bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimization of colorectal cancer vaccine candidate protein GA733‐Fc expression in a baculovirus–insect cell system
Authors: Kim Deuk‐Su , Qiao Lu , Lee Kyung‐Jin , Ko Kisung 
Published: December 2014

AbstractThe baculovirus–insect cell expression system has been used to produce functional recombinant proteins. The antigen GA733 is a cell‐surface glycoprotein highly expressed on most human colorectal carcinoma cells. Conditions for the expression of GA733 fused to the human immunoglobulin IgG Fc fragment (GA733‐Fc) were optimized in the baculovirus expression system. Several variable factors were adjusted to optimize expression, including the cell line (Sf9 and High Five), multiplicity of infection (MOI) value (0.05, 0.1, 0.5, 1 and 3), post‐infection time (48, 72 and 96 h) and harvested sample (cell culture media (CM) or cell lysate (CL)). In addition, two pFastBac Dual vectors carrying the GA733‐Fc gene were constructed to express GA733‐Fc with or without an endoplasmic reticulum (ER) retention sequence KDEL and used to generate recombinant baculoviruses. Western blot showed that expression depended on the conditions used to express the recombinant proteins. The protein production level and secretion capability differed in each cell line. In Sf9 cells, the highest expression in the CM and CL was obtained with GA733‐Fc at 96 h post‐infection at 0.1 MOI and with GA733‐FcK at 96 h post‐infection at 3 MOI, respectively. In High Five cells, the highest expression in the CM and CL was obtained with GA733‐Fc at 48 h post‐infection at 1 MOI and with GA733‐FcK at 48 h post‐infection at 3 MOI, respectively. These results suggest that the MOI value, post‐infection time and subcellular localization affect expression, and that these conditions can be modified to optimize protein expression in the baculovirus–insect cell system.
Mal de Meleda in Indonesia: Mutations in the SLURP1 gene appear to be ubiquitous
Authors: Taylor Jessica A , Bondavalli Davide , Monif Mastura , Yap Lee Mei , Winship Ingrid 
Published: December 2014

AbstractMal de Meleda is a rare autosomal recessive genodermatosis caused by mutations in the ARS B (SLURP1) gene, with possible founder effects in the Mediterranean and Adriatic regions. We report an affected individual from Indonesia without known consanguinity in the family, suggesting that SLURP1 gene mutations are ubiquitous. Recognition of the phenotype can be confirmed by genetic testing, thus facilitating genetic counselling.
Multiple clustered dermatofibroma presenting in a segmental distribution
Authors: Bhabha Friyana K. , Magee Jill , Ng Su Yuen , Grills Claire Elizabeth , Su John , Orchard David 
Published: December 2014

AbstractMultiple dermatofibromas is a rare entity consisting of more than fifteen lesions. Multiple clustered dermatofibroma is a distinct variant of multiple dermatofibromas and is defined as a well‐demarcated plaque composed of individual dermatofibromas. We report a 16‐year‐old boy with multiple clustered dermatofibroma in a segmental distribution, which has previously not been reported in the literature.
Bioequivalence of 0.1% mometasone furoate lotion to 0.1% mometasone furoate hydrogel
Authors: Greive Kerryn A. , Barnes Tanya M. 
Published: December 2014

AbstractBackground/ObjectivesVehicles used for topical therapy can affect drug delivery and patient adherence. This study compared the bioequivalence of 0.1% mometasone furoate lotion (reference) and 0.1% mometasone furoate hydrogel (test). Moisturising capacity and sensitivity/irritancy potential were also determined.MethodsBioequivalence was assessed by vasoconstriction assay and analysis of area under the effect curve (AUEC0–24) according to the Food and Drug Administration (FDA) guidance. In total, 131 individuals were screened in a pilot dose duration‐response study, and 90 responders enrolled. For the pivotal study, lotion and hydrogel (5 mg/cm2) were applied in a double‐blind manner. Vasoconstriction was evaluated by chromameter at 0, 2, 4, 6, 19 and 24 h following lotion and hydrogel removal. Barrier function was measured by assessment of transepidermal water loss (TEWL) and skin hydration. Sensitivity/irritancy potential was assessed by repeat insult patch tests.ResultsThe mean AUEC0–24 of the test hydrogel and reference lotion were −18.200 and −18.953, respectively, with test/reference = 96%, with 90% confidence interval (0.81, 1.12), which was within FDA guidance limits. TEWL was found to significantly decrease by 43 and 29% after 2 and 24 h, respectively, while skin hydration significantly increased by 38% after 24 h following a single application of hydrogel. The hydrogel was also found to be non‐irritating and non‐sensitising. No adverse events were observed.ConclusionsMometasone furoate hydrogel is bioequivalent to mometasone furoate lotion. This novel hydrogel formulation provides effective drug delivery, increases moisturisation and affords greater ease and tolerability of application, improving patients' adherence to therapy.
Cisplatin resistance in germ cell tumours: models and mechanisms
Authors: Jacobsen C. , Honecker F. 
Published: December 2014

