic Liver Cancer system.

Methods

A total of 3414 patients were enrolled. The Kaplan‐Meier and Cox regression methods were used to determine survival predictors. Akaike information criterion was used to compare the prognostic performance of staging systems.

Results

There were 357 (10%) patients having extrahepatic metastasis at the time of diagnosis. Metastases were associated with old age, alcoholism, hepatitis B, poorer liver function, higher α‐foetoprotein level and larger tumour burden (all P < .05). Vascular invasion was associated with metastasis regardless of total tumour volume, and higher α‐foetoprotein level and multiple tumours were associated with metastasis in patients with smaller tumour volume (all P < .05). Patients with both vascular invasion and metastasis had significantly worse outcome compared to patients with either vascular invasion or metastasis (P < .05). In the Cox proportional model, the co‐existence of vascular invasion and metastasis was an independent predictor of decreased survival (P < .05). Re‐allocating 181 Barcelona Clinic Liver Cancer stage C patients with both vascular invasion and metastasis into stage D was associated with lower Akaike information criterion, indicating enhanced prognostic power of the Barcelona Clinic Liver Cancer.

Conclusions

Metastasis is not uncommon, and is strongly associated with tumoural factors and poor long‐term survival in hepatocellular carcinoma. Modification of the Barcelona Clinic Liver Cancer system based on vascular invasion and metastasis may further improve its predictive accuracy in advanced stage patients.
To salt or not to salt?—That is the question in cirrhosis
Authors: Haberl Julia , Zollner Gernot , Fickert Peter , Stadlbauer Vanessa
Published: April 2018

Ascites is the most common complication of patients with cirrhosis, resulting from portal hypertension and vasodilatation. It is associated with an increased risk for the development of hyponatraemia and renal failure and has a high mortality rate of 20% per year. The development of ascites represents a baleful sign in the course of disease in cirrhosis. To prevent complications of cirrhosis and improve quality of life, an effective management of ascites is pivotal. Combined salt restriction and diuretic therapy is recommended as first‐line therapy in numerous clinical practice guidelines. In contrast, there has been a debate on whether a strict salt‐restricted diet for cirrhosis patients should be used at all since salt restriction may increase the risk for malnutrition which in turn may negatively impact on quality of life and survival. This review aims to summarize the current pros and cons regarding salt restriction in patients with cirrhosis and proposes the importance of achieving a sodium balance throughout different stages of cirrhosis.
About the application of the Linnaean names Anthemis italica and A. tinctoria var. triumfettii (Asteraceae, Anthemidae)
Authors: Iamonico Duilio
Published: April 2018

The typification of the Linnaean names Anthemis italica and A. tinctoria var. triumfettii is discussed. Specimens from LINN (no. 1016.4) and SBT (no. 72) are designated as lectotypes. The name A. italica is proposed as a synonym of A. maritima, while A. tinctoria var. triumfettii is currently accepted under the genus Cota, as C. triumfettii.
Methods for prophylactic management of West Nile virus using a stage‐structured avian host‐vector model with vaccination, larvicide, and adulticide
Authors: Schaefer Elsa , Caillouët Kevin A. , Robertson Suzanne L.
Published: April 2018

West Nile virus (WNV) is a vector‐borne disease spread primarily between birds and mosquitoes. In the United States, the main methods used to control WNV are aimed at lowering the vector population through reducing births (larvicide) or increasing the mortality of adults (adulticide). We investigate the potential of a novel control, vaccination of newborn birds (nestlings). We first apply standard optimal control (OC) methodology to a nonautonomous differential equation model for WNV transmission incorporating avian stage structure and allowing larvicide, adulticide, and nestling vaccination. We convert the continuous OC results to practical advice that accounts for restrictions on the frequency of control application in the field. We then develop an alternative optimization algorithm using genetic algorithms and compare control advice for various budget constraints. We find that vaccination is recommended, provided budgets are sufficiently high, and explore how differences in control efficacy and vector biting rates on host stages affect our results.

