bluuebunny/crossref_metadata_2025_split huggingface dataset:
Developing and evaluating risk prediction models with panel current status data
Authors: Chan Stephanie , Wang Xuan , Jazić Ina , Peskoe Sarah , Zheng Yingye , Cai Tianxi 
Published: June 2020

AbstractPanel current status data arise frequently in biomedical studies when the occurrence of a particular clinical condition is only examined at several prescheduled visit times. Existing methods for analyzing current status data have largely focused on regression modeling based on commonly used survival models such as the proportional hazards model and the accelerated failure time model. However, these procedures have the limitations of being difficult to implement and performing sub‐optimally in relatively small sample sizes. The performance of these procedures is also unclear under model misspecification. In addition, no methods currently exist to evaluate the prediction performance of estimated risk models with panel current status data. In this paper, we propose a simple estimator under a general class of nonparametric transformation (NPT) models by fitting a logistic regression working model and demonstrate that our proposed estimator is consistent for the NPT model parameter up to a scale multiplier. Furthermore, we propose nonparametric estimators for evaluating the prediction performance of the risk score derived from model fitting, which is valid regardless of the adequacy of the fitted model. Extensive simulation results suggest that our proposed estimators perform well in finite samples and the regression parameter estimators outperform existing estimators under various scenarios. We illustrate the proposed procedures using data from the Framingham Offspring Study.
Lenalidomide and pomalidomide potently interfere with induction of myeloid‐derived suppressor cells in multiple myeloma
Authors: Kuwahara‐Ota Saeko , Shimura Yuji , Steinebach Christian , Isa Reiko , Yamaguchi Junko , Nishiyama Daichi , Fujibayashi Yuto , Takimoto‐Shimomura Tomoko , Mizuno Yoshimi , Matsumura‐Kimoto Yayoi , Tsukamoto Taku , Chinen Yoshiaki , Kobayashi Tsutomu , Horiike Shigeo , Taniwaki Masafumi , Gütschow Michael , Kuroda Junya 
Published: June 2020

SummaryAn increase in immunosuppressive myeloid‐derived suppressor cells (MDSCs) is associated with disease progression and treatment resistance in multiple myeloma (MM). We investigated the mechanisms underlying MDSC induction, and sought to discover a strategy for prevention of MDSC induction in MM. Using a transwell co‐culture system, four of nine examined human myeloma‐derived cell lines (HMCLs) were potent in inducing monocytic (M)‐MDSCs from normal peripheral blood mononuclear cells (PBMCs). As the results, we identified that secretion of C‐C motif chemokine ligand 5 (CCL5) and macrophage migration inhibitory factor (MIF) by myeloma cells is a prerequisite for induction of MDSCs in MM. The immunomodulatory drug (IMiD) compounds, such as lenalidomide (LEN) and pomalidomide (POM), were identified as potent inhibitors of MDSC induction through bidirectional molecular effects of cereblon (CRBN)‐dependent and ‐independent downregulation of CCL5 and MIF in myeloma cells; and downregulation of C‐C motif chemokine receptor 5, a receptor for CCL5, and induction of interferon regulatory factor 8, a critical transcription factor for monocytic differentiation, in PBMCs. In the present study of the molecular mechanisms underlying MDSC induction, we identified a novel effect of LEN and POM of inhibiting MDSC induction via overlapping regulatory effects in myeloma cells and normal PBMCs.
Robot‐assisted laparoscopic artificial urinary sphincter insertion in women with stress urinary incontinence: a pilot single‐centre study
Authors: Chartier‐Kastler Emmanuel , Vaessen Christophe , Rouprêt Morgan , Bassi Silvia , Cancrini Fabiana , Phé Veronique 
Published: June 2020