SummaryRecent years have led to a better understanding of the mechanisms underlying cisplatin response and resistance in germ cell tumours (GCT), and several promising targets have been identified. Two main mechanisms of the responsiveness to DNA damaging agents have been postulated. Firstly, GCT readily activate a DNA damage response, but show deficits in several damage repair pathways. In particular, they have been found to have defects in interstrand crosslink repair and in homologous recombination (HR). Secondly, GCT, especially embryonal carcinoma (EC) cells, show a hypersensitive apoptotic response to DNA damage, which activates p53, and leads to up‐regulation of the pro‐apoptotic factors Noxa, Puma and Fas in non‐resistant EC. These cells fail to activate p21 which induces a G1/S arrest, but accumulate in G2/M phase. In the absence of functional p53, family members like p73 and GTAp63 might be important in initiating this response. Mechanisms involved in cisplatin resistance are as follows: down‐regulation of Oct4 (e.g. as a result of hypoxia, treatment with retinoic acid or exposure to cisplatin) and failure to induce Puma and Noxa; changes in the expression levels of micro‐RNAs such as miR‐17/‐106b, miR‐302a, or miR‐371 to ‐373; elevated levels of MDM2 and cytoplasmic translocation of p21 by phosphorylation; and activation of the PDGFRβ/PI3K/pAKT pathway. Several approaches to overcome resistance have been successfully examined in vitro and in vivo, including PARP inhibitors, especially in cells showing deficient HR‐repair; stabilization of p53 using nutlin‐3; inhibition of several components of the PI3K/pAKT pathway using small molecules; and DNA demethylation by 5‐azacytidine or 5‐aza‐deoxy‐cytidine, among others. Many of these substances deserve further exploration, alone or in combination with DNA damaging agents, and the most promising approaches should be taken forward to clinical testing. Targeted therapy based on mechanistic insights holds the promise to turn cisplatin‐resistant GCT into a curable disease.
Short‐term outcomes of combined implantation of diffractive multifocal intraocular lenses with different addition power
Authors: Hayashi Ken , Yoshida Motoaki , Hirata Akira , Yoshimura Koichi 
Published: December 2014

AbstractPurposeTo compare short‐term binocular visual function between patients implanted with diffractive multifocal intraocular lenses (MIOLs) of different near addition powers in each eye or the same MIOLs bilaterally.MethodsSeventy patients scheduled for implantation of diffractive MIOLs were divided into two groups: (i) mix and match group, a MIOL with +3.0 dioptre (D) addition power implanted in the dominant eye (Alcon SN60D1) and a MIOL with +4.0D power implanted in the non‐dominant eye (SN60D3) or (ii) same MIOL group, same MIOL (SN60D1) implanted bilaterally. At 3 months postoperatively, we examined binocular visual acuity (VA) at various distances, binocular contrast VA and that with a glare (glare VA), and near stereoacuity.ResultsMean binocular uncorrected (UNVA) or corrected near VA (CNVA) at 0.3 m was significantly better in the mix and match group than in the same MIOL group (p ≤ 0.0066). Binocular uncorrected and distance‐corrected VA at other distances was similar. Binocular UNVA of 0.8 or better was achieved in 77.1% of patients in the mix and match group and 45.7% in the same MIOL group (p = 0.0144). Binocular contrast and glare VA, and stereoacuity did not significantly differ between groups. Spectacle independence and patient satisfaction with near vision were significantly better in the mix and match group (p ≤ 0.0195).ConclusionMix and match implantation of diffractive MIOLs with different addition power provides a better binocular VA curve and spectacle independence than bilateral implantation of the same MIOLs, without compromising contrast sensitivity and stereopsis.
Enhanced depth imaging–optical coherence tomography of the choroid in moderate and severe primary angle‐closure glaucoma
Authors: Li Zheng , Wang Wei , Zhou Minwen , Huang Wenbin , Chen Shida , Li Xingyi , Gao Xinbo , Wang Jiawei , Du Shaolin , Zhang Xiulan 
Published: December 2014

