bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative analysis of pulmonary hypertension in patients treated with imatinib, nilotinib and dasatinib
Authors: Minami Mariko , Arita Takeshi , Iwasaki Hiromi , Muta Tsuyoshi , Aoki Takatoshi , Aoki Kenichi , Yamasaki Satoshi , Matsushima Takamitsu , Kato Koji , Takenaka Katsuto , Tanimoto Kazuki , Kamimura Tomohiko , Ogawa Ryosuke , Akashi Koichi , Miyamoto Toshihiro 
Published: March 2017

SummaryPulmonary hypertension (PH) is a rare, but life‐threatening, adverse event in patients treated with tyrosine kinase inhibitors (TKIs), such as dasatinib, but has not been fully evaluated in patients treated with imatinib or nilotinib. We used echocardiography to noninvasively assess the incidence of PH in 105 patients with chronic myeloid leukaemia (CML) treated with imatinib (n = 37), nilotinib (n = 30) or dasatinib (n = 38). The mean triscupid regurgitation peak gradient (TRPG), which reflects pulmonary arterial pressure, was 22·7 mmHg in the imatinib group, 23·1 mmHg in the nilotinib group and 23·4 mmHg for dasatinib group. These values were not significantly different, but higher than those (19·0 mmHg) in newly diagnosed CML patients. A TRPG > 31 mmHg, marking possible PH onset, was detected in 9 of 105 patients: one (2·7%) treated with imatinib, three (10·0%) with nilotinib and five (13·2%) with dasatinib. Only three patients complained of dyspnoea, whereas the other six were asymptomatic. In addition, there was a tendency toward correlation of TRPG value and age or TKI treatment duration. These results suggested that treatment with not only dasatinib, but also imatinib and nilotinib, can be associated with subclinical PH. Noninvasive echocardiography is useful for screening, especially in older patients with long‐term TKI treatment.
Telomere length is a critical determinant for survival in multiple myeloma
Authors: Hyatt Sam , Jones Rhiannon E. , Heppel Nicole H. , Grimstead Julia W. , Fegan Chris , Jackson Graham H. , Hills Robert , Allan James M. , Pratt Guy , Pepper Chris , Baird Duncan M. 
Published: March 2017

SummaryThe variable clinical outcomes of Multiple Myeloma (MM) patients are incompletely defined by current prognostication tools. We examined the clinical utility of high‐resolution telomere length analysis as a prognostic marker in MM. Cohort stratification, using a previously determined length threshold for telomere dysfunction, revealed that patients with short telomeres had a significantly shorter overall survival (P < 0·0001; HR = 3·4). Multivariate modelling using forward selection identified International Staging System (ISS) stage as the most important prognostic factor, followed by age and telomere length. Importantly, each ISS prognostic subset could be further risk‐stratified according to telomere length, supporting the inclusion of this parameter as a refinement of the ISS.
The Emergence of Episodic Foresight and Its Consequences
Authors: Suddendorf Thomas 
Published: March 2017

AbstractImagining future events and adjusting current behavior accordingly is a hallmark of human cognition. The development of such episodic foresight is attracting increasing research attention. In this article, I review a selection of recent work on the emergence of episodic foresight and its role in different domains, including learning, deliberate practice, affective forecasting, intertemporal choices, and anxiety. Studies suggest that during the preschool years, children begin to consider future scenarios, enabling them to plan, prepare, and shape their future, but many other consequences, such as the role of developing foresight in anticipating hazards, remain unexamined. The potential predictive effects of early individual differences in episodic foresight on later cognitive capacities and developmental outcomes deserve closer scrutiny.
Expression of oxysterol pathway genes in oestrogen‐positive breast carcinomas
Authors: Kloudova Alzbeta , Brynychova Veronika , Vaclavikova Radka , Vrana David , Gatek Jiri , Mrhalova Marcela , Kodet Roman , Soucek Pavel 
Published: March 2017