ObjectiveTo report the functional outcomes of robot‐assisted laparoscopic artificial urinary sphincter (AUS; AMS 800™, American Medical Systems, Minnetonka, MN, USA) implantation and revision in women with stress urinary incontinence (SUI).Patients and MethodsA pilot prospective monocentric study included all consecutive female patients with SUI and undergoing an AUS surgery (implantation or revision) using a robotic approach between 2012 and 2018. The AUS was implanted through a transperitoneal robotic approach. The dissection of the bladder neck was initiated using a posterior approach with a permanent visual control. Intraoperative and early postoperative complications were reported (Clavien–Dindo classification). Continence was defined as no pad usage.ResultsA total of 41 patients, median (interquartile range [IQR]) age 67.5 (57–74.7) years were included. In the group of 27 patients undergoing an AUS implantation, one conversion to laparotomy, one bladder neck and one ureteric injury occurred. The AUS was not implanted in the two latest cases. Twelve minor (Clavien–Dindo Grade I–II) early postoperative complications occurring in 10 patients were reported. The median (IQR) follow‐up was 19 (11–27) months. The continence rate was 84% (21/25 patients). In the group of 14 patients undergoing an AUS revision, no vaginal or bladder injury was reported. One patient had a bowel injury with conversion to laparotomy without AUS insertion. Two major (Clavien–Dindo Grade III–V) early postoperative complications occurred in two patients: one intraoperative bowel injury, which ultimately resulted in the death of the patient and one device infection requiring an explantation of the AUS. The median (IQR) follow‐up was 18 (13.5–24.2) months. The continence rate was 83.3% (10/12 patients).ConclusionThe results obtained after robot‐assisted laparoscopic AUS implantation among women are promising despite the significant morbidity due to previous pelvic surgeries. Longer follow‐up studies are needed.
CB1 receptor‐dependent desensitisation of TRPV1 channels contributes to the analgesic effect of dipyrone in sensitised primary sensory neurons
Authors: Goncalves dos Santos Gilson , Li Ruihui , Ng Melissa Pui Een , Lemes Julia Borges Paes , Vieira Willians Fernando , Nagy Istvan , Tambeli Cláudia Herrera , Parada Carlos Amilcar 
Published: June 2020

Background and PurposeWhile dipyrone is a widely used analgesic, its mechanism of action is not completely understood. Recently, we have reported that the dipyrone metabolite 4‐aminoantipyrine (4‐AA) reduces PGE2‐induced pain‐related behaviour through cannabinoid CB1 receptors. Here, we ascertained, in naive and PGE2‐induced “inflamed” conditions, both in vivo and in vitro, the molecular mechanisms involved in the 4‐AA‐induced analgesic effects.Experimental ApproachThe effect of local administration of 4‐AA (160 μg per paw) on capsaicin (0.12 μg per paw) injection‐induced pain‐related behaviour and 4‐AA's effect on 500‐nM capsaicin‐induced changes in intracellular calcium concentration ([Ca2+]i) in cultured primary sensory neurons were assessed in vivo and in vitro, respectively.Key Results4‐AA reduced capsaicin‐induced nociceptive behaviour in naive and inflamed conditions through CB1 receptors. 4‐AA (100 μM) reduced capsaicin‐induced increase in [Ca2+]i in a CB1 receptor‐dependent manner, when PGE2 was not present. Following PGE2 application, 4‐AA (1–50 μM) increased the [Ca2+]i. Although 4‐AA activated both TRPV1 and TRPA1 channels, increased [Ca2+]i was mediated through TRPV1 channels. Activation of TRPV1 channels resulted in their desensitisation. Blocking CB1 receptors reduced both the excitatory and desensitising effects of 4‐AA.Conclusion and ImplicationsCB1 receptor‐mediated inhibition of TRPV1 channels and TRPV1‐mediated Ca2+‐influx‐ and CB1 receptor‐dependent desensitisation of TRPV1 channels contribute to the anti‐nociceptive effect of 4‐AA in naive and inflamed conditions respectively. Agonists active at both CB1 receptors and TRPV1 channels might be useful as analgesics, particularly in inflammatory conditions.
Skeletal resorption in bryozoans: occurrence, function and recognition
Authors: Batson Peter B. , Tamberg Yuta , Taylor Paul D. , Gordon Dennis P. , Smith Abigail M. 
Published: June 2020