AbstractPurposeTo compare the choroidal thickness (CT) in eyes with moderate and severe primary angle‐closure glaucoma (PACG) with the eyes of healthy controls.MethodsFifty‐nine patients (59 eyes) with PACG and 56 age‐matched normal subjects underwent macular CT scanning using enhanced depth imaging–optical coherence tomography. The subjects with PACG were further classified as having moderate [−12 dB ≤ visual field mean deviation (VF‐MD) ≤ −6 dB] or severe (VF‐MD < −12 dB) glaucoma. The average CT of the PACG eyes at each location was compared to that of normal eyes.ResultsThe CT was significantly increased in moderate and severe PACG eyes compared with the normal eyes at all nine macular locations, with the exception of 1 and 3 mm superior to the fovea. The mean CT under the fovea was 292.0 ± 48.2 μm in the moderate PACG eyes, 277.1 ± 58.3 μm in the severe PACG eyes and 249.9 ± 72.1 μm in the normal eyes, respectively. There were no significant differences between the macular CTs in the eyes with moderate PACG and those in severe PACG eyes (all p > 0.05). Factors associated with a thinner choroid were ageing (p < 0.001), female (p = 0.036) and increasing axial length (p = 0.021). Neither the VF‐MD nor pattern standard deviation was found to be associated with CT.ConclusionsThe CT is greater in patients with PACG, but it does not differ between moderate and severe PACG, suggesting a lack of relationship between CT and the progression of glaucoma based on EDI‐OCT measurements.
The homeostatic role of neuropeptide Y in immune function and its impact on mood and behaviour
Authors: Farzi A. , Reichmann F. , Holzer P. 
Published: December 2014

AbstractNeuropeptide Y (NPY), one of the most abundant peptides in the nervous system, exerts its effects via five receptor types, termed Y1, Y2, Y4, Y5 and Y6. NPY's pleiotropic functions comprise the regulation of brain activity, mood, stress coping, ingestion, digestion, metabolism, vascular and immune function. Nerve‐derived NPY directly affects immune cells while NPY also acts as a paracrine and autocrine immune mediator, because immune cells themselves are capable of producing and releasing NPY. NPY is able to induce immune activation or suppression, depending on a myriad of factors such as the Y receptors activated and cell types involved. There is an intricate relationship between psychological stress, mood disorders and the immune system. While stress represents a risk factor for the development of mood disorders, it exhibits diverse actions on the immune system as well. Conversely, inflammation is regarded as an internal stressor and is increasingly recognized to contribute to the pathogenesis of mood and metabolic disorders. Intriguingly, the cerebral NPY system has been found to protect against distinct disturbances in response to immune challenge, attenuating the sickness response and preventing the development of depression. Thus, NPY plays an important homeostatic role in balancing disturbances of physiological systems caused by peripheral immune challenge. This implication is particularly evident in the brain in which NPY counteracts the negative impact of immune challenge on mood, emotional processing and stress resilience. NPY thus acts as a unique signalling molecule in the interaction of the immune system with the brain in health and disease.
The effectiveness of pharmaceutical interventions for obesity: weight loss with orlistat and sibutramine in a United Kingdom population‐based cohort
Authors: Douglas Ian J. , Bhaskaran Krishnan , Batterham Rachel L. , Smeeth Liam 
Published: December 2014

AimsDrug treatments for obesity have proven efficacy from randomized trials, but their effectiveness in routine clinical practice is unknown. We assessed the effects on weight and body mass index (BMI) of orlistat and sibutramine when delivered in routine primary care.MethodsWe used United Kingdom data from the Clinical Practice Research Datalink to estimate the effects of orlistat or sibutramine on weight and BMI over 3 years following treatment initiation. For comparison, we matched each patient with up to five obese patients receiving neither drug. Mixed effects linear regression with splines was used to model change in weight and BMI. Mean change with 95% confidence intervals (CI) was estimated.ResultsWe identified 100 701 patients receiving orlistat, 15 355 receiving sibutramine and 508 140 non‐intervention patients, with body mass index of 37.2, 36.6 and 33.2 kg m−2, respectively. Patients receiving orlistat lost, on average, 0.94 kg month−1 (0.93 to 0.95) over the first 4 months. Weight gain then occurred, although weight remained slightly below baseline at 3 years. Patients receiving sibutramine lost, 1.28 kg month−1 (1.26 to 1.30) over the first 4 months, but by 3 years had exceeded baseline weight. Non‐intervention patients had slight increases in weight throughout the 3 year period, with gains ranging between 0.01 and 0.06 kg month−1.ConclusionsOrlistat and sibutramine had early effects on weight loss, not sustained over 3 years. As new treatments for obesity are approved, their effectiveness should be measured in routine clinical practice, as effectiveness may be considerably less than seen in randomized trials.
Population‐based cohort studies of type 2 diabetes and stomach cancer risk in Chinese men and women
Authors: Xu Hong‐Li , Tan Yu‐Ting , Epplein Meira , Li Hong‐Lan , Gao Jing , Gao Yu‐Tang , Zheng Wei , Shu Xiao‐Ou , Xiang Yong‐Bing 
Published: December 2014

