bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacokinetics of Tildrakizumab (MK‐3222), an Anti‐IL‐23 Monoclonal Antibody, After Intravenous or Subcutaneous Administration in Healthy Subjects
Authors: Khalilieh Sauzanne , Hodsman Peter , Xu Christine , Tzontcheva Anjela , Glasgow Shirley , Montgomery Diana 
Published: March 2018

AbstractTildrakizumab, a high‐affinity humanized IgG1k antibody that selectively binds interleukin (IL)‐23 p19 subunit of cytokine IL‐23 and neutralizes its function, is under investigation for treatment of moderate‐to‐severe chronic plaque psoriasis. The objective of this analysis was to assess the pharmacokinetics, bioavailability and safety/tolerability of single ascending doses of tildrakizumab after intravenous (IV) and subcutaneous (SC) dosing in healthy subjects. P05661 was a phase 1, single‐dose, randomized, placebo‐controlled study of tildrakizumab IV doses of 0.1, 0.5, 3 and 10 mg/kg, or placebo. P05776 was a phase 1, single‐dose, randomized, placebo‐controlled study of tildrakizumab SC doses of 50 or 200 mg, or placebo. After either single IV or SC dosing, tildrakizumab exhibited slow systemic clearance (CL), limited volume of distribution and a long t1/2. Both the Cmax and the area under the curve (AUC) increased proportionally with doses from 0.1 to 10 mg/kg, or 50–200 mg. The bioavailability of SC dosing was ~80% (90% CI: 62–103%) for 50 mg and ~73% (90% CI: 46–115%) for 200 mg, respectively, versus 0.5 and 3 mg/kg IV. Across both studies, six of 43 evaluable subjects were positive for post‐dose antidrug antibodies; two of these were positive for neutralizing antibodies. Most adverse events (AEs) were mild; the most frequent AEs included upper respiratory tract infection and headache. Single doses of tildrakizumab 0.1, 0.5, 3 and 10 mg/kg administered IV or single doses of 50 and 200 mg administered SC were safe and well tolerated in healthy adult subjects.
Desperately seeking a cure: Treatment seeking and appraisal in irritable bowel syndrome
Authors: Harvey J. Matthew , Sibelli Alice , Chalder Trudie , Everitt Hazel , Moss‐Morris Rona , Bishop Felicity L. 
Published: March 2018

ObjectivesIrritable bowel syndrome (IBS) is common and adversely affects patients' quality of life. Multiple potential treatment options exist for patients (and clinicians) to choose from, with limited evidence to inform treatment selection. The aim was to explore how patients with IBS go about seeking and appraising different treatment modalities, with a view to elucidating the psychological processes involved and identifying opportunities to improve clinical practice.DesignQualitative study nested within a randomized controlled trial of therapist‐delivered and web‐based cognitive behavioural therapy versus treatment‐as‐usual for IBS.MethodsA total of 52 people participated in semi‐structured interviews about their prior experiences of treatments for IBS. Transcripts were analysed using inductive thematic analysis.ResultsKey themes (desperation for a cure, disappointment at lack of cure, appraising the effects of diverse treatments, and hope for positive effects) clustered around an overarching theme of being trapped within a vicious cycle of hope and despair on treatment seeking. A desperation and willingness drove interviewees to try any treatment modality available that might potentially offer relief. Coming to accept there is no cure for IBS helped interviewees escape the vicious cycle. Treatments were appraised for their effects on symptoms and quality of life while also considering, but rarely prioritizing, other aspects including convenience of the regimen itself, whether it addressed the perceived root causes of IBS, perceived side‐effects, and cost.ConclusionTreatment seeking in IBS can be challenging for patients. Supportive discussions with health care professionals about illness perceptions, treatment beliefs, and goals could improve patients' experiences.
Statement of contribution

What is already known on this subject?

Irritable bowel syndrome (IBS) is a highly prevalent chronic relapsing functional gastrointestinal disorder.

Studies show few treatment modalities provide complete symptom relief.

IBS is associated with emotional and physical distress, and negatively impacts personal, social, and professional aspects of quality of life.

What does this study add?

Patients appraise IBS treatments for impact on quality of life and treatment characteristics.

Developing acceptance and coping strategies helps escape treatment‐seeking vicious cycles of hope and despair.