SummaryObjectiveThis study investigated whether gene expression levels of key modulators of the oxysterol signalling pathway modify the prognosis of patients with oestrogen receptor‐positive (ER+) breast carcinomas via interaction with endocrine therapy.ContextThe prognosis of patients with ER+ breast carcinoma depends on several factors. Previous studies have suggested that some oxygenated forms of cholesterol (oxysterols) bind to oestrogen receptor and anti‐oestrogen binding site which may deregulate cholesterol homoeostasis and influence effect of therapy.DesignThe expression levels of 70 oxysterol pathway genes were evaluated in a test set of breast carcinomas differing in ER expression. The genes differentially expressed in ER+ tumours were assessed in a comprehensive set of ER+ tumours to evaluate their clinical significance.PatientsA total of 193 primary patients with breast carcinoma were included.MeasurementsThe transcript levels were determined by quantitative real‐time polymerase chain reaction.ResultsThe expression levels of 23 genes were found to be specifically dysregulated in ER+ tumours compared to ER− tumours of the test set. The expression levels of ABCG2, CYP7B1, CYP24A1, CYP39A1 and CH25H genes were found to be strongly associated with disease stage; however, none of the gene expression levels were associated with disease‐free survival in patients treated with endocrine therapy.ConclusionsThe expression of a number of oxysterol pathway genes is significantly modulated by ER expression and associated with the clinical stage of patients. However, the expression of oxysterol pathway genes was not found to modify the prognosis of ER+ patients with breast carcinoma treated with endocrine therapy.
The lipid‐lowering effect of levothyroxine in patients with subclinical hypothyroidism: A systematic review and meta‐analysis of randomized controlled trials
Authors: Li Xiang , Wang Yupeng , Guan Qingbo , Zhao Jiajun , Gao Ling 
Published: March 2017

SummaryObjectivesDyslipidaemia is common in patients with subclinical hypothyroidism (SCH). To date, there is no universal agreement regarding the lipid‐lowering effect of substitution treatment with L‐T4 in patients with SCH. We aimed to clarify the effect by conducting this systematic review and meta‐analysis of randomized controlled trials (RCTs).DesignWe systematically searched PubMed, the Cochrane Library, ClinicalTrials.gov and EMBASE for RCTs comparing substitution treatment to placebo treatment or observation. We focused on the primary outcomes of changes from baseline of total, low‐density lipoprotein and high‐density lipoprotein cholesterol (TC, LDL‐C and HLD‐C) and triglycerides. Subgroup analyses were performed, assessing the effect of treatment duration, disease severity and ethnicity on the occurrence of discrepancy.ResultsTwelve trials, with 940 participants, were eligible for analysis. Compared with the control group, levothyroxine substitution yielded a mean reduction in TC (−0.29 mmol/L, [−0.42 to −0.16]) and LDL‐C (−0.22 mmol/L, [−0.36 to −0.09]), with no significant effects on HDL‐C (−0.04 mmol/L, [−0.08 to 0.01]) or triglycerides (−0.04 mmol/L, [−0.08 to 0.00]). Trials in which only patients with mild SCH (thyrotropin <10 mIU/L) were enrolled showed equivalent effects. The lowering effects were weaker, but still significant, in long‐term treatment (>6 months) compared with short‐term treatment (≤6 months) for TC (−0.19 mmol/L [−0.35, −0.03] vs −0.50 mmol/L [−0.68, −0.31], P=.047) and LDL‐C (−0.09 mmol/L [−0.16, −0.02] vs −0.46 mmol/L [−0.68, −0.25], P=.006).ConclusionsLevothyroxine treatment has clear benefits on TC and LDL‐C in SCH patients, including those with mild SCH.
A randomised controlled trial of sodium citrate spray for non‐conductive olfactory disorders
Authors: Philpott C.M. , Erskine S.E. , Clark A. , Leeper A. , Salam M. , Sharma R. , Murty G.E. , Hummel T. 
Published: March 2017

ObjectivesPrevious research has suggested that sodium citrate improves hyposmia by decreasing mucus calcium levels in the nose. This study aimed to confirm or refute this effect in a single application and assess potential side‐effects.DesignStudy design was a randomised double‐blind controlled trial of sodium citrate nasal spray (intervention) vs sterile water (control). Fifty‐five patients with non‐conductive olfactory loss were randomised to receive the intervention or placebo.SettingTertiary care clinic.Main outcome measuresThe primary outcome measure was improvement in measured olfactory thresholds for phenyl ethyl alcohol (PEA) over 2 hours. Other outcome measures assessed were improvement in olfactory thresholds in 1‐butanol, eucalyptol and acetic acid; number of responders with a clinically relevant response in each arm; and adverse effects.ResultsA significant effect was seen in the intervention arm for PEA and for 1‐butanol and eucalyptol when compared to the control arm (P<.05); 32% of the intervention arm responded in terms of improved sensitivity towards some of the odours. Minor adverse effects noted included sore throat, nasal paraesthesia, slight rhinorrhoea and itching. The duration of effect of the citrate is transient, peaking at 30‐60 minutes after application.ConclusionsSodium citrate yields some potential as a treatment for non‐conductive olfactory loss; however, these findings require corroboration in further clinical trials looking at longer term regular use of the spray as a viable therapeutic option for patients where it would be applied at frequent intervals such as before mealtimes.
Connecting today's climates to future climate analogs to facilitate movement of species under climate change
Authors: Littlefield Caitlin E. , McRae Brad H. , Michalak Julia L. , Lawler Joshua J. , Carroll Carlos 
Published: March 2017