Recommendations for Resource Managers:

Genetic algorithms are able to incorporate practical restrictions on control application as well as budget constraints. Advice depends on the efficacies of controls as well as model parameters.

At high‐efficacy estimates, adulticide is recommended for low budgets. Vaccination is recommended when budgets are sufficiently high, and sooner for scenarios where nestling hosts have increased vector exposure.

If vector control has low efficacy and nestlings have increased vector exposure relative to older hosts, including vaccination may reduce levels of infectious mosquitoes below those resulting from high‐efficacy vector control alone.
Music‐supported therapy in the rehabilitation of subacute stroke patients: a randomized controlled trial
Authors: Grau‐Sánchez Jennifer , Duarte Esther , Ramos‐Escobar Neus , Sierpowska Joanna , Rueda Nohora , Redón Susana , Veciana de las Heras Misericordia , Pedro Jordi , Särkämö Teppo , Rodríguez‐Fornells Antoni
Published: April 2018

The effect of music‐supported therapy (MST) as a tool to restore hemiparesis of the upper extremity after a stroke has not been appropriately contrasted with conventional therapy. The aim of this trial was to test the effectiveness of adding MST to a standard rehabilitation program in subacute stroke patients. A randomized controlled trial was conducted in which patients were randomized to MST or conventional therapy in addition to the rehabilitation program. The intensity and duration of the interventions were equated in both groups. Before and after 4 weeks of treatment, motor and cognitive functions, mood, and quality of life (QoL) of participants were evaluated. A follow‐up at 3 months was conducted to examine the retention of motor gains. Both groups significantly improved their motor function, and no differences between groups were found. The only difference between groups was observed in the language domain for QoL. Importantly, an association was encountered between the capacity to experience pleasure from music activities and the motor improvement in the MST group. MST as an add‐on treatment showed no superiority to conventional therapies for motor recovery. Importantly, patient's intrinsic motivation to engage in musical activities was associated with better motor improvement.
Evaluation of the neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, and mean platelet volume as inflammatory markers in children with attention‐deficit hyperactivity disorder
Authors: Avcil Sibelnur
Published: April 2018

Aim

The neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), monocyte/lymphocyte ratio (MLR), and mean platelet volume (MPV) have recently been used as indicators of a systemic inflammatory response. The aim of this study was to investigate the relations of the NLR, PLR, MLR, and MPV with attention‐deficit hyperactivity disorder (ADHD).

Methods

The study group consisting of 82 children diagnosed with ADHD was compared with a healthy control (HC) group of 70 age‐, sex‐, and body‐mass‐index‐matched subjects. The NLR, PLR, MLR, and MPV were measured according to the complete blood count.

Results

The NLR, PLR, MLR, MPV, and neutrophil count of the ADHD group were significantly higher than those of the HC group. The lymphocyte counts of the patients were significantly lower than those of the HC group.

Conclusion

Inflammation might play a role in the etiopathogenesis of ADHD. The NLR, PLR, MLR, and MPV may be potential inflammation markers for ADHD in children.
Menstruation‐related headache in adolescents: Point prevalence and associated factors
Authors: Carman Kursat Bora , Arslantas Didem , Unsal Alaettin , Atay Emrah , Ocal Ece Elif , Demirtas Zeynep , Saglan Ramazan , Dinleyici Meltem , Yarar Coskun
Published: April 2018

Background

The aim of this study was to investigate the prevalence of menstruation‐related headache and the impact of associated factors in adolescents.

Methods

This cross‐sectional study was conducted in seven randomly selected high schools, and 3,886 girls attending those schools were invited to take part. After the consent of the school principals, a final total of 2,485 girls (63.9%) were involved in the study. A specific questionnaire was distributed to adolescent girls (14–19 years old). The first part of the survey investigated the features of menstruation (age at first menstruation, duration of period, pad fully soaked per day). The last part of the questionnaire surveyed the presence of headache during the menstrual period. The severity of headache was measured using a visual analog scale. Last, participants were requested to complete the Beck Depression Inventory (BDI). The prevalence of menstruation‐related headache and associated factors were studied.

