bluuebunny/crossref_metadata_2025_split huggingface dataset:
Elevated serum creatinine and hyponatraemia as prognostic factors in canine acute pancreatitis
Authors: Marchetti V , Gori E , Lippi I , Luchetti E , Manca ML , Pierini A 
Published: October 2017

ObjectiveTo evaluate prognostic factors for canine acute pancreatitis (AP) based on clinical and laboratory data that can be easily assessed in veterinary practice.DesignRetrospective study between January 2010 and December 2013.MethodsThe diagnosis of AP was based on clinical signs and an abnormal SNAP® cPL™ test result, concurrently with an ultrasound pattern suggestive of pancreatitis. Dogs were divided into survivors and non‐survivors. We evaluated 12 clinical and laboratory parameters: respiratory rate, rectal temperature, white blood cells, haematocrit, total serum proteins, albumin, creatinine, cholesterol, total and ionised calcium, sodium and potassium. Clinical and clinicopathological data were statistically compared between survivors and non‐survivors. A value of P < 0.05 was considered significant and P < 0.01 as highly significant. The odds ratio (OR) was calculated.ResultsThe study enrolled 50 client‐owned dogs with a diagnosis of AP. Serum creatinine (P = 0.017) and sodium (P = 0.004) correlated significantly with the outcome.Serum sodium < 139.0 mmol/L (139.0 mEq/L) and serum creatinine > 212 μmol/L (2.4 mg/dL) were associated significantly with poor prognosis. Azotaemia (OR 12.5; 95% confidence interval (CI) 1.32–118.48) and hyponatraemia (OR 4.9; 95% CI 1.36–17.64) were associated with increased risk of death.ConclusionsIn dogs with AP, hyponatraemia and azotaemia seem to be significantly associated with an increased risk of death.
Horse‐keeping practices in Australia: findings from a national online survey of horse owners
Authors: Thompson KR , Clarkson L , Riley CB , van den Berg M 
Published: October 2017

ObjectiveTo gain an understanding of general horse‐keeping practices in Australia, including shelter, social contact, exercise, watering and supplementary feeding.MethodsAn online survey was conducted with 505 owners in relation to one ‘representative’ horse in their care.ResultsThe majority (83%) of horses were managed at pasture. Approximately one‐quarter of those horses were housed alone (26%) or with one companion animal (27%). If horses were confined to a stable or small yard, the most recorded means of exercise was riding (65%) at a daily frequency (60%). Over half of the horse owners provided water in a trough or drinker with an automatic refill system (58%) and most horse owners supplied hay to their horses (82%), most commonly in combination with grazing. Areas of potential concern included one‐quarter of stabled horses being prevented from unmediated social and physical contact with conspecifics and one‐fifth of stabled horses being exercised less than daily.ConclusionThe horse‐keeping profile in this study should be considered in the public communication of guidelines as well as interactions between veterinarians and clients.
Examination of the use of intraovarian administration of CaCl2 and zinc gluconate as potential chemosterilants in Bos indicus heifers
Authors: Cavalieri J , Hayes L 
Published: October 2017

ObjectiveTo investigate if administration of potential chemosterilants by transvaginal, ultrasound‐guided intraovarian injection is an alternative to surgical sterilisation.DesignRandomised control study.MethodsBos indicus heifers were treated with intraovarian injections of saline (n = 10), CaCl2 (n = 10), zinc gluconate (ZG; n = 10) or a combination of CaCl2 and ZG (CaCl2 + ZG; n = 10). Heifers were exposed to a bull from 82 to 84 days after treatment and slaughtered between 364 and 396 days after treatment.ResultsAfter treatment administration, the concentrations of haptoglobin and anti‐Müllerian hormone and the total oocyte counts did not differ (P > 0.150) between treatments. Pain responses were observed in heifers treated with ZG and CaCl2 + ZG but not in heifers treated with saline or CaCl2. Total ovarian mass at slaughter was less in heifers treated with CaCl2 compared with the other treatments (P < 0.05). Complete regression of one ovary was observed in 40% (4/10) of the heifers treated with CaCl2. Pregnancies were recorded in ≥ 70% of heifers administered each treatment.ConclusionTreatments used in this study were not able to sterilise most of the B. indicus heifers, but treatment with CaCl2 has the potential to cause complete ovarian atrophy without causing detectable pain.
Population pharmacokinetics of exendin‐(9‐39) and clinical dose selection in patients with congenital hyperinsulinism
Authors: Ng Chee M. , Tang Fei , Seeholzer Steven H. , Zou Yixuan , De León Diva D. 
Published: October 2017