AbstractIncreasing connectivity is an important strategy for facilitating species range shifts and maintaining biodiversity in the face of climate change. To date, however, few researchers have included future climate projections in efforts to prioritize areas for increasing connectivity. We identified key areas likely to facilitate climate‐induced species’ movement across western North America. Using historical climate data sets and future climate projections, we mapped potential species’ movement routes that link current climate conditions to analogous climate conditions in the future (i.e., future climate analogs) with a novel moving‐window analysis based on electrical circuit theory. In addition to tracing shifting climates, the approach accounted for landscape permeability and empirically derived species’ dispersal capabilities. We compared connectivity maps generated with our climate‐change‐informed approach with maps of connectivity based solely on the degree of human modification of the landscape. Including future climate projections in connectivity models substantially shifted and constrained priority areas for movement to a smaller proportion of the landscape than when climate projections were not considered. Potential movement, measured as current flow, decreased in all ecoregions when climate projections were included, particularly when dispersal was limited, which made climate analogs inaccessible. Many areas emerged as important for connectivity only when climate change was modeled in 2 time steps rather than in a single time step. Our results illustrate that movement routes needed to track changing climatic conditions may differ from those that connect present‐day landscapes. Incorporating future climate projections into connectivity modeling is an important step toward facilitating successful species movement and population persistence in a changing climate.
Straight‐to‐test colonoscopy for 2‐week‐wait referrals improves time to diagnosis of colorectal cancer and is feasible in a high‐volume unit
Authors: Banerjea A. , Voll J. , Chowdhury A. , Siddika A. , Thomson S. , Briggs R. , Humes D. J. ,   Nottingham Colorectal Service
Published: March 2017

AbstractAimWe have introduced ‘straight‐to‐test’ (STT) colonoscopy as part of our 2‐week‐wait (2WW) pathway to address increasing numbers of urgent referrals for colorectal cancer (CRC) within the National Health Service. In this study we evaluated the ability of this initiative to shorten the time to diagnosis of CRC.MethodWe amended our 2WW referral form to include performance status and comorbidities. General practitioners were asked to provide data on estimated glomerular filtration rate and full blood count/ferritin. Our 2WW referrals were screened by a colorectal consultant and a nurse specialist. Those deemed unsuitable for STT were offered outpatient assessment (OPA).ResultsOf 553 2WW referrals screened, 352 were considered suitable, 65 of whom failed a telephone assessment or were uncontactable, and accordingly 287 were offered the STT pathway. The STT group was significantly younger than the OPA group (median 65.9 years vs 78.7 years; P < 0.0001). STT colonoscopy significantly reduced the time to first test (13 days vs 22 days; P < 0.0001) and tissue diagnosis from the referral date (17 days vs 24.5 days; P < 0.0001). Thirty‐seven (6.8%) CRCs were detected. Proportionately fewer patients in the STT pathway were managed with ‘best supportive care only’ compared with patients attending OPA (one of 15 vs six of 22, respectively). STT colonoscopy obviated the need for clinic attendance before testing in 287 patients, representing a potential net cost benefit of at least £48 500 in 4 months.ConclusionSTT colonoscopy was safe and effective for selecting out a group of symptomatic patients who could proceed straight to endoscopic examination and receive a diagnosis more rapidly.
Farmer Perceptions and Behaviors Related to Wildlife and On‐Farm Conservation Actions
Authors: Kross Sara M. , Ingram Katherine P. , Long Rachael F. , Niles Meredith T. 
Published: March 2017

AbstractPolicy makers are increasingly encouraging farmers to protect or enhance habitat on their farms for wildlife conservation. However, a lack of knowledge of farmers’ opinions toward wildlife can lead to poor integration of conservation measures. We surveyed farmers to assess their perceptions of ecosystem services and disservices from perching birds, raptors, and bats—three taxa commonly targeted by conservation measures. The majority of farmers thought that perching birds and bats were beneficial for insect pest control and that raptors were beneficial for vertebrate pest control; however, fruit farmers viewed perching birds more negatively than did farmers growing other crops. Farmers using organic methods viewed all three wildlife groups more positively than conventional farmers. Farmer perception toward each wildlife group predicted their action to either attract or deter those taxa, suggesting the need to focus research and outreach on the effects of wildlife on farms for conservation programs to positively influence farmer perceptions.
Pharmacokinetic and pharmacogenetic analysis of immunosuppressive agents after laparoscopic sleeve gastrectomy
Authors: Diwan Tayyab S. , Lichvar Alicia B. , Leino Abbie D. , Vinks Alexander A. , Christians Uwe , Shields Adele R. , Cardi Michael A. , Fukuda Tsuyoshi , Mizuno Tomoyuki , Kaiser Tiffany , Woodle E. Steve , Alloway Rita R. 
Published: March 2017