Although positive associations have been found for diabetes and a number of cancer sites, investigations of stomach cancer are limited and the results lack consistency. In this prospective study we investigated the relationship between type 2 diabetes mellitus (T2DM) and stomach cancer risk in mainland China. We assessed the associations among T2DM, T2DM duration, and stomach cancer risk in two prospective population‐based cohorts, the Shanghai Women's Health Study and the Shanghai Men's Health Study. Included in the study were 61 480 men and 74 941 women. Stomach cancer cases were identified through annual record linkage to the Shanghai Cancer Registry, and verified through home visits and review of medical charts. After a median follow‐up of 7.5 years for the Shanghai Men's Health Study and 13.2 years for the Shanghai Women's Health Study, a total of 755 incident cases of stomach cancer (376 men and 379 women) were identified through to September 2013. Overall, we did not find any evidence that T2DM was associated with an increased risk of stomach cancer either in men (multi‐adjusted hazard ratio = 0.83, 95% confidence interval, 0.59–1.16) or in women (multi‐adjusted hazard ratio = 0.92, 95% confidence interval, 0.68–1.25). Our findings from two large prospective population‐based cohorts suggest that T2DM was not associated with stomach cancer risk.
Effects of testosterone treatment on glucose metabolism and symptoms in men with type 2 diabetes and the metabolic syndrome: a systematic review and meta‐analysis of randomized controlled clinical trials
Authors: Grossmann Mathis , Hoermann Rudolf , Wittert Gary , Yeap Bu B. 
Published: December 2014

SummaryContextThe effects of testosterone treatment on glucose metabolism and other outcomes in men with type 2 diabetes (T2D) and/or the metabolic syndrome are controversial.ObjectiveTo perform a systematic review and meta‐analysis of placebo‐controlled double‐blind randomized controlled clinical trials (RCT) of testosterone treatment in men with T2D and/or the metabolic syndrome.Data sourcesA systematic search of RCTs was conducted using Medline, Embase and the Cochrane Register of controlled trials from inception to July 2014 followed by a manual review of the literature.Study selectionEligible studies were published placebo‐controlled double‐blind RCTs published in English.Data extractionTwo reviewers independently selected studies, determined study quality and extracted outcome and descriptive data.Data synthesisOf the 112 identified studies, seven RCTs including 833 men were eligible for the meta‐analysis. In studies using a simple linear equation to calculate the homeostatic model assessment of insulin resistance (HOMA1), testosterone treatment modestly improved insulin resistance, compared to placebo, pooled mean difference (MD) −1·58 [−2·25, −0·91], P < 0·001. The treatment effect was nonsignificant for RCTs using a more stringent computer‐based equation (HOMA2), MD −0·19 [−0·86, 0·49], P = 0·58). Testosterone treatment did not improve glycaemic (HbA1c) control, MD −0·15 [−0·39, 0·10], P = 0·25, or constitutional symptoms, Aging Male Symptom score, MD −2·49 [−5·81, 0·83], P = 0·14).ConclusionsThis meta‐analysis does not support the routine use of testosterone treatment in men with T2D and/or the metabolic syndrome without classical hypogonadism. Additional studies are needed to determine whether hormonal interventions are warranted in selected men with T2D and/or the metabolic syndrome.
Prevalence of parathyroid carcinoma in 348 patients with multiple endocrine neoplasia type 1 – case report and review of the literature
Authors: Singh Ospina Naykky , Sebo Thomas J. , Thompson Geoffrey B. , Clarke Bart L. , Young William F. 
Published: December 2014