Clinicians could better support patients by discussing their illness perceptions, treatment goals, and values.
Abnormal development of the inferior temporal region in fetuses with Down syndrome
Authors: Guidi Sandra , Giacomini Andrea , Stagni Fiorenza , Emili Marco , Uguagliati Beatrice , Bonasoni Maria Paola , Bartesaghi Renata 
Published: March 2018

AbstractDown syndrome (DS) is a genetic condition associated with impairment in several cognitive domains. Previous evidence showed a notable neurogenesis reduction in the hippocampal region of DS fetuses, which may account for the impairment of declarative memory that characterizes DS starting from early life stages. The fusiform gyrus (FG) and the inferior temporal gyrus (ITG) play a key role in visual recognition memory, a function that is impaired in children and adults with DS. The goal of the current study was to establish whether fetuses with DS (17–21 weeks of gestation) exhibit neuroanatomical alterations in the FG and ITG that may underlie recognition memory impairment. We found that the FG and ITG of fetuses with DS had a reduced thickness and fewer cells in comparison with euploid fetuses. Moreover, DS fetuses had fewer cells expressing the neuronal marker NeuN than euploid fetuses, but a similar number of cells expressing the astrocytic marker GFAP and, consequently, a higher percentage of astrocytes. Immunohistochemistry for calretinin (CR), a marker of GABAergic interneurons, showed that in DS fetuses the ratio of CR‐positive vs. CR‐negative cells was greater than in euploid fetuses, both in the FG (177%) and ITG (161%). An increased ratio of CR‐positive vs. CR‐negative cells was also found in the entorhinal cortex, hippocampus and dentate gyrus. Results provide novel evidence that the FG and ITG of DS fetuses exhibit numerous developmental defects. These defects may underlie the functional alterations in visual recognition memory observed in children with DS.
Tumour growth rate of follicular thyroid carcinoma is not different from that of follicular adenoma
Authors: Kim Mijin , Han Minkyu , Lee Jeong Hyun , Song Dong Eun , Kim Kyunggon , Baek Jung Hwan , Shong Young Kee , Kim Won Gu 
Published: March 2018

SummaryObjectiveDistinguishing malignancy from benign thyroid nodule has always been challenging, especially in follicular lesions. Thyroid nodules with small size and indeterminate cytology do not lead to immediate surgery. We tried to evaluate whether tumour size and tumour growth rate can distinguish follicular thyroid carcinoma (FTC) from follicular adenoma (FA).Design and PatientsThis retrospective study included patients with pathologically proven FTCs (n = 50) and FAs (n = 110) who underwent preoperative serial neck ultrasonography (US) at least 3 times: it comprises 30% of all follicular tumours (32% FAs and 25% FTCs). The growth rates of follicular tumours on serial US were measured using at least 3 consecutive examinations during a median follow‐up of 4.1 years (range, 0.7‐13.3 years) by experienced radiologists.ResultsThe FA and FTC groups showed no significant difference in clinicopathological characteristics, including age, proportion of large nodules (>4 cm) and preoperative cytology. The maximum diameter of thyroid nodule was gradually increased in both groups with statistical significance (P < .001 and P < .001, respectively). No significant differences in change of maximum diameter of thyroid nodule (P = .132) and tumour volume (P = .208) were found between the FA and FTC groups during the follow‐up. The median time to a significant tumour growth from baseline was not different between the FA and FTC groups (1.4 years and 1.7 years, respectively, P = .556). When we divided the patients into four groups (rapid, moderate, slow and no growth) according to the growth velocity of the thyroid tumours, no significant difference in growth velocity was found among the groups.ConclusionsThe tumour size and growth rate of the thyroid nodule itself could not predict malignancy. Diagnostic approaches that use molecular markers would be more important than clinical features for the decision of diagnostic surgery for patients with follicular tumours.
Direct Position‐Based Solver for Stiff Rods
Authors: Deul Crispin , Kugelstadt Tassilo , Weiler Marcel , Bender Jan 
Published: March 2018