AbstractBackgroundSevere obesity has been shown to limit access to renal transplantation in patients with end‐stage renal disease (ESRD). Laparoscopic sleeve gastrectomy (LSG) has been performed in the ESRD population to assist in achieving waitlist and transplant eligibility. Little is known about how LSG impacts the bioequivalence of tacrolimus products and immunosuppression pharmacokinetics.MethodsThis was a prospective, open‐label, single‐dose, crossover, two‐period pharmacokinetic (PK) study. The purpose of this study was to assess single‐dose PK of immediate‐release tacrolimus (IR‐TAC), extended‐release tacrolimus (ER‐TAC), and mycophenolic acid (MPA) in adult ESRD patients post‐LSG.ResultsTwenty‐three subjects were included in the 24‐hour PK assessments. The ratio of geometric means between ER‐TAC and IR‐TAC was 103.5% (90% CI; 89.6%‐119.6%) for AUC0‐24 and 92.5% (90% CI; 80.4%‐106.4%) for Cmax. PK parameters were similar between ER‐TAC and IR‐TAC, except for Cmin (P=.004) and Cmax (P=.04). MPA AUC0‐24 was similar when given with either ER‐TAC or IR‐TAC (P=.32). Patients expressing CYP3A5*1 genotypes had lower tacrolimus AUC0‐24 values vs those with CYP3A5*3/*3 (IR‐TACP<.001; ER‐TACP=.008). Genotype did not impact MPA PK.ConclusionDose modification of immunosuppressants post‐LSG may not be necessary aside from standard therapeutic drug monitoring.
Characteristics of compatible pair participants in kidney paired donation at a single center
Authors: Weng Francis L. , Grogan Tracy , Patel Anup M. , Mulgaonkar Shamkant , Morgievich Marie M. 
Published: March 2017

AbstractCompatible pairs of living kidney donors and their intended recipients can enter into kidney paired donation (KPD) and facilitate additional living donor kidney transplants (LDKTs). We examined 11 compatible pairs (the intended recipients and their intended, compatible donors) who participated in KPD, along with the recipients’ 11 matched, exchange donors. The 11 pairs participated in 10 separate exchanges (three were multicenter exchanges) that included 33 total LDKTs (22 additional LDKTs). All the intended donors were blood group O and female, with a mean living kidney donor profile index (LKDPI) of 27.6 (SD 16.8). The matched donors had a mean LKDPI of 9.4 (SD 31.7). Compatible pairs entered KPD for altruistic reasons (N=2) or due to mismatch of age (N=7) or body/kidney size (N=2) between the recipient and intended donor. In four cases, retrospective calculation of the LKDPI revealed that the matched donor had a higher LKDPI than the intended donor. Of the 22 recipients of LDKTs enabled by the compatible pairs, three were highly sensitized, with PRA >80%. In conclusion, most compatible pairs entered into KPD so that the recipient could receive a LDKT transplant from a donor whose age or body/kidney size were more favorable to post‐transplant outcomes.
SOX10 immunohistochemistry in sweat ductal/glandular neoplasms
Authors: Cassarino David S. , Su Albert , Robbins Bruce A. , Altree‐Tacha David , Ra Seong 
Published: March 2017

Background
SOX10 is a newer Schwannian and melanocytic marker that has generated great interest for its relative sensitivity and specificity in the diagnosis of neural crest‐derived tumors. Previous studies with SOX10 have shown positive immunohistochemical expression in cutaneous eccrine glands and negative expression in eccrine ducts, apocrine glands and hair follicles. Thus, we hypothesized that some sweat gland tumors of presumed eccrine origin would be positive for SOX10, whereas apocrine‐derived sweat gland tumors would not.MethodsA mouse monoclonal anti‐SOX10 (clone BC34: Biocare Medical; Concord, California) immunohistochemical antibody was performed on various sweat gland tumors and basal cell carcinoma.Results
SOX10 showed positivity in spiradenomas (13/13), cylindromas (9/10), hidradenoma papilliferum (10/10), syringocystadenoma papilliferum (8/10), apocrine adenomas (8/10), and negativity in poromas (0/12), syringomas (0/10), and basal cell carcinomas (0/13). There was mixed staining of hidradenomas (6/15).Conclusions
SOX10 immunohistochemistry may be of utility in distinguishing some of the varying adnexal tumors from each other, and from basal cell carcinoma (BCC), but given the staining of both apocrine and eccrine tumors, does not seem to provide information as to their origins as either eccrine or apocrine tumors.
Equine gastric ulcer syndrome in adult donkeys: Investigation on prevalence, anatomical distribution, and severity
Authors: Sgorbini M. , Bonelli F. , Papini R. , Busechian S. , Briganti A. , Laus F. , Faillace V. , Zappulla F. , Rizk A. , Rueca F. 
Published: March 2017