SummaryObjectiveTo report the prevalence of parathyroid carcinoma (PC) in patients with multiple endocrine neoplasia type 1 (MEN1) and review of the literature.BackgroundPrimary hyperparathyroidism (PHP) is the most common manifestation of MEN1. The occurrence of PC in patients with MEN1 is rare and the literature regarding the clinical manifestations – including the prevalence of the disease – is scarce.ContextSingle tertiary care centre experience from 1977 to 2013.DesignElectronic search of the medical records to identify a cohort of patients with MEN1. Literature review based on current case reports.PatientsSingle case of PC in a cohort of 348 patients with MEN1. Ten cases of PC in patients with MEN1 reported in the literature.MeasurementClinical features of PC in patients with MEN1.ResultsThe prevalence of PC in 348 patients with MEN1 was found to be 0·28% (95% CI, 0–1·4%). Based on the current published cases of PC in patients with MEN1, 54·5% were women, mean age at diagnosis was 48·3 years, and the serum PTH concentrations at least four times the upper limit of the reference range in 73% of the cases.ConclusionPC in patients with MEN 1 is rare with a prevalence of 0·28%, and the clinical features are similar to PC in patients without MEN1.
Safety, sterility and stability of direct‐from‐vial multiple dosing intravitreal injection of bevacizumab
Authors: Das Taraprasad , Volety Srinivas , Ahsan Saad M , Thakur Abhay K , Sharma Savitri , Padhi Tapas R , Basu Soumyava , Rao Ch Mohan 
Published: December 2014

AbstractBackgroundThis study aims to determine the stability, sterility and safety of bevacizumab multiple dosing from a single vial without prior aliquoting.MethodsIn‐vitro and human study. Six bevacizumab vials, used in multiple patients on a single day by direct withdrawal from the vial, and stored in 4°C up to a variable period, were tested for stability (high‐performance liquid chromatography; [HPLC]), sterility (culture), conformational stability by circular dichroism and fluorescence spectroscopy and the rubber cork structural integrity (electron microscopy [EM]).ResultsHPLC of all six samples of used bevacizumab and the control bevacizumab sample were similar; culture was negative; and the EM of rubber corks did not show an open communication. Spectroscopic studies indicated drug conformational stability. Further, there was no infection or inflammation in 221 consecutive patients (973 injections) when bevacizumab was stored at 4°C and used for one week.ConclusionBevacizumab does not lose stability when stored at 4°C. It may be used for a week by direct withdrawal from the vial without fear of infection or inflammation if all standard precautions related to intravitreal injection are adhered to.
Deproteinized bovine bone remodeling pattern in alveolar socket: a clinical immunohistological evaluation
Authors: Milani Stefano , Dal Pozzo Laura , Rasperini Giulio , Sforza Chiarella , Dellavia Claudia 
Published: December 2014

AbstractObjectivesConsidering the low rate of deproteinized bovine bone (DBB) graft resorption in vivo and vitro, the aim of this study was to investigate, through an immunohistochemical method, DBB remodeling patterns in human.Material and MethodsSocket preservation, a highly documented and affirmed technique, was selected as the best in vitro model to analyze DBB effect on bone remodeling. Following premolar extraction (T0), 20 patients were randomized into two treatment groups. In the test group (t), the alveolar sockets were grafted with DBB, while in the control group (c) no bone graft was applied and the alveolar sockets were left to heal spontaneously. After 5 months, a re‐entry procedure was performed, and one implant was placed according to manufacturer's protocols (T1). Bone biopsies were harvested for each patient both at T0 and at T1. On the bone samples, immunohistochemical investigations were performed to analyze BMP‐2, BMP‐7, ALP, IL‐6, TNF‐α expression.ResultsBone morphogenetic proteins were more expressed in the control group than in the test group (BMP‐2: P < 0.001; BMP‐7: P = 0.017), while TNF‐α value was larger in the test group (P < 0.001); no statistically significant differences were observed for the other markers. When considering time as the main variable, statistically significant differences were found for BMP‐2 (P < 0.001), BMP‐7 (P < 0.001), IL‐6 (P < 0.001), ALP (P < 0.05), and TNF‐α (P < 0.001). Significant interaction between groups and time was found for BMP‐2 (P < 0.001), BMP‐7 (P < 0.001), TNF‐α (P < 0.001).ConclusionsDeproteinized bovine bone guarantees the activity of bone remodeling processes in human extraction socket at 5 months of healing, bringing to a higher expression of anabolic and catabolic bone markers.