AbstractIn this paper, we present a novel direct solver for the efficient simulation of stiff, inextensible elastic rods within the position‐based dynamics (PBD) framework. It is based on the XPBD algorithm, which extends PBD to simulate elastic objects with physically meaningful material parameters. XPBD approximates an implicit Euler integration and solves the system of non‐linear equations using a non‐linear Gauss–Seidel solver. However, this solver requires many iterations to converge for complex models and if convergence is not reached, the material becomes too soft. In contrast, we use Newton iterations in combination with our direct solver to solve the non‐linear equations which significantly improves convergence by solving all constraints of an acyclic structure (tree), simultaneously. Our solver only requires a few Newton iterations to achieve high stiffness and inextensibility. We model inextensible rods and trees using rigid segments connected by constraints. Bending and twisting constraints are derived from the well‐established Cosserat model. The high performance of our solver is demonstrated in highly realistic simulations of rods consisting of multiple 10 000 segments. In summary, our method allows the efficient simulation of stiff rods in the PBD framework with a speedup of two orders of magnitude compared to the original XPBD approach.
Biocompatibility and osteoconductivity of PLCL coated and noncoated xenografts: An in vitro and preclinical trial
Authors: Mayer Yaniv , Ginesin Ofir , Khutaba Alaa , Machtei Eli E. , Zigdon Giladi Hadar 
Published: March 2018

AbstractBackgroundCells, scaffolds, and growth factors are the key components in bone tissue engineering. Scaffold composition, topography, and architecture influence the amount of regenerated bone in the implantation site. The aims of the study were to compare viability and proliferation of mesenchymal stem cells (MSCs) seeded onto two commercial xenografts: Bio‐Oss (BO) and bioactive bone bovine (BB). Next, these materials were compared for histomorphometric bone formation in a socket preservation model in rats.Materials and MethodsMSCs were seeded onto monolayers of BO or BB granules. Cell viability and proliferation were evaluated after incubation of 0, 2, 20, and 48 h. A total of 24 Sprague Dawley rats underwent unilateral extraction of maxillary molars. Rats were randomly divided into three groups: natural healing (nongrafted socket) or socket preservation with either BO or BB. Rats were sacrificed after 8 weeks, and histomorphometric analysis was done to evaluate bone formation and residual scaffold at the extraction site.ResultsDifferences in the metabolic activity of MSCs that were seeded onto BO or BB was observed at 2 h after seeding: the metabolic activity was elevated compared to baseline in the BB (P = .046) and not changed in the BO wells (P = .84). After 20 h, the metabolic activity of MSCs seeded onto BO was decreasing (P = .005), while cell viability was not changed in the BB group (P = .356). Intergroup comparison revealed higher metabolic activity of MSCs seeded on BB after 48 h compared with BO (P = .016). The in vivo results demonstrated differences in socket healing between the groups: percentage of new bone was higher in the BB compared to BO group (39.1 ± 14.3 vs. 23.7 ± 10.8%, respectively, P = .096). Connective tissue portion was higher in the BO group compared with BB (73.7 ± 11.1 vs. 49.6 ± 13.7%, respectively, P = .018). Residual grafting martial was higher in the BB (11.34 ± 4.18 vs. 2.62 ± 1.23%, P = .011).ConclusionsThe results of this study demonstrating higher vitality and proliferation of MSCs seeded onto BB. Furthermore, following ridge preservation, higher percentage of new bone and lower residual scaffold were found in the BB compared with BO. This enhanced regenerative response might be the result of an enhancement of metabolic activity in cells attached to it. Further research will be needed to understand the precise mechanism.
Brain structure alterations in depression: Psychoradiological evidence
Authors: Zhang Fei‐Fei , Peng Wei , Sweeney John A. , Jia Zhi‐Yun , Gong Qi‐Yong 
Published: March 2018