AimsCongenital hyperinsulinism (HI) is the most common cause of persistent hypoglycaemia in infants and children. Exendin‐(9‐39), an inverse glucagon‐like peptide 1 (GLP‐1) agonist, is a novel therapeutic agent for HI that has demonstrated glucose‐raising effect. We report the first population pharmacokinetic (PopPK) model of the exendin‐(9‐39) in patients with HI and propose the optimal dosing regimen for future clinical trials in neonates with HI.MethodsA total of 182 pharmacokinetic (PK) observations from 26 subjects in three clinical studies were included for constructing the PopPK model using first order conditional estimation (FOCE) with interaction method in nonlinear mixed‐effects modelling (NONMEM). Exposure metrics (area under the curve [AUC] and maximum plasma concentration [Cmax]) at no observed adverse effect levels (NOAELs) in rats and dogs were determined in toxicology studies.ResultsObserved concentration–time profiles of exendin‐(9‐39) were described by a linear two‐compartmental PK model. Following allometric scaling of PK parameters, age and creatinine clearance did not significantly affect clearance. The calculated clearance and elimination half‐life for adult subjects with median weight of 69 kg were 11.8 l h−1 and 1.81 h, respectively. The maximum recommended starting dose determined from modelling and simulation based on the AUC0‐last at the NOAEL and predicted AUC0‐inf using the PopPK model was 27 mg kg−1 day−1 intravenously.ConclusionsThis is the first study to investigate the PopPK of exendin‐(9‐39) in humans. The final PopPK model was successfully used with preclinical toxicology findings to propose the optimal dosing regimen of exendin‐(9‐39) for clinical studies in neonates with HI, allowing for a more targeted dosing approach to achieve desired glycaemic response.
Stress and skin disease quality of life: the moderating role of anxiety sensitivity social concerns
Authors: Dixon L.J. , Witcraft S.M. , McCowan N.K. , Brodell R.T. 
Published: October 2017

SummaryBackgroundStress is an important factor in the onset, exacerbation and reoccurrence of many skin diseases. Little is known about psychological risk factors that affect the association between stress and dermatological conditions. One relevant factor that may modulate this link is anxiety sensitivity (AS) social concerns – the propensity to respond fearfully to anxiety-related sensations (e.g. sweating, flushing) owing to perceived social consequences (e.g. rejection or humiliation).ObjectivesTo gain insight into psychological factors affecting skin disease, we examined the moderating role of AS social concerns in the relationship between stress and skin disease quality of life (QoL).MethodsParticipants [n = 237 (161 female), mean ± SD age 34·18 ± 9·57 years] with active skin disease symptoms were recruited online and completed questionnaires assessing stress, AS social concerns, skin disease QoL and global skin disease symptom severity.ResultsAS social concerns moderated the association between stress and skin-related emotional and social functioning in adults with skin disease. Stress was a significant predictor of the impairment associated with skin disease.ConclusionsStress was linked to skin disease-related emotional and functional impairment associated with skin disease among individuals with high AS social concerns. These results highlight the potential for AS reduction interventions to break the vicious cycle of stress and skin disease symptoms and to improve psychosocial well-being in dermatology patients.
Current challenges and opportunities in treating adult patients with Philadelphia‐negative acute lymphoblastic leukaemia
Authors: Wolach Ofir , Amitai Irina , DeAngelo Daniel J. 
Published: October 2017

SummarySignificant advances have been made in recent years in the field of Philadelphia‐negative acute lymphoblastic leukaemia (ALL). New insights into the biology and genetics of ALL as well as novel clinical observations and new drugs are changing the way we diagnose, risk‐stratify and treat adult patients with ALL. New genetic subtypes and alterations refine risk stratification and uncover new actionable therapeutic targets. The incorporation of more intensive, paediatric and paediatric‐inspired approaches for young adults seem to have a positive impact on survival in this population. Minimal residual disease at different time points can assist in tailoring risk‐adapted interventions for patients based on individual response. Finally, novel targeted approaches with monoclonal antibodies, immunotherapies and small molecules are moving through clinical development and entering the clinic. The aim of this review is to consolidate the abundance of emerging data and to review and revisit the concepts of risk‐stratification, choice of induction and post‐remission strategies as well as to discuss and update the approach to specific populations with ALL, such as young adult, elderly/unfit and relapsed/refractory patients with ALL.
Donor‐derivedCD19‐targeted T cell infusion induces minimal residual disease‐negative remission in relapsed B‐cell acute lymphoblastic leukaemia with no response to donor lymphocyte infusions after haploidentical haematopoietic stem cell transplantation
Authors: Chen Yuhong , Cheng Yifei , Suo Pan , Yan Chenhua , Wang Yu , Chen Yao , Han Wei , Xu Lanping , Zhang Xiaohui , Liu Kaiyan , Chang Lungji , Xiao Lei , Huang Xiaojun 
Published: October 2017