SummaryThe study was performed on 39 live donkeys that underwent gastroscopic examination. The lesions were recorded in accordance with the European College of Equine Internal Medicine Consensus Statement guidelines. The presence of Gasterophilus sp. larvae was also recorded. Larvae were collected and identified to species level. Fisher's exact test was used to compare different prevalence values for sex, age, and anatomical distribution of lesions. Gastric lesions were present in 20/39 (51.3% [35.6–67%]) donkeys; 19/39 (48.7% [95% confidence interval = 33–64.4%]) were affected only by equine squamous gastric disease (ESGD), while 1/39 (2.6% [0–7.5%]) showed both ESGD and equine glandular gastric disease (EGGD), thus 95% of positive donkeys showed lesions located in the nonglandular mucosa. The ESGD grade was 0/4 (48.7% [33–64.4%]) in 19/39, 1/4 (12.8% [2.3–23.3%]) in 5/39, 2/4 (25.6% [11.9–39.5%]) in 10/39, 3/4 in 4/39 (10.3% [0.7–19.8%]) and 4/4 in 1/39 (2.6% [0–7.5%]) donkeys, respectively. The EGGD lesion was a mild depression in the ventral glandular fundus. ESGD was primary in all the donkeys included and lesions were located around the cardia and along the lesser curvature. Gasterophilus sp. larvae were present in all animals and were identified as third‐stage larvae of Gasterophilus intestinalis. No animals showed clinical signs of equine gastric ulcer syndrome (EGUS). No significant differences relating to sex, age or breed were found in the prevalence of EGUS in this study, while the proportion of donkeys affected by ESGD was statistically higher than those affected by EGGD. To the best of our knowledge, this is the first report on the gastroscopic evaluation of EGUS in live donkeys. Our results show a higher prevalence of EGUS in live donkeys than values previously reported by other authors in donkeys that were dead or had been subjected to euthanasia. The detection of third‐stage G. intestinalis larvae was not unexpected since these can be found in the stomach of equids throughout the year, and G. intestinalis has been reported as the most common Gasterophilus sp. in Italy.
Verapamil treatment induces cytoprotective autophagy by modulating cellular metabolism
Authors: Kania Elżbieta , Pająk Beata , O'Prey Jim , Sierra Gonzalez Pablo , Litwiniuk Anna , Urbańska Kaja , Ryan Kevin M. , Orzechowski Arkadiusz 
Published: March 2017

Verapamil, an L‐type calcium channel blocker, has been used successfully to treat cardiovascular diseases. Interestingly, we have recently shown that treatment of cancer cells with verapamil causes an effect on autophagy. As autophagy is known to modulate chemotherapy responses, this prompted us to explore the impact of verapamil on autophagy and cell viability in greater detail. We report here that verapamil causes an induction of autophagic flux in a number or tumor cells and immortalized normal cells. Moreover, we found that inhibition of autophagy in COLO 205 cells, via treatment with the chloroquine (CQ) or by CRISPR/Cas9‐mediated disruption of the autophagy genes Atg7 and Atg5, causes an upregulation of apoptotic markers in response to verapamil. In search of a mechanism for this effect and because autophagy can often mitigate metabolic stress, we examined the impact of verapamil on cellular metabolism. This revealed that in normal prostate cells, verapamil diminishes glucose and glycolytic intermediate levels leading to adenosine 5′‐triphosphate (ATP) depletion. In contrast, in COLO 205 cells it enhances aerobic glycolysis and maintains ATP. Importantly, we found that the autophagic response in these cells is related to the activity of l‐lactate dehydrogenase A (LDHA, EC 1.1.1.27), as inhibition of LDHA reduces both basal and verapamil‐induced autophagy and consequently decreases cell viability. In summary, these findings not only identify a novel mechanism of cytoprotective autophagy induction but they also highlight the potential of using verapamil together with inhibitors of autophagy for the treatment of malignant disease.Enzymesl‐lactate dehydrogenase (LDHA, EC 1.1.1.27).