SummaryDepression is the leading cause of disability around the world, but little is known about its pathology. Currently, the diagnosis of depression is made based on clinical manifestations, with little objective evidence. Magnetic resonance imaging (MRI) has been used to investigate the pathological changes in brain anatomy associated with this disorder. MRI can identify structural alterations in depressive patients in vivo, which could make considerable contributions to clinical diagnosis and treatment. Numerous studies that focused on gray and white matter have found significant brain region alterations in major depressive disorder patients, such as in the frontal lobe, hippocampus, temporal lobe, thalamus, striatum, and amygdala. The results are inconsistent and controversial because of the different demographic and clinical characteristics. However, some regions overlapped; thus, we think that there may be a “hub” in MDD and that an impairment in these regions contributes to disease severity. Brain connections contain both structural connections and functional connections, which reflect disease from a different view and support that MDD may be caused by the interaction of multiple brain regions. According to previous reports, significant circuits include the frontal‐subcortical circuit, the suicide circuit, and the reward circuit. As has been recognized, the pathophysiology of major depressive disorder is complex and changeable. The current review focuses on the significant alterations in the gray and white matter of patients with the depressive disorder to generate a better understanding of the circuits. Moreover, identifying the nuances of depressive disorder and finding a biomarker will make a significant contribution to the guidance of clinical diagnosis and treatment.
Hand eczema and wet work: dose–response relationship and effect of leaving the profession
Authors: Carøe Tanja K. , Ebbehøj Niels E. , Bonde Jens P. E. , Flachs Esben M. , Agner Tove 
Published: March 2018

SummaryBackgroundWet work is an important risk factor for occupational hand eczema.ObjectivesTo examine the effect of job change in workers with occupational hand eczema caused by wet work, and to evaluate the dose–response relationship between intensity of wet work and eczema.MethodThe study is based on a subgroup (n = 954) from a descriptive, registry‐based study including all participants with occupational hand eczema caused by wet work recognized by the Danish Labour Market Insurance Authority in 2010 and 2011. A follow‐up questionnaire was sent out 4–5 years later (response 58%).ResultsChange of profession and being outside the labour market had a positive effect on healing and improvement of hand eczema. Inverse dose–response relationships were found between the amount of time spent with wet hands at work and healing (p = 0.001) and improvement (p < 0.001), and between the frequency of hand washing at work and healing (p = 0.013) and improvement (p < 0.001).ConclusionsLeaving the profession has a positive effect on eczema; however, even minor changes in exposure to wet work were associated with healing and improvement. This information has implications with respect to advice given to patients with occupational hand eczema caused by wet work.
Identification of metastatic papillary thyroid carcinoma in FNA specimens using thyroid peroxidase immunohistochemistry
Authors: Shield P. W. , Crouch S. J. , Papadimos D. J. , Walsh M. D. 
Published: March 2018

IntroductionWe evaluated immunohistochemical staining for thyroid peroxidase (TPO), a glycoprotein found in the apical plasma membrane of thyroid follicular cells, as a marker for metastatic PTC in FNA samples and compared results with thyroglobulin (Tg) and thyroid transcription factor 1 (TTF1) staining.MethodsCell block sections prepared from 100 FNA specimens were stained with a rabbit monoclonal antibody to TPO (EP159). The FNAs included 64 metastatic malignancies from non‐thyroid primary sites, including 18 lung, and 36 cases of thyroid tumours (29 PTC, six cases of medullary thyroid carcinoma and one thyroid anaplastic carcinoma). Thyroid tumours were stained with TTF1 and Tg in addition to TPO. All cases of metastatic lung carcinoma also had TTF‐1 staining results.ResultsTPO staining was negative in all non‐thyroid malignancies. Ninety percent (26/29) of PTC were positive. All positive cases showed strong cytoplasmic staining, although 54% (14/26) showed positivity in less than half of the cells. By comparison, Tg staining of TPC cases was present in 62% and TTF‐1 in 100%. In addition to showing higher sensitivity, interpretation of staining results with TPO was generally easier with than Tg. All metastatic lung adenocarcinomas were positive for TTF‐1 and TPO negative. The six medullary cancers showed positivity in 17%, 0% and 83% with TPO, Tg and TTF‐1, respectively.ConclusionsTPO (mAb EP159) may be a useful addition to immunohistochemical panels for FNA specimens where metastatic PTC is a consideration, particularly in cases where metastatic lung carcinoma features in the differential diagnosis.
Pastor as friend: Reinterpreting Christian leadership
Authors: Adiprasetya Joas 
Published: March 2018

AbstractChristian leadership has long enjoyed the idea of servant‐leadership or doularchy that has been seen as standing against any form of kyriarchy. This article is an attempt to solve the problems left by doularchy and construct a model of philiarchic leadership based on the identity of pastors as friends. Several texts in the Gospel of John will be reinterpreted using the philiarchic lens. The article concludes with three applied ideas that today's Christian leaders should take into consideration.
The Dream of the Red Chamber and Christian theology: Seeking a new philosophy of love from the Christian perspective
Authors: Yuan Gao 
Published: March 2018