SummaryRelapse is a common cause of failure in patients with B‐cell acute lymphoblastic leukaemia (B‐ALL) after haploidentical haematopoietic stem cell transplantation (haplo‐HSCT), and non‐responders to donor lymphoblastic infusion afterHSCThave a very poor prognosis. Although donor‐derivedCD19‐directed chimeric antigen receptor‐modified (CAR) T cells can potentially cure leukaemia, their effectiveness and safety have not been confirmed in relapsed B‐ALLcases after haplo‐HSCT. Between January 2015 and January 2017, two and four patients each received one and two infusions ofCART cells from haplo‐HSCTdonors. Five (83·33%) achieved minimal residual disease (MRD)‐negative remission; one patient was discharged automatically without evaluation after developing severe thrombotic microangiopathies. Four of five responsive patients relapsed after 2–7 months, and one died of sepsis followingMRD‐negative remission after a second infusion. None of the other second infusion recipients achieved a second complete remission. Five patients (83·33%) experienced eight courses of grade 1–3 cytokine release syndrome; two were treated with tocilizumab. Two (33·3%) and one patient developed grade 2 and 3 acute graft‐versus‐host disease (aGVHD), respectively; the former was controlled with glucocorticoids. Donor‐derivedCART‐cell infusion seems be effective and safe for relapsed B‐ALLafter haplo‐HSCT, although larger clinical studies are needed.
Association between maternal haemoglobin and stillbirth: a cohort study among a multi‐ethnic population in England
Authors: Nair Manisha , Churchill David , Robinson Susan , Nelson‐Piercy Cathy , Stanworth Simon J. , Knight Marian 
Published: October 2017

SummaryThe study objectives were to examine the association of maternal haemoglobin with stillbirth and perinatal death in a multi‐ethnic population in England. We conducted a retrospective cohort analysis using anonymised maternity data from 14 001 women with singleton pregnancies ≥24 weeks’ gestation giving birth between 2013 and 2015 in two hospitals ‐ the Royal Wolverhampton NHS Trust and Guy's and St Thomas’ NHS Foundation Trust. Multivariable logistic regression analyses were undertaken to analyse the associations between maternal haemoglobin at first visit and at 28 weeks with stillbirth and perinatal death, adjusting for 11 other risk factors. Results showed that 46% of the study population had anaemia (haemoglobin <110 g/l) at some point during their pregnancy. The risk of stillbirth and perinatal death decreased linearly per unit increase in haemoglobin concentration at first visit (adjusted odds ratio [aOR] stillbirth = 0·70, 95% confidence interval [CI] 0·58–0·85, aOR perinatal death = 0·71, 95% CI 0·60–0·84) and at 28 weeks (aOR stillbirth = 0·83, 95% CI 0·66–1·04; aOR perinatal death = 0·86, 95%CI 0·67–1·12). Compared with women with haemoglobin ≥110 g/l, the risk of stillbirth and perinatal death was five‐ and three‐fold higher in women with moderate‐severe anaemia (haemoglobin <100 g/l) at first visit and 28 weeks, respectively. These findings have clinical and public health importance.
A phase 1 clinical trial evaluating marizomib, pomalidomide and low‐dose dexamethasone in relapsed and refractory multiple myeloma (NPI‐0052‐107): final study results
Authors: Spencer Andrew , Harrison Simon , Zonder Jeffrey , Badros Ashraf , Laubach Jacob , Bergin Krystal , Khot Amit , Zimmerman Todd , Chauhan Dharminder , Levin Nancy , MacLaren Ann , Reich Steven D. , Trikha Mohit , Richardson Paul 
Published: October 2017