Results

Mean subject age was 15.89 ± 1.07 years (range, 14–19 years) and mean age at menarche was 12.96 ± 1.09 years old. The prevalence of menstruation‐related headache was 25.9% (n = 646). Onset of menstruation at <12 years of age, longer duration of menstruation period, dysmenorrhea, daily consumption of coffee and cola and smoking significantly affected the frequency of menstruation‐related headache. Mean BDI score was 21.68 ± 13.65 and was significantly associated with menstruation headache.

Conclusion

Menstruation‐related headache is a common problem in adolescent girls. It might be associated with different comorbidities such as depression. Accordingly, a multidisciplinary treatment approach must be considered to improve the quality of life.
A hypothesis for the existence of two types of tuberculosis, reflecting two distinct types of immune failure to control the pathogen, based upon prevalence of mycobacterium‐specific IgG subclasses
Authors: Menon J. , Hoeppner V. H. , Judd A. , Power C. A. , Bretscher P. A.
Published: April 2018

Most people infected by Mycobacterium tuberculosis, about 90%, contain the pathogen and are healthy. Most investigators have concluded that pathogen‐specific Th1 cells contribute to protection. Pulmonary tuberculosis, the most prevalent form of disease, is associated with destructive granulomas, the formation of which also appears to involve Th1 cells. In what sense then do the two Th1 components of the response, in healthy infected individuals and patients, differ? An insight into this question might provide clues for attaining effective vaccination and better treatment. We approached this question by examining the relative prevalence of different IgG isotypes among anti‐mycobacterium‐specific antibodies in patients and healthy infected individuals as a surrogate marker for the Th1/Th2 phenotype of the response. Our observations lead us to agree that healthy infected individuals generate a predominant Th1 response. Our observations also lead us to propose that many patients make a similar kind of response as healthy infected individuals, but that this response is too weak to contain the infection. We refer to such individuals as having type I tuberculosis. Other patients appear to have a greater and detrimental Th2 component to their immune response than that of healthy infected individuals. We refer to these individuals as having type II tuberculosis. This proposal that there are two types of tuberculosis, reflecting two distinct types of failure by the immune system, will, if correct, be pertinent to vaccine design, treatment of tuberculosis and in making further progress in our understanding the genetics of susceptibility to M. tuberculosis.
Amotosalen/UVA treatment inactivates T cells more effectively than the recommended gamma dose for prevention of transfusion‐associated graft‐versus‐host disease
Authors: Castro Grace , Merkel Patricia A. , Giclas Hannah E. , Gibula Andrew , Andersen Gillian E. , Corash Laurence M. , Lin Jin Sying , Green Jennifer , Knight Vijaya , Stassinopoulos Adonis
Published: April 2018

INTRODUCTION

Transfusion‐associated graft‐versus‐host disease (TA‐GVHD) is a rare complication after transfusion of components containing viable donor T cells. Gamma irradiation with doses that stop T‐cell proliferation is the predominant method to prevent TA‐GVHD. Treatment with pathogen inactivation methodologies has been found to also be effective against proliferating white blood cells, including T cells. In this study, T‐cell inactivation was compared, between amotosalen/ultraviolet A (UVA) treatment and gamma‐irradiation (2500 cGy), using a sensitive limiting dilution assay (LDA) with an enhanced dynamic range.

METHODS AND MATERIALS

Matched plasma units (N = 8), contaminated with 1 × 106 peripheral blood mononuclear cells (PBMCs) per mL, were either treated with amotosalen/UVA or gamma irradiation, or retained as untreated control. Posttreatment, cells were cultured under standardized conditions. T‐cell proliferation was determined by the incorporation of 3H‐thymidine and correlated with microscopic detection.