AbstractThe Dream of the Red Chamber (Honglou meng or The Story of the Stone), composed by Cao Xueqin in the middle of the eighteenth century during the Qing dynasty, is celebrated as the greatest of all classical Chinese novels. However, little effort has been made to explore its theological dimension, as well as the theological interaction with Chinese classical philosophy in the field of Redology (the name for research around this text). This article aims to fill this gap to explore the theological influences upon the thematic ideas of this novel. Attending to the newly discovered theological materials in recent studies, I argue that the author of Honglou meng is not ignorant of Christianity, and in fact, used a triadic image to refer to the trinitarian persons.
Safety of intranasal human insulin: A review
Authors: Schmid Vera , Kullmann Stephanie , Gfrörer Wieland , Hund Verena , Hallschmid Manfred , Lipp Hans‐Peter , Häring Hans‐Ulrich , Preissl Hubert , Fritsche Andreas , Heni Martin 
Published: March 2018

AimsTo conduct a review in order to assess the safety of intranasal human insulin in clinical studies as well as the temporal stability of nasal insulin sprays.Material and methodsAn electronic search was performed using MEDLINE. We selected original research on intranasal human insulin without further additives in humans. The studies included could be of any design as long as they used human intranasal insulin as their study product. All outcomes and adverse side effects were extracted.ResultsA total of 38 studies in 1092 individuals receiving acute human intranasal insulin treatment and 18 studies in 832 individuals receiving human intranasal insulin treatment lasting between 21 days and 9.7 years were identified. No cases of symptomatic hypoglycaemia or severe adverse events (AEs) were reported. Transient local side effects in the nasal area were frequently experienced after intranasal insulin and placebo spray, while other AEs were less commonly reported. There were no reports of participants being excluded as a result of AEs. No instances of temporal stability of nasal insulin were reported in the literature. Tests on insulin that had been repacked into spray flasks showed that it had a chemical stability of up to 57 days.ConclusionsOur retrospective review of published studies on intranasal insulin did not reveal any safety concerns; however, there were insufficient data to ensure the long‐term safety of this method of chronic insulin administration. Improved insulin preparations that cause less nasal irritation would be desirable for future treatment.
Left ventricular structural alterations are accompanied by subclinical systolic dysfunction in type 2 diabetes mellitus patients with concomitant hyperlipidemia: An analysis based on 3D speckle tracking echocardiography
Authors: Wang Qingqing , Tan Kaibin , Xia Hongmei , Gao Yunhua 
Published: March 2018

AimsThe aims of the current study were to analyze and compare the left ventricular (LV) structure and function in type 2 diabetes mellitus (T2DM) patients with or without hyperlipidemia using conventional echocardiography and real‐time three‐dimensional speckle tracking echocardiography (3DSTE) and to determine the variables that could affect LV strain values in these patients.MethodsEighty‐one T2DM patients with normal LVEF (≥55%) were included, 41 of whom had hyperlipidemia as comorbidity. Forty age‐ and gender‐matched healthy volunteers were recruited as the control group. Conventional echocardiography and 3DSTE were performed, and LV global longitudinal strain (GLS), global circumferential strain (GCS), global area strain (GAS), and global radial strain (GRS) were measured.ResultsSignificant differences in two‐dimensional LV geometry were found among three groups (P = .015). Compared with the control group, LV remodeling was more prevalent in the patients with T2DM, and LV hypertrophy was most prevalent in the T2DM patients with hyperlipidemia. GLS and GCS values decreased significantly in the T2DM patients without hyperlipidemia relative to the control group (P < .01 andP < .05). The GLS, GCS, GAS, and GRS values in the T2DM patients with hyperlipidemia were all significantly lower than those in the control group (allP < .001) and were also significantly lower than those in the T2DM patients without hyperlipidemia (P < .01 orP < .05). Both fasting plasma glucose (FPG) and hyperlipidemia were independently associated with all strain values in patients with T2DM.ConclusionsThe combination of conventional echocardiography and 3DSTE could detect subclinical LV abnormalities in T2DM patients with or without hyperlipidemia.