ABSTRACTSkeletal resorption – the physiological removal of mineralised parts by an organism – is an important morphogenetic process in bryozoans. Reports of its occurrence and function across the phylum are patchy, however, and have not previously been synthesised. Here we show that resorption occurs routinely across a wide range of bryozoan clades, colony sizes, growth forms, ontogenetic stages, body wall types, skeletal ultrastructures and mineralogies. Beginning in the early Paleozoic, different modes and functions of resorption have evolved convergently among disparate groups, highlighting its utility as a morphogenetic mode in this phylum. Its functions include branch renovation, formation of branch articulations, excavation of reproductive chambers, part‐shedding, and creation of access portals for budding beyond previously formed skeletal walls. Bryozoan skeletons can be altered by resorption at microscopic, zooidal and colony‐wide scales, typically with a fine degree of control and coordination. We classified resorption patterns in bryozoans according to the morphology and function of the resorption zone (window formation, abscission or excavation), timing within the life of the skeletal element resorbed (primary or secondary), and scale of operation (zooidal or multizooidal). Skeletal resorption is probably greatly underestimated in terms of its utility and role in bryozoan life history, and its prevalence across taxa, especially in fossil forms. It is reported proportionally more frequently in stenolaemates than in gymnolaemates. Some modes of resorption potentially alter or remove the spatial–temporal record of calcification preserved within a skeleton. Consequently, knowledge that resorption has occurred can be relevant for some common applications of skeletal analysis, such as palaeoenvironmental interpretation, or growth and ageing studies. To aid recognition we provide scanning electron microscopy, backscattered electron scanning electron microscopy and transmission electron microscopy examples of skeletal ultrastuctures modified by resorption.
Multimeric TAT peptides are effective in vitro inhibitors of Staphylococcus saprophyticus
Authors: Chiongson Justin Brian V. , Sabido Edna M. , Lin Kuo‐Ging , Alea Glenn V. , Dalisay Doralyn S. , Wu Shih‐Hsiung , Saludes Jonel P. 
Published: June 2020

AbstractTAT (48–60) is a tridecapeptide from the envelope protein of HIV that was previously shown to possess cell‐penetrating properties and antibacterial activity, making it a potential drug delivery agent for anticancer drugs and as antibacterial compound. Previous reports indicated that dimerization enhances the desired bioactivity of TAT; hence, we sought to synthesize multimeric TAT peptides. Herein, we describe the effects of multimerization on the antibacterial activity and secondary structure of the peptide. Terminal modifications such as N‐acetylation and C‐amidation were employed in the design. TATp monomer, dimer, and tetramer were synthesized using solid‐phase peptide synthesis, purified by reversed‐phase HPLC, and then characterized by mass spectrometry. Multimerization of the peptide did not change the secondary structure conformation. The CD analysis revealed a polyproline‐II conformation for all peptide designs. Thus, this study provides a method of increasing the biological activity of the peptide by multimerization while retaining the secondary conformation of its monomeric unit. Furthermore, the bacteria Staphylococcus saprophyticus was found to be susceptible to the dimer and tetramer, with MIC50 of 12.50 μm and <1.56 μm, respectively. This suggests a structure–activity relationship whereby the antibacterial activity increases with increase in valency.
Eukaryotic phosphatase inhibitors enhance colistin efficacy in gram‐negative bacteria
Authors: Barker William T. , Jania Leigh A. , Melander Roberta J. , Koller Beverly H. , Melander Christian 
Published: June 2020

AbstractThe mounting threat of multi‐drug‐resistant (MDR) bacteria places a tremendous strain on the antimicrobial clinical arsenal, forcing physicians to revert to near‐obsolete antibiotics to treat otherwise intractable infections. Antibiotic adjuvant therapy has emerged as a viable alternative to the development of novel antimicrobial agents. This method uses combinations of an existing antibiotic and a non‐antimicrobial small molecule, where the combination either breaks drug resistance or further potentiates antibiotic activity. Through a high‐content screen of eukaryotic kinase inhibitors, our group previously identified two highly potent adjuvants that synergize with colistin, a cyclic, polycationic antimicrobial peptide that serves as a drug of last resort for the treatment of MDR Gram‐negative bacterial infections. Cell signaling proteins implicated in colistin resistance mechanisms display both kinase and phosphatase activities. Herein, we explore the potential for eukaryotic phosphatase inhibitors to be repurposed as colistin adjuvants. From a panel of 48 unique structures, we discovered that the natural product kuwanon G breaks colistin resistance, while the non‐antimicrobial macrolide ascomycin potentiates colistin in polymyxin‐susceptible bacteria.
Vitamin A deficiency exacerbates extrinsic atopic dermatitis development by potentiating type 2 helper T cell‐type inflammation and mast cell activation
Authors: Yang Huan , Chen Jing‐si , Zou Wen‐jing , Tan Qi , Xiao Yi‐zhu , Luo Xiao‐yan , Gao Peisong , Fu Zhou , Wang Hua 
Published: June 2020