SummaryMarizomib (MRZ) is an irreversible, pan‐subunit proteasome inhibitor (PI) in clinical development for relapsed/refractory multiple myeloma (RRMM) and glioma. This study analysed MRZ, pomalidomide (POM) and low‐dose dexamethasone (Lo‐DEX) [PMD] in RRMM to evaluate safety and determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D). Intravenous MRZ (0·3–0·5 mg/m2) was administered over 2 h on days 1, 4, 8, 11; POM (3–4 mg) on days 1–21; and Lo‐DEX (5 or 10 mg) on days 1, 2, 4, 5, 8, 9, 11, 12, 15, 16, 22 and 23 of every 28‐day cycle. Thirty‐eight patients were enrolled that had received a median of 4 (range 1–10) prior lines of therapy; all patients received prior lenalidomide and bortezomib. No dose‐limiting toxicities (DLTs) were observed and 0·5 mg/m2 MRZ was determined to be the RP2D. The most common treatment‐related ≥Grade 3 adverse events were: neutropenia (11/38 patients: 29%), pneumonia (4/38 patients 11%), anaemia (4/38 patients; 11%) and thrombocytopenia (4/38 patients; 11%). The overall response rate and clinical benefit rate was 53% (19/36) and 64% (23/36), respectively. In conclusion, PMD was well tolerated and demonstrated promising activity in heavily pre‐treated, high‐risk RRMM patients.
Minimal residual disease in non‐Hodgkin lymphoma – current applications and future directions
Authors: Chase Matthew L. , Armand Philippe 
Published: October 2017

SummaryNon‐Hodgkin Lymphomas (NHLs) are a heterogeneous group of tumours with distinct treatment paradigms, but in all cases the goal of treatment is to maximize quality and duration of remission while minimizing therapy‐related toxicity. Identification of persistent disease or relapse is most often the trigger to intensify or re‐initiate anti‐neoplastic therapy, respectively. In the current era of NHL treatment, this determination is mostly based on imaging and clinical evaluations, tools with imperfect sensitivity and specificity. The availability of minimal residual disease (MRD) monitoring could transform treatment paradigms by allowing intensification of treatment in at‐risk patients or early intervention for impending relapse. Novel methods based on polymerase chain reaction and next‐generation sequencing are now being studied in NHL with promising results. This review outlines the current status of the field in the use of MRD techniques for diffuse large B‐cell lymphoma, mantle cell lymphoma and follicular lymphoma. Specifically, we address their demonstrated and potential clinical utility in risk stratification, monitoring of remission status, and guiding interim and post‐treatment escalation. Future applications of these techniques could identify novel markers of MRD, improve initial treatment selection, guide treatment escalation or de‐escalation, and allow for real‐time monitoring of patterns of clonal evolution, which together could redefine NHL treatment paradigms.
Dual inhibition of the mTORC1 and mTORC2 signaling pathways is a promising therapeutic target for adult T‐cell leukemia
Authors: Kawata Takahito , Tada Kohei , Kobayashi Masayuki , Sakamoto Takashi , Takiuchi Yoko , Iwai Fumie , Sakurada Maki , Hishizawa Masakatsu , Shirakawa Kotaro , Shindo Keisuke , Sato Hironori , Takaori‐Kondo Akifumi 
Published: October 2017

Adult T‐cell leukemia (ATL) has a poor prognosis as a result of severe immunosuppression and rapid tumor progression with resistance to conventional chemotherapy. Recent integrated‐genome analysis has revealed mutations in many genes involved in the T‐cell signaling pathway, suggesting that the aberration of this pathway is an important factor in ATL pathogenesis and ATL‐cell proliferation. We screened a siRNA library to examine signaling‐pathway functionality and found that the PI3K/Akt/mTOR pathway is critical to ATL‐cell proliferation. We therefore investigated the effect of mammalian target of rapamycin (mTOR) inhibitors, including the dual inhibitors PP242 and AZD8055 and the mTORC1 inhibitors rapamycin and everolimus, on human T‐cell leukemia virus type 1 (HTLV‐1)‐infected‐cell and ATL‐cell lines. Both dual inhibitors inhibited the proliferation of all tested cell lines by inducing G1‐phase cell‐cycle arrest and subsequent cell apoptosis, whereas the effects of the 2 mTORC1 inhibitors were limited, as they did not induce cell apoptosis. In the ATL‐cell lines and in the primary ATL samples, both dual inhibitors inhibited phosphorylation of AKT at serine‐473, a target of mTORC2, as well as that of S6K, whereas the mTORC1 inhibitors only inhibited mTORC1. Furthermore, AZD8055 more significantly inhibited the in vivo growth of the ATL‐cell xenografts than did everolimus. These results indicate that the PI3K/mTOR pathway is critical to ATL‐cell proliferation and might thus be a new therapeutic target in ATL.
An Experimental Investigation of Antisocial Lie‐Telling Among Children With Disruptive Behavior Disorders and Typically Developing Children
Authors: Mugno Allison P. , Malloy Lindsay C. , Waschbusch Daniel A. , Pelham Jr. William E. , Talwar Victoria 
Published: October 2017