RESULTS

Range‐finding experiments showed that after gamma irradiation (2500 cGy), significant T‐cell proliferation could be observed at a 1 × 107 cell culture density, some proliferation at 1 × 106, and none at 1 × 105 cells/well. Based on these facts, a quantitative comparison was carried out between amotosalen/UVA at the highest challenge of 1 × 107 PBMCs/well, and gamma irradiation at 1 × 106 and 1 × 105 PBMCs/well. Complete inactivation of the T cells after amotosalen/UVA treatment was observed, equivalent to greater than 6.2 log inactivation. Complete inactivation of the T cells was also observed after gamma irradiation when 1 × 105 PBMCs/well were cultured (>4.2 log inactivation). Proliferation was observed when 1 × 106 PBMCs/well were cultured (≤5.2 log inactivation) after gamma irradiation.

CONCLUSION

Amotosalen/UVA treatment more effectively inactivates T cells than the current standard of gamma irradiation (2500 cGy) for the prevention of TA‐GVHD.
Assessing opportunities and challenges for establishing a national program to distribute cord blood for research
Authors: Isasi Rosario , Mastronardi Cherie , Golder Mia , Allan David , Walker Mark , Halpenny Mike , Yang Lin , Elmoazzen Heidi , Chargé Sophie
Published: April 2018

BACKGROUND

Research is needed to enhance cord blood (CB) transplantation outcomes and to develop new clinical applications. Based on quality criteria for transplantation, CB collected by public CB banks (CBBs) is often unsuitable for banking, but may still be valuable for research. Canadian researchers have described a need for a centralized program providing ethically sourced CB for research projects. To meet this need, Canadian Blood Services (CBS), in partnership with The Ottawa Hospital, launched the Cord Blood for Research Program (CBRP) in 2014.

STUDY DESIGN AND METHODS

The CBRP developed processes for donor research consent and research project approval with oversight from CBS's CBB and appropriate research ethics boards. The CBRP distributes deidentified CB products to research projects across Canada.

RESULTS

Since its inception, the CBRP has distributed more than 525 CB units to researchers, supporting 11 research projects. Of the mothers who donate their baby's CB, 77% have chosen to consent to its use for research if it is not bankable. The number of CB units currently available for research via the CBRP exceeds the requests from researchers.

CONCLUSION

The CBRP reliably distributes quality CB products that do not qualify for banking to investigators across Canada in an ethical, legal, and transparent manner. This provides an opportunity for the public to directly support research, helps meet the need expressed by Canada's research community, and maximizes the donor's gift. More research is needed to clarify the factors influencing donor and researcher participation in the CBRP.
Compensation schemes for learning a Lingua Franca in the European Union
Authors: Ginsburgh Victor , Moreno‐Ternero Juan D.
Published: April 2018

We discuss compensation schemes that should give incentives to EU countries and citizens to acquire a lingua franca. We consider three possible candidate languages: English, French and German, which are already the most widely spoken languages. In our model, countries can claim compensations linked to the number of (young) citizens who do not speak a given candidate language, and the distance between the official language in the country and the suggested lingua franca. We study two sharing schemes that are rooted in ancient sources: the Aristotelian proportional rule and the Talmud rule. The former prevents coalitional manipulations among countries, whereas the latter guarantees meaningful lower bounds in the sharing process for all countries.
Long‐term effects of tibial plateau leveling osteotomy and tibial tuberosity advancement on tibial plateau subchondral bone density in dogs
Authors: Leach Elizabeth S. , Krotscheck Ursula , Goode Kelsey J. , Hayes Galina M. , Böttcher Peter
Published: April 2018

Objective

To evaluate long‐term loading patterns using subchondral bone density (SBD) distribution of the tibial plateau after tibial plateau leveling osteotomy (TPLO) and tibial tuberosity advancement (TTA).

Study Design

Cross‐sectional study.

Animals

Adult (> 2 years), medium to large breed dogs (>20 kg) that had been treated with TPLO or TTA at least 1 year prior to the study were recruited. A normal cohort of similar age and weight dogs with normal physical and orthopedic examinations served as control.

Methods

Dogs were sedated for computed tomography (CT) of the stifle, and DICOM (digital imaging and communications in medicine) files were processed for CT osteoabsorptiometry (CTOAM). Tibial plateaus were sampled at 6 zones, and CTOAM was used to determine regional and maximal areas of SBD as a marker of joint loading.