AbstractBackgroundVitamin A deficiency (VAD) has been hypothesized to play a role in the pathophysiology of atopic dermatitis (AD).ObjectiveWe sought to verify whether VAD can exacerbate AD development, and explore the possible pathophysiologic mechanism.MethodsWe detected serum vitamin A (VA) concentration in different phenotypes of AD infants (intrinsic AD, iAD and extrinsic AD, eAD), and established ovalbumin (OVA) percutaneous sensitized AD model and passive cutaneous anaphylaxis (PCA) model on VAD and vitamin A supplementation (VAS) model in wild‐type mice (C57BL/6) and established AD model on both normal VA (VAN) and VAD feeding mast cell deficiency mice (ckitw‐sh/w‐sh).ResultsThe average serum VA concentration of eAD was significantly lower than that of iAD, as well as healthy controls. In OVA‐induced C57BL/6 mouse AD model, compared with VAN group, VAD mice manifested significantly more mast cells accumulation in the skin lesions, more severe Th2‐mediated inflammation, including higher serum IgG1 and IgE levels, more IL‐4, IL‐13 mRNA expression in OVA‐sensitized skin, and lower Th1 immune response, including lower serum IgG2a and IFN‐γ mRNA expression in the skin. But there was no significant difference in the expression of IL‐17 mRNA between OVA‐treated skin of VAN and VAD mice. However, in OVA‐induced ckitw‐sh/w‐sh mouse AD model, we did not find any significant differences in the above measurements between VAD and VAN group. In PCA model, VAD mice showed remarkable more blue dye leakage than that in VAN mice. Compared with VAD group, the above‐mentioned inflammatory measurements in VAS group and VAN group were similar in OVA‐induced AD model mice.Conclusions and Clinical RelevanceVAD can exacerbate extrinsic AD by augmenting Th2‐mediated inflammation and mast cell activation. Therapeutic VAS can rescue VAD‐aggravated eAD. It may provide a new strategy for future prevention or treatment of atopic dermatitis.
Implant survival after surgical treatment of peri‐implantitis lesions by means of deproteinized bovine bone mineral with 10% collagen: 10‐year results from a prospective study
Authors: Roccuzzo Mario , Fierravanti Ludovica , Pittoni Dario , Dalmasso Paola , Roccuzzo Andrea 
Published: June 2020

AbstractObjectivesTo evaluate the 10‐year outcomes of a regenerative surgical treatment of single peri‐implantitis intrabony defects, by means of deproteinized bovine bone mineral with 10% collagen (DBBMC).Material and MethodsThe original population consisted of 26 patients with one crater‐like defect, around either SLA or TPS dental implants, with a probing depth ≥6 mm and no implant mobility. After debridement and surface decontamination, the defects were filled with DBBMC. Subsequently, patients were placed in an individualized supportive peri‐implant/periodontal therapy (SPT) program.ResultsFourteen patients (eight SLA and six TPS) reached the 10‐year examination. The overall implant survival rate was 67%, 80% for the SLA, and 55% for the TPS implants. During SPT, five patients were lost to follow‐up, eight patients needed additional antibiotic and/or surgical therapy, and seven patients had the implant removed. PD was reduced from 6.6 ± 1.3 to 3.2 ± 0.7 mm in SLA and from 7.2 ± 1.5 to 3.4 ± 0.6 mm in TPS. BOP decreased from 75.0 ± 31.2% to 7.5 ± 12.1% (SLA) and from 90.0 ± 12.9% to 30.0 ± 19.7% (TPS). Treatment success was found in 5 of the 12 SLA (42%) and in 4 of the 14 TPS (29%).ConclusionsThe proposed reconstructive treatment, followed by SPT, was able to maintain in function the majority of SLA implants, although the overall treatment success was limited and many of TPS implants were removed. Therefore, the decision to treat implants affected by peri‐implantitis should be based on several factors, including surface characteristics.
Matching biodiversity indicators to policy needs
Authors: Stevenson Simone L. , Watermeyer Kate , Caggiano Giovanni , Fulton Elizabeth A. , Ferrier Simon , Nicholson Emily 
Published: June 2020