Children's lie‐telling is surprisingly understudied among children with significant behavioral problems. In the present study, experimental paradigms were used to examine antisocial lie‐telling among ethnically diverse 5‐ to 10‐year‐old children with disruptive behavior disorders (DBD; n = 71) and a typically developing (TD) comparison sample (n = 50) recruited from a southeastern state from 2013 to 2014. Children completed two games that measured the prevalence and skill of their lies: (a) for personal gain and (b) to conceal wrongdoing. Children with DBD were more likely to lie for personal gain than TD children. With age, children were more likely to lie to conceal wrongdoing, but the reverse was true regarding lies for personal gain. Results advance knowledge concerning individual differences in children's lie‐telling.
Bone mineral density in familial partial lipodystrophy
Authors: Fernández‐Pombo Antía , Ossandon‐Otero Javier A. , Guillín‐Amarelle Cristina , Sánchez‐Iglesias Sofía , Castro Ana I. , González‐Méndez Blanca , Rodríguez‐García Silvia , Rodriguez‐Cañete Leticia , Casanueva Felipe F. , Araújo‐Vilar David 
Published: October 2017

SummaryObjectiveType 1 and type 2 familial partial lipodystrophies (FPLD) are characterized by the loss or increase in subcutaneous fat in certain body regions, as well as metabolic disorders. Higher muscle volume and mass have also been described. However, so far, possible bone involvement has not been studied. The aim of this study was to evaluate bone mineral density (BMD) in patients with type 1 and type 2 FPLD.MethodsA total of 143 women were selected and distributed into three groups (17 women with FPLD2, 82 women with FPLD1 and 44 nonlipodystrophic obese female controls). A thorough history and physical examination were carried out on all subjects, as well as the measurement of anthropometric features. BMD along with fat and fat‐free mass (FFM) were determined by DXA (dual‐energy X‐ray absorptiometry). Statistical analyses, primarily using the χ2, ANOVA and ANCOVA tests, were performed, using age, height, fat and FFM as covariables.ResultsAfter eliminating the possible influences of age, height, fat and FFM, we observed that there were no significant differences in total BMD between patients with FPLD and the control group, showing total BMD values of 1.092 ± 0.037 g/cm2 in the FPLD2 group, 1.158 ± 0.013 g/cm2 in the FPLD1 group and 1.173 ± 0.018 g/cm2 in the control group (P = .194). Similarly, no significant differences were found in segmental BMD.ConclusionsUnlike in other types of laminopathy in which bone is affected, in the case of FPLD, there are no differences in BMD compared to nonlipodystrophic subjects.
UK trends of allergic occupational skin disease attributed to fragrances 1996–2015
Authors: Montgomery Rachel L. , Agius Raymond , Wilkinson Stephen M. , Carder Melanie 
Published: October 2017

SummaryBackgroundFragrances are well known to cause allergic contact dermatitis (ACD). Occupationally related cases occur, with certain groups being at higher risk.ObjectiveTo investigate the incidence of occupationally related cases of cutaneous fragrance allergy and to evaluate trends.MethodData on incident cases of occupational ACD caused by fragrances between 1996 and 2015 (inclusive) reported to the EPIDERM surveillance scheme were analysed.ResultsOf the cases reported to EPIDERM during the study period, 5.2% had ACD attributed to fragrances. The highest annual incidence rates were observed in women. Hairdressers, beauticians and people working in related occupations had a 47‐fold higher incidence rate ratio than the reference category (the average of all other occupations combined). Trends analysis suggested a non‐significant increase in fragrance allergy over the study period among all occupations, and beauty and food workers, and a slight decrease in healthcare workers.ConclusionsFragrance allergy is a significant problem in an occupational setting. Although there was no significant change in the incidence of fragrance‐related allergic occupational contact dermatitis (OCD) during the 20‐year study period, this does not mirror the trend in OCD, which is falling. Fragrance allergy continues to be a major contributor to OCD, and contributes to a greater proportion of cases.