Results

Data were collected on 48 stifles in 31 dogs (15 TPLO, 11 TTA, 22 control). Lower Hounsfield unit (HU) values were measured in the caudal and mid‐region of the lateral tibial plateau after TPLO and compared to normal. HU values did not differ between joints treated with TTA and those in the control group.

Conclusion

TPLO may alter stifle load distribution relative to the normal control group. There were no differences between TTA and the control group.

Clinical significance/Impact

Despite ongoing osteoarthritis (OA) in dogs after surgical intervention for cranial cruciate disease, changes in tibial SBD are minor and may not correlate with clinical function.
Bollinger Bands Trading Strategy Based on Wavelet Analysis
Authors: Chen Shaozhen , Zhang Bangqian , Zhou GengJian , Qin Qiaoxu
Published: April 2018

With the popularization of the concept of quantitative investment and the introduction of stock index futures in China, the research on the quantitative trading strategies of stock index futures is emerging gradually. This paper takes the CSI 300 stock index futures as the research object and sets up the Bollinger Bands trading strategy to test it, while considering the factors such as returns, retracement and income risk ratio, etc. Furthermore, the paper uses the wavelet noise reduction to process the data of price and the Bollinger Bands trading strategy to test the processed data. Compared with the results of the first test, the Bollinger Band trading strategy based on wavelet analysis has greater returns, less risk and better applicability.
Relebactam Is a Potent Inhibitor of the KPC-2 β-Lactamase and Restores Imipenem Susceptibility in KPC-Producing Enterobacteriaceae
Authors: Papp-Wallace Krisztina M. , Barnes Melissa D. , Alsop Jim , Taracila Magdalena A. , Bethel Christopher R. , Becka Scott A. , van Duin David , Kreiswirth Barry N. , Kaye Keith S. , Bonomo Robert A.
Published: April 2018

The imipenem-relebactam combination is in development as a potential treatment regimen for infections caused by
Enterobacteriaceae
possessing complex β-lactamase backgrounds. Relebactam is a β-lactamase inhibitor that possesses the diazabicyclooctane core, as in avibactam; however, the R1 side chain of relebactam also includes a piperidine ring, whereas that of avibactam is a carboxyamide. Here, we investigated the inactivation of the
Klebsiella pneumoniae
carbapenemase KPC-2, the most widespread class A carbapenemase, by relebactam and performed susceptibility testing with imipenem-relebactam using KPC-producing clinical isolates of
Enterobacteriaceae
. MIC measurements using agar dilution methods revealed that all 101 clinical isolates of KPC-producing
Enterobacteriaceae
(
K. pneumoniae
,
Klebsiella oxytoca
,
Enterobacter cloacae
,
Enterobacter aerogenes
,
Citrobacter freundii
,
Citrobacter koseri
, and
Escherichia coli
) were highly susceptible to imipenem-relebactam (MICs ≤ 2 mg/liter). Relebactam inhibited KPC-2 with a second-order onset of acylation rate constant (
k
2
/
K
) value of 24,750 M
−1
s
−1
and demonstrated a slow off-rate constant (
k
off
) of 0.0002 s
−1
. Biochemical analysis using time-based mass spectrometry to map intermediates revealed that the KPC-2–relebactam acyl-enzyme complex was stable for up to 24 h. Importantly, desulfation of relebactam was not observed using mass spectrometry. Desulfation and subsequent deacylation have been observed during the reaction of KPC-2 with avibactam. Upon molecular dynamics simulations of relebactam in the KPC-2 active site, we found that the positioning of active-site water molecules is less favorable for desulfation in the KPC-2 active site than it is in the KPC-2–avibactam complex. In the acyl complexes, the water molecules are within 2.5 to 3 Å of the avibactam sulfate; however, they are more than 5 to 6 Å from the relebactam sulfate. As a result, we propose that the KPC-2–relebactam acyl complex is more stable than the KPC-2–avibactam complex. The clinical implications of this difference are not currently known.