AbstractAt the global scale, biodiversity indicators are typically used to monitor general trends, but are rarely implemented with specific purpose or linked directly to decision making. Some indicators are better suited to predicting future change, others are more appropriate for evaluating past actions, but this is seldom made explicit. We developed a conceptual model for assigning biodiversity indicators to appropriate functions based on a common approach used in economics. Using the model, indicators can be classified as leading (indicators that change before the subject of interest, informing preventative actions), coincident (indicators that measure the subject of interest), or lagging (indicators that change after the subject of interest has changed and thus can be used to evaluate past actions). We classified indicators based on ecological theory on biodiversity response times and management objectives in 2 case studies: global species extinction and marine ecosystem collapse. For global species extinctions, indicators of abundance (e.g., the Living Planet Index or biodiversity intactness index) were most likely to respond first, as leading indicators that inform preventative action, while extinction indicators were expected to respond slowly, acting as lagging indicators flagging the need for evaluation. For marine ecosystem collapse, indicators of direct responses to fishing were expected to be leading, while those measuring ecosystem collapse could be lagging. Classification defines an active role for indicators within the policy cycle, creates an explicit link to preventative decision‐making, and supports preventative action.
Maternal employment and socio‐economic status of families raising children born very preterm with motor or cognitive impairments: the EPIPAGE cohort study
Authors: Saurel‐Cubizolles Marie‐Josephe , Marchand‐Martin Laetitia , Pierrat Veronique , Arnaud Catherine , Burguet Antoine , Fresson Jeanne , Marret Stephane , Roze Jean‐Christophe , Cambonie Gilles , Matis Jacqueline , Kaminski Monique , Ancel Pierre‐Yves 
Published: June 2020

AimTo describe maternal employment and the socio‐economic status of the household up to 8 years after the very preterm birth of a child, according to the presence and type of motor or cognitive impairment.MethodA total of 1885 families from the French EPIPAGE cohort of children who were born very preterm between 1997 and 1998 were included. Motor and cognitive impairments were identified in children between the ages of 2 and 8 years in 770 families and were classified according to type. The 1115 families with children born very preterm without these impairments were considered the reference group.ResultsMothers of children with severe motor or cognitive impairments were less often working at 5 years after the birth than the reference mothers (21% and 30% vs 57%; p<0.001). Those working before birth returned to work less often and those not working started to work less often after the birth than did reference mothers. At 8 years, mothers of children with severe impairments reported financial difficulties more often than mothers of children without impairments.InterpretationDespite a fairly protective regulatory framework in France, families of infants born very preterm with severe motor or cognitive impairments are socially underprivileged. Measures to maintain an acceptable standard of living for these families and their children are needed.
Left ventricular diastolic function in mitral stenosis
Authors: Venkateshvaran Ashwin , Govind Satish C. 
Published: June 2020

AbstractThe assessment of left ventricular (LV) function in the setting of mitral stenosis (MS) has been critically examined for decades. Accurate assessment of aberrations in diastolic function is important as these subjects often present with signs and symptoms of heart failure and pulmonary congestion that cannot be solely explained by the severity of mechanical obstruction. Echocardiographic evaluation of diastolic dysfunction includes an evaluation of reduced LV compliance, diminished restoring forces, and enhanced stiffness, which are challenging in the setting of MS owing to altered hemodynamic loading. Conventional echocardiographic and Doppler measures offer limited information. Novel assessments employing speckle tracking echocardiography are relatively less studied. A more comprehensive assessment including clinical evaluation, identification of concomitant disorders, and comorbidities is particularly warranted in older subjects with degenerative MS to suspect diastolic dysfunction and arrive at optimal medical therapy or intervention. This review provides an overview of etiological, pathophysiological, echocardiographic, and invasive assessment of diastolic dysfunction in the setting of MS, with specific focus on strengths and limitations of available echocardiographic and Doppler techniques.
Implications of the Polish 1999 administrative reform for regional socio‐economic development
Authors: Myck Michał , Najsztub Mateusz 
Published: June 2020

AbstractOn 1 January 1999, four major reforms took effect in Poland in the areas of health, education, pensions and local administration. After 20 years, only in the last case does the original structural design remain essentially unchanged. We examine the implications of this reform from the perspective of the distance of municipalities from their regional administrative capital. We show that despite fears of negative consequences for peripheral regions, the reform did not result in slower socio‐economic development for those municipalities that found themselves further from the new administrative centres. We argue that regional inclusiveness in the process of development is likely to be an important factor behind the stability of Poland's administrative design.